Proteasome-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/Proteasome.html ProteasomeProteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they arelocated in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damage

2、d proteins byproteolysis, a chemical reaction that breaks peptide bonds. Enzymes that carry out such reactions are called proteases. Proteasomesare part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Thedegradation process yields

3、 peptides of about seven to eight amino acids long, which can then be further degraded into aminoacids and used in synthesizing new proteins. Proteins are tagged for degradation with a small protein called ubiquitin. The taggingreaction is catalyzed by enzymes called ubiquitin ligases. Once a protei

4、n is tagged with a single ubiquitin molecule, this is a signalto other ligases to attach additional ubiquitin molecules. The result is a polyubiquitin chain that is bound by the proteasome,allowing it to degrade the tagged protein.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/Proteasome.html

5、Proteasome HYPERLINK https:/www.MedChemE/Targets/Proteasome.html HYPERLINK https:/www.MedChemE/Targets/Proteasome.html Inhibitors, HYPERLINK https:/www.MedChemE/Targets/Proteasome.html HYPERLINK https:/www.MedChemE/Targets/Proteasome.html Activators HYPERLINK https:/www.MedChemE/Targets/Proteasome.h

6、tml HYPERLINK https:/www.MedChemE/Targets/Proteasome.html & HYPERLINK https:/www.MedChemE/Targets/Proteasome.html HYPERLINK https:/www.MedChemE/Targets/Proteasome.html Modulators HYPERLINK https:/www.MedChemE/1s-2s-bortezomib.html (1S,2S)-Bortezomib HYPERLINK https:/www.MedChemE/1s-2s-bortezomib.htm

7、l HYPERLINK https:/www.MedChemE/1s-2s-bortezomib-d5.html (1S,2S)-Bortezomib-d5Cat. No.: HY-135396 Cat. No.: HY-135396S(1S,2S)-Bortezomib is an enantiomer of Bortezomib.Bortezomib is a cell-permeable, reversible, andselective proteasome inhibitor, and potentlyinhibits 20S proteasome (K of 0.6 nM) byi

8、targeting a threonine residue.(1S,2S)-Bortezomib-d5 is the deuterium labeled(1S,2S)-Bortezomib. (1S,2S)-Bortezomib is anenantiomer of Bortezomib.Purity: 96.59%Clinical Data: No Development ReportedSize: 1 mg, 5 mg, 10 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK http

9、s:/www.MedChemE/r-mg-132.html (R)-MG-132(S,R,S)-(-)-MG-132; Z-Leu-D-Leu-Leu-al) Cat. No.: HY-13259C HYPERLINK https:/www.MedChemE/rac-calpain-inhibitor-xii.html (Rac)-Calpain HYPERLINK https:/www.MedChemE/rac-calpain-inhibitor-xii.html HYPERLINK https:/www.MedChemE/rac-calpain-inhibitor-xii.html Inh

10、ibitor HYPERLINK https:/www.MedChemE/rac-calpain-inhibitor-xii.html HYPERLINK https:/www.MedChemE/rac-calpain-inhibitor-xii.html XIICat. No.: HY-116171(R)-MG-132 (S,R,S)-(-)-MG-132) is the enantiomerof MG-132. (R)-MG-132 is a proteasome inhibitorwith weaker cell cytotoxicity than MG-132.(R)-MG-132 s

11、tereoisomer is a more potentproteasome inhibitor than MG-132.(Rac)-Calpain Inhibitor XII is a reversible andselective inhibitor of calpain I (-calpain, K=19inM). (Rac)-Calpain Inhibitor XII has loweraffinities for calpain II (m-calpain, K=120 nM)iand cathepsin B (K=750 nM).iPurity: 98.0%Clinical Dat

12、a: No Development ReportedSize: 5 mg, 10 mg, 50 mg, 100 mgPurity: 90.0%Clinical Data: No Development ReportedSize: 5 mg HYPERLINK https:/www.MedChemE/18_alpha_-Glycyrrhetinic_acid.html 18-Glycyrrhetinic HYPERLINK https:/www.MedChemE/18_alpha_-Glycyrrhetinic_acid.html HYPERLINK https:/www.MedChemE/18

