A group of 20-member macrolactones in which there are three remotely substituted pyran rings that are linked by a methylene bridge and an E-disubstituted alkene, and have geminal dimethyls at C8 and C18 carbons. Some interact with PROTEIN KINASE C.
A phylum of small sessile aquatic animals living as small tufted colonies. Some appear like hydroids or corals, but their internal structure is more advanced. Most bryozoans are matlike, forming thin encrustations on rocks, shells, or kelp. (Storer & Stebbins, General Zoology, 6th ed, p443)
Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.
A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.
Changing an open-chain hydrocarbon to a closed ring. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
A group of the proteobacteria comprised of facultatively anaerobic and fermentative gram-negative bacteria.
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
The relationship between two different species of organisms that are interdependent; each gains benefits from the other or a relationship between different species where both of the organisms in question benefit from the presence of the other.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

Effects of bryostatin-1 on chronic myeloid leukaemia-derived haematopoietic progenitors. (1/250)

Bryostatin-1 belongs to the family of macrocyclic lactones isolated from the marine bryozoan Bugula neritina and is a potent activator of protein kinase C (PKC). Bryostatin has been demonstrated to possess both in vivo and in vitro anti-leukaemic potential. In samples derived from chronic myeloid leukaemia (CML) patients, it has been demonstrated that bryostatin-1 induces a macrophage differentiation, suppresses colony growth in vitro and promotes cytokine secretion from accessory cells. We investigated the effect of bryostatin-1 treatment on colony-forming unit-granulocyte macrophage (CFU-GM) capacity in the presence of accessory cells, using mononuclear cells, as well as in the absence of accessory cells using purified CD34-positive cells. Cells were obtained from 14 CML patients as well as from nine controls. Moreover, CD34-positive cells derived from CML samples and controls were analysed for stem cell frequency and ability using the long-term culture initiating cell (LTCIC) assay at limiting dilution. Individual colonies derived from both the CFU-GM and LTCIC assays were analysed for the presence of the bcr-abl gene with fluorescence in situ hybridization (FISH) to evaluate inhibition of malignant colony growth. The results show that at the CFU-GM level bryostatin-1 treatment resulted in only a 1.4-fold higher reduction of CML colony growth as compared to the control samples, both in the presence and in the absence of accessory cells. However, at the LTCIC level a sixfold higher reduction of CML growth was observed as compared to the control samples. Analysis of the LTCICs at limiting dilution indicates that this purging effect is caused by a decrease in output per malignant LTCIC combined with an increase in the normal stem cell frequency. It is concluded that bryostatin-1 selectively inhibits CML growth at the LTCIC level and should be explored as a purging modality in CML.  (+info)

Identification of sibling species of the bryozoan Bugula neritina that produce different anticancer bryostatins and harbor distinct strains of the bacterial symbiont "Candidatus Endobugula sertula". (2/250)

Although the cosmopolitan marine bryozoan Bugula neritina is recognized as a single species, natural products from this bryozoan vary among populations. B. neritina is the source of the anticancer drug candidate bryostatin 1, but it also produces other bryostatins, and different populations contain different bryostatins. We defined two chemotypes on the basis of previous studies: chemotype O contains bryostatins with an octa-2,4-dienoate substituent (including bryostatin 1), as well as other bryostatins; chemotype M lacks bryostatins with the octa-2,4-dienoate substituent. B. neritina contains a symbiotic gamma-proteobacterium "Candidatus Endobugula sertula," and it has been proposed that bryostatins may be synthesized by bacterial symbionts. In this study, B. neritina populations along the California coast were sampled for genetic variation and bryostatin content. Colonies that differ in chemotype also differ genetically by 8% in the mitochondrial cytochrome c oxidase subunit 1 (CO I) gene; this difference is sufficient to suggest that the chemotypes represent different species. Each species contains a distinct strain of "E. sertula" that differs at four nucleotide sites in the small subunit ribosomal RNA (SSU rRNA) gene. These results indicate that the chemotypes have a genetic basis rather than an environmental cause. Gene sequences from an Atlantic sample matched sequences from the California chemotype M colonies, suggesting that this type may be cosmopolitan due to transport on boat hulls.  (+info)

