Synonym
NS018; NS-018; NS 018; Ilginatinib free base;
IUPAC/Chemical Name
(S)-N2-(1-(4-fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2-yl)pyridine-2,6-diamine
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
SMILES Code
CN1N=CC(C2=CC(N[C@H](C3=CC=C(F)C=C3)C)=NC(NC4=NC=CN=C4)=C2)=C1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
NS-018 was highly active against JAK2 with a 50% inhibition (IC50) of <1 nM, and had 30–50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL–JAK2 fusion gene; IC50=11–120 nM), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs. (source: Blood Cancer Journal (2011) 1, e29; doi:10.1038/bcj.2011.29).
Preparing Stock Solutions
The following data is based on the
product
molecular weight
389.43
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
1: Rosenthal A, Mesa RA. Janus kinase inhibitors for the treatment of myeloproliferative neoplasms. Expert Opin Pharmacother. 2014 Jun;15(9):1265-76. doi: 10.1517/14656566.2014.913024. Epub 2014 Apr 25. Review. PubMed PMID: 24766055.
2: Kuroda J, Kodama A, Chinen Y, Shimura Y, Mizutani S, Nagoshi H, Kobayashi T, Matsumoto Y, Nakaya Y, Tamura A, Kobayashi Y, Naito H, Taniwaki M. NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients. Leuk Res. 2014 May;38(5):619-24. doi: 10.1016/j.leukres.2014.03.001. Epub 2014 Mar 11. PubMed PMID: 24679585.
3: Nakaya Y, Shide K, Naito H, Niwa T, Horio T, Miyake J, Shimoda K. Effect of NS-018, a selective JAK2V617F inhibitor, in a murine model of myelofibrosis. Blood Cancer J. 2014 Jan 10;4:e174. doi: 10.1038/bcj.2013.73. PubMed PMID: 24413068; PubMed Central PMCID: PMC3913942.
4: Furqan M, Mukhi N, Lee B, Liu D. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomark Res. 2013 Jan 16;1(1):5. doi: 10.1186/2050-7771-1-5. PubMed PMID: 24252238; PubMed Central PMCID: PMC3776247.
5: Tam CS, Verstovsek S. Investigational Janus kinase inhibitors. Expert Opin Investig Drugs. 2013 Jun;22(6):687-99. doi: 10.1517/13543784.2013.774373. Epub 2013 Feb 23. Review. PubMed PMID: 23432430.
6: Nakaya Y, Shide K, Niwa T, Homan J, Sugahara S, Horio T, Kuramoto K, Kotera T, Shibayama H, Hori K, Naito H, Shimoda K. Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms. Blood Cancer J. 2011 Jul;1(7):e29. doi: 10.1038/bcj.2011.29. Epub 2011 Jul 22. PubMed PMID: 22829185; PubMed Central PMCID: PMC3255248.