13、_alpha_-Glycyrrhetinic_acid.html acid HYPERLINK https:/www.MedChemE/18_alpha_-Glycyrrhetinic_acid.html HYPERLINK https:/www.MedChemE/4-hydroxychalcone.html 4-HydroxychalconeCat. No.: HY-N0375 Cat. No.: HY-N705618-Glycyrrhetinic acid, a diet-derived compound,is an inhibitor of NF-kB and an activator

14、ofproteasome, which serves as pro-longevity andanti-aggregation factor in a multicellularorganism. 18-Glycyrrhetinic acid inducesapoptosis.4-Hydroxychalcone is a chalcone isolated fromlicorice root, with hepatoprotective activity.4-Hydroxychalcone inhibits TNF-induced NF-Bactivation via proteasome i

15、nhibition.Purity: 99.32%Clinical Data: LaunchedSize: 25 mg, 100 mg, 500 mgPurity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 100 mg HYPERLINK https:/www.MedChemE/5-amino-8-hydroxyquinoline.html 5-Amino-8-hydroxyquinoline HYPERLINK https:/www.MedChemE/5-amino-8-hydroxyquinoline.html

16、 HYPERLINK https:/www.MedChemE/ac-nle-pro-nle-asp-amc.html Ac-Nle-Pro-Nle-Asp-AMC(5A8HQ) Cat. No.: HY-W001023Cat. No.: HY-P20165-Amino-8-hydroxyquinoline (5A8HQ), a potentialanticancer candidate, has promising proteasomeinhibitory activity.Ac-Nle-Pro-Nle-Asp-AMC is a specific substrate for26S protea

17、some. Ac-Nle-Pro-Nle-Asp-AMC can beused for the 26S proteasome caspase-like activityanalysis.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/acetyl-calpastatin-184-210-human.html Acetyl-C

18、alpastatin(184-210)(human) HYPERLINK https:/www.MedChemE/acetyl-calpastatin-184-210-human.html HYPERLINK https:/www.MedChemE/acetyl-calpastatin-184-210-human-tfa.html Acetyl-Calpastatin(184-210)(human) HYPERLINK https:/www.MedChemE/acetyl-calpastatin-184-210-human-tfa.html HYPERLINK https:/www.MedCh

19、emE/acetyl-calpastatin-184-210-human-tfa.html TFACat. No.: HY-P1081 Cat. No.: HY-P1081AAcetyl-Calpastatin(184-210)(human) is a potent,selective and reversible calpain inhibitor with Kivalues of 0.2 nM and 6 M for -calpain andcathepsin L, respectively.Acetyl-Calpastatin(184-210)(human) TFA is apotent

20、, selective and reversible calpain inhibitorwith K values of 0.2 nM and 6 M for -calpainiand cathepsin L, respectively.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg2 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesM

21、edChemE HYPERLINK https:/www.MedChemE/Aclacinomycin_A_hydrochloride.html Aclacinomycin HYPERLINK https:/www.MedChemE/Aclacinomycin_A_hydrochloride.html HYPERLINK https:/www.MedChemE/Aclacinomycin_A_hydrochloride.html A HYPERLINK https:/www.MedChemE/Aclacinomycin_A_hydrochloride.html HYPERLINK https:

22、/www.MedChemE/Aclacinomycin_A_hydrochloride.html hydrochloride(Aclarubicin hydrochloride) Cat. No.: HY-N2306A HYPERLINK https:/www.MedChemE/Alicapistat.html Alicapistat(ABT-957) Cat. No.: HY-109001Aclacinomycin A hydrochloride (Aclarubicinhydrochloride), a fluorescent molecule and thefirst described

23、 non-peptidic inhibitor showingdiscrete specificity for the CTRL(chymotrypsin-like) activity of the 20Sproteasome.Alicapistat (ABT-957) is an orally activeselective inhibitor of human calpains 1 and 2 forthe potential use in the treatment of Alzheimersdisease (AD).Purity: 95.16%Clinical Data: Launch

