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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H20FN7
Molecular Weight 389.4296
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ILGINATINIB

SMILES

C[C@@]([H])(c1ccc(cc1)F)N=c2cc(cc([nH]2)N=c3cncc[nH]3)-c4cnn(C)c4

InChI

InChIKey=UQTPDWDAYHAZNT-AWEZNQCLSA-N
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

HIDE SMILES / InChI

Molecular Formula C21H20FN7
Molecular Weight 389.4296
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

NS-018 is a potent inhibitor of Janus kinase 2 (JAK2) enzyme activity and Src-family kinases. It was developed as an oral therapy for the treatment of myelofibrosis. Overall NS-018 has been used in trials studying the treatment of primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia. NS-018 is a highly active JAK2 inhibitor, with an IC50 of 0.72 nM, 46-, 54-, and 31-fold selectivity for JAK2 over JAK1 (IC50, 33 nM), JAK3 (IC50, 39 nM), and Tyk2 (IC50, 22 nM). NS-018 also inhibits Src-family kinases, especially SRC and FYN, and weakly inhibits ABL and FLT3 with 45- and 90-fold selectivity for JAK2, respectively. NS-018 shows potent inhibitory activity against cell lines JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.72 nM [IC50]
22.0 nM [IC50]
33.0 nM [IC50]
39.0 nM [IC50]
PubMed

PubMed

TitleDatePubMed
Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.
2011 Jul
Effect of NS-018, a selective JAK2V617F inhibitor, in a murine model of myelofibrosis.
2014 Jan 10
Patents

Sample Use Guides

In this phase I, dose-escalation portion of a phase I/II study, patients with myelofibrosis received oral NS-018 in continuous 28-day cycles. Once daily NS-018 at 300 mg was chosen as the phase II study dose based on improved tolerability compared with higher doses.
Route of Administration: Oral
NS-018 is a highly active JAK2 inhibitor, with an IC50 of 0.72 nM, 46-, 54-, and 31-fold selectivity for JAK2 over JAK1 (IC50, 33 nM), JAK3 (IC50, 39 nM), and Tyk2 (IC50, 22 nM). NS-018 shows potent inhibitory activity against cell lines JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene (expressing a constitutively activated JAK2) with IC50 of 11-120 nM, but has only minimal cytotoxicity against most other hematopoietic cell lines that have no constitutively activated JAK2.
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:13:51 UTC 2021
Edited
by admin
on Sat Jun 26 02:13:51 UTC 2021
Record UNII
56R994WX4L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ILGINATINIB
INN  
Official Name English
NS-018
Code English
ILGINATINIB [INN]
Common Name English
2,6-PYRIDINEDIAMINE, N2-((1S)-1-(4-FLUOROPHENYL)ETHYL)-4-(1-METHYL-1H-PYRAZOL-4-YL)-N6-2-PYRAZINYL-
Systematic Name English
(S)-N-(1-(4-FLUOROPHENYL)ETHYL)-4-(1-METHYL-1H-PYRAZOL-4-YL)-N'-(PYRAZIN-2-YL)PYRIDINE-2,6-DIAMINE
Systematic Name English
Code System Code Type Description
FDA UNII
56R994WX4L
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
PRIMARY
NCI_THESAURUS
C98109
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
PRIMARY
CAS
1239358-86-1
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
PRIMARY
INN
10731
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
PRIMARY
CAS
1526932-96-6
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
NO STRUCTURE GIVEN
ChEMBL
CHEMBL3545217
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
PRIMARY
DRUG BANK
DB12784
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
PRIMARY
PUBCHEM
46866319
Created by admin on Sat Jun 26 02:13:52 UTC 2021 , Edited by admin on Sat Jun 26 02:13:52 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY