JAK-IN-1 is a novel and potent JAK1/2/3 inhibitor with IC50s of 0.26, 0.8 and 3.2 nM, respectively. JAK-IN-1 shows improved selectivity for JAK3 over JAK1.
Physicochemical Properties
| Molecular Formula | C20H24N6O2 |
| Molecular Weight | 380.443563461304 |
| Exact Mass | 380.196 |
| CAS # | 1334673-53-8 |
| PubChem CID | 54589404 |
| Appearance | White to off-white solid powder |
| LogP | 1 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 28 |
| Complexity | 685 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O=C([C@@H](C(C)(C)C)NC(C1=CNC2=C1N=C(C=N2)C1CC1)=O)N1CC(C#N)C1 |
| InChi Key | SIEMFXMJGAMFQR-INIZCTEOSA-N |
| InChi Code | InChI=1S/C20H24N6O2/c1-20(2,3)16(19(28)26-9-11(6-21)10-26)25-18(27)13-7-22-17-15(13)24-14(8-23-17)12-4-5-12/h7-8,11-12,16H,4-5,9-10H2,1-3H3,(H,22,23)(H,25,27)/t16-/m0/s1 |
| Chemical Name | N-[(2R)-1-(3-cyanoazetidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl]-2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide |
| 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 | JAK-IN-1 suppresses the growth of human CD4 and CD8 T cells in a dose-dependent manner following stimulation with anti-CD3/anti-CD28 antibody-coated beads, emulating in part the activation signals that antigen-presenting cells give to T cells. T cells, one of the main cell types for which JAK3 may be important, are used in both cell-based mechanistic and functional experiments where JAK-IN-1 is active [1]. |
| ln Vivo | Greater inhibitory potency for JAK1/JAK3-driven signaling in whole blood assays as opposed to JAK2- or JAK1/JAK2/TYK2-driven signaling indicates that JAK-IN-1 is specific for JAK3 in vivo. JAK-IN-1 dose-dependent inhibition of IL-2-stimulated JAK-IN-1 plasma concentrations was observed. In a dosage- and concentration-dependent manner, JAK-IN-1 inhibits IL-2-driven STAT5 phosphorylation; at a dose of 10 mg/kg (plasma concentration ~480 nM), roughly 50% inhibition is seen [1]. |
| References |
[1]. 3-Amido pyrrolopyrazine JAK kinase inhibitors: development of a JAK3 vs JAK1 selective inhibitor and evaluation in cellular and in vivo models. J Med Chem. 2013 Jan 10;56(1):345-56. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~66.67 mg/mL (~175.24 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.43 mg/mL (3.76 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 14.3 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: ≥ 1.43 mg/mL (3.76 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 14.3 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 | 2.6285 mL | 13.1427 mL | 26.2854 mL | |
| 5 mM | 0.5257 mL | 2.6285 mL | 5.2571 mL | |
| 10 mM | 0.2629 mL | 1.3143 mL | 2.6285 mL |