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: CHEBI:132774
CAS Number: CAS 808118-40-3
TTD Drug ID: DM4XSQ2

Molecule-Related Drug Atlas

Molecule Type:

DTT

DOT

Drug Status:

Patented Agent(s)

Approved Drug(s)

Clinical Trial Drug(s)

Investigative Drug(s)

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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	[7]
US8598210, Table XV, 2	DMDK98P	N. A.	N. A.	Patented	[8]
US8536181, A41	DMF9LNO	N. A.	N. A.	Patented	[9]
US8598210, Table XV, 5	DMEU5ST	N. A.	N. A.	Patented	[10]
US8536181, C17	DMRTL63	N. A.	N. A.	Patented	[11]
US8598210, Table XV, 4	DM3XWMO	N. A.	N. A.	Patented	[12]
US8921389, 210	DME1A80	N. A.	N. A.	Patented	[13]
US8536181, C35	DMAM51Z	N. A.	N. A.	Patented	[9]
US10100051, Compound 2	DMWESZ1	N. A.	N. A.	Patented	[14]
US8921389, 2	DMX7KDR	N. A.	N. A.	Patented	[13]
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Drug(s) Targeting HIF-prolyl hydroxylase 1 (HPH-1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daprodustat	DMRNGD2	Anaemia	3A90	Approved	[15]
BAY-85-3934	DM7NHLC	Anemia	3A00-3A9Z	Phase 2	[16]
Pyridine-2,4-dicarboxylic acid	DM4G8WX	Discovery agent	N.A.	Investigative	[17]
2-(carboxymethylamino)-2-oxoacetic acid	DMQ2SNL	Discovery agent	N.A.	Investigative	[17]
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Drug(s) Affected By L-lactate dehydrogenase A chain (LDHA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Adenosine	DMM2NSK	Paroxysmal supraventricular tachycardia	BC81.Z	Approved	[19]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[20]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[21]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[24]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[25]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]
Dihydroartemisinin	DMBXVMZ	Malaria	1F40-1F45	Approved	[27]
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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	[28]
2-deoxyglucose	DMIAHVU	Solid tumour/cancer	2A00-2F9Z	Approved	[29]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[30]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[31]
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[32]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[33]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[32]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[34]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[23]
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Drug(s) Affected By Hexokinase-2 (HK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[35]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[36]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[37]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[38]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[39]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[40]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[41]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[42]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[43]
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Drug(s) Affected By Hypoxia-inducible factor 1-alpha (HIF1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[44]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[45]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[46]
Triamterene	DM2HU9I	Congestive heart failure	BD10	Approved	[46]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[47]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[48]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[36]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[49]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[50]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

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]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Gene/Protein Processing	[5]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Gene/Protein Processing	[6]
L-lactate dehydrogenase A chain (LDHA)	OTN7K4XB	LDHA_HUMAN	Gene/Protein Processing	[5]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Gene/Protein Processing	[5]

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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	Cadmium Exposure Inhibits Branching Morphogenesis and Causes Alterations Consistent With HIF-1 Inhibition in Human Primary Breast Organoids. Toxicol Sci. 2018 Aug 1;164(2):592-602. doi: 10.1093/toxsci/kfy112.
7	Partially saturated nitrogen-containing heterocyclic compound. US9422240.
8	Prolyl hydroxylase inhibitors and methods of use. US9598370.
9	Prolyl hydroxylase inhibitors. US8536181.
10	Prolyl hydroxylase inhibitors and method of use. US8722895.
11	Methods for increasing the stabilization of hypoxia inducible factor-1 alpha. US8778412.
12	Prolyl hydroxylase inhibitors and methods of use. US8598210.
13	Naphthyridine derivatives as inhibitors of Hypoxia inducible factor (HIF) hydroxylase. US9695170.
14	Compound of 5-hydroxyl-1,7-naphthyridine substituted by aryloxy or heteroaryloxy, preparation method thereof and pharmaceutical use thereof. US10100051.
15	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
16	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.
17	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.
18	Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
19	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
20	Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics. Toxicol Lett. 2017 Nov 5;281:26-34. doi: 10.1016/j.toxlet.2017.09.001. Epub 2017 Sep 5.
21	Quercetin acts via the G3BP1/YWHAZ axis to inhibit glycolysis and proliferation in oral squamous cell carcinoma. Toxicol Mech Methods. 2023 Feb;33(2):141-150. doi: 10.1080/15376516.2022.2103480. Epub 2022 Aug 9.
22	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
23	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.
24	Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
25	1,25-Dihydroxyvitamin D3 suppresses gene expression of eukaryotic translation initiation factor 2 in human promyelocytic leukemia HL-60 cells. Cell Struct Funct. 2005;30(1):1-6. doi: 10.1247/csf.30.1.
26	Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci. 2011 Mar;120(1):109-22.
27	Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
28	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.
29	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.
30	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.
31	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.
32	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.
33	Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
34	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.
35	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
36	Epinephrine facilitates the growth of T cell lymphoma by altering cell proliferation, apoptosis, and glucose metabolism. Chem Biol Interact. 2023 Jan 5;369:110278. doi: 10.1016/j.cbi.2022.110278. Epub 2022 Nov 22.
37	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
38	Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic. Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):15084-9. doi: 10.1073/pnas.1521316112. Epub 2015 Nov 23.
39	Combination of imatinib and clotrimazole enhances cell growth inhibition in T47D breast cancer cells. Chem Biol Interact. 2015 May 25;233:147-56. doi: 10.1016/j.cbi.2015.03.028. Epub 2015 Apr 8.
40	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
41	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
42	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
43	Ivermectin accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation. Environ Toxicol. 2022 Apr;37(4):754-764. doi: 10.1002/tox.23440. Epub 2021 Dec 14.
44	Cannabidiol disrupts apoptosis, autophagy and invasion processes of placental trophoblasts. Arch Toxicol. 2021 Oct;95(10):3393-3406. doi: 10.1007/s00204-021-03122-z. Epub 2021 Jul 24.
45	AMP-activated protein kinase activity is required for vanadate-induced hypoxia-inducible factor 1alpha expression in DU145 cells. Carcinogenesis. 2004 Dec;25(12):2497-507. doi: 10.1093/carcin/bgh253. Epub 2004 Aug 5.
46	Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
47	NO-sulindac inhibits the hypoxia response of PC-3 prostate cancer cells via the Akt signalling pathway. Int J Cancer. 2009 Jan 1;124(1):223-32. doi: 10.1002/ijc.23934.
48	Simvastatin stimulates vascular endothelial growth factor production by hypoxia-inducible factor-1alpha upregulation in endothelial cells. J Cardiovasc Pharmacol. 2008 Mar;51(3):267-73. doi: 10.1097/FJC.0b013e3181624b44.
49	Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
50	SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1 signaling pathway. Biochem Biophys Res Commun. 2004 Nov 12;324(2):471-80. doi: 10.1016/j.bbrc.2004.09.082.