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.
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.
Hematopoietic progenitor kinase 1 (HPK1) plays a relevant role in regulating T-cell, B-cell and dendritic cell function. As its inactivation both in vitro and in vivo contributes to tumor growth inhibition, HPK1 is considered a therapeutic target to explore in cancer immunotherapy.
Itheos Therapeutics Inc. recently presented the discovery of a first-in-class, potent and selective ENT1 inhibitor, EOS-984 (EOS-301984), for the treatment of solid tumors. Immune checkpoint inhibitors (ICIs) have become essential in treating solid tumors, but only a limited number of patients currently benefit from approved ICIs.
Arcus Biosciences Inc. recently disclosed the chemical structure of AB-521 (casdatifan), an orally available small-molecule inhibitor of hypoxia-inducible factor 2α (HIF-2α) in early clinical development for the treatment of advanced solid tumors with a high prevalence of molecular alterations associated with pseudohypoxia, such as clear cell renal cell carcinoma (ccRCC).
Gilead Sciences Inc. recently disclosed details on the work that led to the discovery of elunonavir (GS-1156), an unboosted HIV protease inhibitor currently in phase I studies.
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).
In a presentation at the American Chemical Society meeting, Halda Therapeutics Inc. described its androgen receptor (AR)-targeting RIPTAC (regulated induced proximity targeting chimera) therapeutics as a new class of heterofunctional small molecules designed to selectively kill cancer cells that express tumor-specific targeting protein (TIP) into a stable intracellular ternary complex with a protein essential for cell survival for the treatment of prostate cancer.
Both casein kinase 1α (CK1α) and zinc finger protein Helios (IKZF2) are among the targets most recently evaluated for the treatment of acute myeloid leukemia (AML). A growing number of molecules against these targets acting as degraders or inhibitors are actively being investigated.
At the ongoing meeting of the American Chemical Society in Denver, F. Hoffmann-La Roche Ltd. has reported the discovery of an orally available and brain-penetrant irreversible asparagine-specific endopeptidase (AEP) inhibitor, RO-7542742, for the potential treatment of neurodegenerative diseases.
