Drug Information

Drug (ID: DG01599) and It's Reported Resistant Information
Name
Altiratinib
Synonyms
Altiratinib; 1345847-93-9; DCC-2701; DP-5164; Altiratinib [USAN]; UNII-T678746713; Altiratinib (USAN); 1,1-Cyclopropanedicarboxamide, N-[4-[[2-[(cyclopropylcarbonyl)amino]-4-pyridinyl]oxy]-2,5-difluorophenyl]-N'-(4-fluorophenyl)-; T678746713; 1,1-Cyclopropanedicarboxamide, N-(4-((2-((cyclopropylcarbonyl)amino)-4-pyridinyl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)-; 1-N'-[4-[2-(cyclopropanecarbonylamino)pyridin-4-yl]oxy-2,5-difluorophenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.; N-[4-[[2-[(Cyclopropylcarbonyl)amino]-4-pyridinyl]oxy]-2,5-difluorophenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide; Altiratinib;DCC2701; Altiratinib(DCC-2701); SCHEMBL139906; GTPL9174; CHEMBL3545365; DCC-270; DCC2701; EX-A902; AOB87118; BCP15682; HY-B0791; BDBM50193395; MFCD28900672; NSC784590; s6412; AKOS026750329; ZINC113198271; CS-3944; NSC-784590; SB18876; NCGC00480913-04; N-(4-((2-((Cyclopropylcarbonyl)amino)pyridin-4-yl)oxy)-2,5-difluorophenyi)-N-(4- fluorophenyl)cyclopropane-1,1-dicarboxamide; B5832; FT-0700171; A14387; D10862; F11464; A887875; J-690136; Q27074416; 1,1-CYCLOPROPANEDICARBOXAMIDE, N-[4-[[2-[(CYCLOPROPYLCARBONYL)AMINO]-4-PYRIDINYL]OXY]-2,5-DIFLUOROPHENYL]-N-(4-FLUOROPHENYL)-; 4-{5-[(E)-2-{4-(2-Chlorophenyl)-5-[5-(methylsulfonyl)-2-pyridinyl]-4H-1,2,4-triazol-3-yl}vinyl]-1,3,4-oxadiazol-2-yl}benzonitrile; N-(4-(2-(cyclopropanecarboxamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
    Click to Show/Hide
Indication
In total 2 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Investigative
[1]
Structure
Target Vascular endothelial growth factor receptor 2 (KDR) VGFR2_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
8
IsoSMILES
C1CC1C(=O)NC2=NC=CC(=C2)OC3=C(C=C(C(=C3)F)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F)F
InChI
InChI=1S/C26H21F3N4O4/c27-15-3-5-16(6-4-15)31-24(35)26(8-9-26)25(36)32-20-12-19(29)21(13-18(20)28)37-17-7-10-30-22(11-17)33-23(34)14-1-2-14/h3-7,10-14H,1-2,8-9H2,(H,31,35)(H,32,36)(H,30,33,34)
InChIKey
GNNDEPIMDAZHRQ-UHFFFAOYSA-N
PubChem CID
54576299
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  RTDM: Regulation by the Disease Microenvironment
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 Sensitivity Data Categorized by Their Corresponding Mechanisms
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.Y1230H (c.3688T>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.71  Å
PDB: 5HNI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.97  Å
PDB: 5HLW
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.65
TM score: 0.96625
Amino acid change:
Y1230H
 : 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 A549 cells Lung Homo sapiens (Human) CVCL_0023
A375 cells Skin Homo sapiens (Human) CVCL_0132
THP-1 cells Blood Homo sapiens (Human) CVCL_0006
K562 cells Blood Homo sapiens (Human) CVCL_0004
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
Sk-N-SH cells Adrenal Homo sapiens (Human) CVCL_0531
HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
EBC-1 cells Lung Homo sapiens (Human) CVCL_2891
MRC-5 cells Lung Homo sapiens (Human) CVCL_0440
PC-3 cells Prostate Homo sapiens (Human) CVCL_0035
HUVEC cells Endothelium Homo sapiens (Human) N.A.
