Compounds > sar 020106
Page last updated: 2024-08-03 14:45:32

sar 020106

Description

SAR 020106: a CHK1 inhibitor; structure in first source [MeSH]

Cross-References

ID SourceID
PubMed CID44203948
CHEMBL ID1928705
SCHEMBL ID1396946
MeSH IDM0544522

Synonyms (30)

Synonym
(r)-5-(8-chloroisoquinolin-3-ylamino)-3-(1-(dimethylamino)propan-2-yloxy)pyrazine-2-carbonitrile
ym8 ,
bdbm50359807
CHEMBL1928705 ,
S7740
SRBJWIBAMIKCMV-GFCCVEGCSA-N ,
sar-020106
sar 020106
sar020106
SCHEMBL1396946
1184843-57-9
AC-29017
sar020106;sar 020106
NCGC00387035-01
AKOS030621761
5-[(8-chloroisoquinolin-3-yl)amino]-3-{[(2r)-1-(dimethylamino)propan-2-yl]oxy}pyrazine-2-carbonitrile
Q27467786
(r)-5-((8-chloroisoquinolin-3-yl)amino)-3-((1-(dimethylamino)propan-2-yl)oxy)pyrazine-2-carbonitrile
AS-16323
EX-A2810
AMY16632
BCP29578
sar020106; sar 020106; sar20106; sar20106; sar 20106
sar20106
sar 20106
CCG-268435
5-[(8-chloroisoquinolin-3-yl)amino]-3-[(2r)-1-(dimethylamino)propan-2-yl]oxypyrazine-2-carbonitrile
A898976
HY-100195
CS-0018190

Protein Targets (11)

Potency Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency7.5637AID1645841
GVesicular stomatitis virusPotency9.5221AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency0.6741AID1645840
Interferon betaHomo sapiens (human)Potency9.5221AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency9.5221AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency9.5221AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency9.5221AID1645842

Inhibition Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Serine/threonine-protein kinase Chk1Homo sapiens (human)IC500.0247AID634542; AID719557; AID719559
Serine/threonine-protein kinase Chk2Homo sapiens (human)IC50100.0000AID634543
Cyclin-dependent kinase 1Homo sapiens (human)IC507.5000AID719550
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC505.0000AID719553

Bioassays (44)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
ISSN: 2472-5560		Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
ISSN: 1521-0111		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
ISSN: 1091-6490		Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
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
ISSN: 1091-6490		Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
ISSN: 1521-0111		A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID717051Permeability across apical to basolateral side in human Caco2 cells2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634556Selectivity for human CHK1 over human BRSK12011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634546Antimitotic activity in etoposide-induced human HT-29 cells assessed as induction of M-phase phosphoprotein 2 expression by ELISA2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634548Inhibition of human CHK1 at 1 uM2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634555Selectivity for human CHK1 over human RSK12011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634558Selectivity for human CHK1 over human BRSK22011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634565Efflux ratio of permeability across apical to basolateral side over basolateral to apical side in human Caco2 cells2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719553Inhibition of human ERG overexpressed in HEK cells2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634569Antitumor activity against human SW620 cells xenografted in nude SCID mouse assessed as delay in tumor growth at 25 to 50 mg/kg, ip2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634549Inhibition of human RSK1 at 1 uM2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719556Ratio of GI50 for human HT-29 cells to IC50 for CHK1-mediated abrogation of etoposide-induced G2 check point arrest in human HT-29 cells2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634563Drug metabolism in human liver microsomes after 30 mins2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719559Inhibition of CHK1 using 5-FAM-KKKVSRSGLYRSPSMPENLNRPR-COOH as substrate after 1 hr by microfluidic assay in presence of ATP2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634562Drug metabolism in mouse liver microsomes after 30 mins2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634564Effective permeability across apical to basolateral side in human Caco2 cells2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634545Cytotoxicity against human HT-29 cells after 96 hrs by SRB assay2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719554Potentiation index, ratio of IC50 for human SW620 cells to IC50 for potentiation of gemcitabine-induced cytotoxicity in human SW620 cells2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID719582Oral bioavailability in BALB/c mouse at 10 mg/kg2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634553Inhibition of human RSK2 at 1 uM2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634559Selectivity for human CHK1 over human RSK22011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID717052Drug metabolism in mouse liver microsomes after 30 mins2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634554Inhibition of human NUAK1 at 1 uM2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634551Inhibition of human IRAK1 at 1 uM2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634561Drug metabolism in rat liver microsomes after 30 mins2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719546Inhibition of CHK1 in human SW620 cells assessed as potentiation of gemcitabine-induced cytotoxicity after 24 to 48 hrs2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634543Competitive inhibition of human CHK2 using ATP as substrate by DELFIA2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634557Selectivity for human CHK1 over human IRAK12011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634547Potentiation of SN38-induced cytotoxicity in human HT-29 cells after 96 hrs by SRB assay relative to control2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634568Potentiation of irinotecan-induced antitumor activity against human SW620 cells xenografted in nude SCID mouse assessed as delay in tumor growth at 40 mg/kg, ip2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719557Inhibition of CHK1 in human HT-29 cells assessed as etoposide-induced G2 check point arrest after 21 hrs by ELISA2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634550Inhibition of human BRSK1 at 1 uM2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634567In vivo inhibition of irinotecan-induced CHK1 phosphorylation at Ser296 residue in human SW620 cells xenografted in nude SCID mouse at 40 mg/kg, ip after 24 hrs by Western blot analysis2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634566Oral bioavailability in SCID mouse at 40 mg/kg2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID634560Selectivity for human CHK1 over human NUAK12011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719550Inhibition of CDK12012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634552Inhibition of human BRSK2 at 1 uM2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID719555Potentiation index, ratio of IC50 for human HT-29 cells to IC50 for potentiation of gemcitabine-induced cytotoxicity in human HT-29 cells2012Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22
ISSN: 1520-4804		Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
AID634542Competitive inhibition of human CHK1 using ATP as substrate by DELFIA2011Journal of medicinal chemistry, Dec-22, Volume: 54, Issue:24
ISSN: 1520-4804		Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
ISSN: 1554-8937		High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.

