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

General Information of Drug (ID: DM9LT60)

• Drug Name: Beta-Carboline-3-carboxylic acid t-butyl ester Drug Info
• Cross-matching ID:
  PubChem CID: 124514
  CAS Number: CAS 93835-05-3
  TTD Drug ID: DM9LT60

Molecule-Related Drug Atlas

Drug(s) Targeting GABA(A) receptor gamma-2 (GABRG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[2]
THIOCOLCHICOSIDE	DMEPWYA	Muscle spasm	MB47.3	Approved	[3]
ZK-93423	DMFWMKZ	Epileptic seizures	8A61-8A6Z	Phase 3	[4]
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[3]
ELTANOLONE	DM38CIV	Premenstrual syndrome	GA34.40	Discontinued in Phase 3	[2]
U-78875	DM2WOPX	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 1	[5]
CGS-9896	DM39PQI	N. A.	N. A.	Terminated	[6]
CGS-17867A	DMMZJY3	Alcohol dependence	6C40.2	Terminated	[7]
TBPS	DMFC3XP	Discovery agent	N.A.	Investigative	[8]
AMENTOFLAVONE	DMLRNV2	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting GABA(A) receptor alpha-5 (GABRA5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[10]
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[11]
Basmisanil	DMQ8J0U	Alzheimer disease	8A20	Phase 2	[12]
RG-7816	DMD16JK	Autism spectrum disorder	6A02	Phase 1	[13]
TBPS	DMFC3XP	Discovery agent	N.A.	Investigative	[10]
AMENTOFLAVONE	DMLRNV2	Discovery agent	N.A.	Investigative	[9]
Ro-15-3505	DM4NW3U	Discovery agent	N.A.	Investigative	[14]
isonipecotic acid	DMO1ZHE	Discovery agent	N.A.	Investigative	[10]
[3H]Ro154513	DMMBWKL	Discovery agent	N.A.	Investigative	[15]
[3H]CGS8216	DMLP68J	Inflammation	1A00-CA43.1	Investigative	[10]

Drug(s) Targeting GABA(A) receptor alpha-2 (GABRA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[16]
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[11]
PF-4480682	DMWYJHC	Neuropathic pain	8E43.0	Discontinued in Phase 2	[17]
CGS-17867A	DMMZJY3	Alcohol dependence	6C40.2	Terminated	[7]
TBPS	DMFC3XP	Discovery agent	N.A.	Investigative	[16]
AMENTOFLAVONE	DMLRNV2	Discovery agent	N.A.	Investigative	[9]
Ro-15-3505	DM4NW3U	Discovery agent	N.A.	Investigative	[14]
isonipecotic acid	DMO1ZHE	Discovery agent	N.A.	Investigative	[16]
[3H]Ro154513	DMMBWKL	Discovery agent	N.A.	Investigative	[15]
[3H]CGS8216	DMLP68J	Inflammation	1A00-CA43.1	Investigative	[16]

Drug(s) Targeting GABA(A) receptor alpha-1 (GABRA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[18]
Zolpidem	DMWOSKJ	Insomnia	7A00-7A0Z	Approved	[19]
Methoxyflurane	DML0RAE	Anaesthesia	9A78.6	Approved	[18]
Nitrazepam	DMEGIQ6	Epilepsy	8A60-8A68	Approved	[18]
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[2]
Clobazam - Lundbeck	DMW1OQ0	Anxiety disorder	6B00-6B0Z	Approved	[18]
Hexobarbital	DMQ314B	Anaesthesia	9A78.6	Approved	[18]
THIOCOLCHICOSIDE	DMEPWYA	Muscle spasm	MB47.3	Approved	[3]
Meprobamate	DMHM93Y	Anxiety		Approved	[18]
Zaleplon	DMGFWSM	Insomnia	7A00-7A0Z	Approved	[20]

Drug(s) Targeting GABA(A) receptor alpha-3 (GABRA3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[21]
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[11]
Adipiplon	DM821BS	Sleep-wake disorder	7A00-7B2Z	Phase 2	[22]
NS-2710	DMMUR6V	Anxiety disorder	6B00-6B0Z	Phase 2	[23]
AZD6280	DMFAZLU	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 1	[24]
TBPS	DMFC3XP	Discovery agent	N.A.	Investigative	[21]
AMENTOFLAVONE	DMLRNV2	Discovery agent	N.A.	Investigative	[9]
Ro-15-3505	DM4NW3U	Discovery agent	N.A.	Investigative	[14]
isonipecotic acid	DMO1ZHE	Discovery agent	N.A.	Investigative	[21]
[3H]Ro154513	DMMBWKL	Discovery agent	N.A.	Investigative	[15]

