Oprozomib (ONX 0912)

Modify Date: 2024-01-05 10:39:24

Oprozomib (ONX 0912) structure	Common Name	Oprozomib (ONX 0912)
	CAS Number	935888-69-0	Molecular Weight	532.609
	Density	1.3±0.1 g/cm3	Boiling Point	849.9±65.0 °C at 760 mmHg
	Molecular Formula	C₂₅H₃₂N₄O₇S	Melting Point	N/A
	MSDS	N/A	Flash Point	467.8±34.3 °C

Use of Oprozomib (ONX 0912)

Oprozomib (ONX 0912; PR047) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.IC50 value: 36 nM/82 nM(20S proteasome β5/LMP7) [1]Target: 20S proteasomeThe anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP, as well as inhibition of migration of MM cells and angiogenesis. Oprozomib is demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It is well tolerated with repeated oral administration at doses resulting in >80% proteasome inhibition in most tissues and elicited an antitumor response in multiple human tumor xenograft and mouse syngeneic models.

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
Synonym	More Synonyms

Description	Oprozomib (ONX 0912; PR047) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.IC50 value: 36 nM/82 nM(20S proteasome β5/LMP7) [1]Target: 20S proteasomeThe anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP, as well as inhibition of migration of MM cells and angiogenesis. Oprozomib is demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It is well tolerated with repeated oral administration at doses resulting in >80% proteasome inhibition in most tissues and elicited an antitumor response in multiple human tumor xenograft and mouse syngeneic models.
Related Catalog	Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome Research Areas >> Cancer
References	[1]. Zhou HJ, et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J Med Chem. 2009 May 14;52(9):3028-38. [2]. Chauhan D, et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood, 2010, 116(23), 4906-4915. [3]. Muchamuel T, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med, 2009, 15(7), 781-787.

Description

Related Catalog

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome

Research Areas >> Cancer

References

[1]. Zhou HJ, et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J Med Chem. 2009 May 14;52(9):3028-38.

[2]. Chauhan D, et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood, 2010, 116(23), 4906-4915.

[3]. Muchamuel T, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med, 2009, 15(7), 781-787.

Density	1.3±0.1 g/cm3
Boiling Point	849.9±65.0 °C at 760 mmHg
Molecular Formula	C₂₅H₃₂N₄O₇S
Molecular Weight	532.609
Flash Point	467.8±34.3 °C
Exact Mass	532.199158
PSA	186.96000
LogP	2.79
Vapour Pressure	0.0±3.2 mmHg at 25°C
Index of Refraction	1.573
Storage condition	-20℃

(S)-2-amino-1-(...

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N/A

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~86%

Oprozomib (ONX 0912)

CAS#:935888-69-0

Literature: Jumaa, Mouhannad; Muchamuel, Tony; Bejugam, Naveen; Wong, Hansen; Kirk, Christopher J.; Vishram Manek, Rahul; Sharma, Sanjeev Patent: US2014/113855 A1, 2014 ; Location in patent: Paragraph 0279; 0305; 0306; 0307; 0308 ;

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Oprozomib (ONX 0912)

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Literature: 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 Journal of Medicinal Chemistry, 2009 , vol. 52, # 9 p. 3028 - 3038

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Oprozomib (ONX 0912)

CAS#:935888-69-0