252916-29-3 Usage
Description
3-[2,4-dimethyl-5-[(E)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid, also known as TSU-68, is an oxindole derivative that functions as an ATP-competitive inhibitor of the tyrosine kinase activity of fibroblast growth factor receptor 1 (FGFR1). It is characterized by its potent inhibitory effects on various growth factor receptors, including Flk-1/KDR, FGFR1, and PDGFRβ.
Uses
Used in Pharmaceutical Industry:
TSU-68 is used as an inhibitor for Flk-1/KDR, FGFR1, and PDGFRβ with Ki values of 2.1 μM, 1.2 μM, and 8 nM, respectively. Its inhibitory effects on these growth factors contribute to its substantial antitumor activity, making it a promising candidate for therapeutic applications in cancer treatment.
Used in Oncology:
TSU-68 is employed as an antitumor agent, targeting vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor β (PDGFRβ), and fibroblast growth factor receptor 1 (FGFR1). By inhibiting these receptors, TSU-68 demonstrates potential in the development of therapeutic strategies for cancer treatment.
Used in Drug Development:
As a potent inhibitor of multiple growth factor receptors, TSU-68 is utilized in the development of novel drug delivery systems and therapeutic approaches to enhance its bioavailability, delivery, and overall efficacy in cancer treatment.
Biological Activity
ATP-competitive PDGFR, VEGF and FGFR inhibitor (IC 50 values are 0.06, 2.43, 3.04 and > 100 μ M at PDGFR β , VEGFR2, FGFR1 and EGFR respectively). Inhibits proliferation of HUVEC and NIH3T3 cells in vitro (IC 50 values are 0.41, 9.3 and 16.5 μ M for VEGF, FGF and PDGF-stimulated growth respectively) and induces > 75% growth inhibition against a broad range of tumor types in vivo . Exhibits antiangiogenic, anti-inflammatory, antimetastatic and proapoptotic activity and is orally active.
in vitro
biochemical kinetic studies using isolated flk-1, fgf receptor 1, and pdgf receptor β kinases revealed that tsu-68 has competitive inhibitory properties with respect to atp. in cellular systems, tsu-68 inhibited receptor tyrosine phosphorylation and mitogenesis after stimulation of cells by appropriate ligands [1].
in vivo
oral or i.p. administration of tsu-68 in athymic mice resulted in significant growth inhibition of a diverse panel of human tumor xenografts of glioma, melanoma, lung, colon, ovarian, and epidermoid origin [1].
references
[1] laird ad, vajkoczy p, shawver lk et al. su6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. cancer res. 2000 aug 1;60(15):4152-60.[2] okamoto i, yoshioka h, takeda k et al. phase i clinical study of the angiogenesis inhibitor tsu-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer. j thorac oncol. 2012 feb;7(2):427-33.
Check Digit Verification of cas no
The CAS Registry Mumber 252916-29-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,5,2,9,1 and 6 respectively; the second part has 2 digits, 2 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 252916-29:
(8*2)+(7*5)+(6*2)+(5*9)+(4*1)+(3*6)+(2*2)+(1*9)=143
143 % 10 = 3
So 252916-29-3 is a valid CAS Registry Number.
InChI:InChI=1/C18H18N2O3/c1-10-12(7-8-17(21)22)11(2)19-16(10)9-14-13-5-3-4-6-15(13)20-18(14)23/h3-6,9,19H,7-8H2,1-2H3,(H,20,23)(H,21,22)/b14-9+
