trequinsin FDA approved compound

9,10-dimethoxy-3-methyl-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one

A vasodilator.

[PubChem] [DrugBank] [Wikipedia] [WikiGenes] [ChEMBL] [ChemSpider] 



Source SMILES: standardizedunstandardized
Compound:
Screen ID SGTC_460
Screen concentration 123.0 μM
Source Miscellaneous
PubChem CID 5537
SMILES CC1=CC(=C(C(=C1)C)N=C2C=C3C4=CC(=C(C=C4CCN3C(=O)N2C)OC)OC)C
Standardized SMILES COc1cc2CCN3C(=O)N(C)C(=Nc4c(C)cc(C)cc4C)C=C3c2cc1OC
Molecular weight 405.4895
ALogP 4.49
H-bond donor count 0
H-bond acceptor count 4
Response signature

Pool Growth Kinetics
% growth inhibition (Het. pool) 6.78
% growth inhibition (Hom. pool) 4.33


HIP profile

Heterozygous deletion strains
Scale: fixedexpanded
Heterozygous profile for 5537
Download HIP data (tab-delimited text)  (excel)
Gene:LSG1(YGL099W)|FD-Score:4.5|P-value:3.42E-6|Clearance:0.79||SGD DESC:Putative GTPase involved in 60S ribosomal subunit biogenesis; required for the release of Nmd3p from 60S subunits in the cytoplasm Gene:SLD5(YDR489W)|FD-Score:3.71|P-value:1.03E-4|Clearance:0.75||SGD DESC:Subunit of the GINS complex (Sld5p, Psf1p, Psf2p, Psf3p), which is localized to DNA replication origins and implicated in assembly of the DNA replication machinery Gene:SSL1(YLR005W)|FD-Score:-3.33|P-value:4.31E-4|Clearance:0||SGD DESC:Component of the core form of RNA polymerase transcription factor TFIIH, which has both protein kinase and DNA-dependent ATPase/helicase activities and is essential for transcription and nucleotide excision repair; interacts with Tfb4p Gene:LSG1(YGL099W)|FD-Score:4.5|P-value:3.42E-6|Clearance:0.79||SGD DESC:Putative GTPase involved in 60S ribosomal subunit biogenesis; required for the release of Nmd3p from 60S subunits in the cytoplasm Gene:SLD5(YDR489W)|FD-Score:3.71|P-value:1.03E-4|Clearance:0.75||SGD DESC:Subunit of the GINS complex (Sld5p, Psf1p, Psf2p, Psf3p), which is localized to DNA replication origins and implicated in assembly of the DNA replication machinery Gene:SSL1(YLR005W)|FD-Score:-3.33|P-value:4.31E-4|Clearance:0||SGD DESC:Component of the core form of RNA polymerase transcription factor TFIIH, which has both protein kinase and DNA-dependent ATPase/helicase activities and is essential for transcription and nucleotide excision repair; interacts with Tfb4p