A Phase I trial of bryostatin-1 in children with refractory solid tumors: a Pediatric Oncology Group study. (3/250)

Bryostatin-1, a macrocyclic lactone, appears to elicit a wide range of biological responses including modulation of protein kinase C (PKC). PKC, one of the major elements in the signal transduction pathway, is involved in the regulation of cell growth, differentiation, gene expression, and tumor promotion. Because of the potential for a unique mechanism of interaction with tumorgenesis, a Phase I trial of bryostatin-1 was performed in children with solid tumors to: (a) establish the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD); (b) establish the pharmacokinetic profile in children; and (c) document any evidence of antitumor activity. A 1-h infusion of bryostatin-1 in a PET formulation (60% polyethylene glycol 400, 30% ethanol, and 10% Tween 80) was administered weekly for 3 weeks to 22 children (age range, 2-21 years) with malignant solid tumors refractory to conventional therapy. Doses ranged from 20 to 57 microg/m2/ dose. Pharmacokinetics were performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. Twenty-two patients on five dose levels were evaluable for toxicities. At the 57 microg/m2/dose level dose-limiting myalgia (grade 3) was observed in three patients; two of those patients also experienced photophobia or eye pain, and one experienced headache. Symptoms occurred in all patients within 24-72 h after the second dose of bryostatin-1 with resolution within 1 week of onset. Other observed toxicities (grades 1 and 2) included elevation in liver transaminases, thrombocytopenia, fever, and flu-like symptoms. The bryostatin-1 infusion was typically well tolerated. Although stable disease was noted in several patients, no complete or partial responses were observed. The recommended Phase II dose of bryostatin-1 administered as a 1-h infusion weekly for 3 of every 4 weeks to children with solid tumors is 44 microg/m2/dose. Myalgia, photophobia, or eye pain, as well as headache, were found to be dose limiting.  (+info)

p90(RSK) blocks bad-mediated cell death via a protein kinase C-dependent pathway. (4/250)

Although activation of protein kinase C (PKC) is known to promote cell survival and protect against cell death, the PKC targets and pathways that serve this function have remained elusive. Here we demonstrate that two potent activators of PKC, 12-O-tetradecanoylphorbol-13-acetate and bryostatin, both stimulate phosphorylation of Bad at Ser(112), a site known to regulate apoptotic cell death by interleukin-3. PKC inhibitors but not PI 3-kinase/Akt inhibitors block 12-O-tetradecanoylphorbol-13-acetate-stimulated Bad phosphorylation. PKC isoforms tested in vitro were unable to phosphorylate Bad at Ser(112), suggesting that PKC acts indirectly to activate a downstream Bad kinase. p90(RSK) and family members RSK-2 and RSK-3 are activated by phorbol ester and phosphorylate Bad at Ser(112) both in vitro and in vivo. p90(RSK) stimulates binding of Bad to 14-3-3 and blocks Bad-mediated cell death in a Ser(112)-dependent manner. These findings suggest that p90(RSK) can function in a PKC-dependent pathway to promote cell survival via phosphorylation and inactivation of Bad-mediated cell death.  (+info)

Differential localization of protein kinase C delta by phorbol esters and related compounds using a fusion protein with green fluorescent protein. (5/250)

Enzyme localization often plays a controlling role in determining its activity and specificity. Protein kinase C (PKC) has long been known to translocate in response to physiological stimuli as well as to exogenous ligands such as the phorbol esters. We report here that different phorbol derivatives and related ligands, selected for differences in chemical structure and profile of biological activity, induce distinct patterns of redistribution of PKC delta. Localization of a PKC delta-green fluorescent protein (GFP) fusion construct was monitored in living Chinese hamster ovary cells as a function of ligand, concentration, and time using confocal laser scanning microscopy. delta-PKC-GFP was expressed predominantly in the cytoplasm, with some in the nucleus and perinuclear region. Phorbol 12-myristate 13-acetate (PMA) induced plasma membrane translocation followed by slower nuclear membrane translocation. As the concentration of PMA increased, the proportion of nuclear to plasma membrane localization increased markedly. In contrast to PMA, bryostatin 1, a unique activator of PKC that induces a subset of PMA-mediated responses while antagonizing others, at all doses induced almost exclusively nuclear membrane translocation. Like PMA, the complete tumor promoter 12-deoxyphorbol 13-tetradecanoate induced plasma membrane and slower nuclear membrane translocation, whereas the inhibitor of tumor promotion 12-deoxyphorbol 13-phenylacetate, which differs only in its side chain, induced a distinctive distribution of PKC delta-GFP. Finally, the novel constrained diacylglycerol derivative B8-DL-B8 induced a slow Golgi localization. We speculate that differential control of PKC delta localization may provide an interesting strategy for producing ligands with differential biological consequences.  (+info)

