discovery of NX-2127, a BTK degrader for B-cell malignancies

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This video describes the discovery of NX-2127, a degrader of Bruton's tyrosine kinase (BTK) for the treatment of certain B-cell malignancies. The content of this video was reported by scientists of Nurix Therapeutics in San Francisco, CA as a Drug Annotation article in the Journal of Medicinal Chemistry. The discovery project started with an advanced compound from previous research - NRX-0492. NRX-0492 showed promising efficacy, but its distribution properties complicated preclinical safety studies. Optimization of distribution by reducing molecular weight resulting in a compound (NX-2127) with improved absorption. In vivo efficacy studies established the ability of NX-2127 to cause BTK degradation through the ubiquitin proteasome system. NX-2127 also causes degradation of IKZF1 and IKVF3, two transcription factors, with likely immunomodulatory benefits. In a mouse xenograft study, NX-2127 reduced tumor growth in both wildtype and mutant tumors. Compound NX-2127 in currently in phase I clinical trials.

This video was created for academic purposes. The creator of the video has no financial stake in the sponsor of the research described in this video.