A newly described small molecule inhibitor called AOH-1996 targets a cancer-associated isoform of PCNA (caPCNA), leading to a very broad therapeutic window. Researchers at City of Hope, a cancer research and treatment organization in California, reported on AOH-1996 in the Aug. 1, 2023, online edition of Cell Chemical Biology. Genes involved in replication and repair pathways are essential for the growth and survival of cancer cells. Proliferating cell nuclear antigen (PCNA) is a key player in DNA replication via a homotrimer formation that acts as a molecular sliding clamp around the DNA double helix.
Oncternal Therapeutics Inc. has received a study may proceed letter from the FDA for a phase I/II dose-escalation study of ONCT-534, a novel dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor signaling inhibitors (ARSIs). The letter was received prior to the 30-day review date.
A research team from Leipzig University, the Max Planck Institute and Heidelberg University, all in Germany, devised a new segmentation algorithm for stroke lesions that improves upon previous methods. They used machine-learning models to effect CT image segmentation in the early stages of acute stroke. The research team published their findings on the fully convolutional graph network in July in the Journal of Medical Imaging.
Fudan University and Shanghaitech University have developed proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase binding agent coupled to Bcl-2-like protein 1 (Bcl-xl; Bcl-X; BCL2L1) targeting moiety via linker. They are reported to be useful for the treatment of cancer, autoimmune disease, myelofibrosis, neurodegeneration, kidney fibrosis, transplant rejection, diabetes and cardiovascular disorders, among others.
Pyrrole fused-ring pyrazole compounds have been prepared by Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd. and characterized as mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1; HPK1; MEKKK1) inhibitors reported to be useful for the treatment of cancer.
Research at Merck KGaA has led to the development of substituted heterocycles acting as kinesin-like protein KIFC1 (HSET) inhibitors reported to be useful for the treatment of cancer.
Innovo Therapeutics Inc. has prepared and tested new isoindolinone derivative compounds characterized as caspase-1 (IL-1β-converting enzyme), interleukin-1β (IL1B; IL-1β) and apoptosis inhibitors reported to be useful for the treatment of osteoarthritis and pain.
Biohaven Therapeutics Ltd. has patented new pyrazolo[1,5-a]pyridin-2,3-yl amides acting as potassium voltage-gated channel subfamily KQT member 2/3 (KCNQ2/3) activators.
CAR T-cell immunotherapy is designed with different targets depending on the receptors they will bind to. CARs can also contain different tools, like the concept of a Swiss army knife, with several utensils for different tasks. The goal is to make them more effective and durable. During the second session of the Spotlight on Immuno-Oncology conference, “Novel CAR designs and approaches,” Robbie Majzner, of Stanford University, described expanding the main components of CAR T cells to acquire new functions and act on different cell pathways.
Lift Biosciences Ltd. has reported a substantially marked increase in cancer killing with the attachment of HER2 chimeric antigen receptor (CAR) to its immunomodulatory alpha neutrophil (IMAN) cell therapy, using the company’s second-generation N-Lift (neutrophil only leukocyte infusion therapy) platform. Positive data support the potential of the In-Lift platform to produce a variety of genetically engineered CAR-IMANs to enhance killing and more targeted immunomodulation for different tumor targets.
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