p97-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/p97.html p97VCP; Cdc48p97 (also referred to as VCP) is a highly conserved and abundant AAA+ (ATPases associated with diverse cellular activities) ATPasethat plays an essential role in cellular proteostasis. p97 participates in a large number of important cellul

2、ar activities, including (i)proteasomal degradation, through its roles in extracting proteins from membranes or molecular complexes; (ii) lysosomaldegradation via autophagy and endolysosomal sorting; (iii) membrane fusion; and (iv) regulation of intracellular signaling, cellproliferation, and surviv

3、al. These diverse cellular functions are powered by the chemical energy from ATP hydrolysis andcoordinated through the interaction of p97 with as many as 40 cofactors that recruit it to specific subcellular locations and todesignated substrates for their remodeling and processing.Mutations in p97 ha

4、ve been linked to a number of neurodegenerative diseases, and overexpression of wild type p97 is observed innumerous cancers. Furthermore, p97 activity has been shown to be essential for the replication of certain viruses, includingpoliovirus, herpes simplex virus (HSV), cytomegalovirus (CMV), and i

5、nfluenza. These observations highlight the potential fortargeting p97 as a therapeutic approach in neurodegeneration, cancer, and certain infectious diseases.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/p97.html p97 HYPERLINK https:/www.MedChemE/Targets/p97.html HYPERLINK https:/www.MedChemE

6、/Targets/p97.html Inhibitors HYPERLINK https:/www.MedChemE/CB-5083.html CB-5083Cat. No.: HY-12861 HYPERLINK https:/www.MedChemE/DBeQ.html DBeQ(JRF 12) Cat. No.: HY-15945CB-5083 is a first-in-class, potent, selective,and orally bioavailable inhibitor of the p97 AAAATPase/VCP. CB-5083 selectively inhi

7、bits p97through its D2 site with the IC of 11 nM.50DBeQ is a selective, potent, reversible, andATP-competitive p97 inhibitor, with an IC value50of 1.5 M and 1.6 M for p97(wt) and p97(C522A),respectively; DBeQ also inhibits Vps4 with anIC of 11.5 M.50Purity: 99.90%Clinical Data: Phase 1Size: 10 mM 1

8、mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.68%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg HYPERLINK https:/www.MedChemE/eeyarestatin-i.html Eeyarestatin HYPERLINK https:/www.MedChemE/eeyarestatin-i.html HYPERLINK https:/www.MedChemE/eeyarestatin-i.html I HYPERLINK https:

9、/www.MedChemE/eeyarestatin-i.html HYPERLINK https:/www.MedChemE/ML240.html ML240Cat. No.: HY-110078 Cat. No.: HY-19795Eeyarestatin I, a potent endoplasmicreticulum-associated protein degradation (ERAD)inhibitor, is a potent protein translocationinhibitor.ML240 is a potent p97 inhibitor, inhibiting p

10、97ATPase with IC value of 100 nM.50Purity: 98.14%Clinical Data: No Development ReportedSize: 5 mg, 10 mgPurity: 99.85%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/ML241-hydrochloride.html ML241 HYPERLINK https:/www.MedChemE/M

11、L241-hydrochloride.html HYPERLINK https:/www.MedChemE/ML241-hydrochloride.html hydrochloride HYPERLINK https:/www.MedChemE/ML241-hydrochloride.html HYPERLINK https:/www.MedChemE/msc1094308.html MSC1094308Cat. No.: HY-19797A Cat. No.: HY-123872ML241 hydrochloride is a potent p97 inhibitor,inhibiting

12、p97 ATPase with IC value of 100 nM.50MSC1094308 is a reversible and allostericinhibitor of the type II AAA ATPase humanubiquitin-directed unfoldase (VCP)/p97 and thetype I AAA ATPase VPS4B, with IC values of 0.7150M and 7.2 M for VPS4B and p97, respectively.Purity: 99.78%Clinical Data: No Developmen

13、t ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.75%Clinical Data:Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/NMS-859.html NMS-859 HYPERLINK https:/www.MedChemE/NMS-859.html HYPERLINK https:/www.MedChemE/NMS-873.html NMS-873Cat. No.: HY-15714 Cat

14、. No.: HY-15713NMS-859 is a potent, covalent VCP (p97)inhibitor, with IC s of 0.37 and 0.36 M for50wild-type VCP in the presence of 60 M and 1 mMATP in cells, respectively.NMS-873 is a potent, selective allosteric VCP/p97inhibitor with an IC value of 30 nM.50Purity: 98.01%Clinical Data: No Developme

15、nt ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.86%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/p97-in-1.html p97-IN-1 HYPERLINK https:/www.MedChemE/p97-in-1.html HYPERLINK https:/www.MedChemE/upcdc-30245.html UPCD

16、C-30245Cat. No.: HY-128724 Cat. No.: HY-123636p97-IN-1 is a potent p97 inhibitor with an IC5098%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: salesMedChemE HYPERLINK https:/www.MedChemE/vcp-p97-inhibitor-1.html VCP/p97 HYPERLINK https:/www.MedChemE/vcp-p97-inhibitor-1.html HYPERLINK https:/www.M