| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
JAK3 (Janus kinase 3). JAK3-IN-1 also inhibits FLT3, TTK, BLK, and TXK as off-targets. The compound shows very low inhibition scores for other JAKs, EGFRWT (IC₅₀ = 409 nM), and TYK2 (IC₅₀ >10,000 nM). Selectivity over BTK (IC₅₀ = 794 nM) and ITK (IC₅₀ = 1070 nM) is >165-fold.
|
|---|---|
| ln Vitro |
Treatment with JAK3-IN-1 (Compound 9; 0–5 µM; 3 hours; BMDMs cells) totally suppressed p-STAT6 elicited by IL-4 at 500 nM, but only slightly inhibited p-STAT6 induced by IFNβ at 500 nM. p-STAT1 at 5.0μM [1]. ..Several tyrosine-protein kinases (TEC) family kinases and fms-related tyrosine kinase 3 (FLT3) were shown to be possible off-targets of JAK3-IN-1 (compound 9), which most potently inhibited JAK3. The protein enzymatically inhibits the kinase TXK (TXK, IC50 = 36 nM). Enzyme assays employing Z'-lyte or LanthaScreen formats reveal detection of FLT3 (IC50 = 13 nM), TTK protein kinase (TTK, IC50 = 49 nM), BLK proto-oncogene (BLK, IC50 = 157 nM), and tyrosine. JAK3-IN-1 exhibited extremely low fractional inhibition against wild-type (WT) EGFR and other JAKs, which is in line with an IC50 against EGFRWT and TYK2 that is >180 times higher (IC50 = 409 nM and >10000, respectively). JAK3-IN-1 has an IC50 that is more than 165 times greater than that of BTK or ITK (IC50 = 794 and 1070 nM, respectively) [1]. At dosages below 3.0 μM, there is no antiproliferative impact. JAK3-IN-1(Compound 9) specifically inhibits the proliferation of JAK3-dependent Ba/F3 cells (IC50 = 69 nM) contrasted to other JAK-dependent Ba/F3 cells [1].
JAK3-IN-1 inhibits JAK3 with an IC₅₀ of 4.8 nM. It completely inhibits IL-4-induced p-STAT6 at 500 nM and only partially inhibits IFNβ-induced p-STAT1 at 5.0 μM. JAK3-IN-1 selectively inhibits JAK3-dependent Ba/F3 cell proliferation with an IC₅₀ of 69 nM, with no antiproliferative effect below 3.0 μM for other JAK-dependent cells. |
| ln Vivo |
JAK3-IN-1 (compound 9) demonstrated reasonable pharmacokinetic features, with a T1/2 of 1.4 h and an area under the curve (AUC) value of 795 ng*hr/mL after an oral dosage of 10 mg/Kg. Utilization is good at 66%. After oral administration of JAK3-IN-1 (Compound 9) (75 mpk, QD) for 8 days, the number of B or T lymphocytes in the lungs and spleens of tumor-bearing mice was not altered, while NK cells were reduced [1].
JAK3-IN-1 shows reasonable pharmacokinetic properties with moderate T₁/₂ of 1.4 h, AUC of 795 ng·hr/mL following a 10 mg/kg oral dose, and good oral bioavailability of 66%. After oral administration (75 mpk, QD) for 8 days, the numbers of B or T lymphocytes are not affected, but NK cell numbers are reduced. |
| Enzyme Assay |
Kinase enzymatic assay: Recombinant JAK3 kinase is incubated with varying concentrations of JAK3-IN-1, ATP, and a peptide substrate in kinase assay buffer at 30°C for 60 min. The reaction is terminated, and phosphorylation is detected using a Z'-lyte or LanthaScreen format. IC₅₀ values are calculated.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: BMDMs Cell Tested Concentrations: 0 µM, 0.1 µM, 0.5 µM, 1 µM, 5 µM Incubation Duration: 3 hrs (hours) Experimental Results: Complete inhibition of IL-4-induced p-STAT6 concentration at 500 nM At 5.0 μM, it only partially inhibits IFNβ-induced p-STAT1. Cell proliferation assay: JAK3-dependent Ba/F3 cells and other JAK-dependent Ba/F3 cells are seeded in 96-well plates and treated with JAK3-IN-1 at varying concentrations (0.1-1000 nM) for 48-72 hours. Cell viability is measured using CellTiter-Glo or MTT assay. IC₅₀ values for inhibition of proliferation are calculated. |
| Animal Protocol |
Mouse pharmacokinetic study: Mice are administered JAK3-IN-1 at 10 mg/kg via oral gavage. Blood samples are collected at various time points. Plasma concentrations are measured by LC-MS/MS. PK parameters including Cmax, Tmax, AUC, half-life, and oral bioavailability are calculated. Immunomodulation study: Mice receive JAK3-IN-1 at 75 mpk QD for 8 days, and lymphocyte populations in lungs and spleens are analyzed by flow cytometry.
|
| ADME/Pharmacokinetics |
JAK3-IN-1 shows moderate T₁/₂ of 1.4 h, AUC of 795 ng·hr/mL following a 10 mg/kg oral dose, and good oral bioavailability of 66%. Molecular weight is 508.02 g/mol, and molecular formula is C₂₆H₃₀ClN₇O₂. Solubility: DMSO ≥100 mg/mL.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data has been published. JAK3-IN-1 is for research use only. Standard laboratory safety practices should be followed when handling this compound. As a JAK3 inhibitor, potential immunosuppressive effects should be considered.
|
| References | |
| Additional Infomation |
JAK3-IN-1 is a potent, selective, and orally active JAK3 inhibitor with an IC₅₀ of 4.8 nM and >180-fold selectivity over JAK1 and JAK2. It has reasonable PK properties with 66% oral bioavailability and selectively inhibits JAK3-dependent cell proliferation. No clinical trials or approved上市 status have been reported.
|
| Molecular Formula |
C26H30CLN7O2
|
|---|---|
| Molecular Weight |
508.02
|
| Exact Mass |
507.214
|
| CAS # |
1805787-93-2
|
| PubChem CID |
92042864
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Index of Refraction |
1.672
|
| LogP |
2.18
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
36
|
| Complexity |
708
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NCC4=CC(=CC=C4)NC(=O)C=C)Cl)OC
|
| InChi Key |
UGXCBYVBIJACEK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H30ClN7O2/c1-4-24(35)30-19-7-5-6-18(14-19)16-28-25-21(27)17-29-26(32-25)31-22-9-8-20(15-23(22)36-3)34-12-10-33(2)11-13-34/h4-9,14-15,17H,1,10-13,16H2,2-3H3,(H,30,35)(H2,28,29,31,32)
|
| Chemical Name |
N-[3-[[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide
|
| Synonyms |
JAK3 IN 1 JAK3IN1 JAK3-IN-1
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~196.84 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.92 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 25.0 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: 2.5 mg/mL (4.92 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9684 mL | 9.8421 mL | 19.6843 mL | |
| 5 mM | 0.3937 mL | 1.9684 mL | 3.9369 mL | |
| 10 mM | 0.1968 mL | 0.9842 mL | 1.9684 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
