NNC 55-0396 (Synonyms: NNC 55-0396 dihydrochloride)

NNC 55-0396 is a selective inhibitor of T-type calcium channels that blocks Cav3.[1] in stably expressing HEK293 cells (IC50 = 6.8 μM) with no discernible effect on high voltage-activated (L-type) channels in INS-1 cells up to a concentration of 100 μM.1 NNC 55-0396 suppresses tremor in two murine models, the GABAA α1-null (20 mg/kg) and harmaline-induced (12.5 mg/kg) tremor models, and was better tolerated than mibefradil.[2] In arterial smooth muscle cells, NCC 55-0396 (IC50 = 80 nM) inhibits voltage-dependent K+ channels but does not affect their voltage sensitivity.[3] NNC 55-0396 (1-5 μM) also suppresses angiogenesis in vitro by inhibiting hypoxia-inducible factor-1α activity, and it slows tumor growth of flank xenografts of U87MG cells in mice when administered at 20 mg/kg.[4]

Reference:
[1]. Huang, L., Keyser, B.M., Tagmose, T.M., et al. NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride]: a new selective inhibitor of T-type calcium channels. J. Pharmacol. Exp. Ther. 309(1), 193-199 (2004).
[2]. Quesada, A., Bui, P.H., Homanics, G.E., et al. Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor. Eur. J. Pharmacol. 659(1), 30-36 (2011).
[3]. Son, Y.K., Hong, D.H., Li, H., et al. Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J. Pharmacol. Sci. 125(3), 312-319 (2014).
[4]. Kim, K.H., Kim, D., Park, J.Y., et al. NNC 55-0396, a T-type Ca2+ channel inhibitor, inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction. J. Mol. Med. (Berlin) 93(5), 499-509 (2015).