Compounds > grn-529
Page last updated: 2024-11-13

grn-529

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

GRN-529: an mGluR5 antagonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID59548652
CHEMBL ID3122220
CHEMBL ID-3122220
SCHEMBL ID3413330
MeSH IDM0579870

Synonyms (26)

Synonym
gtpl6428
grn-529
2-{2-[2-(difluoromethoxy)-5-({5h,6h,7h-pyrrolo[3,4-b]pyridin-6-yl}carbonyl)phenyl]ethynyl}pyridine
CHEMBL3122220
SCHEMBL3413330
1253291-12-1
[4-(difluoromethoxy)-3-(2-pyridin-2-ylethynyl)phenyl]-(5,7-dihydropyrrolo[3,4-b]pyridin-6-yl)methanone
grn-529, >=97% (hplc)
NCGC00402239-03
jitmsirhbavrew-uhfffaoysa-n
Q5514489
(4-difluoromethoxy-3-pyridin-2-ylethynyl-phenyl)-(5,7-dihydro-pyrrolo[3,4-b]pyridin-6-yl)-methanone
AS-16399
(4-(difluoromethoxy)-3-(pyridin-2-ylethynyl)phenyl)(5,7-dihydro-6h-pyrrolo[3,4-b]pyridin-6-yl)methanone
AKOS037643432
grn529
grn 529
(4-(difluoromethoxy)-3-(2-pyridin-2-ylethynyl)phenyl)-(5,7-dihydropyrrolo(3,4-b)pyridin-6-yl)methanone
methanone, (4-(difluoromethoxy)-3-(2-(2-pyridinyl)ethynyl)phenyl)(5,7-dihydro-6h-pyrrolo(3,4-b)pyridin-6-yl)-
d77qdv7e9j ,
(4-(difluoromethoxy)-3-(2-(2-pyridinyl)ethynyl)phenyl)(5,7-dihydro-6h-pyrrolo(3,4-b)pyridin-6-yl)methanone
unii-d77qdv7e9j
chembl-3122220
[4-(difluoromethoxy)-3-(2-pyridinylethynyl)phenyl](5,7-dihydro-6h-pyrrolo[3,4-b]pyridin-6-yl)methanone
DTXSID501030348
methanone, [4-(difluoromethoxy)-3-[2-(2-pyridinyl)ethynyl]phenyl](5,7-dihydro-6h-pyrrolo[3,4-b]pyridin-6-yl)-

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
" This effort led to the discovery of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine (PF470, 14) as a highly potent, selective, and orally bioavailable mGluR5 NAM."( Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulat
Balan, G; Barreiro, G; Boscoe, BP; Chen, L; Chenard, LK; Cianfrogna, J; Claffey, MM; Coffman, KJ; Drozda, SE; Dunetz, JR; Fonseca, KR; Galatsis, P; Grimwood, S; Lazzaro, JT; Mancuso, JY; Miller, EL; Reese, MR; Rogers, BN; Sakurada, I; Shaffer, CL; Skaddan, M; Smith, DL; Stepan, AF; Trapa, P; Tuttle, JB; Verhoest, PR; Walker, DP; Wright, AS; Zaleska, MM; Zasadny, K; Zhang, L, 2014)		0.4
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)		0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency13.45040.01237.983543.2770AID1645841
cytochrome P450 2D6Homo sapiens (human)Potency21.31740.00108.379861.1304AID1645840
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1071428Therapeutic index in rat2014Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3
Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulat
AID1071427Therapeutic index in biliary epithelial hyperplasia rat model2014Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3
Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulat
AID1346254Rat mGlu5 receptor (Metabotropic glutamate receptors)2013Neuropharmacology, Mar, Volume: 66Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression.
AID1346269Human mGlu5 receptor (Metabotropic glutamate receptors)2013Neuropharmacology, Mar, Volume: 66Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (8)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's1 (12.50)29.6817
2010's5 (62.50)24.3611
2020's2 (25.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 22.54

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index22.54 (24.57)
Research Supply Index2.20 (2.92)
Research Growth Index5.43 (4.65)
Search Engine Demand Index18.60 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (22.54)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (12.50%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other7 (87.50%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
amantadine
amant: an antiviral compound consisting of an adamantane derivative chemically linked to a water-solube polyanioic matrix; structure in first source		2.110adamantanes;
primary aliphatic amine		analgesic;
antiparkinson drug;
antiviral drug;
dopaminergic agent;
NMDA receptor antagonist;
non-narcotic analgesic
baclofen
[no description available]		2.0710amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid;
monochlorobenzenes;
primary amino compound		central nervous system depressant;
GABA agonist;
muscle relaxant
glutamic acid
Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.. glutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2.		2.0810glutamic acid;
glutamine family amino acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
ferroptosis inducer;
micronutrient;
mouse metabolite;
neurotransmitter;
nutraceutical
6-methyl-2-(phenylethynyl)pyridine
6-methyl-2-(phenylethynyl)pyridine: an mGlu5 antagonist. 2-methyl-6-(phenylethynyl)pyridine : A methylpyridine that coinsists of 2-methylp[yridine bearing an additional phenylethynyl group at position 6. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw.		2.0810acetylenic compound;
methylpyridines		anxiolytic drug;
metabotropic glutamate receptor antagonist
mavoglurant
mavoglurant: antagonist of metabotropic glutamate receptor 5		2.0810
arbaclofen placarbil
arbaclofen placarbil: an R-baclofen prodrug; may improve the treatment of patients with gastroesophageal reflux disease, spasticity; structure in first source		2.0710
ro 4956371
2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine: a metabotropic glutamate receptor 5 antagonist; structure in first source		2.0710
ConditionIndicatedRelationship StrengthStudiesTrials
Refractory Depression
[description not available]		02.0810
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.5420
Depressive Disorder, Treatment-Resistant
Failure to respond to two or more trials of antidepressant monotherapy or failure to respond to four or more trials of different antidepressant therapies. (Campbell's Psychiatric Dictionary, 9th ed.)		02.0810
Dyskinesia, Medication-Induced
[description not available]		02.110
Delayed Hypersensitivity
[description not available]		02.110
Idiopathic Parkinson Disease
[description not available]		02.110
Dyskinesia, Drug-Induced
Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)		02.110
Parkinson Disease
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)		02.110
Congenital Zika Syndrome
[description not available]		02.2510
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Plasmodium falciparum Malaria
[description not available]		03.8810
Malaria, Falciparum
Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.		03.8810
Autism
[description not available]		02.0710
Aging
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.		02.0710
Autistic Disorder
A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V)		02.0710