Oprozomib

Oprozomib
Clinical data
Pronunciation	/oʊˈprɒzoʊmɪb/ oh-PROZ-oh-mib
Other names	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
	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;
CAS Number	935888-69-0;
PubChem CID	25067547;
IUPHAR/BPS	8739;
ChemSpider	28528375;
UNII	MZ37792Y8J;
KEGG	D10318;
ChEMBL	ChEMBL2103884;
CompTox Dashboard (EPA)	DTXSID201025950 ;
Chemical and physical data
Formula	C25H32N4O7S
Molar mass	532.61 g·mol−1
3D model (JSmol)	Interactive image;
	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^[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]

References

^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed International Nonproprietary Names: List 107" (PDF). World Health Organization. p. 193. Retrieved 24 April 2016.
^ 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.
^ "Amgen Pipeline Chart". Amgen Inc. February 16, 2016. p. 3. Retrieved 24 April 2016.
^ 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.
^ "Oprozomib - Onyx Pharmaceuticals". Adis Insight. Springer Nature Switzerland AG.

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[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.

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Clinical data

Pronunciation	/oʊˈprɒzoʊmɪb/ oh-PROZ-oh-mib
Other names	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
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
CAS Number	935888-69-0
PubChem CID	25067547
IUPHAR/BPS	8739
ChemSpider	28528375
UNII	MZ37792Y8J
KEGG	D10318
ChEMBL	ChEMBL2103884
CompTox Dashboard (EPA)	DTXSID201025950
Chemical and physical data
Formula	C₂₅H₃₂N₄O₇S
Molar mass	532.61 g·mol⁻¹
3D model (JSmol)	Interactive image
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

See also

References