ILGINATINIB MALEATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H20FN7.C4H4O4
Molecular Weight	505.501
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.C[C@H](NC1=NC(NC2=NC=CN=C2)=CC(=C1)C3=CN(C)N=C3)C4=CC=C(F)C=C4

InChI

InChIKey=OVAGJAAQMBYZDS-FXSDFHGDSA-N

InChI=1S/C21H20FN7.C4H4O4/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;5-3(6)1-2-4(7)8/h3-14H,1-2H3,(H2,24,26,27,28);1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C21H20FN7
Molecular Weight	389.4288
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://adisinsight.springer.com/drugs/800034177 | https://www.ncbi.nlm.nih.gov/pubmed/22829185 | https://www.ncbi.nlm.nih.gov/pubmed/27479177

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829185	Inhibitor 8297	0.72 nM [IC50]
Tyrosine-protein kinase TYK2 16 Target ID: CHEMBL3553 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829185	Inhibitor 8297	22.0 nM [IC50]
Tyrosine-protein kinase JAK1 38 Target ID: CHEMBL2835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829185	Inhibitor 8297	33.0 nM [IC50]
Tyrosine-protein kinase JAK3 27 Target ID: CHEMBL2148 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829185	Inhibitor 8297	39.0 nM [IC50]

PubMed

Title	Date	PubMed
Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.	2011 Jul	22829185
Effect of NS-018, a selective JAK2V617F inhibitor, in a murine model of myelofibrosis.	2014 Jan 10	24413068

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 Dec 16 11:12:30 UTC 2023` Edited by `admin` on `Sat Dec 16 11:12:30 UTC 2023`
Record UNII	8P0KTT2T1Z
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ILGINATINIB MALEATE

Common Name

English

NS-018 MALEATE

Common Name

English

N-[(1S)-1-(4- fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)-N'-(pyrazin-2-yl)pyridine-2,6-diamine maleate

Systematic Name

English

2,6-PYRIDINEDIAMINE, N2-((1S)-1-(4-FLUOROPHENYL)ETHYL)-4-(1-METHYL-1H-PYRAZOL-4-YL)-N6-2-PYRAZINYL-, (2Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

(S)-N-(1-(4-FLUOROPHENYL)ETHYL)-4-(1-METHYL-1H-PYRAZOL-4-YL)-N'-(PYRAZIN-2-YL)PYRIDINE-2,6-DIAMINE MALEATE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

916522