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

General Information of Drug (ID: DM62XC3)

• Drug Name: 4,6-Dichloro-1H-indole-2-carboxylic acid Drug Info
• Synonyms: 101861-63-6; 4,6-dichloro-1H-indole-2-carboxylic acid; 4,6-Dichloroindole-2-carboxylic acid; CHEMBL301556; 1H-Indole-2-carboxylicacid, 4,6-dichloro-; 3-(4,6-Dichloro-2-carboxyindol-3-yl)propionic acid; 3-Dccip; KBio2_007460; PubChem7197; Spectrum_001822; SpecPlus_000800; 4,6-Dichloro-1H-indole-2-carboxylicacid; ACMC-1BPUR; AC1Q3MQM; AC1L2SZE; Maybridge1_006804; AC1Q73TA; Oprea1_268024; KBioSS_002327; SCHEMBL727389; DivK1c_006896; KBio2_004892; KBio2_002324; KBio1_001840; CTK0H4782; HMS560N06; DTXSID80144299; MolPort-000-147-351; Mdl-29951

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 127988
  CAS Number: CAS 101861-63-6
  TTD Drug ID: DM62XC3

Molecule-Related Drug Atlas

Drug(s) Targeting Glutamate receptor ionotropic NMDA 2A (NMDAR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[3]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[4]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[5]
SPERMINE	DMD4BFY	N. A.	N. A.	Terminated	[6]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[7]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[8]
DIZOCILPINE	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[9]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[10]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[11]
L-695902	DMT1DNS	N. A.	N. A.	Terminated	[8]

Drug(s) Targeting Glutamate receptor ionotropic NMDA 1 (NMDAR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cycloserine	DMT1I52	Bacterial infection	1A00-1C4Z	Approved	[12]
D-Serine	DM3YH4I	N. A.	N. A.	Phase 4	[13]
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[14]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[4]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[5]
SPERMINE	DMD4BFY	N. A.	N. A.	Terminated	[6]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[15]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[8]
DIZOCILPINE	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[9]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[10]

Drug(s) Targeting Glutamate receptor ionotropic NMDA 2B (NMDAR2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha 1-PI	DMXC1K9	Alpha-1 antitrypsin deficiency	5C5A	Approved	[16]
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[14]
CP-101,606	DMIU19E	Parkinson disease	8A00.0	Phase 2	[17]
CERC-301	DMSABRI	Major depressive disorder	6A70.3	Phase 2	[18]
RGH-896	DMCHZAN	Peripheral neuropathy	8C0Z	Phase 2	[19]
MIJ821	DMN45RI	Major depressive disorder	6A70.3	Phase 2	[20]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[4]
Neu-2000	DMNJTLC	Cardiac arrest	MC82	Phase 1	[21]
EVT100	DMAKWQD	Major depressive disorder	6A70.3	Phase 1	[22]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[5]

Drug(s) Targeting Fructose-1,6-bisphosphatase (FBP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Managlinat dialanetil	DMBYDNE	Type-2 diabetes	5A11	Phase 2	[23]
MB07803	DMHU8SJ	Type-2 diabetes	5A11	Phase 2	[24]
4-(2-amino-1,3-thiazol-4-yl)phenol	DMH5CAQ	Discovery agent	N.A.	Investigative	[25]
Fructose-6-Phosphate	DMU5SAF	Discovery agent	N.A.	Investigative	[12]
1-(4-aminophenylsulfonyl)-3-(2-mercaptoethyl)urea	DM4G0NH	Discovery agent	N.A.	Investigative	[26]
2,5-Anhydroglucitol-1,6-Biphosphate	DMLDHMB	Discovery agent	N.A.	Investigative	[12]
1-(2-mercaptoethyl)-3-(m-tolylsulfonyl)urea	DMIPAMW	Discovery agent	N.A.	Investigative	[26]
4-(4-(4-Nitrophenyl)thiazol-2-ylamino)phenol	DMA9TCD	Discovery agent	N.A.	Investigative	[25]
3-(4-(4-Hydroxyphenyl)thiazol-2-ylamino)phenol	DM8EH07	Discovery agent	N.A.	Investigative	[25]
2-(4-(4-Hydroxyphenyl)thiazol-2-ylamino)phenol	DMOYT8I	Discovery agent	N.A.	Investigative	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fructose-1,6-bisphosphatase (FBP)	TTWHDVK	F16P1_HUMAN; F16P2_HUMAN	Inhibitor	[1]
Glutamate receptor ionotropic NMDA 1 (NMDAR1)	TTLD29N	NMDZ1_HUMAN	Inhibitor	[2]
Glutamate receptor ionotropic NMDA 2A (NMDAR2A)	TTKJEMQ	NMDE1_HUMAN	Inhibitor	[2]
Glutamate receptor ionotropic NMDA 2B (NMDAR2B)	TTN9D8E	NMDE2_HUMAN	Inhibitor	[2]

