Harmalol (hydrochloride hydrate)

Harmalol is a β-carboline alkaloid and an active metabolite of harmaline that has been found in P. harmala and has diverse biological activities.^1,2,3,4,5 It is an inhibitor of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A; IC₅₀ = 0.63 µM) and monoamine oxidase A (MAO-A; IC₅₀ = 0.66 µM).³ It is selective for DYRK1A over Cdk1, Cdk5, CK1α1, Clk4, DYRK2, Pim-1, and GSK3β but also inhibits DYRK1B and Clk1 at 10 µM. It inhibits proliferation of H4 human glioblastoma cells (IC₅₀s = 23.7 µM). Harmalol (0.5-12.5 µM) reduces increases in the levels of the cytochrome P450 (CYP) isoform CYP1A1 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in HepG2 cells and prevents TCDD-induced activation of the aryl hydrocarbon receptor (AhR) in guinea pig hepatic cytosolic extracts.⁴ It reduces glutamate-induced cytotoxicity, cytochrome c release, caspase-3 activation, and the production of reactive oxygen species (ROS) in PC12 cells when used at a concentration of 25 µM.⁵ This product is also available as an analytical reference standard .

1.Brierley, D.I., and Davidson, C.Developments in harmine pharmacology - implications for ayahuasca use and drug-dependence treatmentProg. Neuropsychopharmacol. Biol. Psychiatry39(2)263-272(2012) 2.Nikam, T.D., Nitnaware, K.M., and Ahire, M.L.Alkaloids derived from tryptophan: Harmine and related alkaloidsNatural products. Phytochemistry, botany and metabolism of alkaloids, phenolics and terpenes553-574(2013) 3.Tarpley, M., Oladapo, H.O., Strepay, D., et al.Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studiesEur. J. Pharm. Sci.162105821(2021) 4.El Gendy, M.A.M., Soshilov, A.A., Denison, M.S., et al.Harmaline and harmalol inhibit the carcinogen-activating enzyme CYP1A1 via transcriptional and posttranslational mechanismsFood Chem. Toxicol.50(2)353-362(2012) 5.Han, E.S., and Lee, C.S.Inhibition of glutamate-induced change in mitochondrial membrane permeability in PC12 cells by 1-methylated β-carbolinesBiomol. Ther. (Seoul)11(2)112-118(2003)