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.
Satellos Bioscience Inc. has received orphan drug designation and rare pediatric disease designation from the FDA for SAT-3153 for the potential treatment of Duchenne muscular dystrophy (DMD). The first-in-class oral small-molecule therapeutic is designed to restore the innate muscle regeneration process independent of dystrophin and regardless of exon mutation status.
To identify candidate therapeutic targets for cancers with SF3B1 hotspot mutations, drug-sensitivity screening of an in-house library of 80 small-molecule inhibitors resulted in the identification of a series of candidate SF3B1 mutant (SF3B1[MUT]) synthetic lethal drugs that led to significant reduction of survival in SF3B1(K700E) cells.
One of the main causes of cervical cancer is persistent human papillomavirus (HPV) infection, with E6 and E7 being the main oncogenic genes of HPV3. For this reason, targeting HPV proteins E6 and E7 is a promising therapeutic strategy for the treatment of this disease.
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