8-CPT-2Me-cAMP, sodium salt

8-CPT-2Me-cAMP, sodium salt is a selective agonist of EPAC [1].

Cyclic AMP guanine nucleotide exchange factors (EPACs) are intracellular sensors for cAMP and function as nucleotide exchange factors for the Ras GTPase homologues Rap1 and Rap2 [1].

8-CPT-2Me-cAMP, sodium salt is a selective EPAC agonist. 8-CPT-2Me-cAMP increased Rap1 activation by EPAC1. Meantime, light chain 2 (LC2) of the microtubule-associated protein MAP1A increased this response. In LC2- and EPAC1-transfected cells, 8-CPT-2Me-cAMP increased cell adhesion to laminin [1]. In Jurkat Tcells, 8-CPT-2Me-cAMP (100 μM) activated Rap1, which was not affected by H-89, a PKA inhibitor [2]. In 1-LN prostate cancer cells, 8-CPT-2Me-cAMP increased Epac1, p-AktS473 and p-AktT308 in a dose-dependent way. 8-CPT-2Me-cAMP increased p-AktS473 and AktS473 kinase activity by two-three fold. Also, 8-CPT-2Me-cAMP activated mTORC1 and mTORC2 [3].

In human prostate cancer cells, 8-CPT-2Me-cAMP increased the levels of p-cPLA2S505, COX-2 and PGE2. However, COX-2, EP4 or mTOR inhibitors inhibited this effect and reduced protein and DNA synthesis induced by Epac1. These results suggested Epac1 was a pro-inflammatory modulator and promoted cell proliferation [4].

References:
[1].  Gupta M, Yarwood SJ. MAP1A light chain 2 interacts with exchange protein activated by cyclic AMP 1 (EPAC1) to enhance Rap1 GTPase activity and cell adhesion. J Biol Chem, 2005, 280(9): 8109-8116.
[2].  Fuld S, Borland G, Yarwood SJ. Elevation of cyclic AMP in Jurkat T-cells provokes distinct transcriptional responses through the protein kinase A (PKA) and exchange protein activated by cyclic AMP (EPAC) pathways. Exp Cell Res, 2005, 309(1): 161-173.
[3].  Misra UK, Pizzo SV. Upregulation of mTORC2 activation by the selective agonist of EPAC, 8-CPT-2Me-cAMP, in prostate cancer cells: assembly of a multiprotein signaling complex. J Cell Biochem, 2012, 113(5): 1488-1500.
[4].  Misra UK, Pizzo SV. Evidence for a pro-proliferative feedback loop in prostate cancer: the role of Epac1 and COX-2-dependent pathways. PLoS One, 2013, 8(4): e63150.