Details of the Drug

General Information of Drug (ID: DMUXQG7)

• Drug Name: Phosphate
• Synonyms: orthophosphate; Phosphate ion; 14265-44-2; O-Phosphate; UNII-NK08V8K8HR; NK08V8K8HR; Phosphates; Phosphate ions; PO4; a phosphate group; tetraoxophosphate(V); tetraoxophosphate(3-); Phosphoric acid trianion; tetraoxidophosphate(3-); phosphoric acid, ion(3-); AC1L1AN2; DTXSID7039672; CHEBI:18367; CTK0H5978; NBIIXXVUZAFLBC-UHFFFAOYSA-K; BDBM50155537; AKOS015903596; PO4(3-); CREATINE PHOSPHATE; N-PHOSPHOCREATINE; [PO4](3-); I14-18227

Indication

Disease Entry	ICD 11	Status	REF
Constipation	DD91.1	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 94.971
  Logarithm of the Partition Coefficient (xlogp); -2.3
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: O4P-3
  IUPAC Name: phosphate
  Canonical SMILES: [O-]P(=O)([O-])[O-]
  InChI: InChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)/p-3
  InChIKey: NBIIXXVUZAFLBC-UHFFFAOYSA-K
• Cross-matching ID:
  PubChem CID: 1061
  ChEBI ID: CHEMBL18367
  CAS Number: 14265-44-2
  UNII: NK08V8K8HR
  DrugBank ID: DB14523
  TTD ID: D08VYC
  VARIDT ID: DR00132
  INTEDE ID: DR2121

