E1-E2-E3-Enzyme-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/E1_E2_E3 Enzyme.html E1/E2/E3 HYPERLINK https:/www.MedChemE/Targets/E1_E2_E3 Enzyme.html HYPERLINK https:/www.MedChemE/Targets/E1_E2_E3 Enzyme.html EnzymeE1 activating enzyme; E2 conjugating enzyme; E3 ligating enzyme; Ubiquitin activating enzyme;Ubiquitin conj

2、ugating enzyme; Ubiquitin ligaseUbiquitin (UB) is a protein modifier that regulates many essential cellular processes. To initiate protein modification by UB, the E1enzyme activates the C-terminal carboxylate of UB to launch its transfer through the E1-E2-E3 cascade onto target proteins. The E1enzym

3、e is the activating enzyme, to which ubiquitin is attached in an ATP-dependent reaction by a thioester bond. The E2 enzymeis the conjugating enzyme, to which the ubiquitin is transferred from the E1. The E3 is the ubiquitin ligase, which directly orindirectly catalyzes the transfer of the ubiquitin

4、to the target protein (the substrate), with the formation of an isopeptide bond.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html E1/E2/E3 HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html Enzyme HYPERLINK ht

5、tps:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html Inhibitors, HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html Agonists HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.h

6、tml HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html & HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html HYPERLINK https:/www.MedChemE/Targets/E1/E2/E3 Enzyme.html Activators HYPERLINK https:/www.MedChemE/2-D08.html 2-D08Cat. No.: HY-114166 HYPERLINK https:/www.MedChemE/apg-115.ht

7、ml Alrizomadlin(APG-115; AA-115) Cat. No.: HY-1015182-D08 is a cell permeable, mechanistically uniqueinhibitor of protein SUMOylation. 2-D08 alsoinhibits Axl with an IC of 0.49 nM.50Alrizomadlin (APG-115) is an orally active MDM2protein inhibitor binding to MDM2 protein withIC50 and Ki values of 3.8

8、 nM and 1 nM,respectively. Alrizomadlin blocks the interactionof MDM2 and p53 and induces cell-cycle arrest andapoptosis in a p53-dependent manner.Purity: 98.44%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.16%Clinical Data: Phase 2Size: 1 mg, 5

9、mg, 10 mg HYPERLINK https:/www.MedChemE/AM-8735.html AM-8735Cat. No.: HY-12734 HYPERLINK https:/www.MedChemE/CC122.html Avadomide(CC 122) Cat. No.: HY-100507AM-8735 is a potent and selective MDM2inhibitor with an IC of 25 nM.50Avadomide (CC 122) is an orally active cereblonmodulator. Avadomide modul

10、ates cereblon E3 ligaseactivity and induces apoptosis of diffuse largeB-cell lymphoma (DLBCL) cell lines. Avadomideexhibits potent antitumor and immunomodulatoryactivities.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.50%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10

11、mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/bc-1382.html BC-1382 HYPERLINK https:/www.MedChemE/bc-1382.html HYPERLINK https:/www.MedChemE/bc1618.html BC1618Cat. No.: HY-W062696 Cat. No.: HY-134656BC-1382 is a potent ubiquitin E3 ligase HECTD2inhibitor that specificly disrupts theHECTD2/PIAS1 int

12、eraction (IC 550nM).Anti-inflammatory activity.BC1618, an orally active Fbxo48 inhibitorycompound, stimulates Ampk-dependent signaling (viapreventing activated pAmpk from Fbxo48-mediateddegradation). BC1618 promotes mitochondrialfission, facilitates autophagy and improveshepatic insulin sensitivity.