HOP profile

Homozygous deletion strains
Scale: fixedexpanded
Homozygous profile for 5537
Download HOP data (tab-delimited text)  (excel)
Gene:ADE17(YMR120C)|FD-Score:-5.2|P-value:9.82E-8||SGD DESC:Enzyme of 'de novo' purine biosynthesis; contains both 5-aminoimidazole-4-carboxamide ribonucleotide transformylase and inosine monophosphate cyclohydrolase activities; ADE17 has a paralog, ADE16, that arose from the whole genome duplication; ade16 ade17 mutants require adenine and histidine Gene:ADE6(YGR061C)|FD-Score:-3.77|P-value:8.29E-5||SGD DESC:Formylglycinamidine-ribonucleotide (FGAM)-synthetase, catalyzes a step in the 'de novo' purine nucleotide biosynthetic pathway Gene:APL3(YBL037W)|FD-Score:-3.13|P-value:8.69E-4||SGD DESC:Alpha-adaptin, large subunit of the clathrin associated protein complex (AP-2); involved in vesicle mediated transport Gene:ARO9(YHR137W)|FD-Score:3.25|P-value:5.73E-4||SGD DESC:Aromatic aminotransferase II, catalyzes the first step of tryptophan, phenylalanine, and tyrosine catabolism Gene:BPT1(YLL015W)|FD-Score:-3.97|P-value:3.58E-5||SGD DESC:ABC type transmembrane transporter of MRP/CFTR family, found in vacuolar membrane, involved in the transport of unconjugated bilirubin and in heavy metal detoxification via glutathione conjugates, along with Ycf1p Gene:FMP33(YJL161W_p)|FD-Score:3.32|P-value:4.49E-4||SGD DESC:Putative protein of unknown function; the authentic, non-tagged protein is detected in highly purified mitochondria in high-throughput studies Gene:GIP3(YPL137C)|FD-Score:-3.35|P-value:4.00E-4||SGD DESC:Cytoplasmic protein that regulates protein phosphatase 1 Glc7p; overexpression relocalizes Glc7p from the nucleus and prevents chromosome segregation; may interact with ribosomes, based on co-purification experiments; GIP3 has a paralog, HER1, that arose from the whole genome duplication Gene:GSM1(YJL103C)|FD-Score:3.45|P-value:2.80E-4||SGD DESC:Putative zinc cluster protein of unknown function; proposed to be involved in the regulation of energy metabolism, based on patterns of expression and sequence analysis Gene:KSS1(YGR040W)|FD-Score:3.8|P-value:7.38E-5||SGD DESC:Mitogen-activated protein kinase (MAPK) involved in signal transduction pathways that control filamentous growth and pheromone response; the KSS1 gene is nonfunctional in S288C strains and functional in W303 strains Gene:MHF1(YOL086W-A)|FD-Score:-5.39|P-value:3.59E-8||SGD DESC:Component of the heterotetrameric MHF histone-fold complex; in humans the MMF complex interacts with both DNA and Mph1p ortholog FANCM, a Fanconi anemia complementation group protein, to stabilize and remodel blocked replication forks and repair damaged DNA; mhf1 srs2 double mutants are MMS hypersensitive; ortholog of human centromere constitutive-associated network (CCAN) subunit CENP-S, also known as MHF1 Gene:MSB2(YGR014W)|FD-Score:3.68|P-value:1.17E-4||SGD DESC:Mucin family member involved in signaling; functions in the Cdc42p- and MAP kinase-dependent filamentous growth signaling pathway; is processed into secreted and cell-associated forms by the aspartyl protease, Yps1p; also functions as an osmosensor in parallel to the Sho1p-mediated pathway; potential Cdc28p substrate Gene:PGD1(YGL025C)|FD-Score:3.9|P-value:4.71E-5||SGD DESC:Subunit of the RNA polymerase II mediator complex; associates with core polymerase subunits to form the RNA polymerase II holoenzyme; essential for basal and activated transcription; direct target of Cyc8p-Tup1p transcriptional corepressor Gene:SSP120(YLR250W)|FD-Score:3.09|P-value:9.92E-4||SGD DESC:Protein of unknown function; green fluorescent protein (GFP)-fusion protein localizes to the cytoplasm in a punctate pattern Gene:YCL042W(YCL042W_p)|FD-Score:4.14|P-value:1.72E-5||SGD DESC:Putative protein of unknown function; epitope-tagged protein localizes to the cytoplasm Gene:YDR182W-A(YDR182W-A_p)|FD-Score:3.18|P-value:7.35E-4||SGD DESC:Putative protein of unknown function; identified by fungal homology and RT-PCR Gene:YKL100C(YKL100C_p)|FD-Score:3.69|P-value:1.13E-4||SGD DESC:Putative protein of unknown function with similarity to a human minor histocompatibility antigen and signal peptide peptidases; YKL100C is not an essential gene Gene:YMR160W(YMR160W_p)|FD-Score:4|P-value:3.23E-5||SGD DESC:Protein of unknown function; green fluorescent protein (GFP)-fusion protein localizes to the membrane of the vacuole; mutant has enhanced sensitivity to overexpression of mutant huntingtin; YMR160W is not an essential gene; relative distribution