Proteolytic cleavage of protein kinase Cmu upon induction of apoptosis in U937 cells. (6/250)

Treatment of U937 cells with various apoptosis-inducing agents, such as TNFalpha and beta-D-arabinofuranosylcytosine (ara-C) alone or in combination with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), bryostatin 1 or cycloheximide, causes proteolytic cleavage of protein kinase Cmu (PKCmu) between the regulatory and catalytic domain, generating a 62 kDa catalytic fragment of the kinase. The formation of this fragment is effectively suppressed by the caspase-3 inhibitor Z-DEVD-FMK. In accordance with these in vivo data, treatment of recombinant PKCmu with caspase-3 in vitro results also in the generation of a 62 kDa fragment (p62). Treatment of several aspartic acid to alanine mutants of PKCmu with caspase-3 resulted in an unexpected finding. PKCmu is not cleaved at one of the typical cleavage sites containing the motif DXXD but at the atypical site CQND378/S379. The respective fragment (amino acids 379-912) was expressed in bacteria as a GST fusion protein (GST-p62) and partially purified. In contrast to the intact kinase, the fragment does not respond to the activating cofactors TPA and phosphatidylserine and is thus unable to phosphorylate substrates effectively.  (+info)

Differential roles of the tandem C1 domains of protein kinase C delta in the biphasic down-regulation induced by bryostatin 1. (7/250)

Bryostatin 1 (Bryo), currently in clinical trials, has been shown to induce a biphasic concentration-response curve for down-regulating protein kinase C (PKC) delta, with protection of the enzyme from down-regulation at high Bryo doses. In our ongoing studies to identify the basis for this unique behavior of PKCdelta, we examined the participation of the two ligand binding sites (C1a and C1b) in the regulatory domain of the enzyme. Three mutants of PKCdelta prepared by introducing a point mutation in either C1a or Clb or both C1a and Clb were overexpressed in NIH 3T3 cells. All of the constructs retained a biphasic response to down-regulation assessed after 24-h treatment with Bryo. However, the roles of the individual C1 domains were different for the two phases of the response. For down-regulation, both the C1a and the C1b mutants displayed equivalent 3-4-fold reductions in their affinities for the ligand. For protection from down-regulation, a reduced protection was observed for the C1a mutant, which showed a broader biphasic curve compared with those for wild-type PKCdelta and the Clb mutant. Like wild-type PKCdelta, all of the mutants showed the same subcellular partitioning of the protected enzyme to the particulate fraction of the cells, arguing against changes in sensitivity to Bryo due to differences in localization. Likewise, relatively similar patterns of localization were observed using green fluorescent protein-PKCdelta constructs. We conclude that the C1 domains of PKCdelta do not have equivalent roles in inducing protection against Bryo-induced down-regulation. The C1a domain plays a critical role in conferring the degree of protection at high concentrations of Bryo. Elucidation of the differential effect of Bryo on PKCdelta may suggest strategies for the design of novel ligands with Bryo-like activities.  (+info)

Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia. (8/250)

Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula neritina in 1982 and is currently undergoing evaluation in a number of malignancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymphoma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h continuous infusion every 2 weeks at a dose of 120 microg/m2 per course. Patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion. The dose of vincristine was escalated in groups of three patients as follows: level 1, 0.5 mg/m2; level 2, 1.0 mg/m2; and level 3, 1.4 mg/m2 with vincristine doses capped at 2.0 mg for all patients. Bryostatin 1 alone resulted in one complete remission and two partial remissions. Nine patients received sequential treatment with bryostatin 1 and vincristine. The addition of vincristine at a dose of 2 mg was feasible and caused the expected dose-related sensory neuropathy. Phenotypic analysis by flow cytometric analysis on pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed up-regulation in the coexpression of CD11c/ CD22 on CD20+ B cells in two of four CLL patients studied, which is consistent with in vitro findings of differentiation of CLL cells to a hairy cell phenotype.  (+info)

Bryostatins are a class of naturally occurring marine-derived macrolide lactones that have been isolated from the Bugula neritina, a species of bryozoan. These compounds have attracted significant interest in the medical community due to their potent bioactivities, particularly their ability to modulate various signaling pathways involved in cancer, inflammation, and neurological disorders.

