SKF-96365 (hydrochloride)

SKF-96365 hydrochloride is a TRPC channel antagonist and store-operated calcium entry (SOCE) inhibitor. SKF-96365 hydrochloride reduces calcium ion influx by inhibiting the activity and expression of TRPC6, STIM1 and Orai1. SKF-96365 hydrochloride inhibits voltage-gated sodium current (cardiac I_Na/NaV1.5) and slows myocardial conduction. SKF-96365 hydrochloride inhibits phosphorylation/activation of CaMKIIγ and suppresses the downstream AKT signaling pathway. SKF-96365 hydrochloride induces G₂/M phase cell cycle arrest, apoptosis and cytoprotective autophagy in colorectal cancer cells. SKF-96365 hydrochloride alleviates allergic rhinitis symptoms by reducing inflammatory cytokine levels. SKF-96365 hydrochloride reduces intracellular calcium overload, inhibits Homer1 expression, prevents nuclear damage and suppresses apoptosis. SKF-96365 hydrochloride inhibits the growth of colorectal cancer xenografts in nude mice. SKF-96365 hydrochloride is applicable to research related to allergic rhinitis, colorectal cancer, Parkinson's disease, persistent spontaneous nociception and hyperalgesia^{[1][2][3][4][5]}. In Vitro:SKF-96365 (0-10 μM; applied until steady-state inhibition is reached) hydrochloride inhibits hNaV1.5 currents stably expressed in HEK 293 cells, with an IC₅₀ of 0.94 μM^[2].
SKF-96365 (0-20 μM) hydrochloride dose-dependently inhibits store-operated calcium entry in human colorectal cancer cell lines HCT116 and HT29^[3].
SKF-96365 (0-40 μM, 48-72 h) hydrochloride inhibits the growth of human colorectal cancer cells HCT116 (IC₅₀ = 10.88 μM) and HT29 (IC₅₀ = 14.56 μM), and exhibits significantly lower toxicity against normal colonic epithelial cells NCM460^[3].
SKF-96365 (0-20 μM, 48 h) hydrochloride induces G₂/M cell cycle arrest in human colorectal cancer cells HCT116 and HT29 by regulating key G₂/M transition proteins, including upregulating p21waf/Cip1 and downregulating p-Cdc25c, Cdc25c, and Cyclin B^[3].
SKF-96365 (10 μM, 0-24 h) hydrochloride induces apoptosis in human colorectal cancer cell lines HCT116 and HT29 via the endogenous mitochondrial pathway, a process characterized by early (12 h) mitochondrial membrane depolarization, Bax translocation and cytochrome c release, followed by caspase activation and marked apoptosis (24 h)^[3].
SKF-96365 (0-20 μM, 12 h) hydrochloride induces cytoprotective autophagy in human colorectal cancer cells HCT116 and HT29. This effect appears as early as 12 h (prior to apoptosis) and antagonizes apoptosis by sequestering mitochondria into autophagosomes to reduce cytosolic cytochrome c levels^[3].
SKF-96365 (0-20 μM, 24 h) hydrochloride inhibits the AKT/mTOR signaling pathway and the calcium/Ca²⁺/CaMKIIγ/AKT signaling pathway in human colorectal cancer cell lines HCT116 and HT29^[3].
SKF-96365 (1-50 μM, 24 h) hydrochloride significantly increases the survival rate of PC12 cells treated with MPP⁺, reduces LDH release, alleviates nuclear damage, membrane damage, and late apoptotic cell death, mitigates intracellular calcium overload, and decreases the mRNA and protein expression levels of Homer1^[4].
SKF-96365 (1-10 µM) hydrochloride inhibits melittin-induced inward currents in acutely isolated small and medium-sized dorsal root ganglion cells of rats in a dose-dependent manner^[5].
SKF-96365 (10 µM) hydrochloride inhibits melittin-induced intracellular Ca²⁺ elevation, and the proportion of cells exhibiting this inhibitory effect reaches 46.5% in acutely isolated rat dorsal root ganglion cells sensitive to melittin^[5]. In Vivo:SKF-96365 (200-400 μg; intranasal administration; once daily; for 8 consecutive days) hydrochloride dose-dependently alleviates allergic rhinitis symptoms and suppresses inflammatory responses in BALB/c mice^[1].
SKF-96365 (20 mg/kg; i.p.; once daily for 14 consecutive days) hydrochloride inhibits the growth of colorectal cancer xenografts in athymic BALB/c nude mice by inducing cell cycle arrest, apoptosis and protective autophagy via suppressing the CaMKIIγ/AKT-mediated pathway^[3].