13、Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.83%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/BH3I-1.html BH3I-1 HYPERLINK https:/www.MedChemE/BH3I-1.html HYPERLINK https:/www.MedChemE/bi-0252.ht

14、ml BI-0252(BHI1; BH 3I1) Cat. No.: HY-100383Cat. No.: HY-100765BH3I-1 is a Bcl-2 family antagonist, whichinhibits the binding of the Bak BH3 peptide toBcl-xL with a K of 2.40.2 M in FP assay. BH3I-1ihas a K of 5.3 M against the /d p53 MDM2pair.BI-0252 is an orally active, selective MDM2-p53inhibitor

15、 with an IC of 4 nM. BI-0252 can induce50tumor regressions in all animals of a mouse SJSA-1xenograft, with concomitant induction of the tumorprotein p53 (TP53) target genes and markers ofapoptosis.Purity: 98.0%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98%Cl

16、inical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/bi8622.html BI8622 HYPERLINK https:/www.MedChemE/bi8622.html HYPERLINK https:/www.MedChemE/bi8626.html BI8626Cat. No.: HY-120929 Cat. No.: HY-120204BI8622 is a specific inhibitor of the ubiquitinligase HUWE1 with an I

17、C of 3.1 M.50BI8626 is a specific inhibitor of the ubiquitinligase HUWE1 with an IC of 0.9 M.50Purity: 99.40%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.49%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg2 Tel:

18、 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/brd5529.html BRD5529 HYPERLINK https:/www.MedChemE/brd5529.html HYPERLINK https:/www.MedChemE/c25-140.html C25-140Cat. No.: HY-115497 Cat. No.: HY-120934BRD5529 is a selective CARD9-E3 ubiquitin ligaseTRIM62 protein-p

19、rotein interaction inhibitorwith an IC of 8.6 M.50C25-140, a first-in-class, orally active, andfairly selective TRAF6-Ubc13 inhibitor, directlybinds to TRAF6, and blocks the interaction ofTRAF6 with Ubc13. C25-140 lowers TRAF6 activity,reduces NF-B activation, and combatsautoimmunity.Purity: 98.46%C

20、linical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.84%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/cbl-b-in-1.html Cbl-b-IN-1 HYPERLINK https:/www.MedChemE/cbl-b-in-1.html HYPERLINK ht

21、tps:/www.MedChemE/CC0651.html CC0651Cat. No.: HY-136339 Cat. No.: HY-15301Cbl-b-IN-1 (example 519) is a Cbl-b inhibitor,extracted from patent WO2019148005A1, with an IC98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK

22、 https:/www.MedChemE/dcn1-ubc12-in-3.html DCN1-UBC12-IN-3 HYPERLINK https:/www.MedChemE/dcn1-ubc12-in-3.html HYPERLINK https:/www.MedChemE/di-1859.html DI-1859Cat. No.: HY-142692 Cat. No.: HY-145733DCN1-UBC12-IN-3 is potent and selectiveDCN1-UBC12 inhibitor with an IC of 2.25 nM.50Anticardiac fibrot

23、ic effect.DI-1859 is a potent, selective and covalentinhibitor of DCN1. DI-1859 inhibits neddylationof cullin 3 in cells at low nanomolarconcentrations.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgwww.MedChemE 3 HYP

24、ERLINK https:/www.MedChemE/di-591.html DI-591 HYPERLINK https:/www.MedChemE/di-591.html HYPERLINK https:/www.MedChemE/DKM_2-93.html DKM HYPERLINK https:/www.MedChemE/DKM_2-93.html HYPERLINK https:/www.MedChemE/DKM_2-93.html 2-93Cat. No.: HY-124602 Cat. No.: HY-101836DI-591 is a potent, high-affinity

25、 andcell-permeable inhibitor of the DCN1-UBC12interaction. DI-591 binds to DCN1 and DCN2 with Kvalues of 12nM and 10.4 nM, respectively and hasno appreciable binding to DCN3, DCN4, and DCN5proteins.iDKM 2-93 is a relatively selective inhibitor ofUBA5 with an IC of 430 M.50Purity: 98.36%Clinical Data

26、: No Development ReportedSize: 10 mgPurity: 98.76%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 100 mg, 200 mg, 500 mg HYPERLINK https:/www.MedChemE/Ginkgolic-Acid.html Ginkgolic HYPERLINK https:/www.MedChemE/Ginkgolic-Acid.html HYPERLINK https:/www.MedChemE/Ginkgolic-Acid.html Acid HYPERL

