m6A-centered Drug Response Information
General Information of the Drug (ID: M6ADRUG0006)
| Name |
Meclofenamic acid
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| Synonyms |
Arquel; Meclofenamate; Acide meclofenamique; Acido meclofenamico; Acidum meclofenamicum; Meclophenamic acid; CL 583; INF 4668; Acide meclofenamique [INN-French]; Acido meclofenamico [INN-Spanish]; Acidum meclofenamicum [INN-Latin]; INF-4668; Meclomen (free acid); Meclofenamic acid (USAN/INN); Meclofenamic acid [USAN:INN:BAN]; N-(2,6-Dichloro-3-methylphenyl)anthranilic acid; N-(2,6-Dichloro-m-tolyl)anthranilic acid; N-(3-Methyl-2,6-dichlorophenyl)anthranilic acid; 2-((2,6-Dichloro-3-methylphenyl)amino)benzoic acid; 2-(2,6-Dichloro-3-methylphenyl)aminobenzoic acid; 2-(2,6-dichloro-3-methylanilino)benzoic acid; 2-[(2,6-dichloro-3-methylphenyl)amino]benzoic acid
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| Status | Approved | [1] | |||
| Structure |
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| Formula |
C14H11Cl2NO2
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| InChI |
InChI=1S/C14H11Cl2NO2/c1-8-6-7-10(15)13(12(8)16)17-11-5-3-2-4-9(11)14(18)19/h2-7,17H,1H3,(H,18,19)
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| InChIKey |
SBDNJUWAMKYJOX-UHFFFAOYSA-N
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Full List of m6A Targets Related to This Drug
Apoptosis regulator Bcl-2 (BCL2)
| In total 1 item(s) under this target gene | ||||
| Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene | [2] | |||
| Response Summary | Studies of the aberrant expression of m6A mediators in breast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Apoptosis regulator Bcl-2 (BCL2) and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis. | |||
| Responsed Disease | Breast cancer | ICD-11: 2C60 | ||
| Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
| Pathway Response | Apoptosis | hsa04210 | ||
| PI3K-Akt signaling pathway | hsa04151 | |||
| Cell Process | Cell proliferation | |||
| Cell apoptosis | ||||
Cellular tumor antigen p53 (TP53/p53)
| In total 1 item(s) under this target gene | ||||
| Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene | [3] | |||
| Response Summary | Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced Acute kidney injury. | |||
| Responsed Disease | Acute kidney failure | ICD-11: GB60 | ||
| Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
| Target Regulation | Down regulation | |||
| Pathway Response | Apoptosis | hsa04210 | ||
| Cell Process | Cell apoptosis | |||
| In-vitro Model | HK2 | Normal | Acipenser baerii | CVCL_YE28 |
| In-vivo Model | Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days. | |||
Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4)
| In total 1 item(s) under this target gene | ||||
| Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene | [4] | |||
| Response Summary | Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability. | |||
| Responsed Disease | Acute myeloid leukaemia | ICD-11: 2A60 | ||
| Target Regulator | Fat mass and obesity-associated protein (FTO) | ERASER | ||
| Target Regulation | Down regulation | |||
| Pathway Response | B cell receptor signaling pathway | hsa04662 | ||
| Cell Process | Immune Evasion | |||
| In-vitro Model | MV4-11 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0064 |
| THP-1 | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
| U-937 | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | |
| In-vivo Model | For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 106 MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 106 AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times. | |||
References