m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0106)
Name
Crizotinib
Synonyms
Xalkori (TN); novel ALK inhibitors; Crizotinibum;
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Status Approved [1]
Structure
Formula
C21H22Cl2FN5O
InChI
InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1
InChIKey
KTEIFNKAUNYNJU-GFCCVEGCSA-N
PubChem CID
11626560
TTD Drug ID
D03ZBT
DrugBank ID
DB08865
Full List of m6A Targets Related to This Drug
Hepatocyte growth factor receptor (c-Met/MET)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Target Regulator Wilms tumor 1-associating protein (WTAP) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
References
Ref 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4903).
Ref 2 Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation. Int J Biol Sci. 2020 Jul 19;16(14):2595-2611. doi: 10.7150/ijbs.45886. eCollection 2020.