Increasing knowledge of the cancer glycome and the need for new options to overcome resistance to immune checkpoint inhibitors are leading to an expansion of glycoimmunology. Stanford University professor Carolyn Bertozzi demonstrated that cell-surface glycans may be tagged to become targetable glyco-immune checkpoints.
The University of Minnesota has disclosed monocarboxylate transporter (MCT1) inhibitors reported to be useful for the treatment of cancer, graft-vs.-host disease, nonalcoholic steatohepatitis, obesity and diabetes.
Research at Aurigene Oncology Ltd. has led to the discovery of a mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor AU-MALT1-01 for the potential treatment of B-cell lymphomas including diffuse large B-cell lymphoma (DLBCL).
Caribou Biosciences Inc. has received FDA clearance of its IND application for CB-012, an allogeneic anti-C-type lectin-like molecule-1 (anti-CLL-1) chimeric antigen receptor (CAR) T-cell therapy. CLL-1 is highly expressed on acute myeloid leukemia (AML) cells and leukemic stem cells, but it is not expressed on hematopoietic stem cells.
Structure-guided lead optimization at Merck & Co. Inc. has led to the discovery of MK-1084 as a highly potent and selective KRAS G12C-GDP inhibitor. As reported at the recent AACR-NCI-EORTC conference, the candidate demonstrated an excellent off-target and ion channel profile, with low potential for bile salt export pump (BSEP) inhibition.
Vividion Therapeutics Inc. has disclosed VVD-065, a novel, first-in-class, allosteric molecular glue of the KEAP1-CUL3 E3-ligase complex, for the potential treatment of NRF2-activated cancers. NRF2 (nuclear factor erythroid 2-related factor 2) is a significant mediator of antioxidant response.
The mRNA technology used in vaccines against viral infections could also be developed for cancer therapies. A group of scientists has designed a circular RNA (circRNA) encapsulated in lipid nanoparticles (LNPs) that acts in the mitochondria of tumor cells through the protein gasdermin-D (GSDMD) and reduces adenocarcinoma. The work was published on Oct. 16, 2023, in Nature Cancer.
Ideaya Biosciences Inc. has described piperazine substituted indazole compounds acting as poly(ADP-ribose) glycohydrolase (PARG) inhibitors reported to be useful for the treatment of cancer.
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