27、INK https:/www.MedChemE/Ginkgolic-Acid.html (Ginkgolic acid (15:1); Ginkgolic acid I;Romanicardic acid) Cat. No.: HY-N0077 HYPERLINK https:/www.MedChemE/gs143.html GS143Cat. No.: HY-110261Ginkgolic Acid is a natural compound that inhibitsSUMOylation with an IC50 of 3.0 M in in vitroassay.GS143 is a

28、selective IB ubiquitination inhibitorwith an IC of 5.2 M for SCFTrCP1-mediated50IB ubiquitylation. GS143 suppresses NF-Bactivation and transcription of target genesand does not inhibit proteasome activity. GS143has anti-asthma effect.Purity: 99.92%Clinical Data: No Development ReportedSize: 10 mM 1

29、mL, 5 mg, 10 mgPurity: 98.30%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/hb007.html HB007 HYPERLINK https:/www.MedChemE/hb007.html HYPERLINK https:/www.MedChemE/heclin.html HeclinCat. No.: HY-139662 Cat. No.: HY-110204HB007

30、is a small ubiquitin-related modifier 1(SUMO1) degrader. HB007 induces ubiquitinationand degradation of SUMO1, resulting in reducedtumor growth in vivo. HB007 can be used for theresearch of brain, breast, colon, and lungcancers.Heclin is a HECT E3 ubiquitin ligases inhibitor.Heclin inhibits several

31、HECT ligases in tissueculture cells (IC s=6.8, 6.3, and 6.9 M for50Smurf2, Nedd4, and WWP1 HECT ligase domains,respectively).Purity: 99.20%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 10

32、0 mg HYPERLINK https:/www.MedChemE/hinokiflavone.html Hinokiflavone HYPERLINK https:/www.MedChemE/hinokiflavone.html HYPERLINK https:/www.MedChemE/hoipin-8.html HOIPIN-8Cat. No.: HY-N2360 Cat. No.: HY-122882Hinokiflavone is a novel modulator of pre-mRNAsplicing activity in vitro and in cellulo.Hinok

33、iflavone blocks splicing of pre-mRNAsubstrates by inhibiting spliceosome assembly,specifically preventing B complex formation.HOIPIN-8 is a potent inhibitor of linear ubiquitinchain assembly complex (LUBAC) with an IC of 1150nM.Purity: 99.95%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPuri

34、ty: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/RG7388.html Idasanutlin HYPERLINK https:/www.MedChemE/RG7388.html HYPERLINK https:/www.MedChemE/Indole-3-carbinol.html Indole-3-carbinol(RG7388) Cat. No.: HY-15676 (I3C; 3-Indolemethano

35、l) Cat. No.: HY-N0170Idasanutlin (RG7388) is a potent and selectiveMDM2 antagonist, inhibiting p53-MDM2 binding,with an IC of 6 nM.50Indole-3-carbinol (I3C) inhibits NF-B activityand also is an Aryl hydrocarbon receptor (AhR)agonist, and an inhibitor of WWP1 (WWdomain-containing ubiquitin E3 ligase

36、1).Purity: 99.90%Clinical Data: Phase 3Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.0%Clinical Data: Phase 2Size: 10 mM 1 mL, 200 mg, 1 g4 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/keap1-nrf2-in-4.html Keap1-Nrf2-IN-4 HYPERLINK https:/www.MedChe

37、mE/keap1-nrf2-in-4.html HYPERLINK https:/www.MedChemE/ls-102.html LS-102Cat. No.: HY-144099 Cat. No.: HY-135844Keap1-Nrf2-IN-4 is a potent neddylation inhibitor.Keap1-Nrf2-IN-4 exhibits potent anti-proliferationactivity against MGC-803 cells (IC =2.55 M).50Keap1-Nrf2-IN-4 blocks the migration abilit

