Targeting inhibitor of apoptosis proteins. Medical search. Frequent questions

Our recent study shows that the novel proteasome inhibitor NPI-0052 induces apoptosis even in bortezomib-resistant MM cells. (dana-farber.org)
mPEG-MAL (Thiol PEGylation of Proteins) - A Computationally Designed Inhibitor of an Epstein-Barr Viral Bcl-2 Protein Induces Apoptosis in Infected Cells, Cell, Volume 157, Issue 7, 19 June 2014, Pages 1644-1656, Text . (creativepegworks.com)
Palcitoclax [APG-1252] is a novel and potent inhibitor of the Bcl-2 family of proteins and induces apoptosis in tumor cells. (pharmiweb.com)

These effects of the compounds were associated with inhibition of tyrosine phosphorylation and the mitogen-activated protein kinase pathway. (nih.gov)
In addition to its role in glucose metabolism, this pathway also regulates the redirection of free amino acids to protein synthesis via the mTOR-signaling pathway. (hindawi.com)
Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. (frontiersin.org)
Background The neddylation pathway conjugates NEDD8 to cullin-RING ligases and controls the proteasomal degradation of specific proteins involved in essential cell processes. (nih.gov)
Expression levels of HK2, glucose transporter 1, TXNIP, c‑Myc and mitochondria‑regulated apoptosis pathway proteins were measured through western blotting. (spandidos-publications.com)
Inactivation of the PI3-kinase pathway, but not of Ras-mitogen-activated protein (MAP) kinase signaling, was essential to elicit cytotoxic responses. (ashpublications.org)
To investigate the effect of losartan on vascular remodeling and transforming growth factor-beta and phosphoinositide 3-kinase/protein kinase B pathway. (ijpsonline.com)
Hematoxylin and eosin staining was used to measure the thickness and diameter ratio of the aortic media of mice in each group, Masson staining was used to observe the content of collagen fibers in the aorta of mice in each group, elastic fibers in the aorta of mice in each group were stained, and transforming growth factor-beta and phosphoinositide 3-kinase/protein kinase B pathway protein expression. (ijpsonline.com)
Losartan has protective effect on aortic wall of rats with aortic dissection, and the mechanism may be through inhibiting transforming growth factor-beta 1 pathway, which activates downstream phosphoinositide 3-kinase/protein kinase B pathway related proteins, and then inhibits the expansion and progression of aortic dissection. (ijpsonline.com)
Autophagy and apoptosis-related proteins and IκBα/NF-κB pathway factors were detected. (bvsalud.org)
After radiation, NF-κB was translocated to the nucleus, inflammatory factors were secreted, and IκBα/NF-κB pathway was activated, which promoted autophagy and apoptosis. (bvsalud.org)
YQJD decoction can inhibit the phosphorylation of IκBα/NF-κB pathway related factors, regulate the expression of Beclin-1 and Bcl-2 proteins, and inhibit the occurrence of autophagy and apoptosis of irradiated spermatocyte. (bvsalud.org)
CONCLUSIONS: The research results indicate that ionizing radiation can activate the IκBα/NF-κB signaling pathway in spermatocytes, promote cell autophagy and apoptosis by regulating the expression of Beclin-1 and Bcl-2 factors. (bvsalud.org)
UBX1325, a small molecule inhibitor of Bcl-xL and the first senolytic drug candidate for ophthalmologic diseases targeting a distinctive biologic pathway from anti-VEGF therapies, continues to be well-tolerated with no treatment-related adverse events or dose-limiting toxicities up to 12 weeks. (unitybiotechnology.com)
In the poster section, Joanna Shisler (University of Illinois at Urbana-Champaign [UIUC], Urbana) reported that the modified virus, Ankara, activates nuclear factor κB through the mitogen-activated protein kinase, extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, possibly facilitating the host immune response. (cdc.gov)
Protein turnover is crucial in maintaining cellular homeostasis and this process is largely controlled by the Ubiquitin Proteasome Pathway (UPP). (soci.org)
The pathway consists of an enzymatic cascade that links the polypeptide cofactor Ubiquitin to specific protein targets, which mark them for degradation by the proteasome. (soci.org)
In addition, there are reports on targeting the apoptosis pathway by the incorporation of chemicals such as caspase inhibitors or the use of silencing RNA. (cellculturedish.com)
In the poster section, Joanna Shisler (University of Illinois at Urbana-Champaign [UIUC], Urbana) reported that the modified virus, Ankara, activates nuclear factor κB through the mitogen-activated protein kinase, extracellular signal–regulated kinase (MEK)/extracellular signal–regulated kinase (ERK) pathway, possibly facilitating the host immune response. (cdc.gov)

