Oprozomib

Oprozomib
Clinical data
Pronunciation /oʊˈprɒzoʊmɪb/ oh-PROZ-oh-mib
Synonyms O-methyl-N-(2-methyl-1,3-thiazol-5-carbonyl)-L-seryl-O-methyl-N-{(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl}-L-serinamide
Routes of
administration		 Oral
ATC code
  • None
Legal status
Legal status
  • Investigational drug
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C25H32N4O7S
Molar mass 532.61 g·mol−1
3D model (JSmol)

Oprozomib[1] (codenamed ONX 0912 and PR-047) is an orally active second-generation proteasome inhibitor developed by Proteolix, which was acquired by Onyx Pharmaceuticals, an Amgen subsidiary, in 2009. It selectively inhibits chymotrypsin-like activity of both the constitutive proteasome (PSMB5) and immunoproteasome (LMP7).[2]

It is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase 1b studies ongoing (as of February 16, 2016).[3] Being an epoxyketone derivative, oprozomib is structurally related to carfilzomib and has the added benefit of being orally bioavailable. Like carfilzomib, it is active against bortezomib-resistant multiple myeloma cells.[4]

Oprozomib was granted orphan drug status for the treatment of Waldenstrom's macroglobulinaemia and multiple myeloma in 2014.[5]


See also

  • Ixazomib (trade name Ninlaro) — an orally available boronic acid-derived proteasome inhibitor approved for the treatment of multiple myeloma

References

  1. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed International Nonproprietary Names: List 107" (PDF). World Health Organization. p. 193. Retrieved 24 April 2016.
  2. ↑ Zhou, Han-Jie; Aujay, Monette A.; Bennett, Mark K.; Dajee, Maya; Demo, Susan D.; Fang, Ying; Ho, Mark N.; Jiang, Jing; Kirk, Christopher J.; Laidig, Guy J.; Lewis, Evan R.; Lu, Yan; Muchamuel, Tony; Parlati, Francesco; Ring, Eileen; Shenk, Kevin D.; Shields, Jamie; Shwonek, Peter J.; Stanton, Timothy; Sun, Congcong M.; Sylvain, Catherine; Woo, Tina M.; Yang, Jinfu (14 May 2009). "Design and Synthesis of an Orally Bioavailable and Selective Peptide Epoxyketone Proteasome Inhibitor (PR-047)". Journal of Medicinal Chemistry. 52 (9): 3028–38. doi:10.1021/jm801329v. PMID 19348473.
  3. ↑ "Amgen Pipeline Chart". Amgen Inc. February 16, 2016. p. 3. Retrieved 24 April 2016.
  4. ↑ Chauhan, D; Singh, AV; Aujay, M; Kirk, CJ; Bandi, M; Ciccarelli, B; Raje, N; Richardson, P; Anderson, KC (30 August 2010). "A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma". Blood. 116 (23): 4906–15. doi:10.1182/blood-2010-04-276626. PMC 3321748. PMID 20805366.
  5. ↑ http://webcache.googleusercontent.com/search?q=cache:StNuTZ7KAPQJ:adisinsight.springer.com/drugs/800032242+&cd=24&hl=en&ct=clnk&gl=us


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