NS-018

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205861

CAS#: 1239358-86-1 (free base)

Description: NS-018 is an orally bioavailable, small molecule inhibitor of Janus-associated kinase 2 (JAK2) and Src-family kinases, with potential antineoplastic activity. 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.


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10mg
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100mg
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1g
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25mg
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200mg
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2g
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50mg
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500mg
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5g
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NS-018 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205861
Name: NS-018
CAS#: 1239358-86-1 (free base)
Chemical Formula: C21H20FN7
Exact Mass: 389.17642
Molecular Weight: 389.43
Elemental Analysis: C, 64.77; H, 5.18; F, 4.88; N, 25.18


Related CAS #: 1239358-86-1 (free base)   1239358-85-0 (HCl)   1354799-87-3 (maleate)    

Synonym: NS018; NS-018; NS 018.

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


Technical Data

Appearance:
Solid powder

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).

Harmonized System Code:
293490


Additional Information

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).   
 
 
 


References

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.