Fendiline

Fendiline, a diphenylalkylamine type of antianginal agent, is an L-type calcium channel blocker (IC₅₀ of 17 µM). Fendiline is also a selective K-Ras inhibitor, and has no effect on H-Ras and N-Ras. Fendiline inhibits K-Ras plasma membrane localization (IC₅₀ of 9.64 μM), inhibits K-Ras signal output and blocks the proliferation of pancreatic, colon, lung, and endometrial cancer cell lines expressing oncogenic mutant K-Ras. Fendiline is a STING agonist and is able to inhibit the growth of multiple refractory cold tumors (MC38, CT26 and B16F10)^[1][2][4]. In Vitro:Fendiline (0.3-100 µM) applies extracellularly inhibited the calcium channel current (ICa) in a concentration- and time-dependent manner^[1].
Fendiline does not inhibit K-Ras posttranslational processing but significantly reduced nanoclustering of K-Ras and redistributed K-Ras from the plasma membrane to the endoplasmic reticulum (ER), Golgi apparatus, endosomes, and cytosol^[2].
Fendiline (17 µM; 48 h) significantly inhibits signaling downstream of constitutively active K-Ras and endogenous K-Ras signaling in cells transformed by oncogenic H-Ras^[2].
Fendiline (0-1.25 μM; 72 h) blocks the proliferation of pancreatic, colon, lung, and endometrial cancer cell lines expressing oncogenic mutant K-Ras^[2].
Fendiline competes for [³H]Yohimbine binding to human platelets α2-adrenergic receptors with a K_d of 2.6 µM^[3].
Fendiline (M335) (5-40 μM; 4 h) activates the STING-TBK1-IRF3 axis and induces autophagy (LC3-II upregulation) in a concentration-dependent manner in THP-1 cells^[4].
Fendiline (20 μM; 4 h) fails to activate pTBK1, pIRF3, or upregulate IFNB, ISG15, CXCL10, and IL6 in THP-STING KO cells^[4].
Fendiline (10-30 μM; 6 h) reduces the viral infection efficiency in a dose - dependent manner in THP-1 cells infected with HSV-1-GFP^[4].
Fendiline (20 μM; 6 h) shows stronger antiviral activity against HSV-1-GFP in HeLa-ST^OE cells overexpressing STING than in STING-deficient HeLa cells^[4].
In Vivo:Fendiline (300 μg; intratumoral injection; every 2 days; 20 days) in C57BL/6J mice inoculated with MC38 tumors achieves an 82% tumor growth inhibition rate and increases the numbers of CD8⁺ T cells and NK cells in tumors and spleens^[4].
Fendiline (5-20 mg/kg; intraperitoneal injection; every 2 days; 20 days) in BALB/c mice inoculated with CT26 or B16F10 tumors inhibits tumor growth in a dose - dependent manner and activates the systemic immune system (increasing CD45⁺, CD3⁺, CD8⁺, and NK⁺ cells in the spleen)^[4].