A5065878482- Click Chemistry and Applications
- Chronic Myeloid Leukemia Treatments
- Lung Cancer Treatments and Mutations
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Organic Chemistry Cycloaddition Reactions
- Acute Myeloid Leukemia Research
- Radical Photochemical Reactions
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Chemical Synthesis and Analysis
- Cancer-related Molecular Pathways
- Mast cells and histamine
- Cancer Treatment and Pharmacology
- Synthesis and properties of polymers
- Synthesis of heterocyclic compounds
- Innovative Microfluidic and Catalytic Techniques Innovation
- HER2/EGFR in Cancer Research
- Fungal Plant Pathogen Control
- Advanced biosensing and bioanalysis techniques
- Synthesis and biological activity
- Advanced Breast Cancer Therapies
- Eosinophilic Disorders and Syndromes
Purdue University West Lafayette
2017-2024
Purdue University Institute for Cancer Research
2024
Developing continuous syntheses of lead compounds to support in vivo studies and preclinical evaluation remains an underdeveloped area. We report a telescoped flow synthesis alkynylnaphthyridine compound for the treatment FLT3 mutations acute myeloid leukemia. Different strategies were used develop route, including Design Experiments (DoE), high-throughput experimentation (HTE), application desorption electrospray ionization mass spectrometry (DESI-MS) optimize telescope amidation...
Selpercatinib (LOXO292) and pralsetinib (BLU667) are RET protein tyrosine kinase inhibitors (TKIs) recently approved for treating RET-altered cancers. However, mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation TKIs. While acquired G810C/R/S/V were reported in selpercatinib-treated patients, it was unclear whether all these other potential G810 mutants resistant to selpercatinib pralsetinib. Here, we profiled on six...
Acute myeloid leukemia (AML) is an aggressive malignancy with only a handful of therapeutic options. About 30% AML patients harbor mutated FLT3 kinase, and thus, this cancer-driver has become hotly pursued target. Herein we report new class inhibitors, which potently inhibit the proliferation acute cells at nanomolar concentrations.
Ponatinib is a multikinase inhibitor that used to treat chronic myeloid leukemia patients harboring mutated ABL1(T315I) kinase. Due the potent inhibition of FLT3, RET, and fibroblast growth factor receptors (FGFRs), it also being evaluated against acute (AML), biliary, lung cancers. The profile ponatinib may account for its toxicity, thus analogs with improved kinase selectivity or different profiles could be better tolerated. introduction nitrogen into drug compounds can enhance efficacy...
Aim: Mutated or overexpressed FLT3 drives about 30% of reported acute myeloid leukemia (AML). Currently, inhibitors have shown durable clinical responses but a complete remission AML with remains elusive due to mutation-driven resistance mechanisms. The development that also target other downstream oncogenic kinases may combat the mechanism. Results: 4-substituted aminoisoquinoline benzamides potently inhibit Src-family and FLT3, including secondary mutations, such as FLT3D835. Modifications...
The introduction of imatinib into the clinical scene revolutionized treatment chronic myelogenous leukemia (CML). overall eight-year survival rate for CML has increased from about 6 % in 1970s to over 90 era. However, 20 patients harbor primary or acquired resistance tyrosine kinase inhibitors. ABL1 point mutations BCR-ABL1 fusion protein, such as ABL1(T315I), typically emerge after prolonged inhibitor treatment. Ponatinib (AP24534) is currently only approved drug that active against...
Acute myeloid leukemia (AML) remains one of the most lethal, rarely cured cancers, despite decades active development AML therapeutics. Currently, 5-year survival patients is about 30% and for elderly patients, rate drops to <10%. About harbor an activating mutation in tyrosine kinase domain (TKD) Fms-Like Tyrosine 3 (FLT3) or a FLT3 internal tandem duplication (FLT3-ITD). Inhibitors FLT3, such as Rydapt that was recently approved by FDA, have shown good initial response but often relapse...
Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth survival in patients with acute myeloid leukemia (AML), leading poor overall survival. AML treated investigational drugs targeting mutant FLT3, including Quizartinib Crenolanib, develop resistance these drugs. Development is largely due acquisition cooccurring activation additional pathways, as well emergence mutations. Despite the high prevalence their clinical significance AML,...
Human epidermal growth factor receptor 2 (HER2)-targeted agents have proven to be effective, however, the development of resistance these has become an obstacle in treating HER2+ breast cancer. Evidence implicates HUNK as anti-cancer target for primary and resistant cancers. In this study, a selective inhibitor is characterized alongside phosphorylation event downstream substrate marker activity Rubicon been established that phosphorylated at serine (S) 92. Findings indicate HUNK-mediated...
Abstract Selpercatinib (LOXO-292, LY3527723) and pralsetinib (BLU-667) are first-in-class RET-targeted cancer therapy drugs. However, secondary RET mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation Tyrosine kinase inhibitors (TKIs). While the G810C/R/S/V located at solvent-front site were detected in selpercatinib-treated patients, it was unclear whether all these other potential G810 mutants resistant to...
<div>Abstract<p>Selpercatinib (LOXO292) and pralsetinib (BLU667) are RET protein tyrosine kinase inhibitors (TKIs) recently approved for treating RET-altered cancers. However, mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation TKIs. While acquired G810C/R/S/V were reported in selpercatinib-treated patients, it was unclear whether all these other potential G810 mutants resistant to selpercatinib...
<p>Supplementary information</p>
<p>Supplementary information</p>
<div>Abstract<p>Selpercatinib (LOXO292) and pralsetinib (BLU667) are RET protein tyrosine kinase inhibitors (TKIs) recently approved for treating RET-altered cancers. However, mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation TKIs. While acquired G810C/R/S/V were reported in selpercatinib-treated patients, it was unclear whether all these other potential G810 mutants resistant to selpercatinib...
<p>Supplementary information</p>
<p>Supplementary information</p>
<div>Abstract<p>Selpercatinib (LOXO292) and pralsetinib (BLU667) are RET protein tyrosine kinase inhibitors (TKIs) recently approved for treating RET-altered cancers. However, mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation TKIs. While acquired G810C/R/S/V were reported in selpercatinib-treated patients, it was unclear whether all these other potential G810 mutants resistant to selpercatinib...
Ponatinib is a multikinase inhibitor that used to treat chronic myeloid leukemia patients harboring mutated ABL1(T315I) kinase. Due the potent inhibition of FLT3, RET and FGFRs, it also being evaluated against AML, biliary lung cancers. The profile ponatinib may account for its toxicity, thus analogs with improved kinase selectivity could be better tolerated. A nicotinamide analog ponatinib, HSN748, retains activity ABL1, VEGFRs PDGFRa/b but losses c-Src, FGFRs P38a. Since Src or FGFR...
<p>Ponatinib is a multikinase inhibitor that used to treat chronic myeloid leukemia patients harboring mutated ABL1(T315I) kinase. Due the potent inhibition of FLT3, RET and FGFRs, it also being evaluated against AML, biliary lung cancers. The profile ponatinib may account for its toxicity, thus analogs with improved kinase selectivity could be better tolerated. A nicotinamide analog ponatinib, HSN748, retains activity ABL1, VEGFRs PDGFRa/b but losses c-Src, FGFRs P38a. Since Src or...