SQ22536 is an inhibitor of adenylyl cyclase with an IC50 value of 13 μM, it can inhibit prostaglandin E1-stimulated increase in cAMP in intact platelets[1].

In HMC-1 cells and hCBMCs, SQ22536 at a concentrationof 10 mM completely abrogated protein kinase A activity inboth cells. SQ22536 alone at the concentra-tions used did not alter the basal level of protein kinase Aactivity and did not affect cell viability[2].

In KK/Ta-Akita mice, SQ22536 (2 mg/kg, per day) is able to inhibit the renal protection of liraglutide. The combination of liraglutide and SQ22536 can eliminate the improvement of liraglutide on the pathological damage of glomerular tissue. After SQ22536 treatment, renal cAMP does not increase[3].

References:

[1]. Haslam R J, Davidson M M L, and Desjardins J V. Inhibition of adenylate cyclase by adenosine analogues in preparations of broken and intact human platelets. Biochemistry Journal, 1978, 176: 83-95.

[2]. Cao J, Cetrulo C L, Theoharides T C. Corticotropin-releasing hormone induces vascular endothelial growth factor release from human mast cells via the cAMP/protein kinase A/p38 mitogen-activated protein kinase pathway, 2006, 69(3): 998-1006.

[3]. Fujita H, Morii T, Fujishima H, et al. The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential. Kidney International, 2014, 85(3): 579-589.