Delving into the Latest Updates on JunAP with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

c-Jun antagonist (Sapience Therapeutics)

Target

c-Jun

Mechanism

c-Jun inhibitors(Transcription factor Jun inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Hematologic NeoplasmsSolid tumor

Inactive Indication-

Originator Organization

Sapience Therapeutics, Inc.Startup

Active Organization

Sapience Therapeutics, Inc.Startup

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Author: Albert, Krisztián ; Turczel, Gábor ; Bálint, Dániel ; Alexa, Anita ; Szabó, Pál ; Reményi, Attila ; Póti, Ádám Levente ; Bento, Isabel ; Bojtár, Márton ; Sok, Péter ; Imre, Tímea ; Soós, Tibor ; Pápai, Imre ; Torda, Lili ; Földesi-Nagy, Dóra ; Fekete, Ferenc ; Palkó, Roberta ; Szarka, Eszter ; Monostory, Katalin ; Csókás, Dániel

There has been a surge of interest in covalent inhibitors for protein kinases in recent years. Despite success in oncology, the off-target reactivity of these molecules is still hampering the use of covalent warhead-based strategies. Herein, we disclose the development of precision-guided warheads to mitigate the off-target challenge. These reversible warheads have a complex and cyclic structure with optional chirality center and tailored steric and electronic properties. To validate our proof-of-concept, we modified acrylamide-based covalent inhibitors of c-Jun N-terminal kinases (JNKs). We show that the cyclic warheads have high resilience against off-target thiols. Additionally, the binding affinity, residence time, and even JNK isoform specificity can be fine-tuned by adjusting the substitution pattern or using divergent and orthogonal synthetic elaboration of the warhead. Taken together, the cyclic warheads presented in this study will be a useful tool for medicinal chemists for the deliberate design of safer and functionally fine-tuned covalent inhibitors.

100 Deals associated with JunAP

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