38、y andinduces apoptosis of gastric cancer cells.LS-102 is a selective E3 ubiquitin ligasesynoviolin (Syvn1) inhibitor. LS-102 inhibits theautoubiquitination of synoviolin with an IC of5035 M. LS-102 has the potential for rheumatoidarthritis treatment.Purity: 98%Clinical Data: No Development ReportedS

39、ize: 1 mg, 5 mgPurity: 96.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg HYPERLINK https:/www.MedChemE/m435-1279.html M435-1279 HYPERLINK https:/www.MedChemE/m435-1279.html HYPERLINK https:/www.MedChemE/md-222.html MD-222Cat. No.: HY-141891 Cat. No.: HY-134823M435-1279

40、is a UBE2T inhibitor. M435-1279inhibits the Wnt/-catenin signaling pathwayhyperactivation through blocking UBE2T-mediateddegradation of RACK1.MD-222 is the first-in-class highly potent PROTACdegrader of MDM2. MD-222 consists of ligandsfor Cereblon and MDM2. MD-222 induces rapiddegradation of the MDM

41、2 protein and activationof wild-type p53 in cells. MD-222 has anticancereffects.Purity: 98.43%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.28%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg HYPERLINK https:/www.MedChemE/md-224.html MD-224Cat.

42、 No.: HY-114312 HYPERLINK https:/www.MedChemE/cc-92480.html Mezigdomide(CC-92480) Cat. No.: HY-129395MD-224 is a first-in-class and highly potentsmall-molecule human murine double minute 2(MDM2) degrader based on theproteolysistargeting chimera (PROTAC) concept.MD-224 consists of ligands for Cereblo

43、n andMDM2.Mezigdomide (CC-92480), a cereblon E3 ubiquitinligase modulating drug (CELMoD), acts as amolecular glue. Mezigdomide shows high affinity tocereblon, resulting in potent antimyelomaactivity.Purity: 99.74%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98

44、.02%Clinical Data: Phase 2Size: 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/mi-1061.html MI-1061 HYPERLINK https:/www.MedChemE/mi-1061.html HYPERLINK https:/www.MedChemE/mi-1061-tfa.html MI-1061 HYPERLINK https:/www.MedChemE/mi-1061-tfa.html HYPERLINK https:/www.MedChemE/mi-1061-tfa.htm

45、l TFACat. No.: HY-125858 Cat. No.: HY-125858AMI-1061 is a potent, orally bioavailable, andchemically stable MDM2 (MDM2-p53 interaction)inhibitor (IC =4.4 nM; =0.16 nM). MI-106150 Kipotently activates p53 and induces apoptosis inthe SJSA-1 xenograft tumor tissue in mice.Anti-tumor activity.MI-1061 TF

46、A is a potent, orally bioavailable, andchemically stable MDM2 (MDM2-p53 interaction)inhibitor (IC50=4.4 nM; Ki=0.16 nM). MI-1061 TFApotently activates p53 and induces apoptosis inthe SJSA-1 xenograft tumor tissue in mice.Anti-tumor activity.Purity: 99.62%Clinical Data: No Development ReportedSize: 1

47、0 mM 1 mL, 1 mg, 5 mg, 10 mgPurity: 95.08%Clinical Data: No Development ReportedSize: 1 mg, 5 mg, 10 mg HYPERLINK https:/www.MedChemE/MI-773.html MI-773 HYPERLINK https:/www.MedChemE/MI-773.html HYPERLINK https:/www.MedChemE/Milademetan.html MilademetanCat. No.: HY-17493(DS-3032) Cat. No.: HY-101266

48、MI-773 is a potent MDM2-p53 proteinproteininteraction (PPI) inhibitor with high bindingaffinity against MDM2 (K =8.2 nM). MI-773 hasdantitumor activity.Milademetan (DS-3032) is a specific and orallyactive MDM2 inhibitor for the research of acutemyeloid leukemia (AML) or solid tumors.Milademetan (DS-

