tolnaftate

O-naphthalen-2-yl N-methyl-N-(3-methylphenyl)carbamothioate


Established Yeast Drug Target : ERG1

Tolnaftate prevents ergosterol biosynthesis by inhibiting squalene epoxidase.

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

PubChem MeSH terms: Antifungal Agents



Source SMILES: standardizedunstandardized
Compound:
Screen ID SGTC_2234
Screen concentration 200.0 μM
Source Miscellaneous
PubChem CID 5510
SMILES CC1=CC(=CC=C1)N(C)C(=S)OC2=CC3=CC=CC=C3C=C2
Standardized SMILES CN(C(=S)Oc1ccc2ccccc2c1)c3cccc(C)c3
Molecular weight 307.4094
ALogP 6.29
H-bond donor count 0
H-bond acceptor count 2
Response signature

Pool Growth Kinetics
% growth inhibition (Het. pool) 2.59
% growth inhibition (Hom. pool) 0


HIP profile

Heterozygous deletion strains
Scale: fixedexpanded
Heterozygous profile for 5510
Download HIP data (tab-delimited text)  (excel)

HOP profile

Homozygous deletion strains
Scale: fixedexpanded
Homozygous profile for 5510
Download HOP data (tab-delimited text)  (excel)
Gene:AQY2(YLL052C)|FD-Score:3.16|P-value:7.82E-4||SGD DESC:Water channel that mediates the transport of water across cell membranes, only expressed in proliferating cells, controlled by osmotic signals, may be involved in freeze tolerance; disrupted by a stop codon in many S. cerevisiae strains Gene:SER33(YIL074C)|FD-Score:3.38|P-value:3.59E-4||SGD DESC:3-phosphoglycerate dehydrogenase; catalyzes the first step in serine and glycine biosynthesis; SER33 has a paralog, SER3, that arose from the whole genome duplication Gene:AQY2(YLL052C)|FD-Score:3.16|P-value:7.82E-4||SGD DESC:Water channel that mediates the transport of water across cell membranes, only expressed in proliferating cells, controlled by osmotic signals, may be involved in freeze tolerance; disrupted by a stop codon in many S. cerevisiae strains Gene:SER33(YIL074C)|FD-Score:3.38|P-value:3.59E-4||SGD DESC:3-phosphoglycerate dehydrogenase; catalyzes the first step in serine and glycine biosynthesis; SER33 has a paralog, SER3, that arose from the whole genome duplication

