General Information of the Drug (ID: M6ADRUG0048)
Name
Oxaliplatin
Synonyms
Eloxatin (TN); Medac (TN); Oxaliplatin (TN); Oxaliplatin (JAN/USAN/INN)
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Status Approved [1]
Structure
3D MOL
Formula
C8H14N2O4Pt
InChI
InChI=1S/C6H12N2.C2H2O4.Pt/c7-5-3-1-2-4-6(5)8;3-1(4)2(5)6;/h5-8H,1-4H2;(H,3,4)(H,5,6);/q-2;;+2/t5-,6-;;/m1../s1
InChIKey
DRMCATBEKSVAPL-BNTLRKBRSA-N
PubChem CID
9887053
TTD Drug ID
D0Y3ME
DrugBank ID
DB00526
Full List of m6A Targets Related to This Drug
Poly [ADP-ribose] polymerase 1 (PARP1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Responsed Disease Gastric cancer ICD-11: 2B72
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Responsed Disease Gastric cancer ICD-11: 2B72
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
TNF receptor-associated factor 5 (TRAF5)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [3]
Response Summary 2-polarized tumor-associated macrophages enabled the oxaliplatin resistance via the elevation of METTL3-mediated m6A modification in Colorectal Cancer cells. Furthermore, they found that TNF receptor-associated factor 5 (TRAF5) contributes to the METTL3-triggered OX resistance in CRC cells.
Responsed Disease Colorectal cancer ICD-11: 2B91
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
In-vitro Model LoVo Colon adenocarcinoma Homo sapiens CVCL_0399
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
In-vivo Model HCT-116 cells (3 × 105 cells in 200 uL of saline) were subcutaneously injected into the nude mice to establish xenograft tumors. After 10 days, 10 mg/kg OX or saline was intraperitoneally injected (n = 5 for each group). Si-METTL3 or si-TRAF5 (10 nmol/20 g body weight) was injected twice intratumorally before the start of OX treatment. The mice were examined every 2 days and sacrificed 4 weeks after the OX treatment.
Translocation protein SEC62 (SEC62)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [4]
Response Summary Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment.
Responsed Disease Colorectal cancer ICD-11: 2B91
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
Cell Process Protein degradation
In-vitro Model DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HT29 Colon cancer Mus musculus CVCL_A8EZ
In-vivo Model DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm3, the nude mice were randomly divided into 6 groups.
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: 7433).
Ref 2 METTL3 promotes oxaliplatin resistance of gastric cancer CD133+?stem cells by promoting PARP1 mRNA stability. Cell Mol Life Sci. 2022 Feb 18;79(3):135. doi: 10.1007/s00018-022-04129-0.
Ref 3 Tumor-Associated Macrophages Promote Oxaliplatin Resistance via METTL3-Mediated m(6)A of TRAF5 and Necroptosis in Colorectal Cancer. Mol Pharm. 2021 Mar 1;18(3):1026-1037. doi: 10.1021/acs.molpharmaceut.0c00961. Epub 2021 Feb 8.
Ref 4 Sec62 promotes stemness and chemoresistance of human colorectal cancer through activating Wnt/Beta-catenin pathway. J Exp Clin Cancer Res. 2021 Apr 15;40(1):132. doi: 10.1186/s13046-021-01934-6.