One of the most notable properties of bryostatins is their capacity to act as protein kinase C (PKC) agonists. PKC is a family of enzymes that play critical roles in various cellular processes, including cell growth, differentiation, and apoptosis. By activating PKC, bryostatins can induce differentiation and inhibit proliferation of certain types of cancer cells, making them promising candidates for anti-cancer therapy.

In addition to their effects on PKC, bryostatins have also been shown to modulate other signaling pathways, such as the nuclear factor kappa B (NF-κB) and Akt pathways, which are involved in inflammation and cell survival. These pleiotropic effects make bryostatins interesting targets for the development of novel therapeutic strategies for a range of diseases.

Despite their promising potential, the clinical application of bryostatins has been limited by their low natural abundance and challenging chemical synthesis. Nevertheless, ongoing research efforts continue to explore new methods for large-scale production and optimization of these compounds, with the ultimate goal of harnessing their unique biological activities for medical benefit.

Bryozoa, also known as moss animals, are a phylum of mostly marine aquatic invertebrates that form colonies of tiny, modular individuals called zooids. Each zooid is typically only a few millimeters long and has a set of ciliated tentacles used for feeding and gas exchange.

Bryozoans are filter feeders, using their tentacles to capture plankton and organic particles from the water. They can be found in a variety of habitats, including shallow coastal waters, deep sea environments, and freshwater systems.

The colonies formed by bryozoans can take many different forms, ranging from encrusting mats to branching or leafy structures. Some species produce mineralized skeletons made of calcium carbonate, while others have soft, flexible bodies.

Bryozoa is a relatively small phylum, with around 6,000 known species. While they are not well-known outside of scientific circles, bryozoans play important ecological roles in many aquatic ecosystems, providing habitat and shelter for other organisms and contributing to the formation of complex communities.

Lactones are not a medical term per se, but they are important in the field of pharmaceuticals and medicinal chemistry. Lactones are cyclic esters derived from hydroxy acids. They can be found naturally in various plants, fruits, and some insects. In medicine, lactones have been used in the synthesis of drugs, including certain antibiotics and antifungal agents. For instance, the penicillin family of antibiotics contains a beta-lactone ring in their structure, which is essential for their antibacterial activity.

Macrolides are a class of antibiotics derived from natural products obtained from various species of Streptomyces bacteria. They have a large ring structure consisting of 12, 14, or 15 atoms, to which one or more sugar molecules are attached. Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit, thereby preventing peptide bond formation. Common examples of macrolides include erythromycin, azithromycin, and clarithromycin. They are primarily used to treat respiratory, skin, and soft tissue infections caused by susceptible gram-positive and gram-negative bacteria.

Cyclization is a chemical process that involves forming a cyclic structure or ring-shaped molecule from a linear or open-chain compound. In the context of medicinal chemistry and drug design, cyclization reactions are often used to synthesize complex molecules, including drugs, by creating rings or fused ring systems within the molecule's structure.

Cyclization can occur through various mechanisms, such as intramolecular nucleophilic substitution, electrophilic addition, or radical reactions. The resulting cyclized compounds may exhibit different chemical and biological properties compared to their linear precursors, making them valuable targets for drug discovery and development.

In some cases, the cyclization process can lead to the formation of stereocenters within the molecule, which can impact its three-dimensional shape and how it interacts with biological targets. Therefore, controlling the stereochemistry during cyclization reactions is crucial in medicinal chemistry to optimize the desired biological activity.

Overall, cyclization plays a significant role in the design and synthesis of many pharmaceutical compounds, enabling the creation of complex structures that can interact specifically with biological targets for therapeutic purposes.

