IPAG

IPAG is a potent sigma-1 receptor antagonist with a pKi of 4.3[1]. IPAG induces apoptosis[2].

Research Areas >> Cancer

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

Sigma1 inhibition by IPAG causes the autolysosomal degradation of PD-L1 in PC3 (hormone-insensitive prostate cancer) and MDA-MB-231 (triple-negative breast cancer) cell lines and reduces the levels of functional PD-L1 on the surface of the cells[2]. IPAG treatment produces a mean of 100±8 μg per 106 cells. IPAG can inhibit cell proliferation. Treatment with IPAG decreases cell mass[3]. IPAG treatment suppresses phosphorylation of translational regulator proteins p70S6K, S6, and 4E-BP1[3]. Cell Viability Assay[3] Cell Line: T47D cells Concentration: 10 μM Incubation Time: 24 hours Result: The mean forward scatter height (FSC-H) of DMSO (control) measured 412±5, whereas the mean FSC-H of IPAG treated cells was 390±4. Western Blot Analysis[3] Cell Line: T47D cells Concentration: 10 μM Incubation Time: Result: Decreased levels of phospho-threonine 389-p70S6Kinase (P-S6K), phospho-serine 235/236-ribosomal S6 (P-S6), and phospho-serine 65-4E-BP1 (P-4E-BP1).

[1]. James M Brimson, et al. Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression. Sci Rep. 2020 Jun 8;10(1):9251.

[2]. Halley M Oyer, et al.Small-Molecule Modulators of Sigma1 and Sigma2/TMEM97 in the Context of Cancer: Foundational Concepts and Emerging Themes. Front Pharmacol. 2019 Oct 21;10:1141.

[3]. Felix J Kim, et al. Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression. Biochem Biophys Res Commun. 2012 Sep 21;426(2):177-82.