It is a metabolite of lucanthone. Hycanthone interferes with parasite nerve function, resulting in paralysis and death. This ...
Pharmaceutical drugs that are derivatives of thioxanthone include hycanthone and lucanthone. Thioxanthone at Sigma-Aldrich ...
Known inhibitors of APE1 include 7-nitroindole-2-carboxylic acid (NCA) and lucanthone. Both of these structures possess rings ...
... lucanthone MeSH D03.494.953.704.787 - thiothixene MeSH D03.494.953.852 - xanthones MeSH D03.494.953.852.388 - lucanthone MeSH ...
Examples listed in MeSH include: amoscanate arteether artemether chloroxylenol hycanthone lucanthone metrifonate niridazole ...
The molecular formula C20H24N2OS (molar mass: 340.48 g/mol, exact mass: 340.1609 u) may refer to: Cinanserin Lucanthone ...
... lucanthone (INN) lucartamide (INN) lucatumumab (USAN) lucimycin (INN) lucinactant (USAN) Ludiomil lufenuron (INN) lufironil ( ...
... is a drug used in chemotherapy. It is a prodrug and is converted to the active metabolite hycanthone. Hycanthone ...
InChI=1S/C55H83N17O21S3/c1-20-33(69-46(72-44(20)58)25(12-31(57)76)64-13-24(56)45(59)82)50(86)71-35(41(26-14-61-19-65-26)91-54-43(39(80)37(78)29(15-73)90-54)92-53-40(81)42(93-55(60)88)38(79)30(16-74)89-53)51(87)66-22(3)36(77)21(2)47(83)70-34(23(4)75)49(85)63-10-8-32-67-28(18-94-32)52-68-27(17-95-52)48(84)62-9-7-11-96(5)6/h14,17-19,21-25,29-30,34-43,53-54,64,73-75,77-81H,7-13,15-16,56H2,1-6H3,(H13-,57,58,59,60,61,62,63,65,66,69,70,71,72,76,82,83,84,85,86,87,88)/p+1/t21-,22+,23+,24-,25-,29-,30+,34-,35-,36-,37+,38+,39-,40-,41?,42-,43-,53+,54-/m0/s1 ...
... is a drug used in chemotherapy. It is a semi-synthetic camptothecin analogue indicated for Small Cell Lung Cancer and Ovarian Cancer, approved in South Korea under the trade name Camtobell(R), presented in 2 mg vials for injection.[1] The drug is marketed by ChongKunDang Pharmaceuticals [2] since 2003 [3] Belotecan blocks topoisomerase I with a pIC50 of 6.56,[4] stabilizing the cleavable complex of topoisomerase I-DNA, which inhibits the religation of single-stranded DNA breaks generated by topoisomerase I; lethal double-stranded DNA breaks occur when the topoisomerase I-DNA complex is encountered by the DNA replication machinery, DNA replication is disrupted, and the tumor cell undergoes apoptosis. Topoisomerase I is an enzyme that mediates reversible single-strand breaks in DNA during DNA replication. ...
... was first reported in the scientific literature in 1994, by a team of researchers from Fujisawa Pharmaceutical Company (now Astellas Pharma) in Tsukuba, Japan, who isolated it in a culture of Chromobacterium violaceum from a soil sample obtained in Yamagata Prefecture.[3] It was found to have little to no antibacterial activity, but was potently cytotoxic against several human cancer cell lines, with no effect on normal cells; studies on mice later found it to have antitumor activity in vivo as well.[3]. The first total synthesis of romidepsin was accomplished by Harvard researchers and published in 1996.[4] Its mechanism of action was elucidated in 1998, when researchers from Fujisawa and the University of Tokyo found it to be a histone deacetylase inhibitor with effects similar to those of trichostatin A.[5]. ...
... (often abbreviated to chemo and sometimes CTX or CTx) is a category of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.. By common usage, the term chemotherapy has come to connote the use of rather non-specific intracellular poisons, especially related to inhibiting the process of cell division known as mitosis, and generally excludes agents that more selectively block extracellular growth signals (i.e. blockers of signal transduction). To avoid these connotations for recently developed (against specific molecular or genetic targets) therapies which inhibit of ...
