VTX-27

VTX-27 is a selective protein kinase C θ (PKC θ) inhibitor, with Kis of 0.08 nM and 16 nM for PKC θ and PKC δ.

Signaling Pathways >> Epigenetics >> PKC

Signaling Pathways >> TGF-beta/Smad >> PKC

Research Areas >> Inflammation/Immunology

PKCθ:0.08 nM (Ki)

PKCδ:16 nM (Ki)

PKCα:356 nM (Ki)

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].

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 Cmax concentration 700 ng/mL) and demonstrates potent dose dependent inhibition of IL-2 production[1].

[1]. Jimenez JM, et al. Design and optimization of selective protein kinase C θ (PKCθ) inhibitors for the treatment of autoimmune diseases. J Med Chem. 2013 Mar 14;56(5):1799-810.

12-O-tetradecanoylphorbol-13-acetate | Staurosporine | Midostaurin | Go 6983 | Bisindolylmaleimide I (GF109203X) | Sotrastaurin | Ro-318220 | Chelerythrine chloride | Enzastaurin (LY317615) | Ruboxistaurin hydrochloride | Beta-Amyloid(1-40) | CGP60474 | Darovasertib (LXS-196) | (-)-Indolactam V | HA-100