m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0104)
Name
Apatinib
Synonyms
Apatinib; 811803-05-1; rivoceranib; YN968D1; Apatinib free base; N-(4-(1-Cyanocyclopentyl)phenyl)-2-((pyridin-4-ylmethyl)amino)nicotinamide; UNII-5S371K6132; N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide; 5S371K6132; N-(4-(1-cyanocyclopentyl)phenyl)-2-(pyridin-4-ylmethylamino)nicotinamide; apatinib (in China); Rivoceranib (USAN/INN); GTPL7648; SCHEMBL1814966; CHEMBL3186534; Apatinib free base; YN-968D1; AMY21302; BCP02840; EX-A1794; HY-13342A; MFCD21648511; NSC772886; NSC799333; s5248; ZINC70466461; AKOS024464453; CCG-268625; DB14765; DS-7455; NSC-772886; NSC-799333; SB16590; 3-Pyridinecarboxamide, N-(4-(1-cyanocyclopentyl)phenyl)-2-((4-pyridinylmethyl)amino)-; N-[4-(1-Cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide; NCGC00249393-01; NCGC00249393-08; AC-27461; BA175030; DA-35324; CS-0003200; C76598; D11288; AB01274807-01; AB01274807_02; Q27262801; N-[4-(1-Cyanocyclopentyl)phenyl]-2-[(4-pyridinylmethyl)amino]nicotinamide
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Status Approved [1]
Structure
Formula
C24H23N5O
InChI
InChI=1S/C24H23N5O/c25-17-24(11-1-2-12-24)19-5-7-20(8-6-19)29-23(30)21-4-3-13-27-22(21)28-16-18-9-14-26-15-10-18/h3-10,13-15H,1-2,11-12,16H2,(H,27,28)(H,29,30)
InChIKey
WPEWQEMJFLWMLV-UHFFFAOYSA-N
PubChem CID
11315474
TTD Drug ID
D0SZ6E
DrugBank ID
DB14765
Full List of m6A Targets Related to This Drug
Cellular tumor antigen p53 (TP53/p53)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model QGY-7701 Human papillomavirus-related endocervical adenocarcinoma Homo sapiens CVCL_6859
HHL-5 Normal Homo sapiens CVCL_S956
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
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: 7648).
Ref 2 p53 m(6)A modulation sensitizes hepatocellular carcinoma to apatinib through apoptosis. Apoptosis. 2022 Jun;27(5-6):426-440. doi: 10.1007/s10495-022-01728-x. Epub 2022 May 3.