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Mitochondrial dicarboxylate carrier (SLC25A10)	DTJYKDQ	DIC_HUMAN	Substrate	[2]
Phosphate carrier protein (SLC25A3)	DTCRIWV	MPCP_HUMAN	Substrate	[3]
Calcium-binding mitochondrial carrier protein SCaMC-3 (SLC25A23)	DTLQ0EZ	SCMC3_HUMAN	Substrate	[4]
Sodium-dependent phosphate transporter 2 (SLC20A2)	DTFD4VB	S20A2_HUMAN	Substrate	[5]
Sodium-dependent phosphate transporter 1 (SLC20A1)	DTMULXV	S20A1_HUMAN	Substrate	[5]
Vesicular glutamate transporter 1 (SLC17A7)	DTNK0FR	VGLU1_HUMAN	Substrate	[6]
Vesicular glutamate transporter 2 (SLC17A6)	DT5LHCR	VGLU2_HUMAN	Substrate	[7]
Calcium-binding mitochondrial carrier protein SCaMC-2 (SLC25A25)	DTN7X5J	SCMC2_HUMAN	Substrate	[8]
Calcium-binding mitochondrial carrier protein SCaMC-1 (SLC25A24)	DTVAEDK	SCMC1_HUMAN	Substrate	[9]
Glycerol-3-phosphate permease (SLC37A1)	DTH9SQJ	G6PT2_HUMAN	Substrate	[10]
Probable small intestine urate exporter (SLC17A4)	DTHE530	S17A4_HUMAN	Substrate	[11]
Sodium-dependent phosphate transport protein 4 (SLC17A3)	DTFOJL7	NPT4_HUMAN	Substrate	[12]
Sodium-dependent phosphate transport protein 1 (SLC17A1)	DT8ARWJ	NPT1_HUMAN	Substrate	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
GDP-D-glucose phosphorylase 1 (GDPGP1) Main DME	DE9P5K7	GDPP1_HUMAN	Substrate	[13]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Protein Interaction/Cellular Processes	[14]
Dentin matrix acidic phosphoprotein 1 (DMP1)	OTBWBWW7	DMP1_HUMAN	Gene/Protein Processing	[15]
Growth arrest-specific protein 6 (GAS6)	OTPOPUUE	GAS6_HUMAN	Gene/Protein Processing	[16]
MAP kinase-interacting serine/threonine-protein kinase 1 (MKNK1)	OTGBRJDQ	MKNK1_HUMAN	Gene/Protein Processing	[17]
Matrix extracellular phosphoglycoprotein (MEPE)	OTXJRUW0	MEPE_HUMAN	Regulation of Drug Effects	[18]
Phosphate-regulating neutral endopeptidase PHEX (PHEX)	OTG7N3J7	PHEX_HUMAN	Gene/Protein Processing	[19]
Sodium-dependent phosphate transporter 1 (SLC20A1)	OTC3D894	S20A1_HUMAN	Gene/Protein Processing	[14]
Sodium-dependent phosphate transporter 2 (SLC20A2)	OT6E2DAX	S20A2_HUMAN	Gene/Protein Processing	[14]
Solute carrier family 53 member 1	OTG4FVQB	S53A1_HUMAN	Regulation of Drug Effects	[20]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] SLC25A10 biallelic mutations in intractable epileptic encephalopathy with complex I deficiency. Hum Mol Genet. 2018 Feb 1;27(3):499-504.
• [3] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. J Biol Chem. 2018 Feb 9;293(6):1887-1896.
• [4] Cellular expression and alternative splicing of SLC25A23, a member of the mitochondrial Ca2+-dependent solute carrier gene family. Gene. 2005 Jan 31;345(2):173-82.
• [5] Phosphate transporters and their function. Annu Rev Physiol. 2013;75:535-50.
• [6] SLC17: a functionally diverse family of organic anion transporters. Mol Aspects Med. 2013 Apr-Jun;34(2-3):350-9.
• [7] Type 1 sodium-dependent phosphate transporter (SLC17A1 Protein) is a Cl(-)-dependent urate exporter. J Biol Chem. 2010 Aug 20;285(34):26107-13.
• [8] Ketogenic diet induces expression of the muscle circadian gene Slc25a25 via neural pathway that might be involved in muscle thermogenesis. Sci Rep. 2017 Jun 6;7(1):2885.
• [9] De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise. Am J Hum Genet. 2017 Nov 2;101(5):844-855.
• [10] SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters. PLoS One. 2011;6(9):e23157.
• [11] A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter. Am J Physiol Cell Physiol. 2012 Jun 1;302(11):C1652-60.
• [12] Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate. J Biol Chem. 2010 Nov 5;285(45):35123-32.
• [13] A novel GDP-D-glucose phosphorylase involved in quality control of the nucleoside diphosphate sugar pool in Caenorhabditis elegans and mammals. J Biol Chem. 2011 Jun 17;286(24):21511-23.
• [14] High expression of the Pi-transporter SLC20A1/Pit1 in calcific aortic valve disease promotes mineralization through regulation of Akt-1. PLoS One. 2013;8(1):e53393. doi: 10.1371/journal.pone.0053393. Epub 2013 Jan 4.
• [15] Inorganic phosphate stimulates DMP1 expression in human periodontal ligament fibroblasts embedded in three-dimensional collagen gels. Cells Tissues Organs. 2010;192(2):116-24. doi: 10.1159/000289585. Epub 2010 Feb 24.
• [16] Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification. J Biol Chem. 2010 Mar 5;285(10):7537-44. doi: 10.1074/jbc.M109.055087. Epub 2010 Jan 4.
• [17] Elevated inorganic phosphate stimulates Akt-ERK1/2-Mnk1 signaling in human lung cells. Am J Respir Cell Mol Biol. 2006 Nov;35(5):528-39. doi: 10.1165/rcmb.2005-0477OC. Epub 2006 Jun 8.
• [18] Serum levels of matrix extracellular phosphoglycoprotein (MEPE) in normal humans correlate with serum phosphorus, parathyroid hormone and bone mineral density. J Clin Endocrinol Metab. 2004 Aug;89(8):4158-61. doi: 10.1210/jc.2003-032031.
• [19] Bone as a source of FGF23: regulation by phosphate?. Bone. 2004 Nov;35(5):1192-9. doi: 10.1016/j.bone.2004.06.014.
• [20] Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet. 2015 Jun;47(6):579-81. doi: 10.1038/ng.3289. Epub 2015 May 4.