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Ubiquitin

Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting cIAPs-mediated inhibition of RIP1 and RIP3 activation

7 | Aug 25 2019

Zhang Y et al. identified a new role of PS-341 in the cell death of BMDMs and provided a novel insight into the atherosclerotic inflammation caused by proteasome-mediated macrophage necroptosis. [Read the Full Post]

Phenotypic Drug Screening for Dysferlinopathy Using Patient-Derived Induced Pluripotent Stem Cells

15 | Jul 24 2019

Kokubu Y et al. suggested that increasing the amount of misfolded dysferlin using small molecules could represent an effective future clinical treatment for dysferlinopathy. Stem Cells Translational Medicine2019. [Read the Full Post]

Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study

17 | Jul 08 2019

Swords RT et al. indicated that administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. [Read the Full Post]

Molecular detection of Hsp90 inhibitor suppressing PCV2 replication in host cells

70 | May 13 2019

Liu J et al. highlighted the importance of cellular proteins during PCV2 infection and the possibility of targeting cellular chaperones for developing new anti-rotaviral strategies. [Read the Full Post]

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

96 | Mar 17 2019

Moreau P et al. showed the addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited. (Funded by Millennium Pharmaceuticals; TOURMALINE-MM1 ClinicalTrials.gov number, NCT01564537.). [Read the Full Post]

MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA

129 | Mar 17 2019

Wei X et al. indicated that NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC. [Read the Full Post]

Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment

143 | Feb 05 2019

Yee-Lin V et al. Nutlin-3, a small molecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. [Read the Full Post]

Methods for 20S Immunoproteasome and 20S Constitutive Proteasome Determination Based on SPRI Biosensors

227 | Dec 06 2018

Anna S et al. indicated 20Si and 20Sc were determined in blood plasma samples from healthy donors and patients with acute leukemia. In the case of these patients 20Si was the major component, and its level was more than one order of magnitude higher than in the healthy donors. [Read the Full Post]

Inhibitors of ubiquitin E3 ligase as potential new antimalarial drug leads

224 | Dec 04 2018

Jain J et al. provided better understanding regarding the importance of E3 ligase functions in the malaria parasite as a potential new antimalarial drug target and a new class of antimalarial drug leads. [Read the Full Post]

Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction

216 | Dec 02 2018

Wang L et al. suggested that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI. [Read the Full Post]

Loss of XIAP facilitates switch to TNFα-induced necroptosis in mouse neutrophils

627 | Oct 28 2018

Wicki S et al. may implicated an important role of neutrophils in the development of hyperinflammation and disease progression of patients diagnosed with X-linked lymphoproliferative syndrome type 2, which are deficient in XIAP. [Read the Full Post]

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells

0 | Oct 24 2018

Zhen MC et al. concluded that mTOR could be a key resistance factor of AT406 in HCC cells. [Read the Full Post]

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation

0 | Sep 03 2018

Tao YF et al. may provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]

Identifying Regulatory Posttranslational Modifications of PD-L1: A Focus on Monoubiquitinaton

240 | Aug 04 2018

Horita H et al. highlights the significance of identifying novel PTMs for PD-L1 and reveals potentially critical regulatory mechanisms that may be valuable therapeutic targets. In a broader context, this report validates an approach whereby one can gain insight into novel mechanisms of action by a simple and unbiased analysis of a PTM profile of potentially any endogenous protein of interest. [Read the Full Post]

Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma

313 | Jul 06 2018

Chen X et al. found that ubiquitin-specific protease 14 could be a potential therapeutic target for oral squamous cell carcinoma patients. [Read the Full Post]

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo

823 | Jun 18 2018

Karpel-Massler G et al. suggested that targeting deubiquitinases for glioma therapy is feasible and effective. [Read the Full Post]

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

910 | Jun 18 2018

McGarry E et al. revealed a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. [Read the Full Post]

Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death

611 | Jun 12 2018

Sanchez G et al. suggested that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. [Read the Full Post]

A novel hypoxia-selective epigenetic agent RRx-001 triggers apoptosis and overcomes drug resistance in multiple myeloma cells

