VTX-27

VTX-27 is a selective protein kinase C θ (PKC θ) inhibitor, with K_is of 0.08 nM and 16 nM for PKC θ and PKC δ. IC50 & Target: Ki: 0.08 nM (PKC θ), 16 nM (PKC δ)^[1]. In Vitro: VTX-27 (Compound 27) possesses excellent overall characteristics. Good selectivity of VTX-27 is also seen against other PKC family members, particularly classical isoforms (>1000-fold except PKCβ I, 200-fold) and atypical isoforms (>10000-fold). As anticipated, attaining selectivity over the more closely related novel PKC family members is more challenging, with a good 200-fold being achieved over PKC δ^[1]. In Vivo: VTX-27 shows the best PK profile with a low clearance (7 mL min^-1 kg^-1), long half-life (4.7 h), and good oral bioavailability (65%). A single dose of VTX-27 is administered orally at 6.25, 12.5, 25, and 50 mg/kg (e.g., at 25 mg/kg C_max concentration 700 ng/mL) and demonstrates potent dose dependent inhibition of IL-2 production^[1].