Delanzomib

SKU: orb1223871

Description

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.

Key Properties

• CAS Number: 847499-27-8
• MW: 413.2751
• Purity: >98% (HPLC)
• Formula: C₂₁H₂₈BN₃O₅
• SMILES: 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
• Target: Proteasome
• Solubility: 10 mM in DMSO

Bioactivity

• 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. 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.
• 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. 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CEP-18770 | CEP18770 | CEP 18770

Quick Database Links

Gene Symbol

Proteasome