m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0055)
Name
AZD6482
Synonyms
AZD6482; 1173900-33-8; AZD 6482; (R)-2-(1-(7-methyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)ethylamino)benzoic acid; 2-[[(1R)-1-[7-Methyl-2-(4-morpholinyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]benzoic acid; AZD-6482; CHEMBL2165191; UNII-78G6MP5PZ5; 78G6MP5PZ5; 2-({(1R)-1-[7-Methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl}amino)benzoic acid; 2-{[(1R)-1-[7-methyl-2-(morpholin-4-yl)-4-oxopyrido[1,2-a]pyrimidin-9-yl]ethyl]amino}benzoic acid
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Status Terminated [1]
Structure
Formula
C22H24N4O4
InChI
InChI=1S/C22H24N4O4/c1-14-11-17(15(2)23-18-6-4-3-5-16(18)22(28)29)21-24-19(12-20(27)26(21)13-14)25-7-9-30-10-8-25/h3-6,11-13,15,23H,7-10H2,1-2H3,(H,28,29)/t15-/m1/s1
InChIKey
IRTDIKMSKMREGO-OAHLLOKOSA-N
PubChem CID
44137675
TTD Drug ID
D0D0QA
DrugBank ID
DB14980
Full List of m6A Targets Related to This Drug
PI3-kinase subunit beta (PIK3CB)
 Target Info 
In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Target Regulator Methyltransferase-like 13 (METTL13) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Glycolysis / Gluconeogenesis hsa00010
Cell Process Glucose metabolism
In-vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
In-vivo Model Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm3, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Glycolysis / Gluconeogenesis hsa00010
Cell Process Glucose metabolism
In-vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
In-vivo Model Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm3, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
Experiment 3 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Target Regulator Wilms tumor 1-associating protein (WTAP) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Glycolysis / Gluconeogenesis hsa00010
Cell Process Glucose metabolism
In-vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
In-vivo Model Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm3, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
Experiment 4 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Glycolysis / Gluconeogenesis hsa00010
Cell Process Glucose metabolism
In-vitro Model BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
In-vivo Model Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm3, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
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: 8059).
Ref 2 N(6)-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Gut. 2020 Dec;69(12):2180-2192. doi: 10.1136/gutjnl-2019-320179. Epub 2020 Apr 20.