Design and discovery of an orally efficacious spiroindolinone-based tankyrase inhibitor for the treatment of colon cancer
F Shirai, A Mizutani, Y Yashiroda… - Journal of Medicinal …, 2020 - ACS Publications
Tankyrases (TNKS/TNKS2) belong to the poly (ADP-ribose) polymerase family. Inhibition of
their enzymatic activities attenuates the Wnt/β-catenin signaling, which plays an important …
their enzymatic activities attenuates the Wnt/β-catenin signaling, which plays an important …
Allosteric regulation of DNA binding and target residence time drive the cytotoxicity of phthalazinone-based PARP-1 inhibitors
MR Arnold, MF Langelier, J Gartrell, IT Kirby… - Cell Chemical …, 2022 - cell.com
Allosteric coupling between the DNA binding site to the NAD+-binding pocket drives PARP-
1 activation. This allosteric communication occurs in the reverse direction such that NAD+ …
1 activation. This allosteric communication occurs in the reverse direction such that NAD+ …
Kinetic modelling of the P-glycoprotein mediated efflux with a large-scale matched molecular pair analysis
H Zhao - European Journal of Medicinal Chemistry, 2023 - Elsevier
P-glycoprotein (Pgp) mediated efflux impacts on the drug absorption, distribution,
metabolism and excretion, and confers multidrug resistance to cancer cells. Kinetic …
metabolism and excretion, and confers multidrug resistance to cancer cells. Kinetic …
Gaussian process regression models for the prediction of hydrogen bond acceptor strengths
We present two approaches for the computation of hydrogen bond acceptor strengths, one
by machine‐learning and one by a composite quantum‐mechanical protocol, both based on …
by machine‐learning and one by a composite quantum‐mechanical protocol, both based on …
[HTML][HTML] Diversity-oriented synthesis of bicyclic fragments containing privileged azines
N Luise, PG Wyatt - Bioorganic & Medicinal Chemistry Letters, 2019 - Elsevier
An innovative and efficient reagent-and scaffold-based diversity oriented synthesis (DOS) of
a fragment set was developed for fragment-based drug discovery (FBDD) programs. Twelve …
a fragment set was developed for fragment-based drug discovery (FBDD) programs. Twelve …
High-throughput hydrogen bond strength calculation and its applications in optimizing drug ADME properties
Aim: Modifying the molecule's intrinsic hydrogen bond strength (HBS) is a useful approach
in optimizing its permeability and P-glycoprotein (P-gp) efflux. Quantum mechanics (QM) …
in optimizing its permeability and P-glycoprotein (P-gp) efflux. Quantum mechanics (QM) …
Phthalazinone-based parp-1 inhibitors
M Cohen, M Arnold - US Patent App. 18/579,830, 2024 - Google Patents
NWGMIELHSCQGOG-ZDUSSCGKSA-N 4-[[3-[(6S)-3-(1, 1-difluoroethyl)-6-methyl-6, 8-
dihydro-5H-[1, 2, 4] triazolo [4, 3-a] pyrazine-7-carbonyl] phenyl]-difluoromethyl]-2H …
dihydro-5H-[1, 2, 4] triazolo [4, 3-a] pyrazine-7-carbonyl] phenyl]-difluoromethyl]-2H …