The anti-inflammatory effects of SHE treatment involved blocking of the mitogen-activated protein kinase and signal transducer and activator of transcription 1 signaling pathways. (researchgate.net)
Subsequently, the phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways can be activated, resulting in proliferation and inhibition of apoptosis ( 13 , 14 ). (snmjournals.org)
These events are influenced by and activate other molecular pathways, including phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK),[2] and therapies are now available that target these pathocellular processes. (cancernetwork.com)

Selinexor, a small molecule that inhibits nuclear export protein XPO1, has demonstrated efficacy in solid tumors and hematologic malignancies with the evidence of clinical activity in sarcoma as a single agent. (aacrjournals.org)
Pevonedistat (MLN4924) is a selective small molecule targeting the NEDD8-activating enzyme (NAE) and inhibits an early step in neddylation, resulting in DNA re-replication, cell cycle arrest and death. (nih.gov)
The ligand-binding area of S2RPgrmc1 is of interest as a healing focus on, and an S2RPgrmc1 inhibitor, AG-205 (26, 37), inhibits cancers cell proliferation (26), destabilizes EGFR (28) and reverses S2RPgrmc1 agonist binding (29). (nos-nop.org)
As an inhibitor of HK2, 3‑bromopyruvic acid (3‑BrPA) exhibits good therapeutic efficacy in intrahepatic and extrahepatic tumors and inhibits the proliferation of human tumor cells with high expression levels of c‑Myc in vivo and in vitro . (spandidos-publications.com)
It inhibits the apoptosis of cancer cells by inhibiting caspases, and also promotes cancer cell growth by stabilizing microtubules during mitosis. (biomedcentral.com)
PLX4720, a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. (rcsb.org)
Trouw L., Nilsson S., Goncalvez I., Landberg G. and Blom A. M. (2005) C4b-binding protein binds to necrotic cells and DNA, which limits DNA release and inhibits complement activation. (lu.se)

Valosin-containing protein (VCP, also p97, or Cdc48p in yeast) is an evolutionarily conserved, homo-hexameric, ubiquitin-selective, AAA-ATPase that functions in numerous ubiquitin-dependent protein quality control pathways. (portlandpress.com)
Development of RTK inhibitors selective for FLT3 has emerged as attractive drugs for treatment of AML patients. (ashpublications.org)
By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. (rcsb.org)
In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. (bvsalud.org)
An orally administered, irreversible inhibitor of Bruton's tyrosine kinase (BTK), ibrutinib, is effective at arresting the progression of MCL [ 1 ] as is a highly selective BCL2 inhibitor, venetoclax (ABT-199, Venclexta™) [ 2 ]. (bmj.com)
PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains. (ox.ac.uk)
Here, we present a potent and highly selective dihydroquinazoline-2-one inhibitor, PFI-1, which efficiently blocks the interaction of BET BRDs with acetylated histone tails. (ox.ac.uk)
Preclinical and clinical activity of DZD1516, a full blood-brain barrier-penetrant, highly selective HER2 inhibitor. (medscape.com)

Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs). (wikipedia.org)
Survivin is a member of the inhibitors of apoptosis (IAPs) family. (biomedcentral.com)
Unlike other IAPs, survivin is a bifunctional protein that functions as a key regulator of mitosis and inhibitor of programmed cell death. (biomedcentral.com)
In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. (bvsalud.org)

Highly specific inhibitors of the main anti-apoptotic proteins BCL-2, BCL‐XL and MCL‐1 promise new opportunities for the treatment of AML. (uni-frankfurt.de)

The data provide a rationale for clinical evaluation of these tyrosine kinase inhibitors in AML. (nih.gov)
Receptor tyrosine kinase inhibitors targeting FLT3 have developed as attractive treatment options. (ashpublications.org)
Bruton's tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. (bvsalud.org)
HER-targeted tyrosine-kinase inhibitors. (innspub.net)

