Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM4XSQ2)

• Drug Name: FG-4592 Drug Info
• Synonyms: FG-4592; 808118-40-3; Roxadustat; Roxadustat (FG-4592); UNII-X3O30D9YMX; N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine; FG4592; ASP1517; Glycine, N-[(4-hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]-; X3O30D9YMX; CHEMBL2338329; 2-[(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid; FG 4592; AK198953; n-((4-hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl)glycine; [[(4-Hydroxy-1-methyl-7-phenoxyisoquinolin-3-yl)carbonyl]amino]acetic Acid

Indication

Disease Entry	ICD 11	Status	REF
Anaemia	3A90	Phase 3	[1]
Kidney disease	GC2Z	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 11256664
  ChEBI ID: CHEMBL2338329
  CAS Number: CAS 808118-40-3
  TTD Drug ID: DM4XSQ2

Molecule-Related Drug Atlas

Drug(s) Targeting HIF-prolyl hydroxylase 2 (HPH-2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9422240, 1-298	DMH7DL5	N. A.	N. A.	Patented	[6]
US8598210, Table XV, 2	DMDK98P	N. A.	N. A.	Patented	[7]
US8536181, A41	DMF9LNO	N. A.	N. A.	Patented	[8]
US8598210, Table XV, 5	DMEU5ST	N. A.	N. A.	Patented	[9]
US8536181, C17	DMRTL63	N. A.	N. A.	Patented	[10]
US8598210, Table XV, 4	DM3XWMO	N. A.	N. A.	Patented	[11]
US8921389, 210	DME1A80	N. A.	N. A.	Patented	[12]
US8536181, C35	DMAM51Z	N. A.	N. A.	Patented	[8]
US10100051, Compound 2	DMWESZ1	N. A.	N. A.	Patented	[13]
US8921389, 2	DMX7KDR	N. A.	N. A.	Patented	[12]

Drug(s) Targeting HIF-prolyl hydroxylase 1 (HPH-1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daprodustat	DMRNGD2	Anaemia	3A90	Approved	[14]
BAY-85-3934	DM7NHLC	Anemia	3A00-3A9Z	Phase 2	[15]
Pyridine-2,4-dicarboxylic acid	DM4G8WX	Discovery agent	N.A.	Investigative	[16]
2-(carboxymethylamino)-2-oxoacetic acid	DMQ2SNL	Discovery agent	N.A.	Investigative	[16]

Drug(s) Affected By Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
2-deoxyglucose	DMIAHVU	Solid tumour/cancer	2A00-2F9Z	Approved	[18]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[19]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[21]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[23]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[24]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
HIF-prolyl hydroxylase 1 (HPH-1)	TTMHFRY	EGLN2_HUMAN	Inhibitor	[3]
HIF-prolyl hydroxylase 2 (HPH-2)	TT9ISBX	EGLN1_HUMAN	Inhibitor	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Gene/Protein Processing	[5]

References

• [1] ClinicalTrials.gov (NCT01750190) A Study of FG-4592 for the Treatment of Anemia in Chronic Kidney Disease Patients Not Receiving Dialysis. U.S. National Institutes of Health.
• [2] 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: 8454).
• [3] The latest advances in kidney diseases and related disorders. Drug News Perspect. 2007 Dec;20(10):647-54.
• [4] Crystalline forms of a prolyl hydroxylase inhibitor. US9115085.
• [5] Lactate released from human fibroblasts enhances Ni elution from Ni plate. Toxicology. 2021 Apr 15;453:152723. doi: 10.1016/j.tox.2021.152723. Epub 2021 Feb 14.
• [6] Partially saturated nitrogen-containing heterocyclic compound. US9422240.
• [7] Prolyl hydroxylase inhibitors and methods of use. US9598370.
• [8] Prolyl hydroxylase inhibitors. US8536181.
• [9] Prolyl hydroxylase inhibitors and method of use. US8722895.
• [10] Methods for increasing the stabilization of hypoxia inducible factor-1 alpha. US8778412.
• [11] Prolyl hydroxylase inhibitors and methods of use. US8598210.
• [12] Naphthyridine derivatives as inhibitors of Hypoxia inducible factor (HIF) hydroxylase. US9695170.
• [13] Compound of 5-hydroxyl-1,7-naphthyridine substituted by aryloxy or heteroaryloxy, preparation method thereof and pharmaceutical use thereof. US10100051.
• [14] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [15] Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat) stimulates erythropoietin production without hypertensive effects. PLoS One. 2014 Nov 13;9(11):e111838.
• [16] Design, synthesis, enzyme-inhibitory activity, and effect on human cancer cells of a novel series of jumonji domain-containing protein 2 histone de... J Med Chem. 2010 Aug 12;53(15):5629-38.
• [17] Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
• [18] Insulin regulation of hexose transport in mouse 3T3-L1 cells expressing the human HepG2 glucose transporter. J Biol Chem. 1990 Nov 25;265(33):20106-16.
• [19] Effects of troglitazone on cellular differentiation, insulin signaling, and glucose metabolism in cultured human skeletal muscle cells. Biochem Biophys Res Commun. 2001 Jan 26;280(3):664-74. doi: 10.1006/bbrc.2000.4216.
• [20] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [21] Disturbance of cellular glucose transport by two prevalently used fluoroquinolone antibiotics ciprofloxacin and levofloxacin involves glucose transporter type 1. Toxicol Lett. 2009 Jan 30;184(2):81-4. doi: 10.1016/j.toxlet.2008.10.017. Epub 2008 Oct 28.
• [22] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [23] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [24] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [25] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.