within the vacuolar membrane changes upon DNA replication stress Gene:ADE17(YMR120C)|FD-Score:-5.2|P-value:9.82E-8||SGD DESC:Enzyme of 'de novo' purine biosynthesis; contains both 5-aminoimidazole-4-carboxamide ribonucleotide transformylase and inosine monophosphate cyclohydrolase activities; ADE17 has a paralog, ADE16, that arose from the whole genome duplication; ade16 ade17 mutants require adenine and histidine Gene:ADE6(YGR061C)|FD-Score:-3.77|P-value:8.29E-5||SGD DESC:Formylglycinamidine-ribonucleotide (FGAM)-synthetase, catalyzes a step in the 'de novo' purine nucleotide biosynthetic pathway Gene:APL3(YBL037W)|FD-Score:-3.13|P-value:8.69E-4||SGD DESC:Alpha-adaptin, large subunit of the clathrin associated protein complex (AP-2); involved in vesicle mediated transport Gene:ARO9(YHR137W)|FD-Score:3.25|P-value:5.73E-4||SGD DESC:Aromatic aminotransferase II, catalyzes the first step of tryptophan, phenylalanine, and tyrosine catabolism Gene:BPT1(YLL015W)|FD-Score:-3.97|P-value:3.58E-5||SGD DESC:ABC type transmembrane transporter of MRP/CFTR family, found in vacuolar membrane, involved in the transport of unconjugated bilirubin and in heavy metal detoxification via glutathione conjugates, along with Ycf1p Gene:FMP33(YJL161W_p)|FD-Score:3.32|P-value:4.49E-4||SGD DESC:Putative protein of unknown function; the authentic, non-tagged protein is detected in highly purified mitochondria in high-throughput studies Gene:GIP3(YPL137C)|FD-Score:-3.35|P-value:4.00E-4||SGD DESC:Cytoplasmic protein that regulates protein phosphatase 1 Glc7p; overexpression relocalizes Glc7p from the nucleus and prevents chromosome segregation; may interact with ribosomes, based on co-purification experiments; GIP3 has a paralog, HER1, that arose from the whole genome duplication Gene:GSM1(YJL103C)|FD-Score:3.45|P-value:2.80E-4||SGD DESC:Putative zinc cluster protein of unknown function; proposed to be involved in the regulation of energy metabolism, based on patterns of expression and sequence analysis Gene:KSS1(YGR040W)|FD-Score:3.8|P-value:7.38E-5||SGD DESC:Mitogen-activated protein kinase (MAPK) involved in signal transduction pathways that control filamentous growth and pheromone response; the KSS1 gene is nonfunctional in S288C strains and functional in W303 strains Gene:MHF1(YOL086W-A)|FD-Score:-5.39|P-value:3.59E-8||SGD DESC:Component of the heterotetrameric MHF histone-fold complex; in humans the MMF complex interacts with both DNA and Mph1p ortholog FANCM, a Fanconi anemia complementation group protein, to stabilize and remodel blocked replication forks and repair damaged DNA; mhf1 srs2 double mutants are MMS hypersensitive; ortholog of human centromere constitutive-associated network (CCAN) subunit CENP-S, also known as MHF1 Gene:MSB2(YGR014W)|FD-Score:3.68|P-value:1.17E-4||SGD DESC:Mucin family member involved in signaling; functions in the Cdc42p- and MAP kinase-dependent filamentous growth signaling pathway; is processed into secreted and cell-associated forms by the aspartyl protease, Yps1p; also functions as an osmosensor in parallel to the Sho1p-mediated pathway; potential Cdc28p substrate Gene:PGD1(YGL025C)|FD-Score:3.9|P-value:4.71E-5||SGD DESC:Subunit of the RNA polymerase II mediator complex; associates with core polymerase subunits to form the RNA polymerase II holoenzyme; essential for basal and activated transcription; direct target of Cyc8p-Tup1p transcriptional corepressor Gene:SSP120(YLR250W)|FD-Score:3.09|P-value:9.92E-4||SGD DESC:Protein of unknown function; green fluorescent protein (GFP)-fusion protein localizes to the cytoplasm in a punctate pattern Gene:YCL042W(YCL042W_p)|FD-Score:4.14|P-value:1.72E-5||SGD DESC:Putative protein of unknown function; epitope-tagged protein localizes to the cytoplasm Gene:YDR182W-A(YDR182W-A_p)|FD-Score:3.18|P-value:7.35E-4||SGD DESC:Putative protein of unknown function; identified by fungal homology and RT-PCR Gene:YKL100C(YKL100C_p)|FD-Score:3.69|P-value:1.13E-4||SGD DESC:Putative protein of unknown function with similarity to a human minor histocompatibility antigen and signal peptide peptidases; YKL100C is not an essential gene Gene:YMR160W(YMR160W_p)|FD-Score:4|P-value:3.23E-5||SGD DESC:Protein of unknown function; green fluorescent protein (GFP)-fusion protein localizes to the membrane of the vacuole; mutant has enhanced sensitivity to overexpression of mutant huntingtin; YMR160W is not an essential gene; relative distribution within the vacuolar membrane changes upon DNA replication stress

