lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: GTMHRCTXZNYSIX-IVIUVZLUSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]deltorphin-II from human DOR expressed in CHO cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 7762.47 nM (pChEMBL 5.110000133514404)
Descriptors: MW 1245.54
Compound (SMILES): C=C(C)[C@@H]1CCC(C)=C[C@H]1c1c(O)cc(CCCCC)c(Cc2c(CCCCC)cc(O)c([C@@H]3C=C(C)CC[C@H]3C(=C)C)c2O)c1O
InChIKey: UMJIRNQSAUOZKO-HEZKMHOLSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9ERZ8
Assay: Agonist activity at rat TRPV4 stably transfected in HEK293 cells assessed as increase in calcium influx in presence of ionomycin by Fluo-4-AM dye based spectrofluorimetric method
Measurement: EC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 640.95, ALogP 11.6, HBA 4, HBD 4, PSA 80.92, QED 0.12
Compound (SMILES): CCCCCCCCCCCCCC(=S)NCCCC[C@H](NC(=O)CCOCCOCCOCCOCCNc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O)C(=O)Nc1ccccc1
InChIKey: CYVGGMWMJPYYNF-DYJLHVNUSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of human SIRT2 defatty-acylation activity using peptide substrate in presence of NAD+ by HPLC analysis
Measurement: IC50 > 83000 nM (pChEMBL 4.080999851226807)
Descriptors: MW 951.24, ALogP 6.87, HBA 12, HBD 5, PSA 202.73, QED 0.03
Compound (SMILES): O=C(NCCCN1CCOC1=O)c1cnc(NCc2cc(Br)ccc2Br)nc1NC1CCCC1
InChIKey: HOYFKJXFPMNFPM-UHFFFAOYSA-N
Target: Aurora kinase C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQB9
Assay: Selectivity interaction (NanoBRET assay (HEK293T cells)) EUB0000723a AURKC
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 596.32, ALogP 4.54, HBA 7, HBD 3, PSA 108.48, QED 0.35
Compound (SMILES): CCN(Cc1ccccc1)C(=O)/C=C/c1ccc(OC(=O)N(c2ccccc2)c2ccccc2)c(OC)c1
InChIKey: KOURHYYDCUECQR-LSDHQDQOSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate after 15 mins by Ellman's method
Measurement: IC50 = 24600 nM (pChEMBL 4.610000133514404)
Descriptors: MW 506.6, ALogP 7.09, HBA 4, HBD 0, PSA 59.08, QED 0.23
Compound (SMILES): Nc1nn2c(-c3cccs3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: TWLBRDPBOUDNES-QZQOTICOSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 399.46, ALogP 3.1, HBA 9, HBD 2, PSA 141.09, QED 0.51
Compound (SMILES): C=CC(=O)NCc1ccc(-c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2)cc1
InChIKey: ZIAQTARFHIBGJS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) assessed as reduction in ATP-dependent phosphorylation of ULight-myelin basic protein substrate peptide incubated for 60 mins by LANCE TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 414.51, ALogP 4.5, HBA 3, HBD 3, PSA 86.88, QED 0.47
Compound (SMILES): CN(C)C(=O)c1ccc(-c2cc(C(=O)N(C)C3CCCC3)no2)cc1O
InChIKey: CKEICVFLYGXFOP-UHFFFAOYSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Binding affinity to MLLT3 in human HEK293 cells by NanoBRET assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 357.41, ALogP 2.76, HBA 5, HBD 1, PSA 86.88, QED 0.91
Compound (SMILES): CC1(N)CCN(c2cnc(Sc3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: VPEZYDNNURIHBQ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant human SHP2 PTP domain (237 to 535 residues) using DiFMUP as substrate preincubated for 30 mins and followed by substrate addition and measured by microplate reader method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.34, ALogP 3.83, HBA 6, HBD 2, PSA 81.06, QED 0.84
Compound (SMILES): C[C@@H](c1cccc(C#N)c1)n1cc(Cl)cc(C(N)=O)c1=N.Cl
InChIKey: XUCZRJDRBBJCTE-FVGYRXGTSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25100
