m6A-centered Drug Response Information
General Information of the Drug (ID: M6ADRUG0048)
Name |
Oxaliplatin
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Synonyms |
Eloxatin (TN); Medac (TN); Oxaliplatin (TN); Oxaliplatin (JAN/USAN/INN)
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Status | Approved | [1] | |||
Structure |
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3D MOL
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Formula |
C8H14N2O4Pt
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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
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InChIKey |
DRMCATBEKSVAPL-BNTLRKBRSA-N
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PubChem CID | |||||
TTD Drug ID | |||||
DrugBank ID |
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