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

General Information of DTT (ID: TTDCVZW)

• DTT Name: Gamma-aminobutyric acid B receptor (GABBR) DTT Info
• Gene Name: GABBR1

Molecule-Related Drug & Molecule List

4 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Baclofen	DM0QV1J	Multiple sclerosis	8A40	Approved	[1]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[2]
Gamma Hydroxybutyric Acid	DMGBKVD	Narcolepsy	7A20	Approved	[3]
Progabide	DM671NG	Depression	6A70-6A7Z	Approved	[4]

7 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arabaclofen	DMZB9RI	Fragile X syndrome	LD55	Phase 3	[5]
Arbaclofen placarbil	DMO628K	Fragile X syndrome	LD55	Phase 3	[6]
[3H](R)-(-)-baclofen	DMLRHM5	Multiple sclerosis	8A40	Phase 3	[7]
ASP8062	DMR1MIV	Fibromyalgia	MG30.01	Phase 2	[8]
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[9]
SGS742	DM5XYFH	Schizophrenia	6A20	Phase 2	[10]
SSTarbaclofen	DMRGTZ2	Autism spectrum disorder	6A02	Phase 2	[11]

5 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SUN-09	DMMG47P	Hypertonia	KB08.1	Discontinued in Phase 3	[12]
AZD3355	DMT5ZK3	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[13]
AZD-9343	DM1ZVO3	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 1	[14]
CGP-35348	DMZM70X	Epilepsy	8A60-8A68	Terminated	[16]
SCH 50911	DMW9H4A	Absence seizure	8A68.2	Terminated	[17]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ADX-71943	DMEWFOL	Gastroesophageal reflux disease	DA22.Z	Preclinical	[15]

43 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
((E)-3-Amino-propenyl)-methyl-phosphinic acid	DMEJRVW	Discovery agent	N.A.	Investigative	[18]
((Z)-3-Amino-propenyl)-methyl-phosphinic acid	DM6H0FW	Discovery agent	N.A.	Investigative	[18]
(3-Amino-1-ethyl-propyl)-methyl-phosphinic acid	DMPHCX7	Discovery agent	N.A.	Investigative	[18]
(3-Amino-1-hydroxy-propyl)-methyl-phosphinic acid	DM7HF4I	Discovery agent	N.A.	Investigative	[18]
(3-Amino-phenyl)-phosphonic acid diphenyl ester	DMDGFS0	Discovery agent	N.A.	Investigative	[19]
(3-Amino-propyl)-hexyl-phosphinic acid	DMBJYTD	Discovery agent	N.A.	Investigative	[20]
(3-Amino-propyl)-hydroxymethyl-phosphinic acid	DMGFIJV	Discovery agent	N.A.	Investigative	[18]
(3-Amino-propyl)-phosphonic acid	DMK3JZS	Discovery agent	N.A.	Investigative	[19]
(R)-5-Amino-3-(4-chloro-phenyl)-pentanoic acid	DMW87OE	Discovery agent	N.A.	Investigative	[1]
2-hydroxy-saclofen	DMHO8KQ	Discovery agent	N.A.	Investigative	[21]
3-ammoniopropane-1-sulfinate	DM5SQVC	Discovery agent	N.A.	Investigative	[22]
4-Amino-3-(2-chloro-phenyl)-butyric acid	DMIX81A	Discovery agent	N.A.	Investigative	[9]
4-Amino-3-(4-fluoro-phenyl)-butyric acid	DMVKPF1	Discovery agent	N.A.	Investigative	[9]
4-Amino-3-(5-bromo-thiophen-2-yl)-butyric acid	DMTO8NV	Discovery agent	N.A.	Investigative	[9]
4-Amino-3-(5-chloro-thiophen-2-yl)-butyric acid	DM415DB	Discovery agent	N.A.	Investigative	[9]
4-Amino-3-(5-methyl-thiophen-2-yl)-butyric acid	DMEDRAX	Discovery agent	N.A.	Investigative	[9]
4-Amino-3-benzofuran-2-yl-butyric acid	DM1IHCV	Discovery agent	N.A.	Investigative	[23]
4-Amino-3-thiophen-2-yl-butyric acid	DMZJS2E	Discovery agent	N.A.	Investigative	[9]
amino-propylphosphinic acid	DMT5HOA	Discovery agent	N.A.	Investigative	[7]
AVE-1876	DMC0PY5	Discovery agent	N.A.	Investigative	[24]
BHF-177	DMP21ST	Anxiety disorder	6B00-6B0Z	Investigative	[25]
CGP 46381	DMXV6RD	Discovery agent	N.A.	Investigative	[26]
CGP 47656	DME39UQ	Discovery agent	N.A.	Investigative	[21]
CGP 54626A	DMEHYVS	Discovery agent	N.A.	Investigative	[27]
CGP 55845	DMNMG0I	Discovery agent	N.A.	Investigative	[26]
CGP 56999A	DMR708D	Discovery agent	N.A.	Investigative	[21]
CGP 62349	DMYXE39	Discovery agent	N.A.	Investigative	[28]
CGP 64213	DMR8U1M	Discovery agent	N.A.	Investigative	[21]
CGP 71872	DMJWED7	Discovery agent	N.A.	Investigative	[21]
CGP-29030A	DMS61KA	Pain	MG30-MG3Z	Investigative	[29]
CGP-34938	DM84TSH	Discovery agent	N.A.	Investigative	[18]
CGP-35024	DMHKETG	Discovery agent	N.A.	Investigative	[30]
CGP-35582	DM3J6HM	Discovery agent	N.A.	Investigative	[18]
CGP-36216	DM9U8TO	Discovery agent	N.A.	Investigative	[20]
CGP-44532	DMKF0GH	Drug abuse	6C4G.1Z	Investigative	[31]
GABA-B receptor PAM	DMOF7JL	Anxiety disorder	6B00-6B0Z	Investigative	[25]
Phaclofen	DMALRCH	Discovery agent	N.A.	Investigative	[32]
PMID25050158C14	DMRFQ1W	Discovery agent	N.A.	Investigative	[33]
saclofen	DM3TO27	Discovery agent	N.A.	Investigative	[21]
TG-3030	DM8RSDE	Nicotine dependence	6C4A.2	Investigative	[25]
[125I]CGP 64213	DMIAO4V	Discovery agent	N.A.	Investigative	[34]
[125I]CGP 71872	DMQVW4E	Discovery agent	N.A.	Investigative	[21]
[3H]CGP27492	DMQTBRM	Discovery agent	N.A.	Investigative	[20]