I'm sorry for the confusion, but "Palladium" is not a medical term. It is a chemical element with symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1803 by William Hyde Wollaston. It's used in various applications, including jewelry, dental work, electronics, and chemical reactions. If you have any medical terms you would like me to define, please let me know!

Phorbol esters are a type of chemical compound that is derived from the seeds of croton plants. They are known for their ability to activate certain proteins in cells, specifically the protein kinase C (PKC) enzymes. This activation can lead to a variety of cellular responses, including changes in gene expression and cell growth.

Phorbol esters are often used in laboratory research as tools to study cell signaling pathways and have been shown to have tumor-promoting properties. They are also found in some types of skin irritants and have been used in traditional medicine in some cultures. However, due to their potential toxicity and carcinogenicity, they are not used medically in humans.

Gammaproteobacteria is a class of proteobacteria, a group of Gram-negative bacteria. This class includes several important pathogens that can cause various diseases in humans, animals, and plants. Some examples of Gammaproteobacteria include Escherichia coli (a common cause of food poisoning), Pseudomonas aeruginosa (a leading cause of hospital-acquired infections), Vibrio cholerae (the causative agent of cholera), and Yersinia pestis (the bacterium that causes plague).

Gammaproteobacteria are characterized by their single flagellum, which is used for motility, and their outer membrane, which contains lipopolysaccharides that can elicit an immune response in host organisms. They are found in a wide range of environments, including soil, water, and the guts of animals. Some species are capable of fixing nitrogen, making them important contributors to nutrient cycling in ecosystems.

It's worth noting that while Gammaproteobacteria includes many pathogenic species, the majority of proteobacteria are not harmful and play important roles in various ecological systems.

Phorbol 12,13-dibutyrate (PDB) is not a medical term per se, but a chemical compound used in scientific research. It's a type of phorbol ester, which are tumor promoters and active components of croton oil. PDB is often used as a biochemical tool to study cell signaling pathways, particularly those involving protein kinase C (PKC) activation.

Medically, it may be mentioned in research or clinical studies related to cellular processes, cancer, or inflammation. However, it is not something that a patient would typically encounter in a medical setting.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Molecular structure, in the context of biochemistry and molecular biology, refers to the arrangement and organization of atoms and chemical bonds within a molecule. It describes the three-dimensional layout of the constituent elements, including their spatial relationships, bond lengths, and angles. Understanding molecular structure is crucial for elucidating the functions and reactivities of biological macromolecules such as proteins, nucleic acids, lipids, and carbohydrates. Various experimental techniques, like X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM), are employed to determine molecular structures at atomic resolution, providing valuable insights into their biological roles and potential therapeutic targets.

In the context of medicine and biology, symbiosis is a type of close and long-term biological interaction between two different biological organisms. Generally, one organism, called the symbiont, lives inside or on another organism, called the host. This interaction can be mutually beneficial (mutualistic), harmful to the host organism (parasitic), or have no effect on either organism (commensal).

Examples of mutualistic symbiotic relationships in humans include the bacteria that live in our gut and help us digest food, as well as the algae that live inside corals and provide them with nutrients. Parasitic symbioses, on the other hand, involve organisms like viruses or parasitic worms that live inside a host and cause harm to it.

It's worth noting that while the term "symbiosis" is often used in popular culture to refer to any close relationship between two organisms, in scientific contexts it has a more specific meaning related to long-term biological interactions.

Tetradecanoylphorbol acetate (TPA) is defined as a pharmacological agent that is a derivative of the phorbol ester family. It is a potent tumor promoter and activator of protein kinase C (PKC), a group of enzymes that play a role in various cellular processes such as signal transduction, proliferation, and differentiation. TPA has been widely used in research to study PKC-mediated signaling pathways and its role in cancer development and progression. It is also used in topical treatments for skin conditions such as psoriasis.

Antineoplastic agents are a class of drugs used to treat malignant neoplasms or cancer. These agents work by inhibiting the growth and proliferation of cancer cells, either by killing them or preventing their division and replication. Antineoplastic agents can be classified based on their mechanism of action, such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapy agents.

