GRI 977143

GRI977143 is a specific LPA2 receptor agonist, with an EC50 of 3.3 μM [1].

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> LPL Receptor

Signaling Pathways >> Apoptosis >> Caspase

Research Areas >> Inflammation/Immunology

LPA2 Receptor:3.3 μM (EC50)

GRI977143 (10 μM, 24-72 h) is effective in reducing activation of caspases 3, 7, 8, and 9 and inhibits poly(ADP-ribose)polymerase 1 cleavage and DNA fragmentation in different extrinsic and intrinsic models of apoptosis[1]. GRI977143 is an effective stimulator of extracellular signal-regulated kinase 1/2 activation and promotes the assembly of a macromolecular signaling complex consisting of LPA2, Na+-H+ exchange regulatory factor 2, and thyroid receptor interacting protein 6[1]. Cell Proliferation Assay[1] Cell Line: Vector- and LPA2-transduced MEF cells (2 × 104)[1]. Concentration: 10 μM. Incubation Time: 24-72 h. Result: Did not cause a significant increase in vector cell proliferation except at 72 h (p < 0.05). Apoptosis Analysis[1]. Cell Line: Doxorubicin-induced apoptotic signaling in vector-transduced or LPA2-transduced MEF. Concentration: 10 μM. Incubation Time: 24 h. Result: Reduced caspase 3 and 7 activation on LPA2-transduced MEF cells by 51 ± 3% and was approximately as potent as 3 μM LPA or OTP. Protected against doxorubicin-induced apoptosis by inhibiting caspase 3, 7, 8, and 9 and reducing DNA fragmentation.

[1]. Gyöngyi N. Kiss, et al. Virtual Screening for LPA2-Specific Agonists Identifies a Nonlipid Compound with Antiapoptotic Actions. Mol Pharmacol. 2012 Dec; 82(6): 1162–1173.

[2]. Gyöngyi Nagyné Kiss, et al. PHARMACOLOGICAL AND CELLULAR CHARACTERIZATION OF GRI977143, A NOVEL NONLIPID LPA2 RECEPTOR AGONIST IDENTIFIED BY VIRTUAL SCREENING.