Click on Significant Values for Strain Details

Top 15 HET fitness defect scores (HIP)

Download all HIP Data (tab-delimited text)  (excel)
Deletion Strain FD score P-value Clearance Gene Gene Description
YGL099W4.503.42E-60.79LSG1Putative GTPase involved in 60S ribosomal subunit biogenesis; required for the release of Nmd3p from 60S subunits in the cytoplasm
YDR489W3.711.03E-40.75SLD5Subunit of the GINS complex (Sld5p, Psf1p, Psf2p, Psf3p), which is localized to DNA replication origins and implicated in assembly of the DNA replication machinery
YMR043W2.960.001540.10MCM1Transcription factor involved in cell-type-specific transcription and pheromone response; plays a central role in the formation of both repressor and activator complexes
YKR081C2.860.002090.25RPF2Essential protein involved in the processing of pre-rRNA and the assembly of the 60S ribosomal subunit; interacts with ribosomal protein L11; localizes predominantly to the nucleolus; constituent of 66S pre-ribosomal particles
YGR029W2.610.004520.07ERV1Flavin-linked sulfhydryl oxidase of the mitochondrial intermembrane space (IMS), oxidizes Mia40p as part of a disulfide relay system that promotes IMS retention of imported proteins; ortholog of human hepatopoietin (ALR)
YBL030C2.540.005550.01PET9Major ADP/ATP carrier of the mitochondrial inner membrane; exchanges cytosolic ADP for mitochondrially synthesized ATP; also imports heme and ATP; phosphorylated; required for viability in many lab strains that carry a sal1 mutation; PET9 has a paralog, AAC3, that arose from the whole genome duplication
YDL016C_d2.530.005630.01YDL016C_dDubious open reading frame unlikely to encode a protein, based on available experimental and comparative sequence data; partially overlaps the verified ORF CDC7/YDL153C, the catalytic subunit of a complex that regulates DNA replication
YKR025W2.530.005760.06RPC37RNA polymerase III subunit C37
YFR029W2.470.006720.04PTR3Component of the SPS plasma membrane amino acid sensor system (Ssy1p-Ptr3p-Ssy5p), which senses external amino acid concentration and transmits intracellular signals that result in regulation of expression of amino acid permease genes
YOL026C2.430.007460.00MIM1Mitochondrial protein required for outer membrane protein import; cooperates with Tom70p to import the subset of proteins with multiple alpha-helical transmembrane segments, including Ugo1p, Tom20p, and others; present in a complex with Mim2p in the outer membrane that may create a local environment to facilitate membrane insertion of substrate proteins; also has a role in assembly of Tom20p into the TOM complex
YLR397C2.430.007560.01AFG2ATPase of the CDC48/PAS1/SEC18 (AAA) family, forms a hexameric complex; is essential for pre-60S maturation and release of several preribosome maturation factors; releases Rlp24p from purified pre-60S particles in vitro; may be involved in degradation of aberrant mRNAs
YMR203W2.420.007820.05TOM40Component of the TOM (translocase of outer membrane) complex responsible for recognition and initial import steps for all mitochondrially directed proteins; constitutes the core element of the protein conducting pore
YGR198W2.370.008980.08YPP1Cargo-transport protein involved in endocytosis; interacts with phosphatidylinositol-4-kinase Stt4; GFP-fusion protein localizes to the cytoplasm; YGR198W is an essential gene
YFL038C2.280.011200.01YPT1Rab family GTPase, involved in the ER-to-Golgi step of the secretory pathway; complex formation with the Rab escort protein Mrs6p is required for prenylation of Ypt1p by protein geranylgeranyltransferase type II (Bet2p-Bet4p)
YEL032W2.280.011400.02MCM3Protein involved in DNA replication; component of the Mcm2-7 hexameric complex that binds chromatin as a part of the pre-replicative complex

