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

General Information of Drug (ID: DMCZI62)

• Drug Name: LORECLEZOLE Drug Info
• Synonyms: Loreclezole < Rec INN; R-72063; (Z)-1-(alpha,2,4-Trichlorostyryl)-1H-1,2,4-triazole; (Z)-1-[2-Chloro-2-(2,4-dichlorophenyl)vinyl]-1H-1,2,4-triazole

Indication

Disease Entry	ICD 11	Status	REF
Epileptic seizures	8A61-8A6Z	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 3034012
  ChEBI ID: CHEBI:92491
  CAS Number: CAS 117857-45-1
  TTD Drug ID: DMCZI62

Molecule-Related Drug Atlas

Drug(s) Targeting GABA(A) receptor gamma-3 (GABRG3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zolpidem	DMWOSKJ	Insomnia	7A00-7A0Z	Approved	[4]
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[5]
Clobazam - Lundbeck	DMW1OQ0	Anxiety disorder	6B00-6B0Z	Approved	[6]
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[4]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[7]
Thiamylal	DMHDF7B	Anaesthesia	9A78.6	Approved	[6]
Ganaxolone	DMXJMKF	Epileptic seizures	8A61-8A6Z	Approved	[5]
Mebutamate	DM0KYI4	Anxiety disorder	6B00-6B0Z	Approved	[6]
Metharbital	DM5A38V	Epilepsy	8A60-8A68	Approved	[6]
Etomidate	DMZI3WO	Anaesthesia	9A78.6	Approved	[6]

Drug(s) Affected By Gamma-aminobutyric acid receptor subunit beta-3 (GABRB3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[8]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[9]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[11]
Lindane	DMB8CNL	Infestations of lice and scabies	1G00.Z	Approved	[12]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[13]
Flunitrazepam	DMGR5Z3	Insomnia	7A00-7A0Z	Approved	[14]
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[15]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[16]
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[17]

Drug(s) Affected By Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[8]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[9]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[19]
Vorinostat	DMWMPD4	Adult acute monocytic leukemia		Approved	[9]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[20]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[21]
Naltrexone	DMUL45H	Alcohol dependence	6C40.2	Approved	[22]
SNDX-275	DMH7W9X	Breast cancer	2C60-2C65	Phase 3	[23]
CHLORIDE	DM1TJXA	Solid tumour/cancer	2A00-2F9Z	Phase 3	[24]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
GABA(A) receptor gamma-3 (GABRG3)	TTEX6LM	GBRG3_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2)	OTAOZIGX	GBRB2_HUMAN	Drug Response	[3]
Gamma-aminobutyric acid receptor subunit beta-3 (GABRB3)	OT80C3D4	GBRB3_HUMAN	Drug Response	[3]

References

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• [2] Direct activation of GABAA receptors by loreclezole, an anticonvulsant drug with selectivity for the beta-subunit. Neuropharmacology. 1996;35(12):1753-60.
• [3] Heterogeneity of GABA(A) receptor-mediated responses in the human IMR-32 neuroblastoma cell line. J Neurosci Res. 2000 May 15;60(4):504-10. doi: 10.1002/(SICI)1097-4547(20000515)60:4<504::AID-JNR9>3.0.CO;2-Y.
• [4] 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: 415).
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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• [8] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] GABA receptor subunit composition relative to insecticide potency and selectivity. Toxicol Lett. 2001 Jul 6;122(3):215-22. doi: 10.1016/s0378-4274(01)00366-6.
• [13] 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.
• [14] p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol. J Med Chem. 2011 Dec 8;54(23):8124-35. doi: 10.1021/jm200943f. Epub 2011 Nov 10.
• [15] Retinoic acid, GABA-ergic, and TGF-beta signaling systems are involved in human cleft palate fibroblast phenotype. Mol Med. 2006 Sep-Oct;12(9-10):237-45. doi: 10.2119/2006C00026.Baroni.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors. Mol Pharmacol. 1996 Feb;49(2):253-9.
• [18] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [19] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [20] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [21] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [22] Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.
• [23] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [24] A novel allosteric modulatory site on the GABAA receptor beta subunit. Neuron. 1994 Apr;12(4):775-82. doi: 10.1016/0896-6273(94)90330-1.