Delanzomib [CEP-18770]

Synthetic. Chemical. CAS: 847499-27-8. Formula: C21H28BN3O5. MW: 413.3. Synthetic. Potent, selective, reversible orally bioavailable proteasome inhibitor. Synthetic P2 threonine boronic acid. Targets the chymotrypsin-like beta5 subunit of the constitutive 20S proteasome (IC50=3.8nM). Cross-reacts and inhibits the caspase-like/peptidyl-glutamyl peptide-hydrolyzing (PGPH) beta1 subunit (IC50=~70nM). Displays similar potency for the chymotrypsin-like activity of the proteasome compared to bortezomib. Exhibits a favorable cytotoxicity profile toward normal human epithelial cells, bone marrow progenitors and bone marrow-derived stromal cells relative to bortezomib. Anticancer compound effective against multiple myeloma in vivo. In vitro, blocks the growth of representative human solid and hematological tumor cell lines (IC50s=5.6-34nM). Shown to down-modulate NF-kappaB, induce apoptosis, inhibit angiogenesis and M-CSF-RANKL-induced osteoclastogenesis.