| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Ilginatinib (NS018; NS-018) is an orally bioavailable, small molecule inhibitor of Janus-associated kinase 2 (JAK2) and Src-family kinases, with potential antineoplastic activity. It inhibits JAK2 with an IC50 of 0.72 nM, and exhibits 46-, 54-, and 31-fold selectivity for JAK2 over JAK1 (IC50, 33 nM), JAK3 (IC50, 39 nM), and Tyk2 (IC50, 22 nM). JAK2/Src inhibitor NS-018 competes with ATP for binding to JAK2 as well as the mutated form JAK2V617F, thereby inhibiting the activation of JAK2 and downstream molecules in the JAK2/STAT3 (signal transducer and activator of transcription 3) signaling pathway that plays an important role in normal development, particularly hematopoiesis. In addition, NS-018 inhibits the Src family tyrosine kinases. This eventually leads to the induction of tumor cell apoptosis.
| Targets |
|
|
|---|---|---|
| ln Vitro |
Ilginatinib (NS-018) is a very potent JAK2 inhibitor, showing 46, 54, and 31-fold selectivity for JAK2 over JAK1 (IC50, 33 nM), JAK3 (IC50, 39 nM), and Tyk2 (IC50, 22 nM). Its IC50 is 0.72 nM. Along with mildly inhibiting ABL and FLT3 with 45- and 90-fold selectivity for JAK2, ignitinib (NS-018) also inhibits Src-family kinases, namely SRC and FYN. When it comes to cell lines with mutations in JAK2V617F or MPLW515L, or the TEL-JAK2 fusion gene that expresses a constitutively activated JAK2, NS-018 exhibits potent inhibitory activity with an IC50 of 11-120 nM. However, its cytotoxicity against the majority of other hematopoietic cell lines that lack constitutively activated JAK2 is minimal[1]. When obtained from bone marrow mononuclear cells (BMMNCs) of patients with myelodysplastic syndrome (MDS), ilginatinib (NS-018) (0.5 μM) preferentially reduces the development of colony-forming units, granulocyte/macrophages (CFU-GM). MDS patients' CFU-GM-forming cells show suppression of the phosphorylation of STAT3, the downstream kinase of JAK2, when exposed to ignitinib (NS-018) at a concentration of 1 μM.
|
|
| ln Vivo |
In a mouse Ba/F3-JAK2V617F illness model, ilginatinib (NS-018) (12.5, 25, 50, 100 mg/kg, po) potently prolongs animal survival and decreases splenomegaly[1]. In JAK2V617F transgenic mice, ilginatinib (NS-018) (25, 50 mg/kg, po) dramatically lowers leukocytosis, hepatosplenomegaly, and extramedullary hematopoiesis, enhances nutritional status, and increases survival time.
|
|
| Cell Assay |
|
|
| Animal Protocol |
|
|
| References |
|
|
| Additional Infomation |
NS-018 has been used in trials studying the treatment of Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, and Post-Essential Thrombocythemia Myelofibrosis.
Ilginatinib is an orally bioavailable, small molecule inhibitor of Janus-associated kinase 2 (JAK2) and Src-family kinases, with potential antineoplastic activity. Ilginatinib competes with ATP for binding to JAK2 as well as the mutated form JAK2V617F, thereby inhibiting the activation of JAK2 and downstream molecules in the JAK2/STAT3 (signal transducer and activator of transcription 3) signaling pathway that plays an important role in normal development, particularly hematopoiesis. In addition, ilginatinib inhibits the Src family tyrosine kinases. This eventually leads to the induction of tumor cell apoptosis. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders (MPDs); JAK2V617F is a constitutively activated kinase that activates the JAK/STAT signaling pathway and dysregulates cell growth and function, and its expression transforms hematopoietic cells to cytokine-independent growth. |
| Molecular Formula |
C21H20FN7
|
|---|---|
| Molecular Weight |
389.4288
|
| Exact Mass |
389.176
|
| CAS # |
1239358-86-1
|
| Related CAS # |
Ilginatinib maleate;1354799-87-3;Ilginatinib hydrochloride;1239358-85-0
|
| PubChem CID |
46866319
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
586.8±60.0 °C at 760 mmHg
|
| Flash Point |
308.7±32.9 °C
|
| Vapour Pressure |
0.0±1.6 mmHg at 25°C
|
| Index of Refraction |
1.671
|
| LogP |
2.66
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
29
|
| Complexity |
501
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@@H](C1=CC=C(C=C1)F)NC2=CC(=CC(=N2)NC3=NC=CN=C3)C4=CN(N=C4)C
|
| InChi Key |
UQTPDWDAYHAZNT-AWEZNQCLSA-N
|
| InChi Code |
InChI=1S/C21H20FN7/c1-14(15-3-5-18(22)6-4-15)26-19-9-16(17-11-25-29(2)13-17)10-20(27-19)28-21-12-23-7-8-24-21/h3-14H,1-2H3,(H2,24,26,27,28)/t14-/m0/s1
|
| Chemical Name |
6-N-[(1S)-1-(4-fluorophenyl)ethyl]-4-(1-methylpyrazol-4-yl)-2-N-pyrazin-2-ylpyridine-2,6-diamine
|
| 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 (~256.79 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.42 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 (6.42 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 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 (6.42 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 | 2.5679 mL | 12.8393 mL | 25.6786 mL | |
| 5 mM | 0.5136 mL | 2.5679 mL | 5.1357 mL | |
| 10 mM | 0.2568 mL | 1.2839 mL | 2.5679 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