397 | Jun 03 2018

Das DS et al. provided the rationale for translation of RRx-001, either alone or in combination, to clinical evaluation in MM. [Read the Full Post]

USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth

369 | Jun 03 2018

An T et al. indicated that USP7 could be a potential drug target and its inhibitor P5091 deserves further development as anticancer agent for Wnt hyper-activated CRC therapy. [Read the Full Post]

Investigating proteasome inhibitors as potential adjunct therapies for experimental cerebral malaria

501 | May 11 2018

Howland SW et al. reported here that bortezomib, which has been associated with neurological adverse events, accelerated death in ECM-infected mice. [Read the Full Post]

p53-related protein kinase confers poor prognosis and represents a novel therapeutic target in multiple myeloma

582 | Apr 23 2018

Hideshima T et al. demonstrated that either genetic or pharmacological inhibition of TP53RK triggers MM cell apoptosis via both p53-Myc axis-dependent and axis-independent pathways, validating TP53RK as a novel therapeutic target in patients with poor-prognosis MM. [Read the Full Post]

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

0 | Apr 23 2018

Wang L et al. revealed that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment. [Read the Full Post]

COPS5 amplification and overexpression confers tamoxifen-resistance in ERα-positive breast cancer by degradation of NCoR

1379 | Apr 14 2018

Lu R et al. demonstrated that genetic inhibition of the isopeptidase activity of COPS5 is sufficient to re-sensitize the resistant breast cancer cells to tamoxifen-treatment, offering a potential therapeutic approach for endocrine-resistant breast cancer patients. [Read the Full Post]

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response.

545 | Mar 16 2018

Zhao Z et al. found that the HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

0 | Feb 23 2018

Han T et al. proposed that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs [Read the Full Post]

Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells.

875 | Dec 16 2017

Wang S et al. found that the anti-cancer effect of bortezomib and present this novel combinatorial treatment against colorectal cancer. [Read the Full Post]

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes

951 | Nov 22 2017

Zhelev Z et al. suggested that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects. [Read the Full Post]

Inhibition of the Pentose-phosphate Pathway Selectively Sensitizes Leukemia Lymphocytes to Chemotherapeutics by ROS-independent Mechanism

890 | Nov 21 2017

Zhelev Z et al. suggested that 6-ANA could be used as a supplementary component in anticancer chemotherapy, and would allows therapeutic doses of anticancer drugs to be reduced, thereby minimizing their side-effects. [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

0 | Nov 18 2017

Han T et al. proposed that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides). [Read the Full Post]

Chemotherapy-induced Dkk-1 expression by primary human mesenchymal stem cells is p53 dependent

1011 | Oct 23 2017

Hare I et al. indicated that Dkk-1 has been shown to promote tumor growth in several models of malignancy, suggesting that MSC-derived Dkk-1 could counteract the intent of cytotoxic chemotherapy, and that pharmacologic inhibition of Dkk-1 in patients receiving chemotherapy treatment for certain malignancies may be warranted. [Read the Full Post]

Autophagy-mediated clearance of ubiquitinated mutant huntingtin by graphene oxide

692 | Sep 10 2017

Jin P et al. revealed a novel biological function of GO and may have implications for developing nanomaterial-based therapeutics for neurodegenerative diseases. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

1379 | Aug 09 2017

Cayrol F et al. indicated the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

Analysis of a cAMP regulated coactivator family reveals an alternative phosphorylation motif for AMPK family members

1045 | Aug 08 2017

Sonntag T et al. suggested that the regulation of cellular targets by AMPK family members is more extensive than previously appreciated. [Read the Full Post]

Bifunctional alkylating agent-mediated MGMT-DNA cross-linking and its proteolytic cleavage in 16HBE cells

0 | Jun 24 2017

Cheng J et al. demonstrated that MGMT might turn into a DNA damage promoter by forming DPC when exposed to HN2. Proteolysis, especially DVC1, plays a crucial role in mDPC repair. [Read the Full Post]

NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling.

1283 | Jun 08 2017

Wang Z et al. proposed that NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway. [Read the Full Post]

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

0 | Jun 07 2017

Zhou F et al. uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. [Read the Full Post]

Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

0 | Jun 03 2017

Huang Y et al. provided a rationale for the development of TRAIL-induced apoptosis-based cancer therapies. [Read the Full Post]

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling.

