11 research outputs found
Transient Kinetics of Formation and Reaction of the Uridylyl-Enzyme Form of Galactose-1-P Uridylyltransferase and Its Q168R-Variant: Insight into the Molecular Basis of Galactosemia †
No full textKinetic Mechanism of UDP-Hexose Synthase, a Point Variant of Hexose-1-Phosphate Uridylyltransferase from Escherichia coli
No full textRoles of Two Conserved Amino Acid Residues in the Active Site of Galactose-1-Phosphate Uridylyltransferase: An Essential Serine and a Nonessential Cysteine †
No full textA phase I study of an IDO-1 inhibitor (LY3381916) as monotherapy and in combination with an anti-PD-L1 antibody (LY3300054) in patients with advanced cancer
No full textA Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination With an Anti-PD-L1 Antibody (LY3300054) in Patients With Advanced Cancer
No full textInhibition of Nicotinamide Phosphoribosyltransferase (NAMPT), an Enzyme Essential for NAD+ Biosynthesis, Leads to Altered Carbohydrate Metabolism in Cancer Cells
No full textThe Folate Pathway Inhibitor Pemetrexed Pleiotropically Enhances Effects of Cancer Immunotherapy
No full textPharmacological Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT), an Enzyme Essential for NAD+ Biosynthesis, in Human Cancer Cells
No full textDiscovery of <i>N</i>‑(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3<i>R</i>)‑3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model
No full textA hallmark
of cancer is unbridled proliferation that can result in increased
demand for de novo synthesis of purine and pyrimidine bases required
for DNA and RNA biosynthesis. These synthetic pathways are frequently
upregulated in cancer and involve various folate-dependent enzymes.
Antifolates have a proven record as clinically used oncolytic agents.
Our recent research efforts have produced LSN 3213128 (compound <b>28a</b>), a novel, selective, nonclassical, orally bioavailable
antifolate with potent and specific inhibitory activity for aminoimidazole-4-carboxamide
ribonucleotide formyltransferase (AICARFT), an enzyme in the purine
biosynthetic pathway. Inhibition of AICARFT with compound <b>28a</b> results in dramatic elevation of 5-aminoimidazole 4-carboxamide
ribonucleotide (ZMP) and growth inhibition in NCI-H460 and MDA-MB-231met2
cancer cell lines. Treatment with this inhibitor in a murine based
xenograft model of triple negative breast cancer (TNBC) resulted in
tumor growth inhibition
