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NTS231

Development stage: Preclinical
Lead developer: Nutshell Therapeutics
Modality: Molecular Glues → Targeted Protein Degraders (TPDs) → Small Molecules

Overview

NTS231 is a novel small molecule drug candidate being developed by Nutshell Therapeutics for the treatment of solid tumors characterized by aberrant NRF2 activation. The compound functions as a covalent allosteric molecular glue that stabilizes the interaction between the KEAP1-CUL3 E3-ligase complex and the transcription factor NRF2, leading to the selective degradation of NRF2. In many cancers, constitutive NRF2 activation provides a survival advantage to tumor cells and promotes resistance to chemotherapy and radiotherapy; by inducing NRF2 degradation, NTS231 aims to inhibit tumor growth and overcome therapy resistance. The drug is currently in the IND-enabling stage of development.

Targets

CUL3 (Cullin-3)KEAP1 (Kelch-like ECH-associated protein 1)NFE2L2 (Nuclear factor (erythroid-derived 2)-like 2)

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