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
YGR099W3.070.001060.37TEL2Subunit of the ASTRA complex, involved in chromatin remodeling; subunit of the telomere cap complex DNA-binding protein specific to single-stranded yeast telomeric DNA repeats, required for telomere length regulation and telomere position effect; involved in the stability or biogenesis of PIKKs such as TORC1
YER082C2.850.002210.37UTP7Nucleolar protein, component of the small subunit (SSU) processome containing the U3 snoRNA that is involved in processing of pre-18S rRNA
YAR007C2.730.003150.37RFA1Subunit of heterotrimeric Replication Protein A (RPA), which is a highly conserved single-stranded DNA binding protein involved in DNA replication, repair, and recombination
YAL001C2.700.003420.37TFC3Largest of six subunits of the RNA polymerase III transcription initiation factor complex (TFIIIC); part of the TauB domain of TFIIIC that binds DNA at the BoxB promoter sites of tRNA and similar genes; cooperates with Tfc6p in DNA binding
YDL045C2.330.009860.00FAD1Flavin adenine dinucleotide (FAD) synthetase, performs the second step in synthesis of FAD from riboflavin
YFR002W2.330.009970.00NIC96Linker nucleoporin component of the nuclear pore complex (NPC); also part of the NPC nuclear basket; contributes to nucleocytoplasmic transport and NPC biogenesis; forms stable associations with three FG-nucleoporins (Nsp1p, Nup57p, and Nup49p)
YGL068W2.320.010100.02MNP1Protein associated with the mitochondrial nucleoid; putative mitochondrial ribosomal protein with similarity to E. coli L7/L12 ribosomal protein; required for normal respiratory growth
YGL137W2.300.010600.03SEC27Essential beta'-coat protein of the COPI coatomer, involved in ER-to-Golgi and Golgi-to-ER transport; contains WD40 domains that mediate cargo selective interactions; 45% sequence identity to mammalian beta'-COP
YDR429C2.280.011300.01TIF35eIF3g subunit of the core complex of translation initiation factor 3 (eIF3), which is essential for translation; stimulates resumption of ribosomal scanning during translation reinitiation
YGR048W2.270.011700.06UFD1Substrate-recruiting cofactor of the Cdc48p-Npl4p-Ufd1p segregase; polyubiquitin binding protein that assists in the dislocation of misfolded, ERAD substrates that are subsequently delivered to the proteasome for degradation; involved in regulated destruction of ER membrane proteins such as HMG-CoA reductase (Hmg1/2p) and cytoplasmic proteins (Fbp1p); involved in mobilizing membrane bound transaction factors by regulated Ub/proteasome-dependent processing (RUP)
YBR055C2.200.013900.02PRP6Splicing factor, component of the U4/U6-U5 snRNP complex
YHR083W2.190.014400.03SAM35Essential component of the sorting and assembly machinery (SAM complex or TOB complex) of the mitochondrial outer membrane, which binds precursors of beta-barrel proteins and facilitates their insertion into the outer membrane
YDR235W2.160.015400.01PRP42U1 snRNP protein involved in splicing, required for U1 snRNP biogenesis; contains multiple tetriatricopeptide repeats
YKL172W2.150.015700.02EBP2Required for 25S rRNA maturation and 60S ribosomal subunit assembly; localizes to the nucleolus and in foci along nuclear periphery; constituent of 66S pre-ribosomal particles; cooperates with Rrs1p and Mps3p to mediate telomere clustering by binding Sir4p, but is not involved in telomere tethering
YLR229C2.130.016400.01CDC42Small rho-like GTPase, essential for establishment and maintenance of cell polarity; mutants have defects in the organization of actin and septins

Top 15 HOM fitness defect scores (HOP)

Download all HOP Data (tab-delimited text)  (excel)
Deletion Strain FD score P-value Gene Gene Description
YIL074C3.383.59E-4SER333-phosphoglycerate dehydrogenase; catalyzes the first step in serine and glycine biosynthesis; SER33 has a paralog, SER3, that arose from the whole genome duplication
YLL052C3.167.82E-4AQY2Water channel that mediates the transport of water across cell membranes, only expressed in proliferating cells, controlled by osmotic signals, may be involved in freeze tolerance; disrupted by a stop codon in many S. cerevisiae strains
YML034C-A_d3.080.00103YML034C-A_dDubious ORF unlikely to encode a functional protein, based on available experimental and comparative sequence data
YIR027C3.000.00133DAL1Allantoinase, converts allantoin to allantoate in the first step of allantoin degradation; expression sensitive to nitrogen catabolite repression
YOL015W2.970.00146IRC10Putative protein of unknown function; null mutant displays increased levels of spontaneous Rad52p foci
YKL033W-A_p2.780.00274YKL033W-A_pPutative protein of unknown function; similar to uncharacterized proteins from other fungi
YGR027C2.770.00277RPS25AProtein component of the small (40S) ribosomal subunit; homologous to mammalian ribosomal protein S25, no bacterial homolog; RPS25A has a paralog, RPS25B, that arose from the whole genome duplication
YLR386W2.760.00288VAC14Protein involved in regulated synthesis of PtdIns(3,5)P(2), in control of trafficking of some proteins to the vacuole lumen via the MVB, and in maintenance of vacuole size and acidity; interacts with Fig4p; activator of Fab1p
YDL085W2.760.00292NDE2Mitochondrial external NADH dehydrogenase, catalyzes the oxidation of cytosolic NADH; Nde1p and Nde2p are involved in providing the cytosolic NADH to the mitochondrial respiratory chain
YOR002W2.740.00303ALG6Alpha 1,3 glucosyltransferase, involved in transfer of oligosaccharides from dolichyl pyrophosphate to asparagine residues of proteins during N-linked protein glycosylation; mutations in human ortholog are associated with disease
YKL126W2.720.00331YPK1Serine/threonine protein kinase; phosphorylates and downregulates flippase activator Fpk1p; inactivates Orm1p and Orm2p (inhibitors of serine:palmitoyl-coenzyme A transferase) by phosphorylation in response to compromised sphingolipid synthesis; mutations affect receptor-mediated endocytosis and sphingolipid-mediated and cell integrity signaling pathways; homolog of mammalian kinase SGK; YPK1 has a paralog, YPK2, that arose from the whole genome duplication
YMR122C_d2.670.00381YMR122C_dDubious open reading frame unlikely to encode a functional protein, based on available experimental and comparative sequence data
YGL027C2.650.00408CWH41Processing alpha glucosidase I, ER type II integral membrane N-glycoprotein involved in assembly of cell wall beta 1,6 glucan and asparagine-linked protein glycosylation; also involved in ER protein quality control and sensing of ER stress
YKR090W2.630.00424PXL1Protein that localizes to sites of polarized growth; required for selection and/or maintenance of polarized growth sites, may modulate signaling by the GTPases Cdc42p and Rho1p; contains LIM domains and has similarity to metazoan paxillin; relocalizes from bud neck to cytoplasm upon DNA replication stress
YHR048W_p2.620.00435YHK8_pPresumed antiporter of the major facilitator superfamily; member of the 12-spanner drug:H(+) antiporter DHA1 family; expression of gene is up-regulated in cells exhibiting reduced susceptibility to azoles

