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 proteasome	Bortezomib	Inhibition 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
	Carfilzomib	Inhibition 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
	MLN9708	A second-generation small-molecule proteasome inhibitor that displays antitumor activity in a variety of mouse models of HM.	Phase III for MM
	Marizomib	A novel proteasome inhibitor that exhibits effects in patients with refractory and relapsed MM.	Phase III for Glioblastoma
CRBN	Thalidomide	Binds to CRBN and suppresses its activity.	FDA approved for MM
CRBN	Lenalidomide, Pomalidomide	Binds to CRBN and suppresses its activity.	FDA approved for refractory MM
Mdm2	PRIMA	Restores transcriptional activity of unfolded wild-type or mutant p53.	FDA approved for LiCa and PaCa
	Serdemetan	Increases p53 levels and inhibits proliferation, formation of the capillary tube and migration of HMEC-1 cells.	Phase I for solid tumor
	RG7112	Increases p53 levels and transcriptional activation of p53 target genes.	Phase I for HM
	RG7388	Increases p53 levels and signaling and suppresses neuroblastoma cell growth.	Preclinical/research
	RITA	A small molecule inhibitor preventing the interaction between p53 and Mdm2 in the A-498 and TK-10 cell lines.	Preclinical/research
	HLI373	Increases p53 levels through inhibiting Hdm2-mediated ubiquitination in U2OS cells.	Preclinical/research
	MEL23	Increases p53 levels in U2OS, RKO and HCT116 cultures, and shown to induce RKO and MEF cell death.	Preclinical/research
	Nutlin-3a	Inhibits the growth of HM, GBM and AML cells by activating the p53-dependent apoptotic pathway.	Preclinical/research
	HLI98	Activates p53 signaling and inhibits the tumor cell growth.	Preclinical/research
MdmX	SJ-172550	Inhibits the MDMX-p53 interaction in cultured retinoblastoma cells.	Preclinical/research
	NSC207895	Inhibits MDMX expression in MCF-7 cells.	Preclinical/research
	FL118	Induces p53-dependent senescence in colorectal cancer cells.	Preclinical/research
FBW7	SCF-I2	Inhibits the ubiquitination of substrates via inhibiting SCF^Cdc4.	Preclinical/research
SKP2	Compound #25	Inhibits the activation of Skp2 and exhibits antitumor activity in PC3-induced tumor xenografts.	Preclinical/research
APC	Apcin	Blockades the substrate proteolysis and impedes cell mitotic exit via inhibiting Cdc20.	Preclinical/research
APC	TAME	Prevents the activation of APC by Cdc20 and Cdh1.	Preclinical/research
β-TrCP1	Erioflorin	Inhibits the NF-κB signaling pathway by decreasing the IκB ubiquitination.	Preclinical/research
β-TrCP1	GS143	Inhibits the NF-κB signaling pathway by decreasing the IκB ubiquitination.	Preclinical/research
UBA1	MLN7243	Causes the depletion of cellular ubiquitin conjugates and shows antitumor activity in primary human xenograft.	Phase I for advanced malignant solid tumors
NAE	MLN4924	Blocks the interaction between NAE and NEDD8 by forming an irreversible covalent adduct with NEDD8.	Phase III for higher-risk MDS, CMML, AML
USP1	Pimozide	Decreases GBM in xenograft models.	Phase I/II for GBM
USP7	p5091	Induces apoptosis in MM cells, which are resistant to conventional and bortezomib therapies in mouse tumor model studies.	Preclinical/research
	p22077, p50429	Covalently modifies the catalytic cysteine of USP7.	Preclinical/research
	FT671, FT827	Destabilizes USP7 substrates and results in the inhibition of tumor growth in mice.	Preclinical/research
	HBX19,818, HBX28,258	Binds in USP7 active site and shows effects on cell proliferation, apoptosis and cell cycle.	Preclinical/research
USP14	XL188	A noncovalent active-site inhibitor that promotes the accumulation of p53 and p21.	Preclinical/research
	GNE-6640, GNE-6776	A noncovalent active-site inhibitor of USP14 that induces tumor cell death.	Preclinical/research
	IU1	Enhances the degradation of several proteasome substrates that have been implicated in neurodegenerative disease.	Preclinical/research
USP14, UCHL5	b-AP15	Decreases 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