Selected cell lines that displayed sensitivity towards the specific BH3 mimetics underwent intrinsic apoptosis, which was characterized by loss of mitochondrial membrane potential, exposure of phosphatidylserine and activation of caspases. (uni-frankfurt.de)
Furthermore, 3‑BrPA induced the typical manifestations of mitochondrial‑mediated apoptosis such as decreasing Bcl‑2 expression and increasing Bax, Cyt‑C and Caspase‑3 expression. (spandidos-publications.com)
The present results suggested that 3‑BrPA promoted TXNIP protein expression and reduced HK2 expression in TNBC cells by downregulating c‑Myc expression, inhibiting glycolysis including suppressing lactate generation, intracellular ATP generation and HK activity, inducing mitochondrial‑mediated apoptosis and eventually suppressing TNBC cell proliferation. (spandidos-publications.com)
The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption capacity in MCL cell lines irrespective of their BTKi or venetoclax sensitivity. (bvsalud.org)

Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. (frontiersin.org)
It plays a role in proliferation, apoptosis, angiogenesis, and tumor invasion ( 12 - 14 ), and its expression may be related to resistance to cytotoxic-, antiestrogen-, and HER2 / neu -targeted therapy ( 15 - 18 ). (snmjournals.org)
Thioredoxin‑interacting protein (TXNIP) competes with c‑Myc to reduce glucose consumption in tumor cells to restrain cell proliferation. (spandidos-publications.com)
AD is associated with abnormal proliferation, apoptosis and phenotype of VSMCs[ 4 ]. (ijpsonline.com)
Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma. (innspub.net)
This cascade is highly regulated and impacts virtually all cellular processes including cell cycle progression, cell proliferation, cell differentiation and apoptosis. (soci.org)
Biological Function Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control (PubMed:11162435, PubMed:11024045, PubMed:11084335, PubMed:16729033, PubMed:17294084). (qedbio.com)

The AAA-ATPase (ATPases associated with diverse cellular activities) valosin-containing protein (VCP), is essential for many cellular pathways including but not limited to endoplasmic reticulum-associated degradation (ERAD), DNA damage responses, and cell cycle regulation. (portlandpress.com)
VCP primarily identifies ubiquitylated proteins in these pathways and mediates their unfolding and degradation by the 26S proteasome. (portlandpress.com)
VCP interacts with adaptor proteins to identify ubiquitylated substrates for degradation by the proteasome. (portlandpress.com)
Protein degradation. (nih.gov)
Previous reports have established that UPP modulates intracellular protein degradation. (dana-farber.org)
Specifically, the multi-enzyme protease 26S proteasome degrades misfolded or redundant proteins, while blockade of the proteasomal degradation pathways results in the accumulation of unwanted proteins and cell death. (dana-farber.org)
Because cancer cells proliferate more than normal cells, the rate of protein translation and degradation is also higher in cancer cells. (dana-farber.org)
Substantial efforts are already under way to design drugs that harness cellular machinery for the degradation of specific targets, a strategy known as targeted protein degradation (TPD). (news-medical.net)
As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival (PubMed:16729033). (qedbio.com)

