Rational approaches to improving selectivity in drug design

DJ Huggins, W Sherman, B Tidor - Journal of medicinal chemistry, 2012 - ACS Publications
Appropriate tuning of binding selectivity is a primary objective in the discovery and
optimization of a compound on the path toward developing a drug. The environment in …

New bis ([1, 2, 4] triazolo)[4, 3-a: 3′, 4′-c] quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer …

MM Alanazi, HA Mahdy, NA Alsaif, AJ Obaidullah… - Bioorganic …, 2021 - Elsevier
A new series of bis ([1, 2, 4] triazolo)[4, 3-a: 3′, 4′-c] quinoxaline derivatives were
designed and synthesized to have the main essential pharmacophoric features of VEGFR-2 …

New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis

NA Alsaif, MA Dahab, MM Alanazi, AJ Obaidullah… - Bioorganic …, 2021 - Elsevier
Abstract New series of [1, 2, 4] triazolo [4, 3-a] quinoxalin-4 (5H)-one and [1, 2, 4] triazolo [4,
3-a] quinoxaline derivatives have been designed, synthesized, and biologically assessed for …

Leucine-Rich Repeat Kinases

DR Alessi, SR Pfeffer - Annual Review of Biochemistry, 2024 - annualreviews.org
Activating mutations in leucine-rich repeat kinase 2 (LRRK2) represent the most common
cause of monogenic Parkinson's disease. LRRK2 is a large multidomain protein kinase that …

[PDF][PDF] Discovery of potent and selective covalent inhibitors of JNK

T Zhang, F Inesta-Vaquera, M Niepel, J Zhang… - Chemistry & biology, 2012 - cell.com
The mitogen-activated kinases JNK1/2/3 are key enzymes in signaling modules that
transduce and integrate extracellular stimuli into coordinated cellular response. Here, we …

The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling

AC Dar, KM Shokat - Annual review of biochemistry, 2011 - annualreviews.org
Kinases are highly regulated enzymes with diverse mechanisms controlling their catalytic
output. Over time, chemical discovery efforts for kinases have produced ATP-competitive …

Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum

L Solyakov, J Halbert, MM Alam, JP Semblat… - Nature …, 2011 - nature.com
The role of protein phosphorylation in the life cycle of malaria parasites is slowly emerging.
Here we combine global phospho-proteomic analysis with kinome-wide reverse genetics to …

Specific Btk inhibition suppresses B cell–and myeloid cell–mediated arthritis

JA Di Paolo, T Huang, M Balazs, J Barbosa… - Nature chemical …, 2011 - nature.com
Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular
and molecular mechanisms by which Btk mediates inflammation are poorly understood …

Discovery of new quinoxaline-2 (1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: Design, synthesis, and anti-proliferative evaluation

K El-Adl, HM Sakr, RG Yousef, ABM Mehany… - Bioorganic …, 2021 - Elsevier
VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a
new series of quinoxaline-2 (1H)-one derivatives were designed and synthesized. The …

Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases

B Apsel, JA Blair, B Gonzalez, TM Nazif… - Nature chemical …, 2008 - nature.com
The clinical success of multitargeted kinase inhibitors has stimulated efforts to identify
promiscuous drugs with optimal selectivity profiles. It remains unclear to what extent such …