Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) are involved in the regulation of transcription elongation, DNA damage response and genomic stability balance. A few inhibitors of CDK12- and CDK13-mediated transcription have shown antiproliferative effects in the preclinical setting but have not progressed to clinical testing due to excessive toxicity.
Recursion Pharmaceuticals Inc. has gained IND clearance from the FDA for a phase I/II trial of REC-1245 in a biomarker-enriched patient population, including patients with solid tumors and lymphoma. The trial is expected to begin in the fourth quarter of this year.
B-cell lymphoma 6 (BCL6) is an essential transcriptional factor for the humoral immune response. However, genomic deregulation of BCL6 contributes to the development of different types of lymphoma such as diffuse large B-cell lymphoma (DLBCL).
A paper from Shenzhen University and affiliated organizations covers the discovery of a novel bromodomain-containing protein 4 (BRD4)-specific proteolysis-targeting chimera (PROTAC).
The University of Michigan has published details on the discovery and preclinical characterization of a new potent and selective proteolysis targeting chimera (PROTAC) degrader of BRD9, CW-3308. Synthesis and optimization of two different cereblon ligands led to the discovery of a novel series of highly potent BRD9 degraders, with CW-3308 selected as the lead candidate.
Genetic or pharmacologic inhibition of casein kinase 1α (CK1α) has proven effective in suppressing the proliferation of acute myeloid leukemia (AML) cell lines with wild-type TP53. Researchers from Bristol Myers Squibb Co. recently presented the discovery and preclinical characterization of BMS-986397, a cereblon E3 ligase modulatory drug (CELMoD) designed as a molecular glue degrader of CK1α.
Researchers from the UK Dementia Research Institute at the University of Cambridge have found how to prevent and reverse tau aggregation using target-specific nanobodies. The team holds great expertise in the role of TRIM21 in the tau environment since William McEwan, senior author of the study, first discovered TRIM21 and, a bit later, defined its contribution to tau immunotherapy efficacy.
Plexium Inc. has described the efforts that led to the discovery of PLX-4545, an orally bioavailable molecular glue degrader of IKZF2 for the treatment of cancer that is currently undergoing evaluation in a phase I study in healthy volunteers.
At the recently concluded ACS Fall meeting, Bristol Myers Squibb Co. reported the discovery of potent orally bioavailable B-cell lymphoma 6 protein (BCL6) ligand-directed degraders (LDDs).
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