A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.com)
In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)
Crowding of asymmetric proteins results in an asymmetric lateral pressure across the membrane which can be used by cells in a number of biological processes involving membrane remodeling. (portlandpress.com)
Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. (frontiersin.org)
Additionally, experiments with nonmalignant cells could confirm the clinical relevance of the MCL-1 inhibitor. (uni-frankfurt.de)
Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
We also highlight potential options of targeting senescent cells for the treatment of CKD. (frontiersin.org)
Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
We also highlight potential options for targeting senescent cells in developing therapeutics for CKD patients. (frontiersin.org)
This study was aimed to reveal the role of miR-149-5p in acute myeloid leukemia (AML) cells apoptosis and the possible mechanism involved. (medscimonit.com)
Inhibition of miR-149-5p can induce apoptosis in THP-1 cells. (medscimonit.com)
The genetic silencing of HIF-1α not only repressed IMQ-induced aerobic glycolysis but also sensitized cells to IMQ-induced apoptosis due to faster ATP and Mcl-1 depletion. (oncotarget.com)
Here, we have determined the growth-inhibitory and proapototic mechanisms of 2 small molecule inhibitors of FLT3, AG1295 or PKC412, in hematopoietic progenitor cells, human leukemic cell lines, and primary AML cells expressing FLT3-ITD. (ashpublications.org)
Similar findings were made in bone marrow cells from gene-targeted mice lacking Bim and/or Puma infected with FLT3-ITD and treated with inhibitor, where loss of Puma only provided transient protection from apoptosis, but loss of Bim preserved clonal survival upon FLT3-ITD inhibition. (ashpublications.org)
Several inhibitors have been described, such as AG1295, CEP701, PKC412, and SU-11 248, with cytotoxic effects to cell lines and primary AML cells in vitro expressing mutant FLT3. (ashpublications.org)
Interestingly, real-time PCR and translation inhibition studies revealed that survivin was over-expressed partially through the up-regulation of protein translation instead of gene transcription in A549 cancer cells. (biomedcentral.com)
In addition, 17-AAG-treated A549, HONE-1 and HT-29 cells showed reduced proteasomal activity while inhibition of 26S proteasome activity further increased the amount of survivin protein in cells. (biomedcentral.com)
Heat shock protein 90 (Hsp90) is a molecular chaperone that assists the correct folding and stabilization of various proteins in cells. (biomedcentral.com)
These findings identify an integral role of pDCs in MM pathogenesis and provide the basis for targeting pDC-MM interactions as therapeutic strategy to improve patient outcome.Genomics and proteomics studies have identified therapeutic targets to interrupt growth and/or amplify apoptotic signaling in MM cells to enhance cytotoxicity and overcome drug resistance. (dana-farber.org)
In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. (rcsb.org)
The adenovirus early region 1 (E1) gene, which comprises E1a and E1b, encodes the viral early proteins that are necessary for adenoviral replication and the consequent oncolysis of permissive host cells. (hindawi.com)
A previous study has shown that 4 Gy irradiation induced the apoptosis of spermatocytes and revealed autophagosomes in cells exposed to radiation. (bvsalud.org)
AIM OF THE STUDY: We used spermatocytes (GC-2spd cell line) to investigate the relationship between autophagy and apoptosis of spermatogenic cells after radiation, and the mechanisms of YQJD decoction. (bvsalud.org)
Autophagy agonists, autophagy inhibitors and YQJD were used to intervene cells. (bvsalud.org)
AZD5991 markedly induced apoptosis in these cells. (bvsalud.org)
Supporting this notion, the IAP antagonist BV6 induced dramatic apoptosis in resistant MCL cells and sensitized the resistant MCL cells to venetoclax. (bvsalud.org)
In I/R group, theca and follicular cells were degenerated with apoptosis and dilatation and congestion, edema. (bvsalud.org)
The patient received multiple molecularly targeted therapies, including targeting BTK and BCL2, and haplo-identical CAR T (haplo-CAR T) cells from her daughter without previous allo-hematopoietic stem cell transplantation. (bmj.com)
Applying Darwinian principles to tumour heterogeneity helps to define alternative therapeutic end points, while targeting microenvironmental interactions between mutated tumour cells and their surroundings provide a genetically more stable target. (touchoncology.com)
In the case of therapeutic options two and three by inducing lethal toxicity and thus killing the cancer cells, predominately via a form of programmed cell death termed apoptosis. (touchoncology.com)
AMI-1 also induced apoptosis and decreased the migratory activity in several CRC cells. (oncotarget.com)
For a cell line with high growth rate but low productivity, limiting the metabolism rates through medium optimization can force the cells work on protein production thereby improving product yield. (cellculturedish.com)
Transfection of Livin in cells results in protection from apoptosis induced by FADD, BAX, RIP, RIP3 and DR6. (qedbio.com)
The expression of the anti-apoptotic protein BCL2 has been shown to be deregulated in T-cell acute lymphoblastic leukemia (T-ALL), where different T-ALL cells display a differential response to the BCL2-specific inhibitor venetoclax. (lu.se)
Pertoft H. and Fries E. (1995) Inter-a-inhibitor is required for the formation of the hyaluronan-containing coat on fibroblasts and mesothelial cells. (lu.se)
Chimeric antigen receptors (CAR) recognize specific proteins on the surface of tumor cells. (msdmanuals.com)
In contrast to TCR T cells, CAR T cells recognize only relatively large proteins on the surface of tumor cells. (msdmanuals.com)
Autoantibodies targeting different antigenic determinants on red blood cells (RBCs) and platelets are assumed to cause isolated episodes of hemolytic anemia and thrombocytopenia, respectively. (medscape.com)
I will accomplish this by identifying and mechanistically characterize cell surface proteins that protect leukemia cells against the innate immune system. (lu.se)
To identify cell surface proteins on leukemia cells that inhibit Natural killer cells ( Aim 1a ) or macrophages ( Aim 1b ) using CRISPR screens. (lu.se)
To characterize the function and expression patterns of the identified cell surface proteins in acute myeloid leukemia cells from patients. (lu.se)
The primary barriers for invading respiratory pathogens are the respiratory tract epithelial cells and antimicrobial proteins generated by these cells. (cdc.gov)

