Name	Rheumatoid arthritis
ICD	ICD-11: FA20

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	METTL3 knockdown suppressed Interleukin-6 (IL-6), matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs.
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	FLS (Rat fibroblast synovial cell line)
In-vivo Model	To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and Matrix metalloproteinase-9 (MMP9) levels in human RA-FLSs and rat AIA-FLSs.
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	FLS (Rat fibroblast synovial cell line)
In-vivo Model	To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	In rheumatoid arthritis fibroblast-like synoviocytes, m6A methylation-mediated gene Protein-glutamine gamma-glutamyltransferase 2 (TGM2) served as a promoter of RA-FLS proliferation by inducing DNA replication and cell cycle transition and inhibiting apoptosis through activating NF-Kappa-B signaling. TGM2 can be an attractive target and Sar was a novel anti-RA drug.
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Responsed Drug	Sarsasapogenin		Investigative	Drug Info
Pathway Response	DNA replication			hsa03030
Cell Process	DNA replication
	Cell apoptosis
In-vitro Model	MH7A	Normal	Homo sapiens	CVCL_0427

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and rheumatoid arthritis related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent. The validations of WTAP, Receptor-interacting serine/threonine-protein kinase 2 (RIPK2), JAK3 and TNFRSF10A were in accordance with the m6A and RNA sequencing results.
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Pathway Response	JAK-STAT signaling pathway			hsa04630
	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	MH7A	Normal	Homo sapiens	CVCL_0427
In-vivo Model	The rats were adaptively fed for 1 week and then subcutaneous injection of complete Freund's adjuvant into the left hindfoot toe to establish an adjuvant arthritis (AA) rat model. After induction of the immune response for 20 days, all rats were anesthetized by the intraperitoneal injection of 1% sodium pentobarbital (60 mg/kg) and sacrificed by exsanguination of the abdominal aorta.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase Stromelysin-1 (MMP-3), and MMP-9 levels in human RA-FLSs and rat AIA-FLSs.
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	FLS (Rat fibroblast synovial cell line)
In-vivo Model	To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and rheumatoid arthritis related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent. The validations of WTAP, RIPK2, JAK3 and Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) were in accordance with the m6A and RNA sequencing results.
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Pathway Response	JAK-STAT signaling pathway			hsa04630
	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	MH7A	Normal	Homo sapiens	CVCL_0427
In-vivo Model	The rats were adaptively fed for 1 week and then subcutaneous injection of complete Freund's adjuvant into the left hindfoot toe to establish an adjuvant arthritis (AA) rat model. After induction of the immune response for 20 days, all rats were anesthetized by the intraperitoneal injection of 1% sodium pentobarbital (60 mg/kg) and sacrificed by exsanguination of the abdominal aorta.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and rheumatoid arthritis related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent. The validations of WTAP, RIPK2, Tyrosine-protein kinase JAK3 (JAK3) and TNFRSF10A were in accordance with the m6A and RNA sequencing results.
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Pathway Response	JAK-STAT signaling pathway			hsa04630
	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	MH7A	Normal	Homo sapiens	CVCL_0427
In-vivo Model	The rats were adaptively fed for 1 week and then subcutaneous injection of complete Freund's adjuvant into the left hindfoot toe to establish an adjuvant arthritis (AA) rat model. After induction of the immune response for 20 days, all rats were anesthetized by the intraperitoneal injection of 1% sodium pentobarbital (60 mg/kg) and sacrificed by exsanguination of the abdominal aorta.

Ref 1	METTL3 Promotes Activation and Inflammation of FLSs Through the NF-KappaB Signaling Pathway in Rheumatoid Arthritis. Front Med (Lausanne). 2021 Jul 6;8:607585. doi: 10.3389/fmed.2021.607585. eCollection 2021.
Ref 2	Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther. 2007 Aug;82(2):197-203. doi: 10.1038/sj.clpt.6100122. Epub 2007 Mar 14.
Ref 3	Complete Substrate Inhibition of Cytochrome P450 2C8 by AZD9496, an Oral Selective Estrogen Receptor Degrader. Drug Metab Dispos. 2018 Sep;46(9):1268-1276. doi: 10.1124/dmd.118.081539. Epub 2018 Jun 19.
Ref 4	Clinical pipeline report, company report or official report of Kadmon.
Ref 5	N6-methyladenosine modification of TGM2 mRNA contributes to the inhibitory activity of sarsasapogenin in rheumatoid arthritis fibroblast-like synoviocytes. Phytomedicine. 2022 Jan;95:153871. doi: 10.1016/j.phymed.2021.153871. Epub 2021 Nov 30.
Ref 6	Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A. J Inflamm Res. 2021 Feb 25;14:575-586. doi: 10.2147/JIR.S296006. eCollection 2021.
Ref 7	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: 7422).
Ref 8	Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36. doi: 10.1517/14728214.11.2.315.
Ref 9	Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells. J Pharm Sci. 2007 Oct;96(10):2808-17. doi: 10.1002/jps.20975.
Ref 10	MBX-102/JNJ39659100, a novel peroxisome proliferator-activated receptor-ligand with weak transactivation activity retains antidiabetic properties in the absence of weight gain and edema. Mol Endocrinol. 2009 Jul;23(7):975-88. doi: 10.1210/me.2008-0473. Epub 2009 Apr 23.