| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 10mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
The primary targets of JAK3 Inhibitor VI are Janus kinase 3 (JAK3) and FMS-like tyrosine kinase 3 (FLT3). JAK3 is a non-receptor Janus tyrosine kinase that regulates various cellular functions downstream of activated cytokine receptors in the lymphohematopoietic system. It plays a critical role in immune cell signaling and is a validated target for autoimmune diseases and transplant rejection. JAK3 Inhibitor VI acts as a potent and reversible inhibitor of JAK3 with an IC50 of 27 nM. The compound also inhibits FLT3, a receptor tyrosine kinase involved in hematopoietic cell proliferation, with activity against both wild-type and mutant forms.
|
|---|---|
| ln Vitro |
JI6 (3-1000 nM; 1-4 days) has an IC50 value of around 25 nM and reduces MV4-11 cell viability in a suspended dosage manner [1]. JI6 (1-2000 nM; 48 h) is generally ineffective against parental HCD-57 or cells expressing JAK2V617F, but it effectively suspends the viability of HCD-57 cells expressing FLT3-ITD, FLT3-D835Y, and FLT3-D835H, with an IC50 value of ∼40 nM. Not at all[1]. HCD-57 cells and cell cycle marketing are used to induce JI6 (100-500 nM; 24 h) JI6 (50-500 nM; 3 h) GFP FLT3-ITD and FLT3-D835Y[1].
In vitro, JAK3 Inhibitor VI inhibits JAK3 kinase activity with an IC50 of 27 nM. It displays approximately 16-fold greater selectivity over JAK2. The compound also inhibits FLT3-WT, FLT3-D835Y, and FLT3-D835H with IC50 values of approximately 40, 8, and 4 nM, respectively. JAK3 Inhibitor VI exhibits inhibitory activity against c-Kit with an IC50 of approximately 500 nM. As a cell-permeable compound, it can effectively enter cells and interact with intracellular targets. |
| ln Vivo |
JI6 (15 mg/kg; ip daily for 3 weeks) suppresses the proliferation and prolongs the duration of mold in HCD-57 expressing FLT3-D835Y within immunodeficient microarrays [1]. JI6 (25 mg/kg; po daily for 3 weeks) JI6 (100 mg/kg; a single ip) effectively suppresses FLT3 phosphorylation and downstream signaling in clocks expressing FLT3-D835Y [ ) Inhibition of FLT3- Ischemic potential phenotype of ITD knock-in mice [1].
In vivo, JAK3 Inhibitor VI is being studied in preclinical research for its ability to modulate immune responses and reduce disease activity in conditions such as rheumatoid arthritis, psoriasis, and graft-versus-host disease. As a JAK3 inhibitor, it would be expected to suppress cytokine signaling and immune cell activation in vivo. Its anti-AML activity suggests potential efficacy in leukemia models. However, specific in vivo efficacy data from animal models is not detailed in the available sources. |
| Enzyme Assay |
For JAK3 and FLT3 inhibitors, standard cell-free assays involve measuring the kinase activity of recombinant JAK3 or FLT3 enzymes using peptide substrates. The compound is incubated with the enzyme, ATP, and substrate, and phosphorylation is detected by radioactive (³³P-ATP) or fluorescent methods to determine IC50 values. Selectivity is assessed by profiling against a panel of kinases.
|
| Cell Assay |
Cell viability assay[1] cells Lines: MV4-11, HL60, Karpas 299 and Jurkat cells
Tested Concentrations: 3-1000 nM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited phosphorylation of FLT3 and ERK and Akt in 57 cells [1]. MV4-11 cells at concentrations up to JI6 at 1 μM had no effect on the remaining three cells. Apoptosis analysis[1] Cell Types: FLT3-ITD and FLT3-D835Y transformed HCD-57 cells Tested Concentrations: 100, 500 nM Incubation Duration: 24 hrs (hours) Experimental Results: Apoptosis and increased percentage of necrotic cells, with no effect on apoptosis of parental HCD-57 cells. Cell cycle analysis [1] Cell Types: FLT3-ITD and FLT3-D835Y Transformed HCD-57 cells Tested Concentrations: 100, 500 nM Incubation Duration: 24 hrs (hours) Experimental Results: G2 and S phase cells diminished Dramatically, G1 phase cells increased FLT3-ITD and D835Y cells. Cell viability assay [1] Cell Types: FLT3-ITD and FLT3-D835Y transformed HCD-57 cells Tested Concentrations: 50, 100, 500 nM Incubation Duration: 3 hrs (hours) Experimental Results: Phosphorylation of FLT3, ERK1, ERK2, and Akt was inhi For JAK3 and FLT3 inhibitors, standard cellular assays involve treatment of leukemia cell lines or immune cells with the test compound for 24-72 hours. JAK3/STAT5 or FLT3 signaling is assessed by measuring phosphorylation of downstream targets (e.g., STAT5, ERK) by western blot. Cell viability (MTT or CellTiter-Glo) and proliferation are assessed. Apoptosis is measured by Annexin V/PI staining. |
| Animal Protocol |
Animal/Disease Models: NSG mice (10-12 weeks old, male) were implanted with FLT3-D835Y transformed HCD-57 cells [1]
Doses: 15 mg/kg Route of Administration: daily intraperitoneal (ip) injection for 3 weeks Experimental Results: spleen diminished size and extended the survival time of these mice. For in vivo evaluation of JAK3 and FLT3 inhibitors, standard animal models include tumor xenograft models of AML and autoimmune disease models. The compound is typically administered orally or intraperitoneally for 2-4 weeks. Tumor growth, immune cell populations, cytokine levels, and disease severity are assessed. |
| ADME/Pharmacokinetics |
JAK3 Inhibitor VI has a molecular weight of 383.42 and formula C18H13N3O•CH3SO3H (mesylate salt). As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability and oral bioavailability. The compound is cell-permeable, indicating good cellular penetration. Comprehensive pharmacokinetic studies would be required for therapeutic development.
|
| Toxicity/Toxicokinetics |
Detailed toxicology data for JAK3 Inhibitor VI is not provided in the available sources. As a research compound targeting JAK3 and FLT3, standard preclinical toxicology would be required for therapeutic development. The compound's inhibition of multiple kinases (JAK3, FLT3, c-Kit) suggests potential for both therapeutic effects and off-target toxicities that would need to be carefully evaluated. The compound is for research use only and not for therapeutic applications.
|
| References | |
| Additional Infomation |
5-(3-pyridyl)-3-(1H-pyrrolo-2-ylmethylene)-1H-indole-2-one is a member of the indole class of compounds.
JAK3 Inhibitor VI is also known as JI6 and has the chemical name (3Z)-5-(pyridin-3-yl)-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one. It is a cell-permeable 3'-pyridyl oxindole compound that acts as a potent and reversible inhibitor of JAK3 (IC50 = 27 nM) with ~16-fold selectivity over JAK2. The compound also inhibits FLT3 with IC50 values of ~40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. No regulatory approval has been identified. |
| Molecular Formula |
C19H17N3O4S
|
|---|---|
| Molecular Weight |
383.42
|
| Exact Mass |
383.094
|
| CAS # |
856436-16-3
|
| PubChem CID |
9947841
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.292
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
22
|
| Complexity |
461
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CS(=O)(=O)O.C1=CC(=CN=C1)C2=CC3=C(C=C2)NC(=O)C3=CC4=CC=CN4
|
| InChi Key |
IQNTXIMXKCURDC-YBEGLDIGSA-N
|
| InChi Code |
InChI=1S/C18H13N3O/c22-18-16(10-14-4-2-8-20-14)15-9-12(5-6-17(15)21-18)13-3-1-7-19-11-13/h1-11,20H,(H,21,22)/b16-10-
|
| Chemical Name |
(3Z)-5-pyridin-3-yl-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one
|
| Synonyms |
JAK 3 Inhibitor VI JAK-3 Inhibitor VI JAK3 Inhibitor VI
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6081 mL | 13.0405 mL | 26.0811 mL | |
| 5 mM | 0.5216 mL | 2.6081 mL | 5.2162 mL | |
| 10 mM | 0.2608 mL | 1.3041 mL | 2.6081 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