Methods Melanoma cell lines and patient-derived tumor xenografts (PDTX) treated with pevonedistat were assessed for viability/apoptosis and tumor growth, respectively, to identify sensitive/resistant models. (nih.gov)
0.3 μM) and induced apoptosis in a subset of melanoma cell lines. (nih.gov)
APG-115 is a highly potent MDM2-p53 inhibitor, and our data on liposarcoma presented in last year's ASCO report were promising," said Prof. Xing Zhang, Chief Physician of Melanoma and Sarcoma Medical Oncology Unit of Sun Yat-sen University Cancer Center. (pharmiweb.com)

NU 7026 is an ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK). (tocris.com)
Remarkably, hemizygosity for receptor-interacting protein kinase 1 (Ripk1) allowed Xiap(-/-)cIap1(-/-) double mutants to survive past birth, and prolonged cIap2(-/-)cIap1(-/-) embryonic survival. (ozgene.com)
BRAF(V600E) is the most frequent oncogenic protein kinase mutation known. (rcsb.org)
Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. (rcsb.org)

Treatment of carfilzomib followed by selinexor caused selinexor-sensitive and selinexor-resistant cell lines to be more sensitive to selinexor as determined by an increase in apoptosis. (aacrjournals.org)

Exposure of sensitive cell lines with PFI-1 results in G1 cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. (ox.ac.uk)

The FDA recently approved the first proteasome inhibitor bortezomib (Velcade), formerly known as PS-341, for the treatment of relapsed/refractory MM. However, prolonged treatment with bortezomib is associated with toxicity and the development of drug resistance. (dana-farber.org)
While the validity of this approach was first exemplified by the proteasome inhibitor bortezomib, approved by the FDA in 2003 and used in the treatment of multiple myeloma and mantle cell lymphoma, subsequent advances in understanding the role of different components in the UPP have allowed the development of other high quality chemical probes and inhibitors. (soci.org)

The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone. (frontiersin.org)
Higher XIAP expression in invasive breast cancer is independently associated with poorer prognosis and resistance to chemotherapy, suggesting the potential therapeutic benefit of targeting XIAP. (duke.edu)
Thus, we hypothesize that the IMQ-induced up-regulation of HIF-1α and aerobic glycolysis is a protective response to the metabolic stress generated by IMQ treatment, and thus, co-treatment with inhibitors of HIF-1α and/or glycolysis may be a useful therapeutic strategy to enhance the anti-tumor effects of IMQ in clinical settings. (oncotarget.com)
Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG. (biomedcentral.com)
We showed for the first time that down-regulation of survivin is not a definite therapeutic function of Hsp90 inhibitors. (biomedcentral.com)
In addition, preclinical studies are examining the combination of biochemical inhibitors of growth/survival signaling pathways with standard therapeutic agents to increase overall MM cell apoptosis. (dana-farber.org)
Furthermore, inhibitors targeting "active" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. (rcsb.org)
One of the biggest challenges in developing new cancer therapies is that many proteins are not tractable to the traditional approach in drug discovery of directly inhibiting the function of a therapeutic target. (news-medical.net)
Our study uncovered another unique route for MCL-1 inhibitor to trigger apoptosis, implying that the pro-apoptotic combination of IAP antagonists and apoptosis inducers could be further exploited for MCL patients with multiple therapeutic resistance. (bvsalud.org)
I will also provide in vivo proof of concept for a therapeutic effect by inhibiting the identified cell surface proteins in mouse models of leukemia. (lu.se)
To demonstrate proof of concept for a therapeutic effect by inhibiting the identified cell surface proteins in patient-derived xenograft models of leukemia. (lu.se)

