Details of the Drug

General Information of Drug (ID: DMTHMEI)

Drug Name
INS 316
Synonyms
Uridine 5'-triphosphate; uridine 5'-triphosphate; uridine triphosphate; 63-39-8; Uteplex; UTP; Uridine 5'-(tetrahydrogen triphosphate); 5'-UTP; Uridine 5'-triphosphoric acid; H4utp; UNII-UT0S826Z60; BRN 0071520; INS316; EINECS 200-558-7; uridine-5'-triphosphate; CHEMBL336296; CHEBI:15713; UT0S826Z60; Uridine5'-(tetrahydrogen triphosphate); [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate; uridine5'-triphosphate; uridintriphosphat; uridine tetrahydrogen
Indication
Disease Entry ICD 11 Status REF
Lung cancer 2C25.0 Discontinued in Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 484.14
Topological Polar Surface Area (xlogp) -5.8
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 7
Hydrogen Bond Acceptor Count (hbondacc) 15
Chemical Identifiers
Formula
C9H15N2O15P3
IUPAC Name
[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
Canonical SMILES
C1=CN(C(=O)NC1=O)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O
InChI
InChI=1S/C9H15N2O15P3/c12-5-1-2-11(9(15)10-5)8-7(14)6(13)4(24-8)3-23-28(19,20)26-29(21,22)25-27(16,17)18/h1-2,4,6-8,13-14H,3H2,(H,19,20)(H,21,22)(H,10,12,15)(H2,16,17,18)/t4-,6-,7-,8-/m1/s1
InChIKey
PGAVKCOVUIYSFO-XVFCMESISA-N
Cross-matching ID
PubChem CID
6133
ChEBI ID
CHEBI:15713
CAS Number
63-39-8
DrugBank ID
DB04005
TTD ID
D0Z7FU

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
P2Y purinoceptor 11 (P2RY11) TTYXPCO P2Y11_HUMAN Agonist [2]
P2Y purinoceptor 2 (P2RY2) TTOZHQC P2RY2_HUMAN Modulator [3], [4], [5]
P2Y purinoceptor 4 (P2RY4) TT24DGP P2RY4_HUMAN Agonist [6]
P2Y purinoceptor 6 (P2RY6) TTNVSKA P2RY6_HUMAN Agonist [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 02 Neoplasm
Disease Class ICD-11: 2C82 Prostate cancer
The Studied Tissue Lung tissue
The Studied Disease Lung cancer [ICD-11:2C82]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
P2Y purinoceptor 2 (P2RY2) DTT P2RY2 7.03E-10 0.14 0.52
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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2 Characterization of a Ca2+ response to both UTP and ATP at human P2Y11 receptors: evidence for agonist-specific signaling. Mol Pharmacol. 2003 Jun;63(6):1356-63.
3 Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study. Pediatr Pulmonol. 2001 Aug;32(2):122-8.
4 Methanocarba modification of uracil and adenine nucleotides: high potency of Northern ring conformation at P2Y1, P2Y2, P2Y4, and P2Y11 but not P2Y6 receptors. J Med Chem. 2002 Jan 3;45(1):208-18.
5 P2Y(2) receptor stimulation increases tear fluid secretion in rabbits. Curr Eye Res. 2000 Oct;21(4):782-7.
6 ATP, an agonist at the rat P2Y(4) receptor, is an antagonist at the human P2Y(4) receptor. Mol Pharmacol. 2000 May;57(5):926-31.
7 Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochem Biophys Res Commun. 1996 May 15;222(2):303-8.
8 Development of selective agonists and antagonists of P2Y receptors. Purinergic Signal. 2009 Mar;5(1):75-89.
9 Enzymatic synthesis of UTP gamma S, a potent hydrolysis resistant agonist of P2U-purinoceptors. Br J Pharmacol. 1996 Jan;117(1):203-9.
10 Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors. J Med Chem. 2011 Apr 28;54(8):2878-90.
11 Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate delta-ester modifications as selective agonists of the P2Y(4) receptor. J Med Chem. 2011 Jun 23;54(12):4018-33.
12 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
13 Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. J Med Chem. 2010 Mar 11;53(5):2076-86.
14 Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists. Bioorg Med Chem. 2008 Jun 15;16(12):6319-32.
15 Diisothiocyanate derivatives as potent, insurmountable antagonists of P2Y6 nucleotide receptors. Biochem Pharmacol. 2004 May 1;67(9):1763-70.
16 P2 receptors activated by uracil nucleotides--an update. Curr Med Chem. 2006;13(3):289-312.
17 Pharmacological characterization of the human P2Y11 receptor. Br J Pharmacol. 1999 Nov;128(6):1199-206.
18 NAADP+ is an agonist of the human P2Y11 purinergic receptor. Cell Calcium. 2008 Apr;43(4):344-55.
19 NF546 [4,4'-(carbonylbis(imino-3,1-phenylene-carbonylimino-3,1-(4-methyl-phenylene)-carbonylimino))-bis(1,3-xylene-alpha,alpha'-diphosphonic acid) tetrasodium salt] is a non-nucleotide P2Y11 agonist and stimulates release of interleukin-8 from human monocyte-derived dendritic cells. J Pharmacol Exp Ther. 2010 Jan;332(1):238-47.
20 Synthesis and structure-activity relationships of suramin-derived P2Y11 receptor antagonists with nanomolar potency. J Med Chem. 2005 Nov 3;48(22):7040-8.
21 Invited Lectures : Overviews Purinergic signalling: past, present and future. Purinergic Signal. 2006 May;2(1):1-324.
22 Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
23 Combinatorial synthesis of anilinoanthraquinone derivatives and evaluation as non-nucleotide-derived P2Y2 receptor antagonists. Bioorg Med Chem Lett. 2008 Jan 1;18(1):223-7.
24 Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate. Br J Pharmacol. 1995 Sep;116(1):1619-27.
25 Synthesis and structure-activity relationships of uracil nucleotide derivatives and analogues as agonists at human P2Y2, P2Y4, and P2Y6 receptors. J Med Chem. 2006 Nov 30;49(24):7076-87.
26 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: 324).