935888-69-0

Basic information

• Product Name: ONX-0912
• Synonyms: ONX-0912;OprozoMib;OprozoMib (ONX-0912);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]-L-serinamide;PR 047;0prozoMib(ONX0912);L-Serinamide, O-methyl-N-[(2-methyl-5-thiazolyl)carbonyl]-L-seryl-O-methyl-N-[(1S)-2-[(2R)-2-methyl-2-oxiranyl];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]-
• CAS NO: 935888-69-0
• Molecular Formula: C₂₅H₃₂N₄O₇S
• Molecular Weight: 532.60918
• Product Categories: Inhibitor;Inhibitors
• Mol File: 935888-69-0.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 849.9±65.0 °C(Predicted)
• Appearance: /
• Density: 1.290±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 12.29±0.46(Predicted)
• CAS DataBase Reference: ONX-0912(CAS DataBase Reference)
• NIST Chemistry Reference: ONX-0912(935888-69-0)
• EPA Substance Registry System: ONX-0912(935888-69-0)

Safety Data

• Hazardous Substances Data: 935888-69-0(Hazardous Substances Data)

Usage

Description

ONX-0912 is an orally bioavailable proteasome inhibitor that selectively targets the chymotrypsin-like activity of the 20S proteasome subunits β5 and LMP7 with high specificity and reduced toxicity. It has the potential to be used in the treatment of certain types of cancer and other diseases that require proteasome activity.

Uses

Used in Oncology:
ONX-0912 is used as a targeted therapy for the treatment of multiple myeloma, a type of blood cancer. It inhibits the growth of multiple myeloma cells at nanomolar concentrations without affecting the viability of normal peripheral blood mononuclear cells at 1 μM. Additionally, it has demonstrated the ability to block the growth of xenografted human multiple myeloma cells in mice when administered orally.
Used in Drug Development:
ONX-0912 is used as a research tool for the development of new drugs targeting the proteasome, which plays a crucial role in various cellular processes, including cell cycle regulation, apoptosis, and immune responses. Its high specificity and reduced toxicity make it a promising candidate for the development of more effective and safer treatments for various diseases, including cancer.

Enzyme inhibitor

This orally active inhibitor (FW = 532.61 g/mol; CAS 935888-69-0; Solubility: 105 mg/mL DMSO, <1 mg/mL H2O), also known as ONX 0912 and 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]-Lserinamide, selectively targets the chymotrypsin-like (CT-L) activity of 20S proteasome β5 (IC50 = 36 nM) and 20S proteasome LMP7 (IC50 = 82 nM). In animal tumor model studies, ONX 0912 significantly reduced tumor progression and prolonged survival. Immununostaining of multiple myeloma tumors from ONX 0912-treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Oprozomib is distinct from carfilzomib, even though the same chemistry was employed to selectively target the proteasome. Oprozomib is under development as an oral therapy for hematologic malignancies, including multiple myeloma, and for patients with recurrent or refractory solid tumors (See also Carfilzomib).

Upstream product

• 40004-69-1 2-methyl-1,3-thiazole-5-carboxylic acid 
• 1148157-34-9 C₂HF₃O₂*C₂₀H₂₉N₃O₆ 
• 1148157-29-2 (S)-2-amino-1-((R)-2-methyloxiran-2-yl)-3-phenylpropan-1-one trifluoroacetate 
• 1010136-49-8 C₁₃H₁₉N₃O₆S 
• 79836-78-5 ethyl 2-methylthiazole-5-carboxylate 
• 1010136-50-1 tert-butyl [(1S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]carbamate 
• 935888-09-8 benzyl (2S)-2-[(2S)-2-{[tert-butoxycarbonyl]amino}-3-methoxypropanamido]-3-methoxypropanoate 
• 1148157-33-8 benzyl (2S)-3-methoxy-2-[(2S)-3-methoxy-2-[(2-methyl-1,3-thiazol-5-yl)formamido]propanamido]propanoate 
• 935888-16-7 (S)-2-amino-1-((R)-2-methyloxiran-2-yl)-3-phenylpropan-1-one 
• 1148157-32-7 C₂HF₃O₂*C₁₅H₂₂N₂O₅ 

Relevant articles and documents

IMMEDIATE RELEASE FORMULATIONS FOR OPROZOMIB

This disclosure features immediate release pharmaceutical formulations (e.g., solid dosage forms, e.g., tablets) that are useful for the oral administration of oprozomib, or a pharmaceutically acceptable salt thereof, to a human or animal subject as well as methods of making and using the formulations.

Modified Release Formulations for Oprozomib

This disclosure features modified release pharmaceutical formulations (e.g., extended release pharmaceutical formulations; e.g., solid dosage forms, e.g., tablets) that are useful for the oral administration of oprozomib, or a pharmaceutically acceptable salt thereof, to a human or animal subject as well as methods of making and using the formulations.

Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047)

Proteasome inhibition has been validated as a therapeutic modality in the treatment of multiple myeloma and Non-Hodgkin's lymphoma. Carfilzomib, an epoxyketone currently undergoing clinical trials in malignant diseases, is a highly selective inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome. A chemistry effort was initiated to discover orally bioavailable analogues of carfilzomib, which would have potential for improved dosing flexibility and patient convenience over intravenously administered agents. The lead compound, 2-Me-5-thiazole-Ser(OMe)-Ser(OMe)-Phe-ketoepoxide (58) (PR-047), selectively inhibited CT-L activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) and demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It was well tolerated with repeated oral administration at doses resulting in >proteasome inhibition in most tissues and elicited an antitumor response equivalent to intravenously administered carfilzomib in multiple human tumor xenograft and mouse syngeneic models. The favorable pharmacologic profile supports its further development for the treatment of malignant diseases.