Top 15 HOM fitness defect scores (HOP)

Download all HOP Data (tab-delimited text)  (excel)
Deletion Strain FD score P-value Gene Gene Description
YCL042W_p4.141.72E-5YCL042W_pPutative protein of unknown function; epitope-tagged protein localizes to the cytoplasm
YMR160W_p4.003.23E-5YMR160W_pProtein of unknown function; green fluorescent protein (GFP)-fusion protein localizes to the membrane of the vacuole; mutant has enhanced sensitivity to overexpression of mutant huntingtin; YMR160W is not an essential gene; relative distribution within the vacuolar membrane changes upon DNA replication stress
YGL025C3.904.71E-5PGD1Subunit of the RNA polymerase II mediator complex; associates with core polymerase subunits to form the RNA polymerase II holoenzyme; essential for basal and activated transcription; direct target of Cyc8p-Tup1p transcriptional corepressor
YGR040W3.807.38E-5KSS1Mitogen-activated protein kinase (MAPK) involved in signal transduction pathways that control filamentous growth and pheromone response; the KSS1 gene is nonfunctional in S288C strains and functional in W303 strains
YKL100C_p3.691.13E-4YKL100C_pPutative protein of unknown function with similarity to a human minor histocompatibility antigen and signal peptide peptidases; YKL100C is not an essential gene
YGR014W3.681.17E-4MSB2Mucin family member involved in signaling; functions in the Cdc42p- and MAP kinase-dependent filamentous growth signaling pathway; is processed into secreted and cell-associated forms by the aspartyl protease, Yps1p; also functions as an osmosensor in parallel to the Sho1p-mediated pathway; potential Cdc28p substrate
YJL103C3.452.80E-4GSM1Putative zinc cluster protein of unknown function; proposed to be involved in the regulation of energy metabolism, based on patterns of expression and sequence analysis
YJL161W_p3.324.49E-4FMP33_pPutative protein of unknown function; the authentic, non-tagged protein is detected in highly purified mitochondria in high-throughput studies
YHR137W3.255.73E-4ARO9Aromatic aminotransferase II, catalyzes the first step of tryptophan, phenylalanine, and tyrosine catabolism
YDR182W-A_p3.187.35E-4YDR182W-A_pPutative protein of unknown function; identified by fungal homology and RT-PCR
YLR250W3.099.92E-4SSP120Protein of unknown function; green fluorescent protein (GFP)-fusion protein localizes to the cytoplasm in a punctate pattern
YFL003C3.050.00114MSH4Protein involved in meiotic recombination, required for normal levels of crossing over, colocalizes with Zip2p to discrete foci on meiotic chromosomes, has homology to bacterial MutS protein
YLR414C3.040.00118PUN1Plasma membrane protein with a role in cell wall integrity; co-localizes with Sur7p in punctate membrane patches; null mutant displays decreased thermotolerance; transcription induced upon cell wall damage and metal ion stress
YGR007W3.040.00120ECT1Ethanolamine-phosphate cytidylyltransferase, catalyzes the second step of phosphatidylethanolamine biosynthesis; involved in the maintenance of plasma membrane; similar to mammalian CTP: phosphocholine cytidylyl-transferases
YKL156W3.020.00125RPS27AProtein component of the small (40S) ribosomal subunit; homologous to mammalian ribosomal protein S27, no bacterial homolog; RPS27A has a paralog, RPS27B, that arose from the whole genome duplication; protein abundance increases in response to DNA replication stress

GO enrichment analysis for SGTC_460
No biological processes are significantly enriched (FDR < 0.1).

