Cell lines

T-47D, Calu-6 and HeLa cell lines

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10-6 M

Applications

SR 11302 inhibits effectively the proliferation of T-47D, Calu-6 and HeLa cell lines, and could serve as a candidate for new retinoid therapeutic agent with reduced side effects.

Animal models

AP-1-luciferase transgenic mice

Dosage form

four times over 7 days with 34 nmol dissolved in 300 μl acetone

Application

SR 11302 is one of the most promising drug candidate for chemotherapy and chemoprevention of cancer, and its effect is mediated by blocking AP-1 activity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

• Exp Cell Res (2021): 112550.

SR 11302 is an inhibitor of activator protein-1 (AP-1) [1].AP-1 is a transcription factor that displays antitumor effects in vivo.

SR 11302 is an inhibitor of AP-1 but don’t activate RARs and RXR. SR11302 failed to inhibit the proliferation of F9 cells, the embryonal carcinoma cell line. While, it can inhibit the growth of breast cancer cell line T-47D, the lung cancer line Calu-6 and HeLa cells[1]. SR 11302 had very little effect on either the proliferation or the differentiation of HL-60, fresh APL and NB4 cells, which indicate that AP-1 may not be involved in the signaling pathway of proliferation and differentiation of HL-60, fresh APL and NB4 cells [2].

In an AP-1-luciferase transgenic mouse carcinogenesis model, SR11302 significantly inhibit both AP-1 activation in 7,12-dimethyl benz(a)anthracene-initiated mouse skin and 12-O-tetradecanoylphorbol-13-acetate-induced papilloma formation. While, SR11235, a retinoid with RARE transactivating activity, but lack of AP-1 inhibiting effect, didn’t inhibit papilloma formation and AP-1 activation. These results show that the antitumor effect of retinoids is mediated by blocking AP-1 activity in vivo [3].

References:
[1]. Fanjul A, Dawson MI, Hobbs PD, et al. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature, 1994, 372(6501): 107-111.
[2]. Shiohara M, Dawson MI, Hobbs PD, et al. Effects of novel RAR- and RXR-selective retinoids on myeloid leukemic proliferation and differentiation in vitro. Blood, 1999, 93(6): 2057-2066.
[3]. Huang C, Ma WY, Dawson MI, et al. Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc Natl Acad Sci U S A, 1997, 94(11): 5826-5830.