References

• [1] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [2] 3-(2-carboxyindol-3-yl)propionic acid derivatives: antagonists of the strychnine-insensitive glycine receptor associated with the N-methyl-D-aspart... J Med Chem. 1990 Nov;33(11):2944-6.
• [3] Glycine transport inhibitors for the treatment of schizophrenia: Symptom and disease modification. Curr Opin Drug Discov Devel. 2009 Jul;12(4):468-78.
• [4] Synthesis, ionotropic glutamate receptor binding affinity, and structure-activity relationships of a new set of 4,5-dihydro-8-heteroaryl-4-oxo-1,2,... J Med Chem. 2001 Sep 13;44(19):3157-65.
• [5] 4,10-Dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives: highly potent and selective AMPA receptors antagonists with... Bioorg Med Chem Lett. 2000 May 15;10(10):1133-7.
• [6] Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. J Med Chem. 2010 May 13;53(9):3611-7.
• [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: 456).
• [8] Amino acid bioisosteres: design of 2-quinolone derivatives as glycine-site N-methyl-D-aspartate receptor antagonists, Bioorg. Med. Chem. Lett. 3(2):299-304 (1993).
• [9] Synthesis and evaluation of 6,11-ethanohexahydrobenzo[b]quinolizidines: a new class of noncompetitive N-methyl-D-aspartate antagonists. J Med Chem. 1995 Jun 23;38(13):2483-9.
• [10] Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site of the NMDA receptor with potent in vivo activity. J Med Chem. 2000 Jun 15;43(12):2371-81.
• [11] Synthesis of thieno[2,3-b]pyridinones acting as cytoprotectants and as inhibitors of [3H]glycine binding to the N-methyl-D-aspartate (NMDA) receptor. J Med Chem. 2006 Feb 9;49(3):864-71.
• [12] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
• [14] 4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: a novel, potent, and selective NR1/2B NMDA receptor antagonist. J Med Chem. 1999 Jul 29;42(15):2993-3000.
• [15] 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: 455).
• [16] NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum. PLoS One. 2009;4(4):e5250.
• [17] NMDA receptors as targets for drug action in neuropathic pain. Eur J Pharmacol. 2001 Oct 19;429(1-3):71-8.
• [18] Inhibition of in vivo [(3)H]MK-801 binding by NMDA receptor open channel blockers and GluN2B antagonists in rats and mice. Eur J Pharmacol. 2015 Nov 5;766:1-8.
• [19] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [20] Clinical pipeline report, company report or official report of Cadent Therapeutics.
• [21] Neu2000, an NR2B-selective, moderate NMDA receptor antagonist and potent spin trapping molecule for stroke. Drug News Perspect. 2010 Nov;23(9):549-56.
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [23] MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes. Proc Natl Acad Sci U S A. 2005 May 31;102(22):7970-5.
• [24] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [25] A library of novel allosteric inhibitors against fructose 1,6-bisphosphatase. Bioorg Med Chem. 2009 Jun 1;17(11):3916-22.
• [26] Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4708-12.