No protein complexes are significantly enriched (FDR < 0.1).

Coinhibitory screens
Download Coinhibition data (tab-delimited text)  (excel)

Correlation pval Screen ID Condition Source PubChem
CID		 Tanimoto
Score		 Response
Signature
0.2851.54E-110SGTC_461N-acetylfarnesylcysteine 136.0 μMICCB bioactive library64383810.0238095
0.1817.55E-44SGTC_448monastrol 171.0 μMICCB bioactive library29879270.0813954
0.1441.24E-28SGTC_7651319-0117 244.0 μMChemDiv (Drug-like library)34877460.1276660S ribosome export
0.1293.09E-23SGTC_22067254556 147.0 μMChembridge (Fragment library)43989050.063291160S ribosome export
0.1279.80E-23SGTC_1070indatraline 8.8 μMNIH Clinical Collection103144720.065789560S ribosome export
0.1262.25E-22SGTC_618k072-0232 33.2 μMChemDiv (Drug-like library)58727560.048780560S ribosome export
0.1232.92E-21SGTC_8103825-7150 143.0 μMChemDiv (Drug-like library)223304110.16049460S ribosome export
0.1189.71E-20SGTC_1958st076513 41.9 μMTimTec (Natural product derivative library)7321220.063291160S ribosome export
0.1151.02E-18SGTC_1775st081588 35.2 μMTimTec (Natural product derivative library)14264430.13953560S ribosome export
0.1095.43E-17SGTC_14924158-0558 28.5 μMChemDiv (Drug-like library)39672680.078651760S ribosome export
0.1056.50E-16SGTC_29379044753 11.3 μMChembridge (Drug-like library)64655300.09195460S ribosome export
0.1023.87E-15SGTC_447ml7 120.0 μMICCB bioactive library42160.0759494NEO1-PIK1
0.1024.01E-15SGTC_15494'-methoxyflavonol 74.6 μMTimTec (Pure natural product library)971410.121622
0.1024.63E-15SGTC_970535-0701 19.1 μMChemDiv (Drug-like library)28320130.11111160S ribosome export
0.1001.11E-14SGTC_6653914-0008 307.0 μMChemDiv (Drug-like library)10695490.11236

Screens with compounds having similar structures
Screen ID Chemical Concentration Tanimoto Score PubChem ID Source Molecular Weight AlogP H-bond
donor
count		 H-bond
acceptor
count		 Response
Signature
SGTC_1518st03856790.8 μM0.26666777966TimTec (Pure natural product library)220.221282.31304
SGTC_1945st07599156.6 μM0.2666671084980TimTec (Natural product derivative library)353.457983.6820560S ribosome export
SGTC_1083didemethylchlorpromazine sulfoxide707.39 nM0.264706398788TimTec (Natural product library)353.411623.81805redox potentiating
SGTC_1126isoteolin1.02 μM0.263889133323TimTec (Natural product library)327.374343.08325
SGTC_1855st05619539.6 μM0.2602744028379TimTec (Natural product derivative library)434.323564.2820560S ribosome export
SGTC_1886st05735649.9 μM0.2597424207747TimTec (Natural product derivative library)400.425063.4280760S ribosome export
SGTC_1783st03945987.52 μM0.253968729761TimTec (Natural product derivative library)185.221841.97901Golgi
SGTC_1940st07599051.1 μM0.2531651084979TimTec (Natural product derivative library)391.46293.8280660S ribosome export
SGTC_1531st05929752.4 μM0.243597566702TimTec (Pure natural product library)457.517685.22206
SGTC_15666,7-dimethoxy-4-ethylcoumarin85.4 μM0.234375688761TimTec (Pure natural product library)234.247862.76904