24、edSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mgPurity: 98.0%Clinical Data: Phase 1Size: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/allm.html ALLM(Calpain inhibitor II) Cat. No.: HY-118355 HYPERLINK https:/www.MedChemE/alloxan-hydrate.html Alloxan HYPERLINK https:/www.MedChemE/allo

25、xan-hydrate.html HYPERLINK https:/www.MedChemE/alloxan-hydrate.html hydrateCat. No.: HY-W017227ALLM (Calpain inhibitor II) is a potent inhibitorof calpain and cathepsin proteases. ALLM inhibitsneuronal cell death and improves chronicneurological function after spinal cord injury(SCI).Alloxan hydrate

26、 is a diabetogenic agent to inducediabetes. Alloxan hydrate is a proteasomeinhibitor. Alloxan causes diabetes in experimentalanimals through its ability to destroy theinsulin-secreting B-cells of the pancreas.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data:

27、No Development ReportedSize: 1 g HYPERLINK https:/www.MedChemE/Bortezomib.html Bortezomib(PS-341; LDP-341; NSC 681239) Cat. No.: HY-10227 HYPERLINK https:/www.MedChemE/bortezomib-d8.html Bortezomib-d8(PS-341-d8; LDP-341-d8; NSC 681239-d8) Cat. No.: HY-10227SBortezomib (PS-341) is a reversible and se

28、lectiveproteasome inhibitor, and potently inhibits20S proteasome (K=0.6 nM) by targeting aithreonine residue. Bortezomib disrupts the cellcycle, induces apoptosis, and inhibits NF-B.Bortezomib-d8 (PS-341-d8) is the deuterium labeledBortezomib. Bortezomib (PS-341) is a reversibleand selective proteas

29、ome inhibitor, andpotently inhibits 20S proteasome (K=0.6 nM)iby targeting a threonine residue.Purity: 99.97%Clinical Data: LaunchedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg, 200 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/calpain-inhibitor-vi

30、.html Calpain HYPERLINK https:/www.MedChemE/calpain-inhibitor-vi.html HYPERLINK https:/www.MedChemE/calpain-inhibitor-vi.html Inhibitor HYPERLINK https:/www.MedChemE/calpain-inhibitor-vi.html HYPERLINK https:/www.MedChemE/calpain-inhibitor-vi.html VI HYPERLINK https:/www.MedChemE/calpain-inhibitor-v

31、i.html HYPERLINK https:/www.MedChemE/calpain-inhibitor-1.html Calpain HYPERLINK https:/www.MedChemE/calpain-inhibitor-1.html HYPERLINK https:/www.MedChemE/calpain-inhibitor-1.html Inhibitor-1(SJA6017) Cat. No.: HY-118933Cat. No.: HY-115753Calpain Inhibitor VI (SJA6017) is a synthesizedpeptide aldehy

32、de inhibitor of calpain. CalpainInhibitor VI inhibits purified m-calpain withthe IC of 80 nM. Calpain Inhibitor VI can be50used for the research of cataract.Calpain Inhibitor-1 (compound 36) is a potent andselective cysteine protease calpain 1 (Cal1)inhibitor (IC =100 nM; =2.89 M).50 KiPurity: 98%Cl

33、inical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/calpain-2-in-1.html Calpain-2-IN-1 HYPERLINK https:/www.MedChemE/calpain-2-in-1.html HYPERLINK https:/www.MedChemE/Calpeptin.html CalpeptinCat. No.: HY-

34、145155 Cat. No.: HY-100223Calpain-2-IN-1 (Formula 1A) is a isoform-specificcalpain-2 inhibitor with Ks of 181 nM and 7.8 nMifor calpain-1, and calpain-2,respectively. Calpain-2-IN-1 can be used forthe research of neurodegenerative diseases andother diseases of synaptic function.Calpeptin is a potent

35、, cell penetrating calpaininhibitor, with an ID of 40 nM for Calpain I in50human platelets. Calpeptin is also an inhibitor ofcathepsin K.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 10

36、0 mgwww.MedChemE 3 HYPERLINK https:/www.MedChemE/Capzimin.html CapziminCat. No.: HY-110404 HYPERLINK https:/www.MedChemE/Carfilzomib.html Carfilzomib(PR-171) Cat. No.: HY-10455Capzimin is a potent and moderately specificproteasome isopeptidase Rpn11 inhibitor.Carfilzomib (PR-171) is an irreversiblep

