COMPOSITIONS AND METHODS FOR INDUCING CONFORMATIONAL CHANGES IN CEREBLON AND OTHER E3 UBIQUITIN LIGASES

Publication EP3827836A1 Kind: A1 Mar 18, 2026

Applicants

Celgene Corporation

Inventors

CHAMBERLAIN, Philip Paul, CATHERS, Brian Edwin, LOPEZ-GIRONA, Antonia

Abstract

Provided herein are methods of identifying a test compound that induces a CRBN conformational change or otherwise alters the properties of a CRBN surface as defined herein, wherein conformational change or alteration has an effect on W380, W386 and/or W400 of the CRBN; has an effect on E377 of the CRBN; or has an effect on V388 of the CRBN. Also provided is a method of inducing a CRBN conformational change or otherwise altering the properties of a CRBN surface, comprising contacting the CRBN with such a test compound. Also provided is a method of identifying a substrate ubiquitinated by a E3 ubiquitination ligase complex comprising CRBN as defined herein, wherein the method comprises contacting the CRBN with said text compound. Also provided is a method of designing a test compound based on fit within CMA binding pocket of CRBN as defined herein, wherein said conformational change has an effect on W380, W386 and/or W400 of CRBN; has an effect on E377 of CRBN; or has an effect on V388 of CRBN.

IPC Classifications

G16B 15/30 20190101AFI20260212BHEP A61K 38/00 20060101ALI20260212BHEP A61K 31/517 20060101ALI20260212BHEP A61K 31/454 20060101ALI20260212BHEP C12Q 1/37 20060101ALI20260212BHEP A61P 43/00 20060101ALI20260212BHEP A61P 35/00 20060101ALI20260212BHEP G01N 23/20 20180101ALI20260212BHEP G16B 15/00 20190101ALI20260212BHEP

Designated States

AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR

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