He has a research background studying apoptosis, cytotoxicity, using electrophysiology, and other molecular biological techniques. (wikipedia.org)
Herein, frozen tumors from 36 MGMT methylated patients grouped according to overall survival were extracted and proteins were profiled using surface-enhanced laser desorption/ionization (SELDI) with time-of flight (TOF) proteomics to identify low molecular weight proteins that associated with poor survival outcomes. (nature.com)
We used surface-enhanced laser desorption/ionization (SELDI) with time-of flight (TOF) proteomics to identify low molecular weight proteins that associated with poor survival outcomes. (nature.com)
mPEG-NHS (Amine PEGylation of Peptide) - High Efficiency Diffusion Molecular Retention Tumor Targeting. (creativepegworks.com)
The projects are centered around the molecular strategy of induced proximity, which involves controlling the physical distance between proteins to regulate or perturb biological processes in the cancer cell. (news-medical.net)
These drugs, which include proteolysis-targeting chimeras (PROTACs) and molecular glue degraders, use bifunctional small molecules to connect target proteins with cellular modifiers that lead to their breakdown within the cell. (news-medical.net)
Elucidating the molecular mechanisms of cardiomyocyte apoptosis would be of great importance for tackling apoptosis related heart disease. (molcells.org)
Mark L., Lee W. H., Villoutreix B. O., Proctor D., Blackbourn, D., Spiller B. O. and Blom A. M. (2004) KSHV complement control protein mimics human molecular mechanisms for inhibition of the complement system. (lu.se)

This stabilization and retention of IκB in the nucleus resulted in inhibition of NFκB and transcriptional suppression of the critical antiapoptotic protein, survivin. (aacrjournals.org)
In conclusion, our findings reveal that the inhibition of BCL-2 proteins, especially MCL-1, by BH3 mimetics can be a promising strategy in AML treatment. (uni-frankfurt.de)
Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity (PubMed:11024045, PubMed:16729033). (qedbio.com)

On binding of insulinlike growth factors to the receptor, adaptor proteins, such as insulin-receptor substrate-1 (IRS-1) and IRS-2, are recruited to the phosphorylation site of the cytoplasmic domain ( 19 - 21 ). (snmjournals.org)
More recent advances in induced proximity include methods that result in apoptosis, phosphorylation, and epigenetic modulation, all of which are promising avenues for cancer therapy. (news-medical.net)
Amit Choudhary, PhD, and his team from Harvard Medical School are exploring whether small molecules called phosphorylation-inducing chimeric small molecules (PHICS), which bring kinases into close proximity with a target proteins, can enhance phosphorylation in cancer targets. (news-medical.net)

We are also working on the discovery of DeltaFosB inhibitors, neurexin modulators, and FGF14/Nav1.6 channel complex protein-protein interaction inhibitors as CNS probes and potential therapeutics. (utmb.edu)
This discovery led to the development of proteasome inhibitors as therapeutics in cancer. (dana-farber.org)

Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. (cancerindex.org)
However, Hsp90 interferes with a number of molecules that up-regulate the intracellular level of survivin, raising the question that clinical use of Hsp90 inhibitors may indirectly induce survivin expression and subsequently enhance cancer anti-drug responses. (biomedcentral.com)
Inhibitor of apoptosis (IAP) proteins cIAP1, cIAP2, and XIAP (X-linked IAP) regulate apoptosis and cytokine receptor signalling, but their overlapping functions make it difficult to distinguish their individual roles. (ozgene.com)

Our research efforts on developing chemical probes include design and synthesis of small molecules targeting EPAC, which are exchange proteins directly activated by cAMP including cAMP-regulated guanine nucleotide exchange factors. (utmb.edu)
The induced proximity model aims to overcome this hurdle by altering the target protein's function without requiring that small molecules be direct inhibitors. (news-medical.net)

