Delanzomib

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.

847499-27-8

CEP-18770 | CEP18770 | CEP 18770

>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

C21H28BN3O5

413.2751

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.