Novel 2-indolinone thiazole hybrids as sunitinib analogues: Design, synthesis, and potent VEGFR-2 inhibition with potential anti-renal cancer activity

Concise synthesis and biological activity evaluation of novel pyrazinyl–aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death

“…12 The VEGFR family proteins consist of VEGFR-1 (FMS-like tyrosine kinase [FLT]-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (FLT-4). 13 Several VEGFR inhibitors have been marketed as antitumor drugs and a range of inhibitors are undergoing clinical or preclinical studies, such as regorafenib (BAY 73-4506, Stivarga®, Reg), 14–16 sunitinib, 17 pazopanib, 18 apatinib (YN968D1, Apat), 19,20 and so on. Small MTA Reg is an oral multiple kinase inhibitor that targets several protein kinases at least including VEGFR 1–3, platelet-derived growth factor receptor-β (PDGFR-β), fibroblast growth factor receptor (FGFR), and Raf.…”

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Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. [5][6][7][8][9][10][11][12][13][14][15][16][17][5][6][7][8][9][10][11][12][13][14][15][16][17][18][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][5][6][7][8][9][10][11][12][13][14][15][16][17]<...>

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Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

“…Biphenylurea/thiourea derivatives tethered with heteroarylsulfonamide motifs were also found to be novel VEGFR2 inhibitors with significant inhibition compared to sorafenib [ 93 ]. Novel 2 indolinone-thiazole hybrid molecules effectively bound at the ATP binding site of VEGF-2 and showed a tumoricidal action with an IC 50 value of 3.9 ± 0.13 µM, greater than Sunitinib [ 94 ]. Apart from that, many peptides-based pan-VEGF inhibitors with druggable binding sites might be crucial for discovering novel and selective VEGF inhibitors to manage the burden of cancer growth [ 95 ].…”

Synthesis and biological evaluation of new derivatives of thieno-thiazole and dihydrothiazolo-thiazole scaffolds integrated with a pyrazoline nucleus as anticancer and multi-targeting kinase inhibitors

“…28 Additionally, thiazole derivatives were reported to exert cytotoxic potency against several types of cancer disease via suppression of various kinases such as; JAK2 and EGFR, VEGFR and BRAF kinases. [29][30][31][32][33] In addition, different researches conrmed the potent anticancer activities of the compounds containing thiophene and thiazole heterocycles via inhibition of BRAF kinase activity. 34,35 Consequently, the combined substructures (thiophene and thiazole scaffolds) may produce synergistic effects to boost the anticancer activities without compromising their original effective qualities.…”