Abnormal metabolism and the evasion of apoptosis are considered hallmarks of cancers. (hindawi.com)

The mechanistic effects of selinexor in sarcomas as a monotherapy and in combination with proteasome inhibitor, carfilzomib, across a panel of cell lines in vitro and few in xenograft mouse models were investigated. (aacrjournals.org)
Moreover, the glucose analog 2-DG and the Hsp90 inhibitor 17-AAG, which destabilizes the HIF-1α protein, synergized with IMQ to induce tumor cell apoptosis in vitro and significantly inhibited tumor growth in vivo . (oncotarget.com)
mPEG-Maleimide (Thiol PEGylation of Proteins) - In vitro folding of KvAP, a voltage gated K+ channel, Biochemistry. (creativepegworks.com)
mPEG-NHS (PEGylated Polymers for Gene Delivery) - BSA Nanoparticles for siRNA Delivery: Coating Effects on Nanoparticle Properties, Plasma Protein Adsorption, and In Vitro siRNA Delivery, International Journal of Biomaterials, Volume 2012, Article ID 584060, 10 pages, Text . (creativepegworks.com)
In this study, we demonstrate that miR-23a participates in the regulation of cardiomyocyte apoptosis in vitro and in vivo . (molcells.org)

Scholars@Duke publication: Expression of X-Linked Inhibitor of Apoptosis Protein (XIAP) in Breast Cancer Is Associated with Shorter Survival and Resistance to Chemotherapy. (duke.edu)
XIAP, the most potent inhibitor of cell death pathways, is linked to chemotherapy resistance and tumor aggressiveness. (duke.edu)
Currently, multiple XIAP-targeting agents are in clinical trials. (duke.edu)
We retrospectively analyzed non-metastatic, non-inflammatory, primary, invasive breast cancer samples for XIAP mRNA (n = 2341) and protein (n = 367) expression. (duke.edu)

Dual targeting BTK and BCL2 with ibrutinib and venetoclax has improved outcomes in MCL patients who were predicted not to respond to conventional therapy, but it is unlikely to be curative. (bmj.com)
Dual targeting BTK and BCL2 with ibrutinib and venetoclax has increased complete response rate compared with ibrutinib monotherapy in MCL patients but it is unlikely that this combination therapy will lead to a long term cure of the disease [ 3 ]. (bmj.com)

Because of these results, a human clinical trial with selinexor in combination with a proteasome inhibitor is planned for the treatment of sarcoma. (aacrjournals.org)
Selinexor, an inhibitor of XPO1, has shown preclinical and clinical activity in sarcoma. (aacrjournals.org)
Currently, several small-molecule inhibitors and antibodies directed against the IGF-1R are being developed and tested in phase I and II clinical trials. (snmjournals.org)
PKC412 is one of several FLT3 inhibitors that is currently evaluated in late-stage clinical trials in AML patients carrying FLT3 mutations. (ashpublications.org)
Through the showcase at ASCO, Ascentage Pharma is demonstrating its capabilities of global clinical development in apoptosis. (pharmiweb.com)
Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice. (medscape.com)

Proteins Analysis Individual soluble receptor arrays had been utilized regarding to manufacturer's guidelines. (nos-nop.org)

VCP identifies ubiquitylated substrates through numerous dedicated adaptor proteins and unfolds substrates by threading them through a central pore in the hexamer ( Figure 1 ). (portlandpress.com)

Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT) are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression. (ox.ac.uk)

Instead, targeting Hsp90 with small molecule inhibitors will induce the over-expression of survivin in certain cancer cell lines and subsequently enhances the ability of cell survival in drug-treated situations. (biomedcentral.com)

Cell viability and apoptosis were detected through Cell Counting Kit‑8 and flow cytometry assays, respectively. (spandidos-publications.com)
Troubleshooting tips were on protein glycosylation, fatty acid and cholesterol supplementation, using metabolism characteristics to improve production, reducing apoptosis , increasing cell viability, and handling waste issues. (cellculturedish.com)
What media components can reduce apoptosis and increase cell viability beyond critical density? (cellculturedish.com)