Nitrogen mustards arose from the derivatization of sulphur mustard gas after military personnel exposed to it during World War I were observed to have decreased white blood cell counts.[15] Since the sulphur mustard gas was too toxic to be used in humans, Gilman hypothesized that by reducing the electrophilicity of the agent, which made it highly chemically reactive towards electron-rich groups, then less toxic drugs could be obtained. To this end, he made analogues that were less electrophilic by exchanging the sulphur with a nitrogen, leading to the nitrogen mustards.[16] With an acceptable therapeutic index in humans, nitrogen mustards were first introduced in the clinic in 1946.[17] Aliphatic mustards were developed first, such as mechlorethamine hydrochloride (mustine hydrochloride) which is still used in the clinic today. In the 1950s, aromatic mustards like chlorambucil were introduced as less toxic alkylating agents than the aliphatic nitrogen mustards, proving to be less electrophilic ...
Cyclin-dependent kinases (CDKs) 4 and 6 are enzymes that have been shown to promote cell division and multiplication in both normal and cancer cells. Many cancer cells have shown abnormalities that increase the activity of CDK, leading to the inactivation of certain tumor suppressor genes.[3][10] When used in combination with other drugs such as an ALK or an MEK inhibitor, ribociclib has been shown to have a synergistic effect, resulting in improved responses.[11][12] Again, this is likely a result of "crosstalk" between signaling pathways. Simply blocking one pathway in cancer tumorigenesis can sometimes result in "tumor compensation", where the tumor compensates for the blocked signaling pathway by utilizing other pathways to survive. By blocking several pathways at once, it is thought that the tumor is less able to compensate, and a greater anti-tumor response is often observed. Utilizing ribociclib in combination with other agents has been shown to reduce the development of resistance to ...
In the mid-1990s Beutler, in collaboration with Jack Sipe, a neurologist at Scripps, ran several clinical trials exploring the utility of cladribine in multiple sclerosis, based on the drug's immunosuppressive effects. Sipe's insight into MS, and Beutler's interest in MS due to his sister having it, led a very productive collaboration.[18]:17[22] Ortho-Clinical, a subsidiary of J&J, filed an NDA for cladribine for MS in 1997 but withdrew it in the late 1990s after discussion with the FDA proved that more clinical data would be needed.[23][24] Ivax acquired the rights for oral administration of cladribine to treat MS from Scripps in 2000,[25] and partnered with Serono in 2002.[24] Ivax was acquired by Teva in 2006,[26][27] and Merck KGaA acquired control of Serono's drug business in 2006.[28] An oral formulation of the drug with cyclodextrin was developed[29]:16 and Ivax and Serono, and then Merck KGaA conducted several clinical studies. Merck KGaA submitted an application to the European ...
There are several ways molecules (in this case, also known as ligands) can interact with DNA. Ligands may interact with DNA by covalently binding, electrostatically binding, or intercalating.[1] Intercalation occurs when ligands of an appropriate size and chemical nature fit themselves in between base pairs of DNA. These ligands are mostly polycyclic, aromatic, and planar, and therefore often make good nucleic acid stains. Intensively studied DNA intercalators include berberine, ethidium bromide, proflavine, daunomycin, doxorubicin, and thalidomide. DNA intercalators are used in chemotherapeutic treatment to inhibit DNA replication in rapidly growing cancer cells. Examples include doxorubicin (adriamycin) and daunorubicin (both of which are used in treatment of Hodgkin's lymphoma), and dactinomycin (used in Wilm's tumour, Ewing's Sarcoma, rhabdomyosarcoma). Metallointercalators are complexes of a metal cation with polycyclic aromatic ligands. The most commonly used metal ion is ruthenium(II), ...
... (INN; previously known as SM-5887) is an anthracycline used in the treatment of lung cancer.[1] It is marketed in Japan since 2002 by Sumitomo under the brand name Calsed.[2] Amrubicin acts by inhibiting topoisomerase II, and has been compared in clinical trials with topotecan, a Topoisomerase I inhibitor.[3][4] It has also been studied for the treatment of bladder carcinoma[5] and gastric cancer.[6] Amrubicin was the first anthracycline derivative created by de novo synthesis and was first published in 1989 by scientists from Sumitomo.[7] ...
where CL is total body clearance (L/h), BSA is total body surface area (m2), AAG and ALB represent alpha1 acid glycoprotein and albumin plasma concentrations (g/L) respectively, and AGE is the patients age (years).[13] HEP12 represents a measure of hepatic dysfunction, affecting clearance of docetaxel. This final model accounted for a modest proportion of patients and identified most of the patients varying from the model (population median of CL = 35.6 L/h) as having hepatic dysfunction, indicating hepatic function as the most unpredictable factor with regards to clearance variability.[13] Patients with significant hepatic dysfunction had an approximately 30% decrease in clearance of docetaxel and were also at a higher risk of toxicity poisoning from docetaxel treatment.[13] Clearance has been shown from population pharmacokinetic studies to decrease significantly with age, increased alpha1 acid glycoprotein and albumin concentrations and decreased body surface area.[13] Renal impairment is ...
