BI 224436

BI 224436 is a novel HIV-1 noncatalytic site integrase inhibitor with EC₅₀ values of less than 15 nM against different HIV-1 laboratory strains. IC50 & Target: EC50: 15 nM (HIV-1)^[1] In Vitro: BI 224436 has cellular cytotoxicity of more than 90 μM. BI 224436 has a low, 2.1-fold decrease in antiviral potency in the presence of 50% human serum. BI 224436 retains full antiviral activity against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. BI 224436 displays an additive effect in combination with most approved antiretrovirals, including INSTIs. BI 224436 has drug-like in vitro absorption, distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell permeability, solubility, and low cytochrome P450 inhibition^[1]. In Vivo: BI 224436 exhibits excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic flow [CL], 0.7%; bioavailability [F], 54%), monkey (CL, 23%; F, 82%), and dog (CL, 8%; F, 81%)^[1].