37、roteasome inhibitor with an IC of 5 nM in50ANBL-6 and RPMI 8226 cells.Purity: 99.32%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mgPurity: 99.96%Clinical Data: LaunchedSize: 5 mg, 10 mg, 50 mg, 100 mg, 200 mg HYPERLINK https:/www.MedChemE/carfilzomib-d8.html Carfilzomib-d8 HYPERLINK h

38、ttps:/www.MedChemE/carfilzomib-d8.html HYPERLINK https:/www.MedChemE/cyclotheonellazole-a.html Cyclotheonellazole HYPERLINK https:/www.MedChemE/cyclotheonellazole-a.html HYPERLINK https:/www.MedChemE/cyclotheonellazole-a.html ACat. No.: HY-10455S Cat. No.: HY-P3356Carfilzomib-d8 is deuterium labeled

39、 Carfilzomib.Carfilzomib (PR-171) is an irreversible proteasomeinhibitor with an IC50 of 5 nM in ANBL-6 and RPMI8226 cells.Cyclotheonellazole A is a natural macrocyclicpeptide and a potent elastase inhibitor (IC =0.03450nM). Cyclotheonellazole A inhibits chymotrypsinwith an IC value of 0.62 nM.50Pur

40、ity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/dazcapistat.html DazcapistatCat. No.: HY-132850 HYPERLINK https:/www.MedChemE/Delanzomib.html Delanzomib(CEP-18770) Cat. No.: HY-10454Dazcapis

41、tat is a potent calpain inhibitor, withIC s of 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 96.0%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/dihydroeponemycin.html Dihydroeponemycin HYPERLINK https:/www.M

42、edChemE/dihydroeponemycin.html HYPERLINK https:/www.MedChemE/Epoxomicin.html EpoxomicinCat. No.: HY-108553(BU-4061T) Cat. No.: HY-13821Dihydroeponemycin, an analogue of the antitumorand antiangiogenic natural product eponemycin,selectively targets the 20S proteasome.Epoxomicin (BU-4061T) is an epoxy

43、ketone-containingnatural product and a potent, selective andirreversible proteasome inhibitor.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.81%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 100 g, 1 mg, 5 mg, 10 mg, 20 mg HYPERLINK https:/www.MedChemE/FK-448_Fr

44、ee_base.html FK-448 HYPERLINK https:/www.MedChemE/FK-448_Free_base.html HYPERLINK https:/www.MedChemE/FK-448_Free_base.html Free HYPERLINK https:/www.MedChemE/FK-448_Free_base.html HYPERLINK https:/www.MedChemE/FK-448_Free_base.html base HYPERLINK https:/www.MedChemE/FK-448_Free_base.html HYPERLINK

45、https:/www.MedChemE/Gabexate-mesylate.html Gabexate HYPERLINK https:/www.MedChemE/Gabexate-mesylate.html HYPERLINK https:/www.MedChemE/Gabexate-mesylate.html mesylateCat. No.: HY-100193(FOY) Cat. No.: HY-B0385FK-448 Free base is an effective and specificinhibitor of chymotrypsin, with an IC of 72050

46、nM.Gabexate mesylate is a Factor X inhibitor; serineprotease inhibitor .Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.12%Clinical Data: LaunchedSize: 10 mM 1 mL, 10 mg, 100 mg4 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/gsk349

47、4245.html GSK3494245(DDD01305143) Cat. No.: HY-127102 HYPERLINK https:/www.MedChemE/immunoproteasome-inhibitor-1.html Immunoproteasome HYPERLINK https:/www.MedChemE/immunoproteasome-inhibitor-1.html HYPERLINK https:/www.MedChemE/immunoproteasome-inhibitor-1.html inhibitor HYPERLINK https:/www.MedChe

