Delving into the Latest Updates on OM-153 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

OM-153

Target

TNKS1 x TNKS2

Action

inhibitors

Mechanism

TNKS1 inhibitors(tankyrase inhibitors), TNKS2 inhibitors(tankyrase 2 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Colonic Cancer

Inactive Indication-

Originator Organization

Symeres BV

Active Organization

Symeres BV

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC28H24FN7O2

InChIKeyARCOJIXZDJYBCH-IYARVYRRSA-N

CAS Registry2406278-81-5

Author: Grødeland, Gunnveig ; Wegert, Anita ; Scholz, Hanne ; Sowa, Sven T. ; Leenders, Ruben G.G. ; Krauss, Stefan ; Høyem, Merete ; Holmen, Lone ; Brinch, Shoshy A. ; Meerts, Ilonka A.T.M. ; Waaler, Jo ; Olsen, Petter A. ; Espada, Sandra ; Amundsen-Isaksen, Enya ; Galera-Prat, Albert ; Lehtiö, Lari ; Aizenshtadt, Aleksandra ; Hammarström, Clara

Significance::

This study uncovers the effectiveness and therapeutic window for a novel tankyrase inhibitor in mouse tumor models.

23 Dec 2021·Journal of medicinal chemistryQ1 · MEDICINE

Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II

Q1 · MEDICINE

Article

Author: Galera-Prat, Albert ; Aertssen, Sjoerd ; Smits, Johannes N. ; Sowa, Sven T. ; Damen, Eddy ; Wegert, Anita ; Waaler, Jo ; Krauss, Stefan ; Brinch, Shoshy Alam ; Murthy, Sudarshan ; Leenders, Ruben G. G. ; Amundsen-Isaksen, Enya ; Nazaré, Marc ; Nieczypor, Piotr ; Lehtiö, Lari

Tankyrase 1 and 2 (TNKS1/2) catalyze post-translational modification by poly-ADP-ribosylation of a plethora of target proteins. In this function, TNKS1/2 also impact the WNT/β-catenin and Hippo signaling pathways that are involved in numerous human disease conditions including cancer. Targeting TNKS1/2 with small-molecule inhibitors shows promising potential to modulate the involved pathways, thereby potentiating disease intervention. Based on our 1,2,4-triazole-based lead compound 1 (OM-1700), further structure-activity relationship analyses of East-, South- and West-single-point alterations and hybrids identified compound 24 (OM-153). Compound 24 showed picomolar IC₅₀ inhibition in a cellular (HEK293) WNT/β-catenin signaling reporter assay, no off-target liabilities, overall favorable absorption, distribution, metabolism, and excretion (ADME) properties, and an improved pharmacokinetic profile in mice. Moreover, treatment with compound 24 induced dose-dependent biomarker engagement and reduced cell growth in the colon cancer cell line COLO 320DM.

100 Deals associated with OM-153

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