SU 6668 Chemical Properties

storage temp. 

+2C to +8C

solubility 

DMSO : 50 mg/mL (161.11 mM; Need ultrasonic)

form 

Dark yellow solid

color 

Orange to red

SU 6668 Usage And Synthesis

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

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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