49、3032) induces G1 cell cyclearrest, senescence and apoptosis.Purity: 98.05%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.33%Clinical Data: Phase 2Size: 10 mM 1 mL, 1 mg, 5 mg, 10 mgwww.MedChemE 5 HYPERLINK https:/www.MedChemE/milademetan-tosylate-hydrate

50、.html Milademetan HYPERLINK https:/www.MedChemE/milademetan-tosylate-hydrate.html HYPERLINK https:/www.MedChemE/milademetan-tosylate-hydrate.html tosylate HYPERLINK https:/www.MedChemE/milademetan-tosylate-hydrate.html HYPERLINK https:/www.MedChemE/milademetan-tosylate-hydrate.html hydrate(DS-3032b;

51、 DS-3032 tosylate hydrate) Cat. No.: HY-101266B HYPERLINK https:/www.MedChemE/ml-792.html ML-792Cat. No.: HY-108702Milademetan (DS-3032) tosylate hydrate is aspecific and orally active MDM2 inhibitor forthe research of acute myeloid leukemia (AML) orsolid tumors. Milademetan (DS-3032) tosylatehydrat

52、e induces G1 cell cycle arrest, senescenceand apoptosis.ML-792 is a potent and selective inhibitor ofSAE/SUMO1 and SAE/SUMO2 in enzymatic assays(IC values of 3 and 11 nM, respectively)50compared with NAE/NEDD8 and UAE/ubiquitin (IC50values of 32 M and 100 M, respectively).Purity: 98.21%Clinical Data

53、: Phase 2Size: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.66%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/MX69.html MX69 HYPERLINK https:/www.MedChemE/MX69.html HYPERLINK https:/www.MedChemE/n106.html N106Cat. No.: HY-100892

54、 Cat. No.: HY-110273MX69 is an inhibitor of MDM2/XIAP, used forcancer treatment.N106 is a first-in-class sarcoplasmic reticulumcalcium ATPase (SERCA2a) SUMOylation activator.N106 directly activates the SUMO-activatingenzyme, E1 ligase. N106 can be used for heartfailure research.Purity: 99.99%Clinica

55、l Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/NAcM-OPT.html NAcM-OPTCat. No.: HY-111505 HYPERLINK https:/www.MedChemE/AMG-232.html Navtemadlin(AMG 232; KRT-232) Cat. No.

56、: HY-12296NAcM-OPT is an orally bioavailable cullinneddylation 1 (DCN1) inhibitor, which potentlyinhibits the DCN1-UBE2M interaction.Navtemadlin (AMG 232) is a potent, selective andorally available inhibitor of p53-MDM2interaction, with an IC of 0.6 nM. Navtemadlin50binds to MDM2 with a K of 0.045 n

57、M.dPurity: 99.81%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.43%Clinical Data: Phase 1Size: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/navtemadlin-d7.html Navtemadlin-d7 HYPERLINK https:/www.MedChemE/navtemadlin-d7.html HYPERLINK

58、https:/www.MedChemE/NSC232003.html NSC232003(AMG 232-d7; KRT-232-d7) Cat. No.: HY-12296SCat. No.: HY-103236Navtemadlin-d7 (AMG 232-d7) is the deuteriumlabeled Navtemadlin. Navtemadlin (AMG 232) is apotent, selective and orally available inhibitorof p53-MDM2 interaction, with an IC of 0.650nM. Navtem

59、adlin binds to MDM2 with a K of 0.045dnM.NSC232003 is a highly potent and cell-permeableUHRF1 inhibitor, which inhibits DNA methylationin vitro and disrupts DNMT1/UHRF1 interactions ata cellular level.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.66%Clinical Data: No De

60、velopment ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/nsc624206.html NSC624206 HYPERLINK https:/www.MedChemE/nsc624206.html HYPERLINK https:/www.MedChemE/nsc697923.html NSC697923Cat. No.: HY-103436 Cat. No.: HY-13811NSC624206 is an inhibitor of ubiquitin