bisthianostat (CF367) / Shanghai Theorion Pharma - LARVOL DELTA

Mechanism of hydroxamic acid group metabolism to carboxylic acid: Oxidation versus hydrolysis. (PubMed, Drug Metab Dispos) - "By using the histone deacetylase inhibitor, bisthianostat as a model drug, this study provided novel insights into the role of cytochrome P450 (P450) enzymes in the metabolism of the hydroxamic acid group into the carboxylic acid metabolite (M351)...However, this study revealed a previously unrecognized metabolic pathway: cytochrome P450-mediated oxidative cleavage. The results of this study provided novel mechanistic insights into the metabolism of hydroxamic acids, with significant implications for rational drug design, metabolic prediction, and safety evaluation of this important pharmacophore."

Journal

[VIRTUAL] A PHASE IA STUDY OF BISTHIANOSTAT, A NOVEL PAN-HDAC INHIBITOR IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED RESULTS OF CH-020PI STUDY (EHA 2021) - P1 | "The median number of previous lines of therapy was 3 (range, 2-9) and included treatment with bortezomib (100%), ixazomib (13.3%), immunomodulatory drugs (lenalidomide/thalidomide, 93.3%). It exhibited modest anti-tumor efficacy in our cohort of RRMM pts. According to pharmacokinetic evaluation data, dose escalation will not proceed and a triple-weekly oral administration schedule is currently ongoing, Future trials in the combination with established MM therapy will be investigated in phase 1b study to enhance its efficacy via synergistic effect."

Clinical • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Nephrology • Neutropenia • Oncology • Pneumonia

Pharmacodynamic, pharmacokinetic, and phase 1a study of bisthianostat, a novel histone deacetylase inhibitor, for the treatment of relapsed or refractory multiple myeloma. (PubMed, Acta Pharmacol Sin) - "Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. The overall single-agent efficacy was modest, stable disease (SD) was identified in four (50%) patients at the end of first dosing cycle (day 28). These preliminary in-patient results suggest that bisthianostat is a promising HDACi drug with a comparable safety window in R/R MM, supporting for its further phase 1b clinical trial in combination with traditional MM therapies."

Epigenetic controller • Journal • P1 data • PK/PD data • Hematological Malignancies • Lymphoma • Multiple Myeloma • T Cell Non-Hodgkin Lymphoma