Identification | Back Directory | [Name]
SU 6668 | [CAS]
210644-62-5 | [Synonyms]
SU 6668 (Z)-SU6668 (Z)-TSU-68 (Z)-Orantinib PDGFR Tyrosine Kinase Inhibitor VI, SU6668 PDGFR Tyrosine Kinase Inhibitor VI, SU6668 - CAS 210644-62-5 - Calbiochem 3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoicacid 3-(2,4-Dimethyl-5-{[(3Z)-2-oxo-1H-indol-3-ylidene]methyl}-1H-pyrrol-3-yl)propanoic acid 3-(2,4-Dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid 5-((Z)-1,2-Dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-propanoic acid 1H-Pyrrole-3-propanoic acid, 5-((Z)-(1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl- (Z)?-?3-?(2,?4-?Dimethyl-?5-?((2-?oxoindolin-?3-?ylidene)?methyl)?-?1H-?pyrrol-?3-?yl)?propanoic acid (SU-6668) | [Molecular Formula]
C18H18N2O3 | [MDL Number]
MFCD09743433 | [MOL File]
210644-62-5.mol | [Molecular Weight]
310.35 |
Hazard Information | Back Directory | [Uses]
PDGFR Tyrosine Kinase Inhibitor VI, SU6668 is a potent ATP-competitive inhibitor against tyrosine kinases. | [General Description]
A cell-permeable indolinone compound that acts as a potent ATP-competitive inhibitor against RTKs (receptor tyrosine kinases) Kit, PDGFRβ, VEGFR2 (Flk-1/KDR), FGFR1 activity in vitro (IC50 = 0.01, 0.1, 3.9, and 3.8 μM, respectively) and PDGF/VEGF/bFGF-mediated angiogenesis and tumor development in vivo. Although initially characterized as an RTK inhibitor, SU6668 is now also known to target ser/thr kinases Aurora A, Aurora B, TBK1 (NAK/T2K), and AMPK (IC50 = 0.85, 0.047, 1.4, and 1.8 μM, respectively), as well as non-receptor TKs Lyn and Yes (IC50 = 4.3 and 5.8 μM, respectively). | [Synthesis]
A mixture of 3-(5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)propionic acid (10 g, 51 mmol), 2-indolone (6.5 g, 49 mmol) and sodium hydroxide (40 g, 58 mmol) was dissolved in 50 ml of water and the reaction was stirred for 4 hr at 50 °C. After completion of the reaction, the mixture was cooled to room temperature, filtered and the filtrate was acidified with 12N hydrochloric acid to pH 3. The precipitated solid was collected by vacuum filtration, washed with 10 ml of water and dried under vacuum overnight. The crude product was washed twice with hot ethanol, then the solid was collected by vacuum filtration, washed with 10 ml of ethanol and dried under vacuum to give 13.8 g (91% yield) of (Z)-3-(2,4-dimethyl-5-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrol-3-yl)propionic acid.1HNMR (360 MHz, DMSO-d6) data were as follows: δ 13.38 (s, br, 1H, NH-1'), 12.05 (s, br, 1H, COOH), 10.70 (s, br, 1H, NH-1), 7.69 (d, J=7.39 Hz, 1H, H-4), 7.53 (s, 1H, H-vinyl), 7.06 (t, J=7.39 Hz, 1H, H-6), and 6.95 (t, J=7.39Hz, 1H, H-5), 6.85 (d, J=7.39Hz, 1H, H-7), 2.63 (t, J=7.45Hz, 2H, CH2CH2COOH), 2.34 (t, J=7.45Hz, 2H, CH2CH2COOH), 2.28 (s, 3H, CH3), 2.24 ( s, 3H, CH3). Mass spectral data: MS m/z 311 ([M+1]+, 100). | [in vivo]
SU6668 (4-200 mg/kg/day; p.o. for 21 d) induces dose-dependent inhibition of A431 tumor growth in athymic mice[1].
SU6668 (75 mg/kg/day; i.p. for 22 d) significantly suppresses tumor angiogenesis and vascularization in mice[1].
SU6668 (200 mg/kg/day; p.o. for 11-27 d) induces striking regression of large established A431 xenografts in athymic mice[1]. Animal Model: | Female athymic mice (BALB/c, nu/nu) were implanted A431 tumor cells[1] | Dosage: | 4, 40, 75, 200 mg/kg | Administration: | P.o. daily for 21 days | Result: | Induced 97% growth inhibition against A431 tumor at the dose of 97%.
No mortality was observed in any treatment group.
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| [IC 50]
Flk-1/KDR: 2.1 μM (IC50); PDGFRβ: 0.008 μM (IC50); FGFR1: 1.2 μM (IC50) | [References]
[1] Patent: US6878733, 2005, B1. Location in patent: Page/Page column 215 [2] Patent: US6878733, 2005, B1. Location in patent: Page/Page column 215 [3] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 1, p. 181 - 185 [4] Journal of Medicinal Chemistry, 1999, vol. 42, # 25, p. 5120 - 5130 [5] Patent: US6395734, 2002, B1 |
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Sigma-Aldrich
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SPIRO PHARMA
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