VTX-27 (VTX27) is a novel, potent and selective protein kinase C θ (PKC θ) inhibitor with Ki values of 0.08 nM and 16 nM for PKC θ and PKC δ. Protein kinase C θ (PKCθ) has a central role in T cell activation and survival; however, the dependency of T cell responses to the inhibition of this enzyme appears to be dictated by the nature of the antigen and by the inflammatory environment.
Physicochemical Properties
| Molecular Formula | C₂₀H₂₄CLFN₆O |
| Molecular Weight | 418.90 |
| Exact Mass | 418.168 |
| CAS # | 1321924-70-2 |
| PubChem CID | 53354074 |
| Appearance | White to off-white solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 625.8±55.0 °C at 760 mmHg |
| Flash Point | 332.3±31.5 °C |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.624 |
| LogP | 2.48 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 29 |
| Complexity | 573 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC(C)[C@](C)([C@@H]1CN(CCN1)C2=C(C=C(C(=N2)C3=C4C=CC=NC4=NN3)F)Cl)O |
| InChi Key | HXWARSZQGAFXJM-MGPUTAFESA-N |
| InChi Code | InChI=1S/C20H24ClFN6O/c1-11(2)20(3,29)15-10-28(8-7-23-15)19-13(21)9-14(22)17(25-19)16-12-5-4-6-24-18(12)27-26-16/h4-6,9,11,15,23,29H,7-8,10H2,1-3H3,(H,24,26,27)/t15-,20+/m0/s1 |
| Chemical Name | (2R)-2-[(2S)-4-[3-chloro-5-fluoro-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)pyridin-2-yl]piperazin-2-yl]-3-methylbutan-2-ol |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | VTX-27 (compound 27) exhibits outstanding comprehensive properties. Other PKC family members are likewise selectively bound by VTX-27, particularly classical isoforms (>1000-fold, with the exception of PKCβI, 200-fold) and atypical isoforms (>10000-fold). As anticipated, it proved more difficult to achieve 200-fold selectivity over PKC delta for the more closely related new PKC family members [1]. |
| ln Vivo | VTX-27 exhibited ideal pharmacological characteristics, including a long half-life (4.7 hours), low clearance (7 mL min-1 kg-1), and good oral bioavailability (65%). Single doses of VTX-27 showed strong dose-dependent suppression of IL-2 production when given orally at 6.25, 12.5, 25, and 50 mg/kg (e.g., 25 mg/kg Cmax concentration 700 ng/mL) [1]. |
| References |
[1]. 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~298.40 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3872 mL | 11.9360 mL | 23.8720 mL | |
| 5 mM | 0.4774 mL | 2.3872 mL | 4.7744 mL | |
| 10 mM | 0.2387 mL | 1.1936 mL | 2.3872 mL |