In this study, we observed that the expression of anti-apoptotic BCL2 family genes, such as BCL2, BCL2L1, and MCL1, is highly varied in T-ALL patients, and inhibitors targeting proteins coded by these genes display differential. (lu.se)

Cocrystal structures showed that PFI-1 acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD4 and BRD2. (ox.ac.uk)

Protein crowding induces membrane curvatures through an entropic mechanism. (portlandpress.com)

The purpose of this paper is to provide a review of site-specific treatment options that involve the targeting of angiogenesis in gynecologic malignancies. (cancernetwork.com)
Growth factors such as fibroblast growth factor (FGF), vascular endothelial cell growth factor (VEGF), and angiopoietin-1 (Ang1) are upregulated to stimulate angiogenesis, while downregulation of endogenous protein inhibitors (thrombospondin 1 and interferon) disrupts the balance of physiologic angiogenesis. (cancernetwork.com)

The purpose of this study is to determine whether targeting Hsp90 can alter survivin expression differently in different cancer cell lines and to explore possible mechanisms that cause the alteration in survivin expression. (biomedcentral.com)
Here, we demonstrated that Hsp90 inhibitors, geldanamycin and 17-AAG, induced the over-expression of survivin in three different human cancer cell lines as shown by Western blotting. (biomedcentral.com)

Both compounds induced up-regulation of proapoptotic BH3-only proteins Bim and Puma, and subsequent cell death. (ashpublications.org)
Sjöberg A., Trouw L., McGrath F., Hack E. C. and Blom A. M. (2006) Regulation of complement activation by C-reactive protein: targeting of the inhibitory activity of C4b-binding protein. (lu.se)

Long JP, Li XN and Zhang F: Targeting metabolism in breast cancer: How far we can go? (spandidos-publications.com)
Finally, cell metabolism characteristics can also impact the balance between biomass formation and protein production. (cellculturedish.com)

Selinexor induced IκB nuclear localization as a single agent, and the effect was enhanced by stabilization of IκB when pretreated with the proteasome inhibitor carfilzomib. (aacrjournals.org)
XPO1, the main nuclear export protein, transports cargo proteins containing nuclear localization signals out of the nucleus ( 1-3 ). (aacrjournals.org)
Webb, J. H., Villoutreix, B. O., Dahlbäck, B. and Blom A. M. (2001) Localization of a hydrophobic binding site for protein S on the b-chain of C4BP. (lu.se)

RHAMM regulates MMTV-PyMT-induced lung metastasis by connecting STING-dependent DNA damage sensing to interferon/STAT1 pro-apoptosis signaling. (medscape.com)

miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. (molcells.org)

Pretreatment with the proteasome inhibitor carfilzomib can further stabilize IκB, which is sequestered in the nucleus to inhibit transcriptional activity of NFκB and suppresses expression of survivin, thereby inducing apoptosis. (aacrjournals.org)

2004. Characterization of a peptide inhibitor of JAK2 that mimics SOCS-1 function. (innspub.net)
Blom A. M. , Mörgelin M., Öyen M., Jarvet J. and Fries E. (1999) Structural characterization of inter-a-inhibitor - evidence for an extended shape. (lu.se)

Anatomy19

Organisms9

Diseases10

Chemicals and Drugs104

Analytical, Diagnostic and Therapeutic Techniques and Equipment17

Phenomena and Processes49

Disciplines and Occupations1

Technology, Industry, Agriculture1

Information Science3

Induces Apoptosis3

Pathway19

Mitogen-activa3

Inhibits7

Selective8

IAPs4

Anti-apoptotic proteins1

Tyrosine kinase inh4

Mitochondrial4

Proliferation7

Degradation9

Cells42

Melanoma3

Kinase4

Increase in apoptosis1

Induction of apoptosis1

Proteasome inhibitor bortezomib2

Therapeutic11

Molecular8

Inhibition3

Phosphorylation3

Therapeutics2

Regulate3

Small molecules2

Cancers1

Vitro5

XIAP4

Venetoclax2

Clinical6

Receptor1

Adaptor proteins1

Progression1

Survival1

Viability3

Bcl21

Mimetic1

Mechanism1

Angiogenesis2

Hsp902

Regulation2

Metabolism2

Localization3

Interferon1

Regulates1

Suppresses1

Characterization2