48、mE/immunoproteasome-inhibitor-1.html HYPERLINK https:/www.MedChemE/immunoproteasome-inhibitor-1.html 1Cat. No.: HY-144452GSK3494245 (DDD01305143) is a potent, orallyactive, and selective inhibitor of thechymotrypsin-like activity of the parasiteproteasome binding in a site sandwiched betweenthe 4 an

49、d 5 subunits (IC50=0.16 M for WT L.donovani proteasomes).Immunoproteasome inhibitor 1 is a potent,reversible, time-independent immunoproteasomeand proteasome inhibitor (Ks of 1.18, 0.27,i1.91 M in 5c, 1i, 5i submits, respectively).Immunoproteasome inhibitor 1 can be used for thetreatment of certain

50、neoplastic diseases.Purity: 98.66%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/MLN2238.html Ixazomib(MLN2238) Cat. No.: HY-10453 HYPERLINK https:/www.MedChemE/MLN9708.html

51、Ixazomib HYPERLINK https:/www.MedChemE/MLN9708.html HYPERLINK https:/www.MedChemE/MLN9708.html citrate(MLN9708) Cat. No.: HY-10452Ixazomib (MLN2238) is a selective, potent, andreversible proteasome inhibitor, which inhibitsthe chymotrypsin-like proteolytic (5) site of the20S proteasome with an IC50

52、of 3.4 nM (Ki of 0.93nM).Ixazomib citrate (MLN9708) is a reversibleinhibitor of the chymotrypsin-like proteolytic 5site of the 20S proteasome with an IC of 3.450nM and a K of 0.93 nM.iPurity: 99.85%Clinical Data: LaunchedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mgPurity: 99.89%Clinical Data: Launche

53、dSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/KZR-504.html KZR-504 HYPERLINK https:/www.MedChemE/KZR-504.html HYPERLINK https:/www.MedChemE/lactacystin.html LactacystinCat. No.: HY-101786 Cat. No.: HY-16594KZR-504 is a highly selective inhibitor ofimmunoproteasome low m

54、olecular mass polypeptide 2(LMP2), with IC s of 51 nM, 4.274 M for LMP250and LMP7, respectively. KZR-504 is of interest forthe treatment of autoimmune disease.Lactacystin, an antibiotic Streptomyces spp.metabolite, is a potent and selectiveproteasome inhibitor with an IC of 4.8 M for5020S proteasome

55、. Lactacystin also inhibits thelysosomal enzyme cathepsin A. Lactacystin inhibitscell growth and induces neurite outgrowth.Purity: 98.82%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.08%Clinical Data: No Development ReportedSize: 500 g, 1 mg HYPERLINK https:

56、/www.MedChemE/leptosphaerodione.html Leptosphaerodione HYPERLINK https:/www.MedChemE/leptosphaerodione.html HYPERLINK https:/www.MedChemE/lmp7-in-1.html LMP7-IN-1Cat. No.: HY-N10332 Cat. No.: HY-142920Leptosphaerodione, isolated fromRemotididymella sp. Fungus, is a potentubiquitin-proteasome system

57、(UPS)inhibitor. Leptosphaerodione exhibits cytotoxicityin HeLa cells with IC value of 3.2 M. Anti-tumor50agent.LMP7-IN-1, a Boronic acid derivative, is a potentand selective immunoproteasome subunit LMP7(5i) inhibitor with an IC of 1.83 nM50(WO2021143923A1; compound 20).Purity: 98%Clinical Data: No

58、Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/lxe408.html LXE408 HYPERLINK https:/www.MedChemE/lxe408.html HYPERLINK https:/www.MedChemE/M-3258.html M3258Cat. No.: HY-131350 Cat. No.: HY-111790LXE408 is an orally a

59、ctive, non-competitive andkinetoplastid-selective proteasome inhibitor.LXE408 has an IC of 0.04 M for50 L. donovaniproteasome and an EC50 of 0.04 M for L. donovani.LXE408 has a low propensity to cross the bloodbrain barrier.M3258 is an orally bioavailable, potent,reversible and highly selective immu

60、noproteasomesubunit LMP7 (5i) inhibitor. M3258 exerts highbiochemical (IC50=3.6 nM) and cellular (IC50=3.4nM) potency against the LMP7 subunit.Purity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL,