Oprozomib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Oprozomib (ONX-0912;PR-047) 是一种有效的、口服生物可利用的蛋白酶体抑制剂，可抑制 20S 蛋白酶体 β5/LMP7 的胰凝乳蛋白酶样 (CT-L) 活性，IC50 为 36/82 nM。

Oprozomib (ONX-0912;PR-047) is a potent, orally bioavailable proteasome inhibitor that inhibits chymotrypsin-like (CT-L) activity of 20S proteasome β5/LMP7 with IC50 of 36/82 nM; triggers apoptosis in MM cells, associated with PARP cleavage and caspase activation, causes in vitro and in vivo cytotoxicity in multiple myeloma, also enhances anti-MM activity of bortezomib, lenalidomide dexamethasone, or pan-histone deacetylase inhibitor.Blood Cancer Phase 2 Clinical(In Vitro):Oprozomib inhibits 20S chymotrypsin-like (CT-L) with an IC50 of 55?±?19?nM. Oprozomib inhibits human leukemia Molt-4 cells CT-L with an IC50 of 66 nM.Oprozomib (ONX 0912; 1-1000 nM; 48 hours) significantly decreases the viability of human multiple myeloma (MM) cell lines.The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP.(In Vivo):Oprozomib (PR-047) selectively inhibits chymotrypsin-like (CT-L) activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) and demonstrates an absolute bioavailability of up to 39% in rodents and dogs.Oprozomib promotes antitumor activity in multiple animal models by oral administration at doses below the maximum tolerated dose (MTD).Oprozomib (30?mg/kg by oral gavage once daily for 5 consecutive days followed by 2 days of rest) treatment decreases tumor burden in C57Bl/6 and NOD.SCID.IL2Rγ-/- mice.

Oprozomib inhibits 20S chymotrypsin-like (CT-L) with an IC50 of 55?±?19?nM. Oprozomib inhibits human leukemia Molt-4 cells CT-L with an IC50 of 66 nM.Oprozomib (ONX 0912; 1-1000 nM; 48 hours) significantly decreases the viability of human multiple myeloma (MM) cell lines.The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP. Cell Viability Assay Cell Line:Human MM cell lines (MM.1S, INA-6, RPMI-8226, MM.1R, Dox-40, KMS12, and OPM2) Concentration:1, 10, 100, 1000 nM Incubation Time:48 hours Result:Exhibited anti-MM activity.Western Blot Analysis Cell Line:MM.1S cells Concentration:7 nM and 10 nM Incubation Time:48 hours Result: Treatment with 3nM triggered a marked increase in proteolytic cleavage of PARP, a signature event during apoptosis. Induced cleavage of caspase-3, an upstream activator of PARP.Induced activation of both casapse-8 (extrinsic) and caspase-9 (intrinsic) apoptotic pathways.

Oprozomib (PR-047) selectively inhibits chymotrypsin-like (CT-L) activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) and demonstrates an absolute bioavailability of up to 39% in rodents and dogs. Oprozomib promotes antitumor activity in multiple animal models by oral administration at doses below the maximum tolerated dose (MTD). Oprozomib (30?mg/kg by oral gavage once daily for 5 consecutive days followed by 2 days of rest) treatment decreases tumor burden in C57Bl/6 and NOD.SCID.IL2Rγ-/- mice. Animal Model:C57Bl/6 and NOD.SCID.IL2Rγ-/- mice bearing established human RPMI-8226-luc myeloma cells Dosage:30?mg/kg Administration:Oral gavage once daily for 5 consecutive days followed by 2 days of rest Result:Decreased human MM tumor burden and protects mice from bone destruction.

ONX-0912 | ONX0912 | ONX 0912 | PR-047 | PR047 | PR 047

Proteasome/Ubiquitin

Proteasome

20Sproteasome

Cancer

Blood cancer

935888-69-0

532.6092

C25H32N4O7S

>98% (HPLC)

DMSO: ≥ 50 mg/mL

O=C(C1=CN=C(C)S1)N[C@@H](COC)C(N[C@@H](COC)C(N[C@@H](CC2=CC=CC=C2)C([C@]3(C)OC3)=O)=O)=O

L-Serinamide, O-methyl-N-[(2-methyl-5-thiazolyl)carbonyl]-L-seryl-O-methyl-N-[(1S)-2-[(2R)-2-methyl-2-oxiranyl]-2-oxo-1-(phenylmethyl)ethyl]-

(-20℃)

With Ice Pack

≥ 2 years