References

• [1] Synthesis and pharmacology of the baclofen homologues 5-amino-4-(4-chlorophenyl)pentanoic acid and the R- and S-enantiomers of 5-amino-3-(4-chlorop... J Med Chem. 1999 Jun 3;42(11):2053-9.
• [2] Gabapentin increases a tonic inhibitory conductance in hippocampal pyramidal neurons. Anesthesiology. 2006 Aug;105(2):325-33.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse. Pharmacol Biochem Behav. 1998 Jan;59(1):239-47.
• [5] Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology (Berl). 2013 Jul;228(1):75-84.
• [6] Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen.J Pharmacol Exp Ther.2009 Sep;330(3):911-21.
• [7] 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: 242).
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] 3-Thienyl- and 3-furylaminobutyric acids. Synthesis and binding GABAB receptor studies. J Med Chem. 1991 Aug;34(8):2557-60.
• [10] SGS742: the first GABA(B) receptor antagonist in clinical trials. Biochem Pharmacol. 2004 Oct 15;68(8):1479-87.
• [11] Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Sci Transl Med. 2012 Sep 19;4(152):152ra128.
• [12] The effects of the GABA agonist, baclofen, on sleep and breathing. Eur Respir J. 1995 Feb;8(2):230-4.
• [13] Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial.Gut.2013 Sep;62(9):1248-55.
• [14] The GABA(B) receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I study. Aliment Pharmacol Ther. 2009 Nov 1;30(9):937-46.
• [15] Evaluation of peripheral versus central effects of GABA(B) receptor activation using a novel, positive allosteric modulator of the GABA(B) receptor ADX71943, a pharmacological tool compound with a fully peripheral activity profile. Br J Pharmacol. 2014 Nov;171(21):4941-54.
• [16] The selective GABAB antagonist CGP-35348 blocks spike-wave bursts in the cholesterol synthesis rat absence epilepsy model. Brain Res. 1996 Aug 12;729(2):147-50.
• [17] Activation of nigral dopamine neurons by the selective GABA(B)-receptor antagonist SCH 50911. J Neural Transm. 1999;106(5-6):383-94.
• [18] Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists. J Med Chem. 1995 Aug 18;38(17):3297-312.
• [19] Phosphorus analogues of gamma-aminobutyric acid, a new class of anticonvulsants. J Med Chem. 1984 May;27(5):654-9.
• [20] Biological activity of 3-aminopropyl (methyl) phosphinic acid, a potent and selective GABAB agonist with CNS activity, Bioorg. Med. Chem. Lett. 3(4):515-518 (1993).
• [21] Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature. 1997 Mar 20;386(6622):239-46.
• [22] A study of 3-amino-N-hydroxypropanesulfonamide derivatives as potential GABAB agonists and their fragmentation to 3-aminopropanesulfinic acid, Bioorg. Med. Chem. Lett. 6(14):1709-1714 (1996).
• [23] Synthesis and pharmacological evaluation of gamma-aminobutyric acid analogues. New ligand for GABAB sites. J Med Chem. 1987 Apr;30(4):743-6.
• [24] Company report (Sanofi)
• [25] 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: 241).
• [26] The human GABA(B1b) and GABA(B2) heterodimeric recombinant receptor shows low sensitivity to phaclofen and saclofen. Br J Pharmacol. 2000 Nov;131(6):1050-4.
• [27] GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature. 1998 Dec 17;396(6712):674-9.
• [28] Characterisation and partial purification of the GABA(B) receptor from the rat cerebellum using the novel antagonist [3H]CGP 62349. Brain Res Mol Brain Res. 1999 Aug 25;71(2):279-89.
• [29] Effects of a novel piperazine derivative (CGP 29030A) on nociceptive dorsal horn neurons in the rat. Drugs Exp Clin Res. 1992;18(11-12):447-59.
• [30] Inhibition of transient LES relaxations and reflux in ferrets by GABA receptor agonists. Am J Physiol. 1999 Oct;277(4 Pt 1):G867-74.
• [31] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [32] Astrocytes and interneurons in memory processing in the chick hippocampus: roles for G-coupled protein receptors, GABA(B) and mGluR1. Neurochem Res. 2009 Oct;34(10):1712-20.
• [33] Discovery of a Negative Allosteric Modulator of GABAB Receptors. ACS Med Chem Lett. 2014 May 27;5(7):742-7.
• [34] Ca(2+) requirement for high-affinity gamma-aminobutyric acid (GABA) binding at GABA(B) receptors: involvement of serine 269 of the GABA(B)R1 subunit. Mol Pharmacol. 2000 Mar;57(3):419-26.