Alkylating agents work by adding alkyl groups to DNA, which can cause cross-linking of DNA strands and ultimately lead to cell death. Antimetabolites interfere with the metabolic processes necessary for DNA synthesis and replication, while topoisomerase inhibitors prevent the relaxation of supercoiled DNA during replication. Mitotic inhibitors disrupt the normal functioning of the mitotic spindle, which is essential for cell division. Targeted therapy agents are designed to target specific molecular abnormalities in cancer cells, such as mutated oncogenes or dysregulated signaling pathways.

It's important to note that antineoplastic agents can also affect normal cells and tissues, leading to various side effects such as nausea, vomiting, hair loss, and myelosuppression (suppression of bone marrow function). Therefore, the use of these drugs requires careful monitoring and management of their potential adverse effects.

A Structure-Activity Relationship (SAR) in the context of medicinal chemistry and pharmacology refers to the relationship between the chemical structure of a drug or molecule and its biological activity or effect on a target protein, cell, or organism. SAR studies aim to identify patterns and correlations between structural features of a compound and its ability to interact with a specific biological target, leading to a desired therapeutic response or undesired side effects.

By analyzing the SAR, researchers can optimize the chemical structure of lead compounds to enhance their potency, selectivity, safety, and pharmacokinetic properties, ultimately guiding the design and development of novel drugs with improved efficacy and reduced toxicity.

Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti ... Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided ... As of 2010 20 different bryostatins had been isolated. The low concentration in bryozoans (to extract one gram of bryostatin, ... Total syntheses have been published for bryostatins 1, 2, 3, 7, 9 and 16. Among them, Wender's total synthesis of bryostatin 1 ...
... produces the bryostatins, a group of around twenty bioactive natural products. The bryostatins are under investigation for ... Despite that, there is a challenge in the utilization of bryostatins in medical treatments, given that it is only found in ... Trindade-Silva, Amaro E; Lim-Fong, Grace E; Sharp, Koty H; Haygood, Margo G (2010-12-01). "Bryostatins: biological context and ... Ruan BF, Zhu HL (2012). "The chemistry and biology of the bryostatins: potential PKC inhibitors in clinical development". Curr ...
Bryostatins were first isolated from Bryozoa. Salinosporamides are derived from Salinispora tropica. Ziconotide is derived from ...
"The Bryostatins' Tale", Chemical and Engineering News 89.43, October 24, 2011, pp. 10-17 Manning, Thomas J.; Land, Michael; ... "Identifying bryostatins and potential precursors from the bryozoan 'Bugula neritina'", Natural Product Research 19.5 (2005) 467 ... "Identifying bryostatins and potential precursors from the bryozoanBugula neritina". Natural Product Research. 19 (5): 467-491. ...
A group of chemicals called bryostatins can be extracted from the marine bryozoan Bugula neritina. In 2001 pharmaceutical ...
The Saksena-Evans reduction has since been used in the synthesis of several products, particularly the bryostatins. Evans- ...
Certain antineoplastic agents, bryostatins 4 and 5, have been extracted from Aplidium californicum and are being evaluated. ...
... neritina attracted interest as a source of cytotoxic chemicals, bryostatins, under clinical investigation as anti-cancer ... B The Bryostatins' Tale Chemical and Engineering News, Vol 89, No 43 PP. 10 - 17 Oct 24, 2011 accessed Dec 19, 2017 "Bryostatin ...
Throughout his career, he pursued the total synthesis of complex natural products, culminating in his work on bryostatins. Keck ...
Using this strategy, Pettit and his research group discovered multiple anti-cancer compounds, including bryostatins, ...
... and the bryostatins (from the bryozoan Bugula neritina). Natural products sometimes have pharmacological activity that can be ...
"The Bryostatins' Tale", Chemical and Engineering News 89.43, October 24, 2011, pp. 10-17 Gordon, R. Sharov, AA Eds. (2017). ... "Identifying bryostatins and potential precursors from the bryozoan 'Bugula neritina'", Natural Product Research 19.5 (2005) 467 ...
Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti ... Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided ... As of 2010 20 different bryostatins had been isolated. The low concentration in bryozoans (to extract one gram of bryostatin, ... Total syntheses have been published for bryostatins 1, 2, 3, 7, 9 and 16. Among them, Wenders total synthesis of bryostatin 1 ...
"This finding is essential for the formulation of the combination therapy using low nanomolar concentrations of bryostatins. ... While HDACs can be administered in continuous dosing protocol, bryostatins can be administered following a cyclical dosing ... we determined which combinations of bryostatins and HDACs inhibitors synergize to antagonize HIV-1 latency," says Eduardo Muñoz ...
Bryostatins are a family of natural products consisting of large macrocyclic lactone rings. They are produced in tiny amounts ... Bryostatins were discovered almost 50 years ago and have been of intense interest to scientists thanks to their therapeutic ... Bryostatins are, however, very scarce. Fortunately, the compounds are exceptionally potent - a single gram is enough to treat ... This is just as well as, when the US National Cancer Institute (NCI) went hunting for bryostatins in 1991, 12.7 tonnes of the ...
The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological ... The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. As "E. sertula" is to date ... Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, ... uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins ...
Chapter 8 The Bryostatins. Chapter 9 The Isolation, Characterization, and Development of a Novel Class of Potent Antimitotic ...
Although ~21 natural bryostatins have been isolated, however only bryostatin-1 (1) has received much interest among medicinal ... Bryostatins are complex macrolactones isolated from marine organisms Bryozoan Bugula neritina. They are potent modulators of ... In a nutshell, the natural as well as synthetic bryostatins have generated a strong hope to emerge as treatment for cancer ... Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review. ...
Bryostatins: the asymmetric synthesis of the C1-C9 and C17-C27 fragments. De Brabander, J. K.; Vandewalle, M. Synthesis 1994, ... Bryostatins: the asymmetric synthesis of C1-C9 and C11-C16 fragments. De Brabander, J. K.; Vanhessche, K.; Vandewalle, M. ...
Bryostatins are a group of macrolide lactones first discovered in the late 1960s in a species of bryozoan, Bugula neritina. It ...
Action of phorbol esters, bryostatins, and retinoic acid on cholesterol sulfate synthesis: Relation to the multistep process of ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
HN - 2008 BX - Acylated Homoserine Lactone MH - Bryostatins UI - D054713 MN - D02.540.505.112 MS - A group of 20-member ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
HN - 2008 BX - Acylated Homoserine Lactone MH - Bryostatins UI - D054713 MN - D02.540.505.112 MS - A group of 20-member ...
Bryostatins, Carotenoids, β-Carotene, β-Carotene isolation, Lutein isolation, Zeaxanthin, Zeaxanthin isolation, Lycopene, ...
Bryostatins. Brioestatinas. Ciclitóis. Cyclitols. Ciclitoles. Compostos Azabicíclicos. Azabicyclo Compounds. Compuestos de ...