Drug(s) Targeting Gamma-aminobutyric acid receptor (GAR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[18]
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[25]
THIOCOLCHICOSIDE	DMEPWYA	Muscle spasm	MB47.3	Approved	[3]
Clonazepam	DMTO13J	Absence epilepsy		Approved	[26]
Piperazine	DMTY9LU	Ascariasis	1F62	Approved	[27]
Alpidem	DMN7Y9K	Anxiety disorder	6B00-6B0Z	Approved	[28]
Moxidectin	DMYGHX5	Onchocerciasis	1F6A	Approved	[29]
DP-VPA	DMGOXPQ	Bipolar disorder	6A60	Approved	[30]
ANDROSTERONE	DMITJAK	N. A.	N. A.	Phase 3	[25]
ZK-93423	DMFWMKZ	Epileptic seizures	8A61-8A6Z	Phase 3	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
GABA(A) receptor alpha-1 (GABRA1)	TT1MPAY	GBRA1_HUMAN	Inhibitor	[1]
GABA(A) receptor alpha-2 (GABRA2)	TTBMV1G	GBRA2_HUMAN	Inhibitor	[1]
GABA(A) receptor alpha-3 (GABRA3)	TT37EDJ	GBRA3_HUMAN	Inhibitor	[1]
GABA(A) receptor alpha-5 (GABRA5)	TTNZPQ1	GBRA5_HUMAN	Inhibitor	[1]
GABA(A) receptor gamma-2 (GABRG2)	TT06RH5	GBRG2_HUMAN	Inhibitor	[1]
Gamma-aminobutyric acid receptor (GAR)	TTNJYV2	NOUNIPROTAC	Inhibitor	[1]

References

• [1] Design, synthesis, and subtype selectivity of 3,6-disubstituted -carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents f... Bioorg Med Chem. 2010 Nov 1;18(21):7548-64.
• [2] Neurosteroid analogues. 10. The effect of methyl group substitution at the C-6 and C-7 positions on the GABA modulatory and anesthetic actions of (... J Med Chem. 2005 Apr 21;48(8):3051-9.
• [3] 3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds. J Med Chem. 2006 Sep 7;49(18):5571-7.
• [4] Structural requirements for agonist actions at the benzodiazepine receptor: studies with analogues of 6-(benzyloxy)-4-(methoxymethyl)-beta-carbolin... J Med Chem. 1990 Mar;33(3):1062-9.
• [5] 3-Phenyl-substituted imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas that have high affinity at the GABAA/benzodiazepin... J Med Chem. 1996 Sep 13;39(19):3820-36.
• [6] Synthesis, pharmacology, and structure-activity relationships of novel imidazolones and pyrrolones as modulators of GABAA receptors. J Med Chem. 2006 Mar 23;49(6):1855-66.
• [7] 2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones: functionally selective benzodiazepine binding site ligands on the GABAA receptor. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3441-4.
• [8] 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: 414).
• [9] Semisynthetic preparation of amentoflavone: A negative modulator at GABA(A) receptors. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2281-4.
• [10] 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: 408).
• [11] New anticonvulsants: Schiff bases of gamma-aminobutyric acid and gamma-aminobutyramide. J Med Chem. 1980 Jun;23(6):702-4.
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [14] The GABA(A) receptor as a target for photochromic molecules. Bioorg Med Chem. 2010 Nov 15;18(22):7731-8.
• [15] Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepines: high-affinity, selective probes for alpha 5-containing GABA... J Med Chem. 1996 Apr 26;39(9):1928-34.
• [16] 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: 405).
• [17] WO patent application no. 2014,1515,17, Methods of improving microvascular integrity.
• [18] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [19] Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat.Brain Res Bull.2006 Dec 11;71(1-3):200-7.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [21] 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: 406).
• [22] Discriminative stimulus properties of GABAA receptor positive allosteric modulators TPA023, ocinaplon and NG2-73 in rats trained to discriminate chlordiazepoxide or zolpidem. Eur J Pharmacol. 2011 Oct 1;668(1-2):190-3.
• [23] GABAA receptor subtype-selective modulators. I. alpha2/alpha3-selective agonists as non-sedating anxiolytics. Curr Top Med Chem. 2011;11(9):1176-202.
• [24] AZD6280, a novel partial -aminobutyric acid A receptor modulator, demonstrates a pharmacodynamically selective effect profile in healthy male volunteers.J Clin Psychopharmacol.2015 Feb;35(1):22-33.
• [25] Neurosteroid analogues. 11. Alternative ring system scaffolds: gamma-aminobutyric acid receptor modulation and anesthetic actions of benz[f]indenes. J Med Chem. 2006 Jul 27;49(15):4595-605.
• [26] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [27] Cyclooctadepsipeptides--an anthelmintically active class of compounds exhibiting a novel mode of action. Int J Antimicrob Agents. 2003 Sep;22(3):318-31.
• [28] Synthesis and binding affinity of 2-phenylimidazo[1,2-alpha]pyridine derivatives for both central and peripheral benzodiazepine receptors. A new se... J Med Chem. 1997 Sep 12;40(19):3109-18.
• [29] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [30] DP-VPA D-Pharm. Curr Opin Investig Drugs. 2002 Jun;3(6):921-3.