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

General Information of Drug (ID: DMTGR25)

• Drug Name: L-745,870 Drug Info
• Synonyms: 158985-00-3; L-745870; UNII-J3OLN3XSX7; J3OLN3XSX7; L-745,870; CHEMBL267014; L 745,870; 3-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine; 3-(4-[4-Chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo[2,3-b]pyridine trihydrochloride; 3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; 3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine; CPMPP-3; Tocris-1002; Lopac-L-131; Biomol-NT_000049; AC1NSK75; L745870; Lopac0_000791; GTPL3303; BPBio1_001299; SCHEMBL1059886; CHEBI:92099

Indication

Disease Entry	ICD 11	Status	REF
Psychotic disorder	6A20-6A25	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 5311200
  ChEBI ID: CHEBI:92099
  CAS Number: CAS 158985-00-3
  TTD Drug ID: DMTGR25

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D4 receptor (D4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[4]
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[5]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[6]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[7]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[8]
ABT-724	DMDQVY4	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[9]
Lu-35138	DMQ7A35	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[10]
NGD-94-4	DMZ9WLO	Schizophrenia	6A20	Discontinued in Phase 1	[11]
PD-165167	DMD0GB4	Schizophrenia	6A20	Preclinical	[8]
SPI-376	DMC1WAJ	Schizophrenia	6A20	Preclinical	[8]

Drug(s) Affected By Baculoviral IAP repeat-containing protein 1 (NAIP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[13]
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[14]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[15]
Bortezomib	DMNO38U	Leukemia		Approved	[16]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[19]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D4 receptor (D4R)	TTE0A2F	DRD4_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Baculoviral IAP repeat-containing protein 1 (NAIP)	OTLA925F	BIRC1_HUMAN	Gene/Protein Processing	[3]

References

• [1] 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: 3303).
• [2] Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology (Berl). 2009 Apr;203(2):265-77.
• [3] A dopamine D4 receptor antagonist attenuates ischemia-induced neuronal cell damage via upregulation of neuronal apoptosis inhibitory protein. J Cereb Blood Flow Metab. 2005 Jul;25(7):794-806. doi: 10.1038/sj.jcbfm.9600078.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 ... J Med Chem. 2004 Aug 12;47(17):4155-8.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [9] Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats. Proc Natl Acad Sci U S A. 2004 April 27; 101(17): 6758-6763.
• [10] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237)
• [11] I. NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Aug;282(2):1011-9.
• [12] 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.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [15] Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis. Br J Haematol. 2009 Mar;144(5):667-76. doi: 10.1111/j.1365-2141.2008.07504.x. Epub 2008 Nov 20.
• [16] Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study. Turk J Haematol. 2015 Sep;32(3):206-12. doi: 10.4274/tjh.2014.0058.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression of P-glycoprotein, Fas and of the novel anti-apoptosis factors IAP (inhibitory of apoptosis proteins). Cancer Lett. 2002 Jun 6;180(1):91-101. doi: 10.1016/s0304-3835(01)00834-5.
• [19] 5-Fluorouracil up-regulates interferon pathway gene expression in esophageal cancer cells. Anticancer Res. 2005 Sep-Oct;25(5):3271-8.
• [20] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [21] Rapid induction of IAP family proteins and Smac/DIABLO expression after proapoptotic stimulation with doxorubicin in RPMI 8226 multiple myeloma cells. Exp Mol Pathol. 2007 Dec;83(3):405-12. doi: 10.1016/j.yexmp.2007.04.001. Epub 2007 Apr 18.