Oprozomib

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Oprozomib
Oprozomib.svg
Clinical data
Pronunciation/ˈprɒzmɪb/ oh-PROZ-oh-mib
Other namesO-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
  • N-[(2S)-3-methoxy-1-[[(2S)-3-methoxy-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC25H32N4O7S
Molar mass532.61 g·mol−1
3D model (JSmol)
  • COC[C@H](NC(=O)[C@H](COC)NC(=O)c1cnc(C)s1)C(=O)N[C@@H](Cc2ccccc2)C(=O)[C@@]3(C)CO3
  • InChI=1S/C25H32N4O7S/c1-15-26-11-20(37-15)24(33)29-19(13-35-4)23(32)28-18(12-34-3)22(31)27-17(21(30)25(2)14-36-25)10-16-8-6-5-7-9-16/h5-9,11,17-19H,10,12-14H2,1-4H3,(H,27,31)(H,28,32)(H,29,33)/t17-,18-,19-,25+/m0/s1
  • Key:SWZXEVABPLUDIO-WSZYKNRRSA-N

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 Waldenström'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 HJ, Aujay MA, Bennett MK, Dajee M, Demo SD, Fang Y, et al. (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, et al. (December 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. ^ "Oprozomib - Onyx Pharmaceuticals". Adis Insight. Springer Nature Switzerland AG.