Publications by authors named "N A Vellore"
Protein degradation using proteolysis targeting chimeras (PROTACs) represents a promising therapeutic strategy. PROTACs are heterobifunctional molecules that consist of a target-binding moiety and an E3 ligase binding moiety, connected by a linker. These fragments are frequently united via amide bonds.
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- NKG2D is a receptor that helps activate immune responses against infections and stress but can also contribute to chronic inflammation and autoimmune diseases, making it a target for new treatments.
- The study outlines a strategy for identifying small molecules that can inhibit NKG2D's protein interactions via a unique mechanism that alters the receptor's structure.
- Researchers used various biochemical methods and drug design techniques to enhance the effectiveness and properties of one series of inhibitors, showing it's feasible to disrupt the NKG2D interaction with its ligands through allosteric modulation.
We discovered that the survival and growth of many primary acute myeloid leukemia (AML) samples and cell lines, but not normal CD34+ cells, are dependent on SIRT5, a lysine deacylase implicated in regulating multiple metabolic pathways. Dependence on SIRT5 is genotype-agnostic and extends to RAS- and p53-mutated AML. Results were comparable between SIRT5 knockdown and SIRT5 inhibition using NRD167, a potent and selective SIRT5 inhibitor.
View Article and Find Full Text PDFBCR-ABL1 point mutation-mediated resistance to tyrosine kinase inhibitor (TKI) therapy in Philadelphia chromosome-positive (Ph) leukemia is effectively managed with several approved drugs, including ponatinib for BCR-ABL1-mutant disease. However, therapy options are limited for patients with leukemic clones bearing multiple BCR-ABL1 mutations. Asciminib, an allosteric inhibitor targeting the myristoyl-binding pocket of BCR-ABL1, is active against most single mutants but ineffective against all tested compound mutants.
View Article and Find Full Text PDFBCR-ABL1 tyrosine kinase inhibitors (TKIs) are the cornerstone of treatment in chronic myeloid leukemia. Although there are now four TKIs approved for use in the front-line setting, acquired TKI resistance via secondary kinase domain mutations remains a problem for patients. K0706 is a novel BCR-ABL1 TKI currently under clinical investigation with structural elements similar to those of ponatinib and dasatinib.
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