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

General Information of Drug (ID: DMQU4XM)

• Drug Name: 7,8-dihydrobiopterin Drug Info
• Synonyms: Quinonoid dihydrobiopterin; q-BH2; L-erythro-q-dihydrobiopterin; dihydrobiopterin; L-erythro-7,8-Dihydrobiopterin; L-erythro-dihydrobiopterin; 7,8-Dihydro-L-biopterin; 6779-87-9; 2-amino-6-((1r,2s)-1,2-dihydroxypropyl)-7,8-dihydro-4(1h)-pteridinone; 2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-7,8-dihydropteridin-4(3H)-one; 2toh; 4(1H)-pteridinone, 2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-7,8-dihydro-; 4(1H)-Pteridinone, 2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-, [S-(R*,S*)]-; 4(1H)-Pteridinone; 7,8-Dihydro-L-Biopterin

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 135398687
  ChEBI ID: CHEBI:43029
  CAS Number: CAS 6779-87-9
  TTD Drug ID: DMQU4XM

Molecule-Related Drug Atlas

Drug(s) Targeting Nitric-oxide synthase inducible (NOS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[4]
SD-6010	DM9DEYL	Osteoarthritis	FA00-FA05	Phase 3	[5]
MPL-S	DMNDCFY	Endotoxic shock	1G41	Phase 3	[6]
Pimagedine HCl	DMPWH30	Diabetic kidney disease	GB61.Z	Phase 2/3	[7]
GW274150	DMZMCB1	Asthma	CA23	Phase 2	[8]
BXT-51072	DMD8GNB	Cardiovascular disease	BA00-BE2Z	Phase 2	[9]
HP-228	DMNZ35F	Postoperative pain	MG30-MG3Z	Phase 2	[10]
CR-3294	DMHJEZS	Diarrhea	ME05.1	Phase 2	[11]
KD-7040	DME1WV2	Pain	MG30-MG3Z	Phase 2	[12]
LT-1951	DM5N04G	Coronary artery disease	BA80	Phase 1/2	[13]

Drug(s) Targeting Bacterial Dihydroneopterinaldolase (Bact folB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bropirimine	DMMT1YQ	Virus infection	1A24-1D9Z	Discontinued in Phase 3	[2]
6-Hydroxymethyl-7,8-Dihydropterin	DMYF60K	Discovery agent	N.A.	Investigative	[2]
7,8-Dihydroneopterin	DM5TXY1	Discovery agent	N.A.	Investigative	[2]
9-Methylguanine	DM54FRI	Discovery agent	N.A.	Investigative	[2]
8-Amino-1,3-Dimethyl-3,7-Dihydropurine-2,6-Dione	DM84D9W	Discovery agent	N.A.	Investigative	[2]

Drug(s) Targeting Tyrosine 3-monooxygenase (TH)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Phenylalanine	DMQXI9F	Malnutrition	5B50-5B71	Approved	[14]
L-Tyrosine	DM9O8DT	Malnutrition	5B50-5B71	Approved	[15]
Tetrahydrobiopterin	DMINZ4W	Malnutrition	5B50-5B71	Approved	[16]
Metyrosine	DMBYCU0	Pheochromocytoma	5A75	Approved	[17]
L1-79	DMLHPVW	Autism spectrum disorder	6A02	Phase 2	[18]
ProSavin	DMJ42E6	Parkinson disease	8A00.0	Phase 1/2	[19]
OXB-102	DMXF9DM	Parkinson disease	8A00.0	Phase 1/2	[20]
alpha-propyldopacetamide	DMQKMX3	Discovery agent	N.A.	Investigative	[21]
Meta-Tyrosine	DM0748C	Discovery agent	N.A.	Investigative	[2]
3-iodotyrosine	DMNZMH6	Discovery agent	N.A.	Investigative	[21]

Drug(s) Affected By Amyloid-beta precursor protein (APP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Selenium	DM25CGV	N. A.	N. A.	Approved	[23]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[24]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[26]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[27]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[28]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[29]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Aluminium	DM6ECN9	Hyperhidrosis	EE00	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Dihydroneopterinaldolase (Bact folB)	TTG9CFY	FOLB_ECOLI	Inhibitor	[2]
Nitric-oxide synthase inducible (NOS2)	TTF10I9	NOS2_HUMAN	Inhibitor	[1]
Tyrosine 3-monooxygenase (TH)	TTUHP71	TY3H_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Regulation of Drug Effects	[3]

References

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• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] Activation of PPAR prevents endothelial dysfunction induced by overexpression of amyloid- precursor protein. Cardiovasc Res. 2012 Dec 1;96(3):504-12. doi: 10.1093/cvr/cvs266. Epub 2012 Aug 10.
• [4] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [5] A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Ann Rheum Dis. 2013 Feb;72(2):187-95.
• [6] Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages. Infect Immun. 1997 Aug;65(8):3239-47.
• [7] Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia. Brain Res. 2008 Sep 16;1230:138-49.
• [8] GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int. 2003 Mar;63(3):853-65.
• [9] Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress. Am J Physiol Cell Physiol. 2000 Dec;279(6):C1880-8.
• [10] HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro. J Pharmacol Exp Ther. 1995 Nov;275(2):584-91.
• [11] Efficacy of CR3294, a new benzamidine derivative, in the prevention of 5-fluorouracil-induced gastrointestinal mucositis and diarrhea in mice. Cancer Chemother Pharmacol. 2010 October; 66(5): 819-827.
• [12] WO patent application no. 2014,0214,08, Method for treating cancer by anticancer agent co-administration.
• [13] Critical role of L-arginine in endothelial cell survival during oxidative stress. Circulation. 2003 May 27;107(20):2607-14.
• [14] Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. Curr Med Chem. 2007;14(4):455-67.
• [15] Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: comparison with that on tyrosine hydroxylase activity. Neurosci Lett. 2006 Jul 3;401(3):261-5.
• [16] Biochemistry of postmortem brains in Parkinson's disease: historical overview and future prospects. J Neural Transm Suppl. 2007;(72):113-20.
• [17] Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension. 1991 Jul;18(1):1-8.
• [18] Effect of L1-79 on Core Symptoms of Autism Spectrum Disorder: A Case Series. Clin Ther. 2019 Oct;41(10):1972-1981.
• [19] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [20] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [21] 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: 1243).
• [22] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [23] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [24] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [25] Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein. J Neurochem. 2007 Apr;101(1):77-86. doi: 10.1111/j.1471-4159.2006.04375.x. Epub 2007 Jan 4.
• [26] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [27] Chelation and intercalation: complementary properties in a compound for the treatment of Alzheimer's disease. J Struct Biol. 2000 Jun;130(2-3):209-16. doi: 10.1006/jsbi.2000.4285.
• [28] Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid-differentiated human neuroblastoma cells. J Neurochem. 2005 Nov;95(4):1059-68. doi: 10.1111/j.1471-4159.2005.03440.x. Epub 2005 Sep 7.
• [29] Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
• [30] 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.
• [31] Synergistic effects of iron and aluminum on stress-related gene expression in primary human neural cells. J Alzheimers Dis. 2005 Nov;8(2):117-27; discussion 209-15. doi: 10.3233/jad-2005-8204.