靶向泛素蛋白酶体系统(UPS)的化合物

Target Compounds

化合物

Molecular mechanisms分子机制Status状态
20S proteasomeBortezomibInhibition of proteasome-mediated proteolysis, which may lead to cell cycle arrest or apoptosis or inhibit the tumor growth.FDA approved for MM, MCL, NSCLC and PaCa
CarfilzomibInhibition of proteasome-mediated proteolysis, which may lead to cell cycle arrest or apoptosis or inhibit the tumor growth.FDA approved for relapsed and refractory MM
MLN9708A second-generation small-molecule proteasome inhibitor that displays antitumor activity in a variety of mouse models of HM.Phase III for MM
MarizomibA novel proteasome inhibitor that exhibits effects in patients with refractory and relapsed MM.Phase III for Glioblastoma
CRBNThalidomideBinds to CRBN and suppresses its activity.FDA approved for MM
Lenalidomide, PomalidomideBinds to CRBN and suppresses its activity.FDA approved for refractory MM
Mdm2PRIMARestores transcriptional activity of unfolded wild-type or mutant p53.FDA approved for LiCa and PaCa
SerdemetanIncreases p53 levels and inhibits proliferation, formation of the capillary tube and migration of HMEC-1 cells.Phase I for solid tumor
RG7112Increases p53 levels and transcriptional activation of p53 target genes.Phase I for HM
RG7388Increases p53 levels and signaling and suppresses neuroblastoma cell growth.Preclinical/research
RITAA small molecule inhibitor preventing the interaction between p53 and Mdm2 in the A-498 and TK-10 cell lines.Preclinical/research
HLI373Increases p53 levels through inhibiting Hdm2-mediated ubiquitination in U2OS cells.Preclinical/research
MEL23Increases p53 levels in U2OS, RKO and HCT116 cultures, and shown to induce RKO and MEF cell death.Preclinical/research
Nutlin-3aInhibits the growth of HM, GBM and AML cells by activating the p53-dependent apoptotic pathway.Preclinical/research
HLI98Activates p53 signaling and inhibits the tumor cell growth.Preclinical/research
MdmXSJ-172550Inhibits the MDMX-p53 interaction in cultured retinoblastoma cells.Preclinical/research
NSC207895Inhibits MDMX expression in MCF-7 cells.Preclinical/research
FL118Induces p53-dependent senescence in colorectal cancer cells.Preclinical/research
FBW7SCF-I2Inhibits the ubiquitination of substrates via inhibiting SCFCdc4.Preclinical/research
SKP2Compound #25Inhibits the activation of Skp2 and exhibits antitumor activity in PC3-induced tumor xenografts.Preclinical/research
APCApcinBlockades the substrate proteolysis and impedes cell mitotic exit via inhibiting Cdc20.Preclinical/research
TAMEPrevents the activation of APC by Cdc20 and Cdh1.Preclinical/research
β-TrCP1ErioflorinInhibits the NF-κB signaling pathway by decreasing the IκB ubiquitination.Preclinical/research
GS143Inhibits the NF-κB signaling pathway by decreasing the IκB ubiquitination.Preclinical/research
UBA1MLN7243Causes the depletion of cellular ubiquitin conjugates and shows antitumor activity in primary human xenograft.Phase I for advanced malignant solid tumors
NAEMLN4924Blocks the interaction between NAE and NEDD8 by forming an irreversible covalent adduct with NEDD8.Phase III for higher-risk MDS, CMML, AML
USP1PimozideDecreases GBM in xenograft models.Phase I/II for GBM
USP7p5091Induces apoptosis in MM cells, which are resistant to conventional and bortezomib therapies in mouse tumor model studies.Preclinical/research
p22077, p50429Covalently modifies the catalytic cysteine of USP7.Preclinical/research
FT671, FT827Destabilizes USP7 substrates and results in the inhibition of tumor growth in mice.Preclinical/research
HBX19,818, HBX28,258Binds in USP7 active site and shows effects on cell proliferation, apoptosis and cell cycle.Preclinical/research
USP14XL188A noncovalent active-site inhibitor that promotes the accumulation of p53 and p21.Preclinical/research
GNE-6640, GNE-6776A noncovalent active-site inhibitor of USP14 that induces tumor cell death.Preclinical/research
IU1Enhances the degradation of several proteasome substrates that have been implicated in neurodegenerative disease.Preclinical/research
USP14, UCHL5b-AP15Decreases viability in MM cell lines and patient MM cells, inhibits proliferation of MM cells via the downregulation of CDC25C, CDC2 and cyclin B1.Preclinical/research

MM多发性骨髓瘤,MCL套细胞淋巴瘤,NSCLC非小细胞肺癌,PaCa胰腺癌,HM血液系统恶性肿瘤,LiCa肝癌,MDS骨髓增生异常综合征,CMML慢性粒细胞白血病,AML急性骨髓性白血病,GBM胶质细胞瘤

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