Delving into the Latest Updates on CM-1758 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

HDACs

Mechanism

HDAC inhibitors(Histone deacetylase inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Bladder Cancer

Inactive Indication-

Originator Organization

Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas

Active Organization

Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Calasanz, María José ; Gómez-Echarte, Nahia ; Charalampopoulou, Stella ; Miranda, Estibaliz ; Paiva, Bruno ; Martinez-Calle, Nicolás ; San José-Enériz, Edurne ; Gimenez-Camino, Naroa ; Alignani, Diego ; Barrena, Naroa ; Garate, Leire ; Alfonso-Pierola, Ana ; Oyarzabal, Julen ; Pineda-Lucena, Antonio ; Prósper, Felipe ; Martin-Subero, José Ignacio ; Pérez-Ruiz, Ana ; Isasa, Marta ; Hilscher, Sebastian ; Muñoz, Javier ; San Martín-Uriz, Patxi ; Vilas-Zornoza, Amaia ; Rabal, Obdulia ; Tamariz-Amador, Luis Esteban ; Larrayoz, María José ; Valcárcel, Luis V ; García, Fernando ; Schutkowski, Mike ; Agirre, Xabier ; Sáez, Elena

AbstractDespite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer–promoter chromatin regulatory complex, including bromodomain proteins. This acetylation is essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444/CM-1758 in acute myeloid leukemia. In summary, these compounds may represent effective differentiation-based therapeutic agents across acute myeloid leukemia subtypes with a potential mechanism for the treatment of acute myeloid leukemia.

100 Deals associated with CM-1758

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