LSD1-IN-14, a powerful and specific inhibitor of LSD1 (with an IC50 value of 0.89 μM), effectively suppresses the growth of A549 and THP-1 cells and promotes the apoptosis of tumor cells [1].

LSD1-IN-14 (compound x43) demonstrates significant efficacy in inhibiting the proliferation of A549 and THP-1 cells at concentrations ranging from 0 to 20 μM over 72 hours, achieving IC50 values of 1.62 μM and 1.21 μM, respectively [1]. At lower concentrations (0-3 μM; 72 hours), it notably increases the expression of H3K4me2 and H3K9me2 in A549 cells in a dose-responsive manner, alongside inducing apoptosis in 53.6% of these cells, also in a concentration-dependent fashion [1]. Furthermore, LSD1-IN-14 showcases remarkable metabolic stability in human liver microsomes with a half-life of 103.3 minutes and minimal inhibition of cytochrome P450 enzymes, indicated by a Cl int(mic) value of 13.4 μL/min/mg when tested at 1 mM for 60 minutes [1]. This compound exhibits profound antiproliferative effects and mechanistic insights into epigenetic modulation and apoptosis induction, making it a promising candidate for further research [1].

LSD1-IN-14, administered at dosages of 2 mg/kg intravenously (i.v.) and 10 mg/kg intragastrically (i.g.) to male Sprague-Dawley rats, exhibits an acceptable half-life and oral bioavailability. Pharmacokinetic analysis revealed: for i.v. administration, a peak concentration (C max) of 41.1 ng/mL, a half-life (T 1/2) of 1.0 hour, a steady-state volume of distribution (Vd ss) of 6.6 L/kg, a clearance rate (Cl) of 156 mL/min/kg, and an area under the curve (AUC 0-t) of 126 ng.h/mL extending to 152 ng.h/mL (AUC 0-∞). For i.g. administration, the peak concentration reached 575 ng/mL at a T max of 0.8 hours, a half-life of 2.8 hours, with an AUC 0-t of 211 ng.h/mL extending to 214 ng.h/mL (AUC 0-∞), reflecting an oral bioavailability of 11.9%. These findings suggest LSD1-IN-14 has promising pharmacokinetic properties for further development.