Li, Xiaokai; Srinivasan, Sharan R.; Connarn, Jamie; Ahmad, Atta; Young, Zapporah T.; Kabza, Adam M.; Zuiderweg, Erik. R. P.; Sun, Duxin; Gestwicki, Jason E. published the artcile< Analogues of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, As Anti-Cancer Agents>, Product Details of C10H9NOS2, the main research area is benthiazolyl cationic rhodacyanine preparation allosteric Hsp70 inhibitor antitumor; Hsp90; breast cancer; mortalin; p53; proteostasis.
The rhodacyanine, MKT-077, has antiproliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of mol. chaperones. However, MKT-077 is rapidly metabolized, which limits its use as either a chem. probe or potential therapeutic. The synthesis and characterization of MKT-077 analogs designed for greater stability is reported. The most potent mols., such as I (JG-98), were at least 3-fold more active than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50 values of 0.4 ± 0.03 and 0.7 ± 0.2 μM, resp.). The analogs modestly destabilized the chaperone clients, Akt1 and Raf1, and induced apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved at least 7-fold (t1/2 = 37 min) compared to MKT-077 (t1/2 < 5 min). Finally, NMR titration experiments suggested that these analogs bind an allosteric site that is known to accommodate MKT-077. These studies advance MKT-077 analogs as chem. probes for studying Hsp70s roles in cancer. ACS Medicinal Chemistry Letters published new progress about Antiproliferative agents. 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Product Details of C10H9NOS2.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica