Ca2+ channel agonist 1

Ca2+ channel agonist 1 is an agonist of N-type Ca2+ channel and an inhibitor of Cdk2, with EC50s of 14.23 μM and 3.34 μM, respectively, and is used as a potential treatment for motor nerve terminal dysfunction.

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Neurological Disease

CDK2:3.34 μM (EC50)

N-Type Ca2+ Channel:14.23 μM (EC50)

Ca2+ channel agonist 1 (Compound 13d) is an agonist of N-type Ca2+ channel and an inhibitor of Cdk2, with EC50s of 14.23 μM and 3.34 μM, respectively. Ca2+ channel agonist 1 exhibits a ca. 2-fold increased agonism and a 22-fold decreased cdk2 kinase activity versus the standard, (R)-roscovitine[1].

Briefly, the pipet solution consists of 70 nM Cs2SO4, 60 mM CsCl, 1 mM MgCl2, and 10 mM HEPES at pH 7.4. Cultured cells are bathed in a saline composed of 130 mM choline chloride (ChCl), 10 mM tetraethylammonium chloride (TEA-Cl), 2 mM CaCl2, 1 mM MgCl2, and 10 mM HEPES at pH 7.4. Patch pipettes are fabricated from borosilicate glass, and capacitive currents and passive membrane responses to voltage commands are subtracted. Currents are amplified by an amplifier, filtered at 5 kHz, and digitized at 10 kHz for subsequent analysis. A liquid junction potential of −11.3 mV is subtracted during recordings. To measure effects on calcium channel tail currents, the tail current integral is measured before and after application of a derivative (including Ca2+ channel agonist 1), with the integral of each trace being normalized to its peak.

[1]. Liang M, et al. Synthesis and biological evaluation of a selective N- and p/q-type calcium channel agonist. ACS Med Chem Lett. 2012 Oct 1;3(12):985-990.

Abemaciclib(LY2835219) | Ribociclib (LEE011) | Dinaciclib (SCH727965) | THZ1 2HCl | Roscovitine (CYC202) | Neomycin sulfate | THZ531 | RO-3306 | Flavopiridol | Nifedipine | NVP 2 | BAY-1143572 Racemate | CYC-065 | Acetylcholine chloride | AZD5438