Drug Information

Drug (ID: DG01534) and It's Reported Resistant Information
Name
AZD-8330
Synonyms
AZD8330; 869357-68-6; AZD-8330; ARRY-424704; ARRY-704; AZD 8330; 2-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide; UNII-G4990BOZ66; ARRY-424704, ARRY-704; 2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide; G4990BOZ66; 2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxopyridine-3-carboxamide; C16H17FIN3O4; 2-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide.; ARRY 424704; ARRY704; MLS006011055; SCHEMBL388533; GTPL8474; CHEMBL3182621; CHEBI:91424; DTXSID50235986; QCR-188; SYN1195; ARRY424704; BCPP000359; BDBM520648; HMS3295M05; HMS3655B04; AOB87392; BCP02466; EX-A2349; NSC772563; NSC799353; s2134; ZINC43152942; AKOS027420927; BCP9000368; CCG-269348; CS-0217; DB06061; NSC-772563; NSC-799353; ARRY-704, ARRY-424704; NCGC00346567-01; NCGC00346567-12; 2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxopyridine-3-carboxamide; AC-32863; AS-16990; HY-12058; SMR004702847; SW219692-1; US11147816, AZD8330; X7393; AZD8330,ARRY-424704, ARRY-704; AZD8330(ARRY-424704; ARRY-704); J-505617; BRD-K37687095-001-01-0; Q27074802; 2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxyethoxyl)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide; ARRY-424704; ; ; 2-(2-Fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxopyridine-3-carboxamide
    Click to Show/Hide
Indication
In total 1 Indication(s)
Myeloproliferative syndrome [ICD-11: 2A20]
Discontinued in Phase 1
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Target Janus kinase 2 (JAK-2) JAK2_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
6
IsoSMILES
CC1=CC(=C(N(C1=O)C)NC2=C(C=C(C=C2)I)F)C(=O)NOCCO
InChI
InChI=1S/C16H17FIN3O4/c1-9-7-11(15(23)20-25-6-5-22)14(21(2)16(9)24)19-13-4-3-10(18)8-12(13)17/h3-4,7-8,19,22H,5-6H2,1-2H3,(H,20,23)
InChIKey
RWEVIPRMPFNTLO-UHFFFAOYSA-N
PubChem CID
16666708
ChEBI ID
CHEBI:91424
TTD Drug ID
D0MP0X
DrugBank ID
DB06061
Type(s) of Resistant Mechanism of This Drug
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.C121S (c.361T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 7B7R
Mutant Type Structure Method: X-ray diffraction Resolution: 2.01  Å
PDB: 7F2X
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.36
TM score: 0.87257
Amino acid change:
C121S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.F53L (c.157T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.Q56P (c.167A>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K57N (c.171G>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.I111S (c.332T>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.F129L (c.385T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V211D (c.632T>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway
References
Ref 1 Increase in constitutively active MEK1 species by introduction of MEK1 mutations identified in cancersBiochim Biophys Acta Proteins Proteom. 2019 Jan;1867(1):62-70. doi: 10.1016/j.bbapap.2018.05.004. Epub 2018 May 9.

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