Ubenimex

• CAS: 58970-76-6
• Catalog Number: ACM58970766
• Category: Main Products
• Molecular Weight: 308.37
• Molecular Formula: C16H24N2O4
• Description: Ubenimex (INN), also known more commonly as bestatin, is a competitive, reversible protease inhibitor. It is an inhibitor of arginyl aminopeptidase (aminopeptidase B), leukotriene A4 hydrolase (a zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities), alanyl aminopeptidase (aminopeptidase M/N), leucyl/cystinyl aminopeptidase (oxytocinase/vasopressinase), and membrane dipeptidase (leukotriene D4 hydrolase). It is being studied for use in the treatment of acute myelocytic leukemia. It is derived from Streptomyces olivoreticuli. Ubenimex has been found to inhibit the enzymatic degradation of oxytocin, vasopressin, enkephalins, and various other peptides and compounds.
• Synonyms: 3-(r)-amino-2-(s)-hydroxy-4-phenylbutanoyl-(s)-leucine;n-(3-amino-2-hydroxy-1-oxo-4-phenylbutyl)-,(s-(r*,s*))-l-leucin;nk421;UBENIMEX;N-[(2S,3R)-3-AMINO-2-HYDROXY-1-OXO-4-PHENYLBUTYL]-L-LEUCINE;N-((2S,3R)-3-AMINO-2-HYDROXY-4-PHENYLBUTYRYL)-L-LEUCINE;[(2S,3R)-3-AMINO-2-HYDROXY-4-PHENYLBUTYRYL]-L-LEUCINE;[(2S,3R)-3-AMINO-2-HYDROXY-4-PHENYLBUTANOYL]-LEU
• IUPAC Name: (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoicacid
• Canonical SMILES: CC(C)CC(C(=O)O)NC(=O)C(C(CC1=CC=CC=C1)N)O
• InChI Key: VGGGPCQERPFHOB-RDBSUJKOSA-N
• Boiling Point: 604.7ºC at 760 mmHg
• Melting Point: 245ºC
• Flash Point: 319.5ºC
• Density: 1.197 g/cm³
• Appearance: White crystalline powder
• EC Number: 261-529-2
• Exact Mass: 308.17400
• LogP: 1.62400
• PSA: 112.65
• Refractive Index: 1.557
• Safety Description: 22-24/25
• Stability: Stable at normal temperatures and pressures.
• Storage Conditions: 2-8ºC
• WGK Germany: 3

Case Study

Ubenimex as an Immunomodulatory Agent in Advanced Squamous Non-Small-Cell Lung Cancer Therapy

Nakamichi S, et al. Clinical Lung Cancer, 2024, 25(1), 85-90.

A phase II clinical study (TORG2241) investigates the therapeutic potential of ubenimex, an aminopeptidase inhibitor with immunostimulatory and antitumor properties, in combination with pembrolizumab, nab-paclitaxel, and carboplatin for previously untreated advanced squamous non-small-cell lung cancer (NSCLC). Ubenimex is administered orally alongside a four-cycle chemotherapy regimen, followed by maintenance therapy with ubenimex and pembrolizumab for up to two years.
This single-arm, multicenter trial employs a dose-escalation strategy (30 mg, 60 mg, and 120 mg) using a standard 3 + 3 design to determine the maximum tolerable dose, targeting a dose-limiting toxicity rate of 33%. The study's primary endpoint is the objective response rate, assessed by an independent review committee. The inclusion of ubenimex aims to enhance the immune response, potentially improving treatment efficacy.
As the first clinical investigation of ubenimex in this context, the trial's findings will provide critical insights into its role in combination therapy for NSCLC. If successful, ubenimex may offer a novel approach to augmenting immunotherapy and chemotherapy, influencing future treatment protocols for advanced squamous NSCLC.