Delanzomib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的口服活性蛋白酶体抑制剂，针对胰凝乳蛋白酶样蛋白酶体活性的 IC50 为 3.8 nM。

A potent, orally active proteasome inhibitor with IC50 of 3.8 nM against chymotrypsin-like proteasome activity; demonstrates marginal inhibition of the tryptic and peptidyl glutamyl activities of the proteosome; down-modulates the NF-kappaB activity and the expression of several NF-kappaB downstream effectors, induces apoptotic cell death in MM cells; demonstrates tumor regression in MM xenografts with favorable tumor selectivity profile.Blood Cancer Phase 1 Discontinued(In Vitro):Delanzomib (CEP-18770; 20 nM; 12-24 hours) treatment results in a progressive appearance of cleaved caspases-3, -7, and -9 between 12 and 24 hours’exposure in the human MM cell lines, RPMI-8226, and U266.Delanzomib (CEP-18770; 5-40 nM; 4-24 hours) treatment induces an accumulation of ubiquitinated proteins over 4 to 8 hours.Delanzomib (CEP-18770) inhibits endothelial cell survival, vasculogenesis, and osteoclastogenesis in vitro; and displays a favorable cytotoxicity profile toward normal cells.(In Vivo):Delanzomib (CEP-18770; 7.8-13 mg/kg; oral administration; twice a week; for 4 weeks) treatment results in a more sustained pharmacodynamic inhibition of proteasome activity in tumors relative to normal tissues, complete tumor regression of multiple myeloma (MM) xenografts and improves overall median survival in a systemic model of human MM.

Delanzomib (CEP-18770; 20 nM; 12-24 hours) treatment results in a progressive appearance of cleaved caspases-3, -7, and -9 between 12 and 24 hours’exposure in the human MM cell lines, RPMI-8226, and U266. Delanzomib (CEP-18770; 5-40 nM; 4-24 hours) treatment induces an accumulation of ubiquitinated proteins over 4 to 8 hours.Delanzomib (CEP-18770) inhibits endothelial cell survival, vasculogenesis, and osteoclastogenesis in vitro; and displays a favorable cytotoxicity profile toward normal cells. Apoptosis Analysis Cell Line:RPMI-8226, U266, and K562 cells Concentration:20 nM Incubation Time:12 hours, 24 hours Result:Resulted in a progressive appearance of cleaved caspases-3, -7, and -9 between 12 and 24 hours’exposure in the human MM cell lines.Western Blot Analysis Cell Line:RPMI-8226, U266, and K562 cells Concentration:5 nM, 10 nM, 20 nM, 40 nM Incubation Time:4 hours, 8 hours, 12 hours, 24 hours Result:Induced an accumulation of ubiquitinated proteins over 4 to 8 hours.

Delanzomib (CEP-18770; 7.8-13 mg/kg; oral administration; twice a week; for 4 weeks) treatment results in a more sustained pharmacodynamic inhibition of proteasome activity in tumors relative to normal tissues, complete tumor regression of multiple myeloma (MM) xenografts and improves overall median survival in a systemic model of human MM. Animal Model:SCID mice injected with RPMI 8226 cells Dosage:7.8 mg/kg, 10 mg/kg, 13 mg/kg Administration:Oral administration; twice a week; for 4 weeks Result:Resulted in a more sustained pharmacodynamic inhibition of proteasome activity in tumors relative to normal tissues.

CEP-18770 | CEP18770 | CEP 18770

Proteasome/Ubiquitin

Proteasome

Chymotrypsin-likeproteasome

Cancer

Blood cancer

847499-27-8

413.2751

C21H28BN3O5

>98% (HPLC)

10 mM in DMSO

CC(C)C[C@@H](B(O)O)NC([C@@H](NC(C1=NC(C2=CC=CC=C2)=CC=C1)=O)[C@H](O)C)=O

Boronic acid, B-[(1R)-1-[[(2S,3R)-3-hydroxy-1-oxo-2-[[(6-phenyl-2-pyridinyl)carbonyl]amino]butyl]amino]-3-methylbutyl]-

(-20℃)

With Ice Pack

≥ 2 years