| Identification | Back Directory | [Name]
CEP-18770 | [CAS]
847499-27-8 | [Synonyms]
CS-252
CT 47098
CIP 18770
CEP-18770
Delanzomib
NPH 007098
Delanzomib, >=98%
DelanzoMib (CEP-18770)
CEP-18770 (DelanzoMib)
DelanzoMib, Free Base, >99%
CEP-18770;CEP 18770;CEP18770
((R)-1-((2S,3R)-3-Hydroxy-2-(6-phenylpicolinaMido)butanaMido)-3-Methylbutyl)boronic acid
(R)-1-((2S,3R)-3-hydroxy-2-(2-phenylpicolinamido)butanamido)-3-methylbutan-2-ylboronic acid
((R)-1-((2S,3R)-3-hydroxy-2-(6-phenylpicolinamido)butanamido)-3-methylbutan-2-yl)boronic acid
(1R)-1-[(2S,3R)-3-hydroxy-2-[(6-phenylpyridin-2-yl)formamido]butanamido]-3-methylbutyl]boronic acid
[(1R)-1-[[(2S,3R)-3-Hydroxy-2-[[(6-phenylpyridin-2-yl)carbonyl]amino]-1-oxobutyl]amino]-3-methylbutyl]boronic acid
Boronic acid, B-[(1R)-1-[[(2S,3R)-3-hydroxy-1-oxo-2-[[(6-phenyl-2-pyridinyl)carbonyl]aMino]butyl]aMino]-3-Methylbutyl]-
Delanzomib
[(1R)-1-[[(2S,3R)-3-Hydroxy-2-[[(6-phenylpyridin-2-yl)carbonyl]amino]-1-oxobutyl]amino]-3-methylbutyl]boronic acid | [Molecular Formula]
C21H28BN3O5 | [MDL Number]
MFCD18251439 | [MOL File]
847499-27-8.mol | [Molecular Weight]
413.28 |
| Chemical Properties | Back Directory | [Melting point ]
178-190°C (dec.) | [density ]
1.207 | [storage temp. ]
Hygroscopic, -20°C Freezer, Under Inert Atmosphere | [solubility ]
Acetonitrile (Slightly), Chloroform (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
9.67±0.43(Predicted) | [color ]
White to Off-White | [Stability:]
Hygroscopic |
| Hazard Information | Back Directory | [Description]
Delanzomib is an orally bioavailable inhibitor of chymotrypsin-like proteasome activity (IC50 = 3.8 nM in isolated human erythrocytes) that only marginally inhibits tryptic and peptidyl glutamyl proteasome activity.1 Delanzomib pre-treatment (20 nM) in vitro inhibits IκBα degradation, NF-κB activation, and the expression of NF-κB-regulated genes, including IκBα, XIAP, TNF-α, IL-1β, ICAM-1, and VEGF. Delanzomib induces apoptosis in multiple myeloma cell lines and inhibits proliferation in a panel of human hematologic and solid tumor cell lines (IC50s = 5.6-34.2 nM). It reduces tumor weight in an RPMI 8226 human multiple myeloma mouse xenograft model when administered intravenously at doses ranging from 1.5-4 mg/kg twice daily and leads to complete tumor regression at a chronic oral dose of 13 mg/kg. Delanzomib reduces the serum level of circulating cytokines, prevents renal tissue damage, and increases lifespan in a mouse model of fatal lupus nephritis. 2 | [Uses]
Delanzomib is an orally active proteasome inhibitor. Delanzomib has been shown to down-modulate NF-κB, induce apoptosis, inhibit angiogenesis and M-CSF-RANKL-induced osteoclastogenesis. | [Definition]
ChEBI: Delanzomib is a C-terminal boronic acid peptide inhibitor which induces apoptosis in multiple myeloma, hematological and solid tumor cell lines. It has a role as a proteasome inhibitor, an apoptosis inducer and an antineoplastic agent. It is a threonine derivative, a phenylpyridine, a C-terminal boronic acid peptide and a secondary alcohol. It is functionally related to a L-threonine. | [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[1]. | Animal Model: | SCID mice injected with RPMI 8226 cells[1] | | 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.
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| [target]
proteasome | [References]
[1] ROBERTO PIVA. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib.[J]. Blood, 2008: 2765-2775. DOI: 10.1182/blood-2007-07-100651
[2] MATTHEW M. SEAVEY. Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE[J]. International immunopharmacology, 2012, 12 1: Pages 257-270. DOI: 10.1016/j.intimp.2011.11.019 |
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