Oprozomib

Oprozomib

Systematic (IUPAC) name
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
Clinical data
Pronunciation	oh-PROZ-oh-mib
Routes of administration	Oral
Legal status
Legal status	Investigational drug
Identifiers
CAS Number	935888-69-0
ATC code	None
PubChem	CID 25067547
IUPHAR/BPS	8739
ChemSpider	28528375
UNII	MZ37792Y8J
KEGG	D10318
ChEMBL	CHEMBL2103884
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
Chemical data
Formula	C25H32N4O7S
Molar mass	532.61 g·mol^−1
SMILES 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 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 (INN,^[1] codenamed ONX 0912 and PR-047) is an orally active second-generation proteasome inhibitor developed by Onyx Pharmaceuticals, an Amgen subsidiary. It is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase 1b studies ongoing (as of February 16, 2016).^[2] Being an epoxyketone derivative, oprozomib is structurally related to carfilzomib and has the added benefit of being orally bioavailable. It selectively inhibits chymotrypsin-like activity of both the constitutive proteasome (PSMB5) and immunoproteasome (LMP7).^[3] Like carfilzomib, it is active against bortezomib-resistant multiple myeloma cells.^[4]

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. "Amgen Pipeline Chart". Amgen Inc. February 16, 2016. p. 3. Retrieved 24 April 2016.
3. 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.
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. PMID 20805366. Retrieved 24 April 2016.