1321924-70-2

1321924-70-2 structure

Name: VTX-27
Chemical Name: (R)-2-((S)-4-(3-chloro-5-fluoro-6-(1H-pyrazolo[3,4-b]pyridin-3-yl)pyridin-2-yl)piperazin-2-yl)-3-methylbutan-2-ol
CAS Number: 1321924-70-2
Molecular Formula: C₂₀H₂₄ClFN₆O
Molecular Weight: 418.896
Catalog: Signaling Pathways Epigenetics PKC
Create Date: 2018-01-31 00:10:31
Modify Date: 2024-01-23 16:13:23
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.

Name	(R)-2-((S)-4-(3-chloro-5-fluoro-6-(1H-pyrazolo[3,4-b]pyridin-3-yl)pyridin-2-yl)piperazin-2-yl)-3-methylbutan-2-ol
Synonyms	(2R)-2-{(2S)-4-[3-Chloro-5-fluoro-6-(1H-pyrazolo[3,4-b]pyridin-3-yl)-2-pyridinyl]-2-piperazinyl}-3-methyl-2-butanol 2-Piperazinemethanol, 4-[3-chloro-5-fluoro-6-(1H-pyrazolo[3,4-b]pyridin-3-yl)-2-pyridinyl]-α-methyl-α-(1-methylethyl)-, (αR,2S)-

Description	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.
Related Catalog	Signaling Pathways >> Epigenetics >> PKC Signaling Pathways >> TGF-beta/Smad >> PKC Research Areas >> Inflammation/Immunology
Target	PKCθ:0.08 nM (Ki) PKCδ:16 nM (Ki) PKCα:356 nM (Ki)
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 Cmax concentration 700 ng/mL) and demonstrates potent dose dependent inhibition of IL-2 production[1].
References	[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.