Research

Studies (9)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's6 (66.67)24.3611
2020's3 (33.33)2.80

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other9 (100.00%)84.16%
SubstanceStudiesClassesRolesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
staurosporine
1
indolocarbazole alkaloid;
organic heterooctacyclic compound		apoptosis inducer;
bacterial metabolite;
EC 2.7.11.13 (protein kinase C) inhibitor;
geroprotector		2011201113.0low000010
gemcitabine
1
organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
environmental contaminant;
immunosuppressive agent;
photosensitizing agent;
prodrug;
radiosensitizing agent;
xenobiotic		2012201212.0low000010
irinotecan
2
carbamate ester;
delta-lactone;
N-acylpiperidine;
pyranoindolizinoquinoline;
ring assembly;
tertiary alcohol;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
prodrug		2011201212.5medium000020
SubstanceStudiesClassesRolesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
pyrazines
3
diazine;
pyrazines		Daphnia magna metabolite2010201312.0high000120
deoxycytidine
1
pyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite		2010201014.0low000100
camptothecin
1
delta-lactone;
pyranoindolizinoquinoline;
quinoline alkaloid;
tertiary alcohol		antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
genotoxin;
plant metabolite		2010201014.0low000100
gemcitabine
1
organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
environmental contaminant;
immunosuppressive agent;
photosensitizing agent;
prodrug;
radiosensitizing agent;
xenobiotic		2010201014.0low000100
irinotecan
1
carbamate ester;
delta-lactone;
N-acylpiperidine;
pyranoindolizinoquinoline;
ring assembly;
tertiary alcohol;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
prodrug		2010201014.0low000100
ConditionIndicatedStudiesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
Cancer of Colon0
1
2012201212.0medium000010
Cancer of Head0
1
2013201311.0medium000010
Colonic Neoplasms0
1
2012201212.0medium000010
Colorectal Cancer0
1
2013201311.0medium000010
Colorectal Neoplasms0
1
2013201311.0medium000010
Congenital Zika Syndrome0
1
202020204.0medium000010
Disease Models, Animal0
1
202020204.0medium000010
Head and Neck Neoplasms0
1
2013201311.0medium000010
Neuroblastoma0
1
2012201212.0medium000010
Zika Virus Infection0
1
202020204.0medium000010

Bioavailability (2)

ArticleYear
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Molecular pharmacology, , Volume: 96, Issue:5		2019
Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
Journal of medicinal chemistry, , Nov-26, Volume: 55, Issue:22		2012

Dosage (1)

ArticleYear
Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.
Journal of medicinal chemistry, , Nov-26, Volume: 55, Issue:22		2012