Drug Information

Drug (ID: DG01578) and It's Reported Resistant Information

• Name: NS-018
• Synonyms: NS-018; ilginatinib; 1239358-86-1; UNII-56R994WX4L; 56R994WX4L; 6-N-[(1S)-1-(4-fluorophenyl)ethyl]-4-(1-methylpyrazol-4-yl)-2-N-pyrazin-2-ylpyridine-2,6-diamine; (S)-N2-(1-(4-fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2-yl)pyridine-2,6-diamine; (S)-N2-[1-(4-fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2-yl)pyridine-2,6-diamine; GTPL7839; CHEMBL4303389; SCHEMBL14954406; NS018; HY-19631A; NS-018NS-018; ZINC68245917; CS-5358; DB12784; A922051; Q27088043; (S)-N-(1-(4-Fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N'-(pyrazin-2-yl)pyridine-2,6-diamine; (S)-N2-[1-(4-fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2yl)pyridine-2,6-diamine; 2,6-Pyridinediamine, N2-((1S)-1-(4-fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N6-2-pyrazinyl-; N2-[(1S)-1-(4-Fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2-yl)pyridine-2,6-diamine
• Indication:
  In total 1 Indication(s)
  Chronic myelogenous leukaemia [ICD-11: 2A20]; Phase 1/2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [1]
• Target: Tyrosine-protein kinase ABL1 (ABL); ABL1_HUMAN; [1]
• Formula: 6
• IsoSMILES: C[C@@H](C1=CC=C(C=C1)F)NC2=CC(=CC(=N2)NC3=NC=CN=C3)C4=CN(N=C4)C
• InChI: 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
• InChIKey: UQTPDWDAYHAZNT-AWEZNQCLSA-N
• PubChem CID: 46866319
• TTD Drug ID: D06JHV
• DrugBank ID: DB12784

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [1]

• Molecule Alteration: Missense mutation; p.A572V (c.1715C>T)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Sf9 cells; Ovary; Homo sapiens (Human); CVCL_0549
• Experiment for Molecule Alteration: Colony formation assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.A572V (c.1715C>T) in gene JAK3 cause the resistance of NS-018 by aberration of the drug's therapeutic target

Hematologic cancer [ICD-11: 2B3Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [1]

• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Sf9 cells; Ovary; Homo sapiens (Human); CVCL_0549
• Experiment for Molecule Alteration: Colony formation assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.V617F (c.1849G>T) in gene JAK2 cause the sensitivity of NS-018 by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Thrombopoietin receptor (TPOR) [1]

• Molecule Alteration: Missense mutation; p.W515L (c.1544G>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Sf9 cells; Ovary; Homo sapiens (Human); CVCL_0549
• Experiment for Molecule Alteration: Colony formation assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.W515L (c.1544G>T) in gene MPL cause the sensitivity of NS-018 by unusual activation of pro-survival pathway

References

• Ref 1: Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasmsBlood Cancer J. 2011 Jul;1(7):e29. doi: 10.1038/bcj.2011.29. Epub 2011 Jul 22.