1278 | May 02 2017

Cheng M et al reported that receptor for activated C kinase 1 (RACK1) negatively regulates Dishevelled stability and Wnt signaling. RACK1 interacts with Dvl proteins and promotes their lysosomal degradation, and this effect is enhanced by autophagy induction. RACK1 also interacts with LC3 and enhances the association of LC3 with Dvl2, thereby leading to degradation of Dvl proteins through autophagy. These findings reveal a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability. [Read the Full Post]

Tetrachlorobenzoquinone induces Nrf2 activation via rapid Bach1 nuclear export/ubiquitination and JNK-P62 signaling

1167 | Apr 21 2017

Su C et al. found that TCBQ-induced activation of Nrf2 involves c-Jun N-terminal kinase (JNK)-P62 signaling. [Read the Full Post]

Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression

1441 | Mar 09 2017

Jones RJ et al. concluded LTP may reactivate EBV-positive resting memory B cells thereby enhancing EBV lytic cycle and host immune suppression. [Read the Full Post]

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response

1320 | Feb 25 2017

The HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

1869 | Feb 19 2017

Douglass AN, et al.'s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2065 | Jan 08 2017

Douglass AN, et al.‘’s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a new avenue to prevent malaria. [Read the Full Post]

Bifunctional alkylating agent-mediated MGMT-DNA cross-linking and its proteolytic cleavage in 16HBE cells

1960 | Dec 31 2016

Cheng J et al. demonstrated that MGMT might turn into a DNA damage promoter by forming DPC when exposed to HN2. [Read the Full Post]

Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

2058 | Nov 01 2016

Huang Y et al. provided a rationale for the development of TRAIL-induced apoptosis-based cancer therapies. [Read the Full Post]

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling

1739 | Sep 28 2016

Cheng M et al. revealed a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability. [Read the Full Post]

ERK induces degradation of tumor suppressor FBW7 in pancreatic cancer

6186 | Mar 18 2015

Ji et al. demonstrated a correlation between low expression of FBW7 and ERK activation in pancreatic cancer. [Read the Full Post]

MiR-146-NF-κB pathway is a key axis in the regulation of FOXP3-deficient prostate cancers

3183 | Mar 12 2015

Liu et al. from University of Alabama at Birmingham reveal FOXP3-microRNA-146(miR-146)-NF-κB axis as a critical signaling pathway in regulating the survival of prostate cancer cells both in vitro and in vivo. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

8527 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

Proteasome inhibitor salvages messense mutated dysferlin in muscular dystrophy patients

3199 | Feb 09 2015

Azakir et al. demonstrated proteasome inhibitor is able to increase the expression of messense mutated dyferlin, and restores the membrane resealing capacity of myoblasts. [Read the Full Post]

Suppressing HER3 signaling by interfering with its Sec61-dependent contranlational translocation

3054 | Feb 03 2015

Ruiz-Saenz et al. demonstrated a novel approach specifically reduces HER3 expression. [Read the Full Post]

The mechanism of action of new antitumor drug FL118

3388 | Dec 25 2014

Recently, Ling et al. demonstrated the mechanism of FL118 antitumor action. The drug suppress tumor growth by promotion of MdmX degradation and consequent stimulation of p53 signaling. [Read the Full Post]

Hippo signaling mediates hypoxia tumorgenesis via SIAH2

3610 | Dec 05 2014

Ma et al. gives a insight into the mechanism of Hippo signaling by investigating the pathway deactivation induced by hypoxia. [Read the Full Post]

Not all DUBs are equal

3347 | Mar 21 2014

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. [Read the Full Post]

MLN9708 is a proteasome inhibitor and is the first to enter clinical trials

3200 | Feb 19 2014

MLN9708 is a selective, orally bioavailable, second-generation proteasome inhibitor. [Read the Full Post]

RO4929097 is a small molecule gamma secretase inhibitor

3180 | Feb 13 2014

RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. [Read the Full Post]

Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans

2828 | Jan 26 2014

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

MLN9708 is a proteasome inhibitor and is the first to enter clinical trials as an oral preparation

2677 | Jan 14 2014

MLN9708 immediately hydrolyzed to MLN2238, the biologically active form, on exposure to aqueous solutions or plasma. [Read the Full Post]

Bortezomib is a highly selective reversible inhibitor of the 26S proteasome

2777 | Jan 09 2014

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

Bortezomib is the first clinically approved proteasome inhibitor for treating multiple human malignancies

2855 | Dec 16 2013

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

Bortezomib is the first therapeutic proteasome inhibitor

2862 | Nov 26 2013

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. [Read the Full Post]

Semagacestat was compared with placebo in more than 2600 patients

2835 | Oct 21 2013

Semagacestat reduces the secretion of Aβ42, Aβ40 and Aβ38 from H4 human glioma cells stably overexpressing human wild-type APP into the culture medium [Read the Full Post]

PD168393 is a strongly effective EGFR inhibitors

2784 | Jul 18 2013

PD 168393 is docked into the ATP binding pocket of EGFR TK. PD168393 completely suppresses EGF-dependent receptor autophosphorylation in A431 cells during continuous exposure, with continous suppression even after 8 hr in compound-free medium. [Read the Full Post]

MG132 is a specific potent reversible and cell permeable proteasome inhibitor

2575 | Jun 20 2013

MG-132 displays >1000 times more activity than ZLLal in inhibiting the ZLLL-MCA-degrading activity of 20S proteasome with IC50 of 100 nM versus 110 μM. MG-132 also inhibits calpain with IC50 of 1.2 μM. [Read the Full Post]

MG132 is a specific potent reversible and cell permeable proteasome inhibitor

3148 | Apr 22 2013

MG-132 displays >1000 times more activity than ZLLal in inhibiting the ZLLL-MCA-degrading activity of 20S proteasome with IC50 of 100 nM versus 110 μM. MG-132 also inhibits calpain with IC50 of 1.2 μM. MG-132 induces neurite outgrowth in PC12 cells at an optimal concentration of 20 nM. [Read the Full Post]

PS341 was tested in a small Phase I clinical trial on patients with multiple myeloma cancer

2330 | Mar 25 2013

PS-341 is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma[1] and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease. [Read the Full Post]

DPP 4 is regulated transcriptionally RGS4

2639 | Dec 04 2012

[Read the Full Post]

DPP-4 of cisplatin ECCC involved downregulate

3082 | Nov 02 2012

Th Rho kinase and PI-3-kinase in ECCC completely yet Constantly described. In this study we have tried to determine whether to f HA and CD44 on Rho kinase and PI-3-kinase signaling progression ECCC Interact rdern [Read the Full Post]

BORTEZOMIB: AN INHIBITOR OF PROTEASOMAL DEGRADATION

2278 | Aug 28 2012

BORTEZOMIB Proteasomes are one of the very important small organelles present in the cell. They have an important role in cell cycle regulation by degrading un-necessary proteins present in the cell. Sometimes in cancerous cells, the proteins that play a role in inhibiting un-regulated proliferation of cells are degraded by proteasomes. Inhibition of proteasomes in order to inhibit un-regulated growth is an attractive target in cancer therapy. Different proteasome inhibiting compounds have been used conventionally for the treatment of cancer e.g.,green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib is the first proteasomal inhibitor that has got approval for clinical studies for the treatment of cancer. [Read the Full Post]

BORTEZOMIB: AN ANTI-PROTEASOMAL AGENT

3382 | Jul 01 2012

BORTEZOMIB: INTRODUCTION In cell among the tiny organelles proteasomes are the foremost vital ones. They play necessary role in the correct regulation of the cell cycle by removing the proteins that don't seem to be necessary for cell. In cancer cell it rarely happens that the proteins which are involved in the controlling the dysregulated growth of the cells are excised by proteasomes. A promising target for the therapy of cancer is to inhibit proteasomes so that the uncontrolled growth is inhibited. A variety of compounds were typically used for cancer therapy that inhibits proteasomes. Among them EGCG additionally referred to as Epigallocatechin-3-gallate, Disulfiram and Salinosporamide-A that are present in green tea were used. The primary inhibitor of proteasomes that got approved to enter clinical trials for cancer therapy is Bortezomib. [Read the Full Post]

