Acrizanib (hydrochloride)

Acrizanib hydrochloride (LHA510 hydrochloride) is a small-molecule vascular endothelial growth factor receptor 2 (VEGFR-2, KDR) inhibitor. Acrizanib hydrochloride inhibits the proliferation of BaF3-Tel-KDR cells dependent on VEGFR-2 activity, with an IC₅₀ of 17.4 nM. Acrizanib hydrochloride can be used in research related to choroidal neovascularization and neovascular age-related macular degeneration^[1]. In Vitro:Acrizanib hydrochloride potently inhibits VEGFR-2-dependent proliferation of BaF3-Tel-KDR cells, with an IC₅₀ of 17.4 nM^[1].
Acrizanib (1 μM) hydrochloride exhibits residual kinase activity of ≤ 10% against only 13 wild-type kinases in a KINOMEscan screening targeting 442 kinases, including VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ, KIT, DDR1, DDR2, and TIE1^[1].
Acrizanib (1 μM; 0-30 min) hydrochloride has an RLM-derived Cl_int of 156 μL/min/mg in rat liver microsomal stability assays^[1].
Acrizanib hydrochloride binds to synthetic melanin, with B_max1 and B_max2 values of 368 and 134 nmol/mg, respectively, and K_d1 and K_d2 values of 6.4 and 0.56 μM^[1]. In Vivo:Hydrochloride of Acrizanib (1% suspension; 3.5 μL/eye; topical ocular administration; tid) inhibits neovascular area by 99% in the laser-induced CNV model of C57BL/6 mice^[1].
Hydrochloride of Acrizanib (3% suspension; 4 μL/eye; topical ocular administration; bid) inhibits neovascular area by 94% in the laser-induced CNV model of Brown Norway rats^[1].
Hydrochloride of Acrizanib (1% suspension; 4 μL/eye; topical ocular administration; tid) inhibits neovascular area by 90% in laser-induced CNV models of Brown Norway rats^[1].
Dose-response experiments of Acrizanib hydrochloride in a laser-induced CNV model of Brown Norway rats show that the ED₅₀ values for qd, bid and tid administration are 1.4%, 1.0% and 0.5%, respectively; the ED₉₀ values for bid and tid administration are 2.6% and 1.2%, respectively, while the ED₉₀ for qd administration is not determined^[1].
Hydrochloride of Acrizanib (2% suspension; 30 μL; unilateral topical ocular administration; tid; 7 days) achieves sustained exposure in the retina and retinal pigment epithelium/choroid of pigmented New Zealand White × New Zealand Red F1 rabbits; based on an analysis of exposure differences between dosed and undosed eyes, the paper reports that 37% and 57% of the total AUC in the RPE/choroid and retina, respectively, are attributable to direct local delivery of the eye drops^[1].