Name	Acute myocardial infarction
ICD	ICD-11: BA41

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Myocardial infarction (MI) is one of the leading causes of death. WTAP promoted myocardial I/R injury through promoting ER stress and cell apoptosis by regulating m6A modification of Cyclic AMP-dependent transcription factor ATF-4 (ATF4) mRNA. H/R effects on ER stress and apoptosis were all blocked by silencing of WTAP, promoted by WTAP overexpression, and ameliorated by administration of ER stress inhibitor, 4-PBA.
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Endoplasmic reticulum stress
	Cell apoptosis
In-vitro Model	AC16 [Human hybrid cardiomyocyte]	Normal	Homo sapiens	CVCL_4U18
In-vivo Model	Left anterior descending coronary artery (LAD) was ligated for 20 minutes, followed by 48 h reperfusion. Controls underwent same procedures except LAD ligation. WTAP shRNA vector or its negative control (shNC) was injected into the left ventricular anterior wall 24 h before I/R. A pressure volume catheter was used for cardiac function assay.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	IOX1, which is an inhibitor of ALKBH5, was loaded on HSSS to form HSSS-I, which could effectively ameliorate cardiac dysfunction in acute myocardial infarction. The surface-modified bioengineered ferritin nanocage targeted the dying cells in the infarct area under the guidance of Scavenger receptor class F member 1 (SCARF1). These cells were then phagocytosed through recognition of their TfR1 receptor.
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Cell Process	Lysosomal escape
In-vivo Model	Wild-type C57 (female, 12-16 weeks old), ALKBH5 /- mice (female and male, 12-16 weeks old), and SPF-grade SD rats (female, 180-230 g) were used to establish the AMI model.Sodium pentobarbital diluted to 10 mg/mL was used to anesthetize the mice or rat at the dose of 50 mg/kg through an intraperitoneal injection. By using a small animal ventilator with endotracheal intubation, thoracotomy was performed at the left fourth intercostal region. The heart was exposed, and the left anterior descending coronary artery (LCA) was occluded through a 6-0 silk suture that was placed 2-3 mm distal to the origin of the LCA with a slipknot. The apical region turned white, and ST segment elevation and T wave inversion of ECG showed that the AMI model was successfully established. Forty-five minutes after ischemia, the slipknot was released, and the ischemic region was reperfused. PBS (0.2 ml), HSSS (23.5 mg/kg, 0.2 ml), IOX1 (10 mg/kg, 0.2 ml), and HSSS-I (33.5 mg/kg, containing 10 mg/kg IOX1, 0.2 ml) were administered through caudal vein injection for 14 days at the frequency of one time per day.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	ALKBH5-mediated m6A demethylation improved the mRNA stability of YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Transcriptional coactivator YAP1 (YAP1).This finding suggests a novel potential therapeutic strategy for myocardial infarction cardiac regeneration.
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vivo Model	Cas9 and sgRNA were microinjected into the fertilized eggs of C57BL/6J mice, which were then transplanted to obtain positive F0 mice. The statuses of F0 mice were confirmed by PCR and sequencing. Next, positive F0 mice were mated with C57BL/6J mice to yield stable F1 generation mice. F1 and F2 transgenic mice were used in this study.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	IOX1, which is an inhibitor of ALKBH5, was loaded on HSSS to form HSSS-I, which could effectively ameliorate cardiac dysfunction in acute myocardial infarction. The surface-modified bioengineered ferritin nanocage targeted the dying cells in the infarct area under the guidance of Scarf1. These cells were then phagocytosed through recognition of their Transferrin receptor protein 1 (TFRC) receptor.
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Cell Process	Lysosomal escape
In-vivo Model	Wild-type C57 (female, 12-16 weeks old), ALKBH5 /- mice (female and male, 12-16 weeks old), and SPF-grade SD rats (female, 180-230 g) were used to establish the AMI model.Sodium pentobarbital diluted to 10 mg/mL was used to anesthetize the mice or rat at the dose of 50 mg/kg through an intraperitoneal injection. By using a small animal ventilator with endotracheal intubation, thoracotomy was performed at the left fourth intercostal region. The heart was exposed, and the left anterior descending coronary artery (LCA) was occluded through a 6-0 silk suture that was placed 2-3 mm distal to the origin of the LCA with a slipknot. The apical region turned white, and ST segment elevation and T wave inversion of ECG showed that the AMI model was successfully established. Forty-five minutes after ischemia, the slipknot was released, and the ischemic region was reperfused. PBS (0.2 ml), HSSS (23.5 mg/kg, 0.2 ml), IOX1 (10 mg/kg, 0.2 ml), and HSSS-I (33.5 mg/kg, containing 10 mg/kg IOX1, 0.2 ml) were administered through caudal vein injection for 14 days at the frequency of one time per day.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	METTL3 deficiency contributes to heart regeneration after MI via METTL3-pri-miR-143-(miR-143)-Yap/Ctnnd1 axis.
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	neonatal ventricular myocytes (Mouse hearts were enzymatically digested to acquire the primary neonatal ventricular myocytes)
	AC16 [Human hybrid cardiomyocyte]	Normal	Homo sapiens	CVCL_4U18

Ref 1	WTAP promotes myocardial ischemia/reperfusion injury by increasing endoplasmic reticulum stress via regulating m(6)A modification of ATF4 mRNA. Aging (Albany NY). 2021 Mar 26;13(8):11135-11149. doi: 10.18632/aging.202770. Epub 2021 Mar 26.
Ref 2	Clinical pipeline report, company report or official report of Innovent.
Ref 3	Amelioration of acute myocardial infarction injury through targeted ferritin nanocages loaded with an ALKBH5 inhibitor. Acta Biomater. 2022 Mar 1;140:481-491. doi: 10.1016/j.actbio.2021.11.041. Epub 2021 Dec 5.
Ref 4	Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett. 2001 May 7;11(9):1225-7. doi: 10.1016/s0960-894x(01)00188-3.
Ref 5	ALKBH5 regulates cardiomyocyte proliferation and heart regeneration by demethylating the mRNA of YTHDF1. Theranostics. 2021 Jan 1;11(6):3000-3016. doi: 10.7150/thno.47354. eCollection 2021.
Ref 6	Effects of Rifampin on the Pharmacokinetics of a Single Dose of Istradefylline in Healthy Subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201. doi: 10.1002/jcph.1003. Epub 2017 Sep 7.
Ref 7	Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans. Drug Metab Dispos. 2014 May;42(5):818-27. doi: 10.1124/dmd.113.056580. Epub 2014 Feb 19.
Ref 8	Loss of m(6)A methyltransferase METTL3 promotes heart regeneration and repair after myocardial injury. Pharmacol Res. 2021 Dec;174:105845. doi: 10.1016/j.phrs.2021.105845. Epub 2021 Aug 21.
Ref 9	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17. doi: 10.1021/jm9004708.
Ref 10	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. (Target id: 1496).