In the late nineteenth century. Finsen successfully demonstrated phototherapy by employing heat-filtered light from a carbon-arc lamp (the "Finsen lamp") in the treatment of a tubercular condition of the skin known as lupus vulgaris, for which he won the 1903 Nobel Prize in Physiology or Medicine.[5] In 1913 another German scientist, Meyer-Betz, described the major stumbling block of photodynamic therapy. After injecting himself with haematoporphyrin (Hp, a photosensitiser), he swiftly experienced a general skin sensitivity upon exposure to sunlight-a recurrent problem with many photosensitisers.[5] The first evidence that agents, photosensitive synthetic dyes, in combination with a light source and oxygen could have potential therapeutic effect was made at the turn of the 20th century in the laboratory of Hermann von Tappeiner in Munich, Germany. Germany was leading the world in industrial dye synthesis at the time.[5] While studying the effects of acridine on paramecia cultures, Oscar Raab, a ...
During the 1950s and 1960s, the National Cancer Institute carried out a wide-ranging program of screening plant and marine organism material. As part of that program extract from the sea squirt Ecteinascidia turbinata was found to have anticancer activity in 1969.[1] Separation and characterisation of the active molecules had to wait many years for the development of sufficiently sensitive techniques, and the structure of one of them, Ecteinascidin 743, was determined by KL Rinehart at the University of Illinois in 1984.[2] Rinehart had collected his sea squirts by scuba diving in the reefs of the West Indies.[3] Recently, the biosynthetic pathway responsible for producing the drug has been determined to come from Candidatus Endoecteinascidia frumentensis, a microbial symbiont of the tunicate.[4] The Spanish company PharmaMar licensed the compound from the University of Illinois before 1994[citation needed] and attempted to farm the sea squirt with limited success.[3] Yields from the sea squirt ...
... was first made in 1963 by Ozegowski and Krebs in East Germany (the former German Democratic Republic).[9] Until 1990 it was available only in East Germany. East German investigators found that it was useful for treating chronic lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma and lung cancer. Bendamustine received its first marketing approval in Germany, where it is marketed under the tradename Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited. It is indicated as a single-agent or in combination with other anti-cancer agents for indolent non-Hodgkin's lymphoma, multiple myeloma, and chronic lymphocytic leukemia. SymBio Pharmaceuticals Ltd. holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries. In March 2008, Cephalon received approval from the United States Food and Drug Administration to market bendamustine in the US, where it is sold under the ...
Research on this class of drugs began in the 1950s at SRI International, where scientists were focused on developing new chemotherapies and antifolates that would be effective against tumor cells.[1] In the late 1970s, researchers at Memorial Sloan Kettering Cancer Center discovered that cancerous cells take in natural folate through a protein identified as plasma membrane transporter (now referred to as "reduced folate carrier type 1" or "RFC-1"). Further research showed that when normal cells evolve into cancerous cells they often overproduce RFC-1 to ensure they get enough folate.[6] A subsequent scientific collaboration was ultimately formed among SRI International, Memorial Sloan Kettering Cancer Center, and the Southern Research Institute with the intention of developing an antifolate with greater therapeutic selectivity - an agent that could be more effectively internalized into tumors (transported into the cells through RFC-1) and would be more toxic to cancer cells than normal cells.[6] ...
Another amino acid-like drug is the antineoplastic agent melphalan. Tumor cells spend less time in resting phases than normal cells so at any given time, they are more likely to be metabolically active than most normal host cells. The rationale behind incorporating an alkylating function in a molecule resembling a primary cellular metabolite was to get a greater safety margin by fooling tumor cells into taking up the toxin preferentially. ...
... (INN), abbreviated as CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug,[2] thus it crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use, although it is also used to treat Hodgkin lymphoma as a second-line option.[3] Lomustine has a long time to nadir (the time when white blood cells reach their lowest number). Unlike carmustine, lomustine is administered orally. It is a monofunctional alkylating agent, alkylates both DNA and RNA, has the ability to cross-link DNA.[4] As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.[5] Lomustine is cell-cycle nonspecific. It has also been used in veterinary practice as a treatment for mast cell tumors in ...
