Rationale for treating wet AMD in human using an oral pill consisting of a VEGFR/PDGFR inhibitor X-82. Invest. Ophthalmol. Visual Sci. 54, 3272–3272 (2013). Google Scholar US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT02535286 (2017). ...
The structures reveal that MEK1 and MEK2 each have a unique inhibitor-binding pocket adjacent to the MgATP-binding site. The presence of the potent inhibitor induces several conformational changes in the unphosphorylated MEK1 and MEK2 enzymes that lock them into a closed but catalytically inactive...
FDA approves first-in-class SYK inhibitor. Nat. Rev. Drug Discov. 17, 385 (2018). PubMed Google Scholar Burke, J. R. et al. Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci. Transl Med. https://doi.org/10.1126/...
We present here a workflow for designing a kinase-targeted library (KTL) with the goal of capturing known kinase inhibitor chemical space. We validated our design retrospectively using recent, high-throughput screening data and found significant enrichment of kinase inhibitor hits while retaining ...
Several optimization studies conducted on Roscovitine, devoted to the selection of the substituent at the position 6 of the purine scaffold, led to the identification of CR8, a potent and selective kinase inhibitor [182]. To develop less hydrophobic compounds which could be more soluble ...
The Lamarchian genetic algorithm (LGA) was applied to deal with the protein-inhibitor interactions. Some important parameters were set as follows: the initial number of individuals in population is 50; the elitism value is 1, which automatically survives into nest generation. The mutation rate is...
inhibitor-kinase pair falls below a pre-specified threshold level, the pair could be classified as non-interacting, while if it falls above this threshold it could be classified as interacting. The selection of the threshold value will affect the sensitivity and specificity of the classification, ...
T cells cultured in the presence of p38i, with the inhibitor washed out before adoptive transfer, demonstrated improved homing to the spleen and tumors compared with control cells (Figures 7A–7C). Furthermore, we found an increase in the absolute number of p38i-treated Pmel TEM cells with ...
Identification of selective cyclin-dependent kinase 2 inhibitor from the library of pyrrolone-fused benzosuberene compounds: An in silico exploration. J. Biomol. Struct. Dynam. 40, 7693–7701 (2022). Article CAS Google Scholar Naqvi, A. A., Mohammad, T., Hasan, G. M. & Hassan, M. ...
carbonic anhydrase; cheminformatics; docking simulation; dual inhibitor; fingerprint; kinase; machine learning; polypharmacology1. Introduction A molecule targeting a single disease-related protein often causes insufficient efficacy, even potent from the viewpoint of target engagement. Therapeutic strategies ...