BORTEZOMIB: AN ANTI-PROTEIN DEGRADATION AGENT

4300 | Jun 20 2012

BORTEZOMIB Proteasomes belong to one of the important small organelles present in cell. Cell cycle is regulated by these proteasomes as they remove any unnecessary protein from cell. Usually during the cancer state the proteins which inhibit uncontrolled cell development of cancer are chopped down by these proteasomes. To stop chop these abnormal proteins properly inhibition of proteasomes is necessary which offers a good target for cancer therapy. For cancer treatment a lot of various compounds are being employed that cause proteasomes inhibition for example e.g., green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib was entitled to be first inhibitor that got approval to enter clinical studies for treatment of cancer. [Read the Full Post]

BORTEZOMIB; INHIBITING PROTEIN DEGRADATION

3534 | May 17 2012

BORTEZOMIB Poteasomes are one of the very important small organelles present in the cell. They have an important role in cell cycle regulation by degrading un-necessary proteins present in the cell. Sometimes in cancerous cells, the proteins that play a role in inhibiting un-regulated proliferation of cells are degraded by proteasomes. Inhibition of proteasomes in order to inhibit un-regulated growth is an attractive target in cancer therapy. Different proteasome inhibiting compounds have been used conventionally for the treatment of cancer e.g., green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib is the first proteasomal inhibitor that has got approval for clinical studies for the treatment of cancer. [Read the Full Post]

BORTEZOMIB – PROTEASOMAL INHIBITOR

3210 | Apr 26 2012

BORTEZOMIB: One of the most important categories of enzymes in the cell is the protein degrading enzymes called as proteosomes. They degrade all types of un-wanted proteins in the cells hence can regulate some important pathways in the cells like gene expression and cell cycle. The compounds which obstruct the activity of these enzymes play an important role in process of inhibition of degradation of cancer inhibiting proteins. Due to these properties proteosome inhibiting molecules like EGCG (Epigallocatechin-3-gallate) known as green tea as well, Disulfiram and Salinosporamide-A have been found to use for treatment of cancer. The first approved proteosomal inhibiting drug for clinical studies is Bortezomib and it is a very famous inhibitor of this class of enzymes. [Read the Full Post]

BORTEZOMIB – A PROTEASOME INHIBITOR

2935 | Apr 10 2012

BORTEZOMIB: There are different enzymes are present in the cell and amongst these enzymes Proteasomes are large enzymes which play function of degrading un-wanted proteins of cells, therefore these enzymes regulate some of the most important pathways including cell cycle and genetic expression. Those compounds which hinder the actions of these proteasomes play important functions in the process of inhibiting the degradation of tumor inhibiting proteins. Because of these properties the proteasome inhibitors such as EGCG (Epigallocatechin-3-gallate) also known as green tea, Salinosporamide-A and Disulfiram have been applied for cancer treatment. Bortezomib is the first approved proteasome inhibitor for clinical trials; this is the most famous inhibitor of this category. [Read the Full Post]

BORTEZOMIB – THE FIRST PROTEASOME INHIBITOR

2451 | Mar 19 2012

Introduction: Inhibition of the Proteasomes In the cellular environment there is a continuous movement of cells through cycles of life and death. Material is up taken and used to create new cells or energy, while protein signaling cascades regulate everything so that the host organism survives. However, during these essential processes proteins become damaged, unraveled or simply surplus to requirements, in this situation there exists clean up mechanisms to recycle as much material as possible. The major (>80%) pathway for this process is the proteasome pathway which in conjunction with the Ubiquitin pathway performs clean up routines in the cellular environment. The proteasome is a tubular protein sealed with another protein containing a tyrosine kinase domain. This tubular protein allows “tagged” protein to enter and bind within the tube section. Then catalytic activity begins to dismantle the protein and pass subunits out into the cytosole for reuse. Protein are recognized for destruction due to the actions of the Ubiquitin protein kinases. [Read the Full Post]