... acts as an inhibitor of poly ADP ribose polymerase (PARP) which aids in single strand DNA repair. Cells that have BRCA1/2 mutations are susceptible to the cytotoxic effects of PARP inhibitors because of an accumulation of DNA damage.[2] Talazoparib is theorized to have a higher potency than olaparib due to the additional mechanism of action called PARP trapping. PARP trapping is the mechanism of action where the PARP molecule is trapped on the DNA, which interferes with the cells ability to replicate. Talazoparib is found to be ~100 fold more efficient in PARP trapping than olaparib.[9] However, this increased potency may not translate directly to clinical effectiveness as many other factors must be considered.[4][9] ...
Crosslinked DNA is repaired in cells by a combination of enzymes and other factors from the nucleotide excision repair (NER) pathway, homologous recombination, and the base excision repair (BER) pathway. To repair interstrand crosslinks in eukaryotes, a 3' flap endonuclease from the NER, XPF-ERCC1, is recruited to the crosslinked DNA, where it assists in 'unhooking' the DNA by cleaving the 3' strand at the crosslink site. The 5' strand is then cleaved, either by XPF-ERCC1 or another endonuclease, forming a double-strand break (DSB), which can then be repaired by the homologous recombination pathway.[17] DNA crosslinks generally cause loss of overlapping sequence information from the two strands of DNA. Therefore, accurate repair of the damage depends on retrieving the lost information from an undamaged homologous chromosome in the same cell. Retrieval can occur by pairing with a sister chromosome produced during a preceding round of replication. In a diploid cell retrieval may also occur by ...
... (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer.[3] This includes breast cancer and non-small cell lung cancer.[3] It is given by injection into a vein or by mouth.[3][1] Common side effects include bone marrow suppression, pain at the site of injection, vomiting, feeling tired, numbness, and diarrhea.[3] Other serious side effects include shortness of breath.[3] Use during pregnancy may harm the baby.[3] Vinorelbine is in the vinca alkaloid family of medications.[1] It is believed to work by disrupting the normal function of microtubules and thereby stopping cell division.[3] Vinorelbine was approved for medical use in the United States in 1994.[3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] The wholesale price in the developing world as of 2014 is between 18.10 and 42.82 USD per 50 mg vial.[5] This amount in ...
Clinical symptoms include diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills and rash. Laboratory abnormalities may include: neutropenia, hypertriglyceridemia, hyperglycemia and elevated levels of liver enzymes. Idelalisib's safety and effectiveness to treat relapsed FL and relapsed SLL were established in a clinical trial with 123 participants with slow-growing (indolent) non-Hodgkin lymphomas. All participants were treated with idelalisib and were evaluated for complete or partial disappearance of their cancer after treatment (objective response rate, or ORR). Results showed 54% of participants with relapsed FL and 58% of participants with SLL experienced ORR.[7] The U.S. label for idelalisib has a boxed warning describing toxicities that can be serious and fatal, including liver toxicity, severe diarrhea, colon inflammation, lung tissue inflammation (pneumonitis) and intestinal perforation, and the manufacturer was required to put in place a Risk Evaluation and ...
... can lower the body's ability to fight off infection. Those taking it should get permission from a doctor to receive immunizations and vaccinations. It is also recommended that, while on the drug, one should avoid those having recently received oral polio vaccine. This drug was formerly not recommended during pregnancy and early evidence indicated pregnant women on the drug (or the related azathioprine) showed a seven-fold incidence of fetal abnormalities as well as a 20-fold increase in miscarriage.[12] There were also anecdotal reports linking mercaptopurine with spontaneous abortion, leading to the US FDA rating both AZA and mercaptopurine as category D drugs. However, Davis et al. 1999 found mercaptopurine, compared to methotrexate, was ineffective as a single-agent abortifacient; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a suction abortion.[13] A more recent, larger study, however, performed by ...
After and/or before[11] the curative resection of colorectal cancer, chemotherapy based on 5-fluorouracil and folinic acid reduces the risk of relapse. The benefit is clinically relevant when cancer has spread to locoregional lymph nodes or penetrated through the wall of the rectum or colon (stage III, Dukes C). The addition of oxaliplatin improves relapse-free survival, but data on overall survival have not yet been published in extenso. When cancer has not spread to the locoregional lymph nodes, nor penetrated through the wall of the rectum or colon (stage II, Dukes B) the benefit of chemotherapy is marginal[citation needed] and the decision on whether to give adjuvant chemotherapy should be carefully evaluated by discussing with the patient the realistic benefits and the possible toxic side effects of treatment. This is even more relevant when the oncologist proposes treatment with oxaliplatin.[why?] ...