Polyene macrolide antibiotic with unknown composition. It is obtained from Streptomyces aureofaciens. It is used as an antifungal agent, an antiprotozoal agent, and in the treatment of BENIGN PROSTATIC HYPERTROPHY ...
This graph shows the total number of publications written about "Lucensomycin" by people in UAMS Profiles by year, and whether "Lucensomycin" was a major or minor topic of these publications ...
Bryostatins [D02.540.576.500.937] * Candicidin [D02.540.576.500.968] * Epothilones [D02.540.576.500.984] ...
Bryostatins [D02.540.576.500.937] * Candicidin [D02.540.576.500.968] * Epothilones [D02.540.576.500.984] ...
"Bryostatins" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... This graph shows the total number of publications written about "Bryostatins" by people in this website by year, and whether " ... Below are the most recent publications written about "Bryostatins" by people in Profiles. ...
MeSH Terms: Bryostatins; Cell Differentiation/drug effects; Culture Media; Dose-Response Relationship, Drug; Humans; Lactones/ ...
Bryostatins / pharmacology* Actions. * Search in PubMed * Search in MeSH * Add to Search ...
1. Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells.. Jalava ... 4. Comparison of effects of bryostatins 1 and 2 and 12-O-tetradecanoylphorbol-13-acetate on protein kinase C activity in A549 ...
Bryostatins Preferred Term Term UI T692456. Date02/28/2007. LexicalTag NON. ThesaurusID NLM (2008). ... Bryostatins Preferred Concept UI. M0507120. Registry Number. 0. Scope Note. A group of 20-member macrolactones in which there ... Bryostatins. Tree Number(s). D02.355.291.933.875.250. D02.540.576.500.937. D02.540.576.625.937.250. D04.345.241.654.937.250. ...
Bryostatins Preferred Term Term UI T692456. Date02/28/2007. LexicalTag NON. ThesaurusID NLM (2008). ... Bryostatins Preferred Concept UI. M0507120. Registry Number. 0. Scope Note. A group of 20-member macrolactones in which there ... Bryostatins. Tree Number(s). D02.540.576.500.937. Unique ID. D054713. RDF Unique Identifier. http://id.nlm.nih.gov/mesh/D054713 ...
Dive into the research topics where George Kyei is active. These topic labels come from the works of this person. Together they form a unique fingerprint ...
Bryostatins - Preferred Concept UI. M0507120. Scope note. A group of 20-member macrolactones in which there are three remotely ...
The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological ... The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. As "E. sertula" is to date ... Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, ... uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins ...
5. Identification and Biological Activities of Bryostatins from Japanese Bryozoan. Ueno, S., R.C. Yanagita, K. Murakami, A. ...
Blue N0000166474 Bromthymol Blue N0000179057 bronopol N0000170884 Brucella Vaccine N0000178894 brucine N0000178792 Bryostatins ...
From the species Bugula neritina, chemicals called bryostatins can be extracted, and these are used in medical research for ...
Trost, Barry M; Yang, Hanbiao; Dong, Guangbin (2011) Total syntheses of bryostatins: synthesis of two ring-expanded bryostatin ... catalysis may lead to biologically active targets containing such subunits illustrated by dactyolide and the bryostatins. ...
Bryostatins, Carotenoids, β-Carotene, β-Carotene isolation, Lutein isolation, Zeaxanthin, Zeaxanthin isolation, Lycopene, ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins D2.540.505.112 D2.540.576.500.937 Buddleja B1.650.940.800.575.100.892.124 B1.650.940.800.575.100.583.800.124 ...
Bryostatins. Briostatinas. Brioestatinas. Cucurbitacins. Cucurbitacinas. Cucurbitacinas. Cyclitols. Ciclitóis. Ciclitoles. ...
Bryostatins Bryozoa BTB-POZ Domain Buchnera Bucladesine Bucrylate Budd-Chiari Syndrome Buddhism Buddleja Budesonide Budesonide ...
  • Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti-AIDS/HIV agents and in people with Alzheimer's disease. (wikipedia.org)
  • The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. (scite.ai)
  • Total syntheses of natural bryostatins have impressively improved, and a noteworthy synthesis of bryostatin 1 has been reported, requiring 57 steps,' says Paul Wender at Stanford University, US, who led the study. (chemistryworld.com)
  • The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. (scite.ai)
  • Chemical synthesis still seems the best option, but bryostatins are complex and structurally challenging so the synthetic routes to these molecules are long. (chemistryworld.com)
  • Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided to JL Hartwell's anticancer drug discovery group at the National Cancer Institute (NCI) by Jack Rudloe. (wikipedia.org)
  • This is just as well as, when the US National Cancer Institute (NCI) went hunting for bryostatins in 1991, 12.7 tonnes of the bryozoan only yielded 18g of the compound. (chemistryworld.com)
  • These post-β-Branching steps generate the vinyl methylester moieties which are found in all natural product bryostatins. (wikipedia.org)
  • Bryostatins are a family of natural products consisting of large macrocyclic lactone rings. (chemistryworld.com)
  • As "E. sertula" is to date uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins in large enough quantities for development into a pharmaceutical. (scite.ai)
  • Bryostatins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (musc.edu)
  • Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided to JL Hartwell's anticancer drug discovery group at the National Cancer Institute (NCI) by Jack Rudloe. (wikipedia.org)
  • This graph shows the total number of publications written about "Bryostatins" by people in this website by year, and whether "Bryostatins" was a major or minor topic of these publications. (musc.edu)
  • 1. Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells. (nih.gov)
  • 4. Comparison of effects of bryostatins 1 and 2 and 12-O-tetradecanoylphorbol-13-acetate on protein kinase C activity in A549 human lung carcinoma cells. (nih.gov)