Authors Qiu, QQ; Zhu, JL; Chen, QT; Jiang, ZQ; Xu, JT; Jiang, XT; Huang, WL; Liu, ZQ; Ye, J; Xu, XJ in ACADEMIC PRESS INC ELSEVIER SCIENCE published article about IN-VITRO; INHIBITION; GP; EFFLUX; CELLS; MDR; PHARMACOKINETICS; MODULATION; MECHANISM; CANCER in [Qiu, Qianqian; Zhu, Jilan; Chen, Qiutong; Jiang, Ziqian; Xu, Jiting; Jiang, Xueting; Liu, Zhongquan; Ye, Jing; Xu, Xiaojuan] Yancheng Teachers Univ, Sch Pharm, Jiangsu Prov Key Lab Coastal Wetland Bioresources, Yancheng 224007, Peoples R China; [Huang, Wenlong] China Pharmaceut Univ, Ctr Drug Discovery, State Key Lab Nat Med, Nanjing, Jiangsu, Peoples R China; [Huang, Wenlong] China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing, Jiangsu, Peoples R China in 2019, Cited 49. Name: 3-Methylbenzoic acid. The Name is 3-Methylbenzoic acid. Through research, I have a further understanding and discovery of 99-04-7
P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major impediment for clinical cancer therapy. 19 novel aromatic amides with triazole-core as MDR reversal agents were designed and synthesized via click chemistry to reverse MDR. Among them, compound 42 was identified as the most promising candidate with high potency (EC50 = 78.1 +/- 5.4 nM), low cytotoxity (SI > 1282) and persistent duration in reversing doxorubicin (DOX) resistance in K562/A02 cells. 42 also enhanced the potency of other P-gp associated cytotoxic agents with different structures. In further study, remarkably increased intracellular accumulation of Rh123 and DOX in K562/A02 cells was achieved by compound 42, while CYP3A4 activity had no change by compound 42. These results indicate that compound 42 as a relatively safe modulator of P-gp-mediated MDR has good potential for further development.
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Reference:
Isothiazole – Wikipedia,
,Isothiazole – ScienceDirect.com