An article Cink4T, a quinazolinone-based dual inhibitor of Cdk4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy WOS:000459358600010 published article about DEPENDENT KINASE INHIBITOR; MICROTUBULE POLYMERIZATION; CDK4-SPECIFIC INHIBITORS; BIOLOGICAL EVALUATION; SELECTIVE INHIBITORS; CRYSTAL-STRUCTURE; NONPLANAR ANALOG; CYCLIN D1-CDK4; IN-VITRO; PROTEIN in [Sonawane, Vinay; Chaudhuri, Bhabatosh] De Montfort Univ, Leicester Sch Pharm, Leicester LE1 9BH, Leics, England; [Siddique, Mohd Usman Mohd; Sinha, Barij Nayan; Jayaprakash, Venkatesan] Birla Inst Technol, Dept Pharmaceut Sci & Technol, Ranchi 835215, Bihar, India; [Jadav, Surender Singh] Indian Inst Chem Technol, CSIR, Hyderabad 500007, Telangana, India in 2019, Cited 79. The Name is 2-Aminobenzamide. Through research, I have a further understanding and discovery of 88-68-6. COA of Formula: C7H8N2O
Inhibition of cyclin dependent kinase 4 (Cdk4) prevents cancer cells from entering the early G(0)/G(1) phase of the cell division cycle whereas inhibiting tubulin polymerization blocks cancer cells’ ability to undergo mitosis (M) late in the cell cycle. We had reported earlier that two non-planar and relatively non-toxic fascaplysin derivatives, an indole and a tryptoline, inhibit Cdk4 with IC50 values of 6.2 and 10 mu M, respectively. Serendipitously, we had also found that they inhibited tubulin polymerization. The molecules were efficacious in mouse tumor models. We have now identified Cink4T in a 59-compound quinazolinone library, designed on the basis of ligand-based virtual screening, as a compound that inhibits Cdk4 and tubulin. Its IC50 value for Cdk4 inhibition is 0.47 mu M and >50 mu M for inhibition of Cdk1, Cdk2, Cdk6, Cdk9. Cink4T inhibits tubulin polymerization with an IC50 of 0.6 mu M. Molecular modelling studies on Cink4T with Cdk4 and tubulin crystal structures lend support to these observations. Cancer cell cycle analyses confirm that Cink4T blocks cells at both G(0)/G(1) and M phases as it should if it were to inhibit both Cdk4 and tubulin polymerization. Our results show, for the very first time, that virtual screening can be used to design novel inhibitors that can potently block two crucial phases of the cell division cycle. (C) 2019 Elsevier Masson SAS. All rights reserved.
COA of Formula: C7H8N2O. About 2-Aminobenzamide, If you have any questions, you can contact Sonawane, V; Siddique, MUM; Jadav, SS; Sinha, BN; Jayaprakash, V; Chaudhuri, B or concate me.
Reference:
Thiomorpholine – Wikipedia,
,Thiomorpholine | C4H9NS – PubChem