GO enrichment analysis for SGTC_2234
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
0.1578.20E-34SGTC_22167189485 200.0 μMChembridge (Fragment library)7312730.0746269
0.1506.94E-31SGTC_14863970-0793 4.5 μMChemDiv (Drug-like library)28443300.0483871
0.1411.96E-27SGTC_267212a-hydroxy-5-deoxydehydromunduserone 100.0 μMMicrosource (Natural product library)46208980.111111
0.1164.59E-19SGTC_30539095903 49.5 μMChembridge (Drug-like library)171740180.0972222Golgi
0.1081.13E-16SGTC_2680butyl paraben 22.2 μMMicrosource (Natural product library)71840.101695amide catabolism
0.1072.13E-16SGTC_22077258803 200.0 μMChembridge (Fragment library)36667990.118644
0.1072.43E-16SGTC_1990st072050 59.8 μMTimTec (Natural product derivative library)172339480.0694444
0.1064.44E-16SGTC_30489093155 49.5 μMChembridge (Drug-like library)252360020.112676
0.1041.12E-15SGTC_12230764-0573 147.0 μMChemDiv (Drug-like library)16097970.144928
0.1041.24E-15SGTC_2665lovastatin 100.0 μMMiscellaneous532320.0543478
0.0961.32E-13SGTC_32609137109 49.5 μMChembridge (Drug-like library)174783460.20689760S ribosome export
0.0938.13E-13SGTC_29799012552 45.5 μMChembridge (Drug-like library)171009050.0895522
0.0912.00E-12SGTC_12201838-0075 193.0 μMChemDiv (Drug-like library)55296450.0945946
0.0912.67E-12SGTC_23379009472 200.0 μMChembridge (Fragment library)57423830.180328
0.0912.82E-12SGTC_31179124945 49.5 μMChembridge (Drug-like library)175920650.109589

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_8760720-096356.8 μM0.265625765861ChemDiv (Drug-like library)319.76285.59904
SGTC_7171532-024673.2 μM0.2653069561992ChemDiv (Drug-like library)185.221842.54512Golgi
SGTC_20945332512191.67 μM0.259259755774Chembridge (Fragment library)215.247821.59512
SGTC_5423381-024489.3 μM0.251112843ChemDiv (Drug-like library)360.448863.67603
SGTC_13621611-0397101 μM0.2527816ChemDiv (Drug-like library)227.258523.65612
SGTC_12033992-3522103 μM0.2465755322312ChemDiv (Drug-like library)429.388534.56418
SGTC_2841900476138.96 μM0.2459022991039Chembridge (Drug-like library)289.756744.08412amide catabolism
SGTC_13401486-1359257 μM0.2372884309068ChemDiv (Drug-like library)285.31950.99324
SGTC_3051909377849.47 μM0.22727317217378Chembridge (Drug-like library)338.443343.5903
SGTC_23027771753200 μM0.2264152203047Chembridge (Fragment library)217.286842.13412