Protease form factor Xia (FXIa) is a therapeutic target for thrombosis prevention due to its well-known contribution to VTE and ischemic stroke in humans. Researchers from Janssen Pharmaceutica NV presented an antithrombotic target FXIa inhibitor obtained through a non-classical interactions strategy to improve the pharmacokinetic and pharmacological activity for the treatment of thrombosis. In the series, the potency was increased by using water-mediated hydrogen bonds to reduce polar hydrogen bond donors and using methyl to displace high-energy waters.
Phenylketonuria (PKU) is an inborn error of metabolism caused by heritable phenylalanine hydroxylase gene mutations that result in decreased metabolism of phenylalanine (Phe) causing brain damage. The most severe phenotype termed PKU occurs when untreated individuals achieve plasma Phe concentrations of >1200 microM/L, which are neurotoxic.
Methylthioadenosine phosphorylase (MTAP) is an enzyme ubiquitously expressed in all tissues. MTAP homozygous deletion occurs in 10-15% of different cancers such as leukemia, lymphoma, lung, brain, breast and others.
Methyltransferase-like 3 (METTL3) regulates mRNA translation and contributes to the most frequent modification to mRNA, the situation of a methyl group on the N6-position of A (m6A) during transcription.
Targeting the adenosine A2A receptor, a critical mediator of immunosuppression on the tumor microenvironment, has emerged as a strategy to improve cancer immunotherapy, and several A2A receptor antagonists are under clinical evaluation both as monotherapy and in combination with checkpoint inhibitors.
Tumor necrosis factor-α (TNF-α) is a cytokine involved in the regulation of inflammation in several autoimmune and inflammatory disorders such as rheumatoid arthritis, ulcerative colitis, or psoriasis. Anti-TNF biological treatments in place are effective but there is a need for alternatives with novel pharmacological profiles to overcome their limitations.
Interleukin-4 (IL-4) plays an important role in regulating inflammation. While several antibody-based options targeting IL-4 have been reported, strategies based on small molecule inhibitors have proven difficult to find.
For people living with HIV, the single greatest achievement to date has been the emergence of antiretroviral treatments (ART) that completely block the virus, resulting in reduced mortality and morbidity and improved quality of life. But taking one pill a day for life cannot be the end of this journey, speakers said during the International AIDS Society meeting held July 23 to 26 in Brisbane, Australia.
Gri Bio Inc. reported data on its type 2 natural killer T (NKT) cell activator GRI-0803 at the Autoimmunity Conference hosted by FASEB earlier in August. The company is developing GRI-0803 in autoimmune diseases, with an initial focus of systemic lupus erythematosus (SLE).
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.