Phenamil

Phenamil is a selective inhibitor of transient receptor potentials (TRPs) and acid-sensing ion channels (ASICs) ^[1]. Phenamil is an amiloride analogs and a more potent and less reversible epithelial sodium channel (ENaC) blocker with an IC50 of 400 nM ^[2]. Phenamil inhibited TRPP3 -mediated Ca2+ transport with an IC50 of 140 nM in a Ca2+ uptake assay ^[3].

Phenamil (10 µM) Treatment of M2-10B4 (M2) mouse (mesenchymal stem cells) MSCs for 6 days with 10 µM phenamil markedly stimulated expression of the genes encoding ALP, Runx2, OCN, and osterix. Phenamil induces osteogenic gene expression and mineralization in both MSC and primary calvariae organ cultures ^[4]. Phenamil (10 µM) induced the expression of PPARγ within 24 h in 3T3-F442A preadipocyte cell lines. Phenamil act as a new proadipogenic compound ^[5].

Phenamil (15 or 30 mg/kg; 21 days) reduced chronic-hypoxia-induced pulmonary artery hypertension (PAH). Infusion of phenamil during hypoxia treatment inhibited pulmonary vascular remodeling ^[6].

References:
[1]. Chan M C, Weisman A S, Kang H, et al. The amiloride derivative phenamil attenuates pulmonary vascular remodeling by activating NFAT and the bone morphogenetic protein signaling pathway[J]. Molecular and cellular biology, 2011, 31(3): 517-530.
[2]. Hirsh A J, Molino B F, Zhang J, et al. Design, synthesis, and structure− activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and chronic bronchitis[J]. Journal of medicinal chemistry, 2006, 49(14): 4098-4115.
[3]. Dai X Q, Ramji A, Liu Y, et al. Inhibition of TRPP3 channel by amiloride and analogs[J]. Molecular pharmacology, 2007, 72(6): 1576-1585.
[4]. Park K W, Waki H, Kim W K, et al. The small molecule phenamil induces osteoblast differentiation and mineralization[J]. Molecular and cellular biology, 2009, 29(14): 3905-3914.
[5]. Park K W, Waki H, Choi S P, et al. The small molecule phenamil is a modulator of adipocyte differentiation and PPARγ expression [S][J]. Journal of lipid research, 2010, 51(9): 2775-2784.
[6]. Chan M C, Weisman A S, Kang H, et al. The amiloride derivative phenamil attenuates pulmonary vascular remodeling by activating NFAT and the bone morphogenetic protein signaling pathway[J]. Molecular and cellular biology, 2011, 31(3): 517-530.