HUVEC cells Endothelium Homo sapiens (Human) N.A.
U87-MG cells Brain Homo sapiens (Human) CVCL_0022
SkMEL5 cells Skin Homo sapiens (Human) CVCL_0527
SkMEL28 cells Skin Homo sapiens (Human) CVCL_0526
MV-4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
M-NFS-60 cells Blood Mus musculus (Mouse) CVCL_3543
KM-12 cells Colon Homo sapiens (Human) CVCL_1331
HMVEC cells Blood vessel Homo sapiens (Human) N.A.
EAhy926 cells N.A. Homo sapiens (Human) CVCL_3901
CHO-K cells Ovary Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus) CVCL_0213
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
B16/F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Mouse xenograft efficacy model; MKN-45 xenograft mouse pharmacokinetic/pharmacodynamic model; Orthotopic U87-MG xenograft efficacy model; Orthotopic U87-MG xenograft survival model; PyMT syngeneic breast cancer model Mus musculus
Experiment for
Molecule Alteration		 Enzyme-linked immunosorbent assay; Western blot analysis
Experiment for
Drug Resistance		 Resazurin cell viability assay
Key Molecule: Hepatocyte growth factor receptor (MET) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.M1250T (c.3749T>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.71  Å
PDB: 5HNI
Mutant Type Structure Method: X-ray diffraction Resolution: 2.20  Å
PDB: 5HOR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.55
TM score: 0.98376
Amino acid change:
M1250T
 : 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 A549 cells Lung Homo sapiens (Human) CVCL_0023
A375 cells Skin Homo sapiens (Human) CVCL_0132
THP-1 cells Blood Homo sapiens (Human) CVCL_0006
K562 cells Blood Homo sapiens (Human) CVCL_0004
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
Sk-N-SH cells Adrenal Homo sapiens (Human) CVCL_0531
HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
EBC-1 cells Lung Homo sapiens (Human) CVCL_2891
MRC-5 cells Lung Homo sapiens (Human) CVCL_0440
PC-3 cells Prostate Homo sapiens (Human) CVCL_0035
HUVEC cells Endothelium Homo sapiens (Human) N.A.
HUVEC cells Endothelium Homo sapiens (Human) N.A.
U87-MG cells Brain Homo sapiens (Human) CVCL_0022
SkMEL5 cells Skin Homo sapiens (Human) CVCL_0527
SkMEL28 cells Skin Homo sapiens (Human) CVCL_0526
MV-4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
M-NFS-60 cells Blood Mus musculus (Mouse) CVCL_3543
KM-12 cells Colon Homo sapiens (Human) CVCL_1331
HMVEC cells Blood vessel Homo sapiens (Human) N.A.
EAhy926 cells N.A. Homo sapiens (Human) CVCL_3901
CHO-K cells Ovary Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus) CVCL_0213
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
B16/F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Mouse xenograft efficacy model; MKN-45 xenograft mouse pharmacokinetic/pharmacodynamic model; Orthotopic U87-MG xenograft efficacy model; Orthotopic U87-MG xenograft survival model; PyMT syngeneic breast cancer model Mus musculus
Experiment for
Molecule Alteration		 Enzyme-linked immunosorbent assay; Western blot analysis
Experiment for
Drug Resistance		 Resazurin cell viability assay
References
Ref 1 Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2Mol Cancer Ther. 2015 Sep;14(9):2023-34. doi: 10.1158/1535-7163.MCT-14-1105. Epub 2015 Aug 18.
Ref 2 Altiratinib blocks Toxoplasma gondii and Plasmodium falciparum development by selectively targeting a spliceosome kinase. Sci Transl Med. 2022 Aug 3;14(656):eabn3231.

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