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000341aCl ADRA1D
Measurement: Ki = 1481 nM (pChEMBL 5.829999923706055)
Descriptors: MW 300.75, ALogP 2.2, HBA 4, HBD 2, PSA 95.66, QED 0.91
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCN(Cc3ccccc3)CC2)ccc1OC(=O)N(c1ccccc1)c1ccccc1
InChIKey: ICKSGIYUZRTUTJ-CZIZESTLSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate after 15 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 547.66, ALogP 6.39, HBA 5, HBD 0, PSA 62.32, QED 0.24
Compound (SMILES): O=C1c2cccc(O)c2C(=O)C1(O)O
InChIKey: WADCFSVAUBQADP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 17100 nM (pChEMBL 4.769999980926514)
Descriptors: MW 194.14, ALogP -0.55, HBA 5, HBD 3, PSA 94.83, QED 0.38
Compound (SMILES): O=C(CCN1CCCc2ccccc21)Nc1cccc2cccnc12
InChIKey: FMALHFGGWXYUHY-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 478.63 nM (pChEMBL 6.320000171661377)
Descriptors: MW 331.42, ALogP 4.02, HBA 3, HBD 1, PSA 45.23, QED 0.79
Compound (SMILES): OCCCNc1ccnc2c1nc(-c1ccco1)n2C1CCCC1
InChIKey: CXELNJALEVTKCV-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of human recombinant PDE2A using cGMP as substrate incubated for 20 mins measured by Kinase Glo reagent based microplate reader assay
Measurement: IC50 = 40700 nM (pChEMBL 4.389999866485596)
Descriptors: MW 326.4, ALogP 3.6, HBA 6, HBD 2, PSA 76.11, QED 0.68
Compound (SMILES): O=c1[nH]cc(C2CCCCC2)c2nccn12
InChIKey: IRDDESQGXYVSBF-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using peptide substrate in presence of [gamma33P]ATP by image analyser
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 217.27, ALogP 2.07, HBA 3, HBD 1, PSA 50.16, QED 0.79
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)cc2sc(N[C@H]3CCCC[C@@H]3O)nc12
InChIKey: QPANAVQRQRUDJJ-KBPBESRZSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-TetR cells incubated for 1 hr followed by PDGF-DD stimulation and measured after 5 mins by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 401.49, ALogP 2.97, HBA 9, HBD 3, PSA 115.41, QED 0.58
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccccc23)cc1
InChIKey: HYCPLKOVNZFNAS-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged HDAC6 expressed in baculovirus infected Sf9 insect cells using Boc-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 329.36, ALogP 4.25, HBA 4, HBD 3, PSA 74.25, QED 0.3
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4cccc(-c5cc[nH]n5)c4)c3n2)cn1
InChIKey: MEZZCEDCBNWCRR-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human full length recombinant DYRK1A using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 341.37, ALogP 4.29, HBA 5, HBD 1, PSA 72.53, QED 0.53
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)c(N3CCN(C)CC3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: DXEYGTAOOLIULQ-ZCXCRYNXSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 1b NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by Celltiter Glo assay
Measurement: IC50 = 0.034 nM (pChEMBL 10.470000267028809)
Descriptors: MW 843, ALogP 4.76, HBA 10, HBD 4, PSA 181.12, QED 0.16
Compound (SMILES): CN1C(=O)c2c(F)cccc2Oc2cc(N[C@H]3CC[C@H](O)CC3)ncc21
InChIKey: GFDDTDKCZCGJLM-HAQNSBGRSA-N
Target: Mitogen-activated protein kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13164
Assay: Inhibition of recombinant human ERK5 using myelin basic protein as substrate by [gamm33P]ATP based HotSpot radiometric assay
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 357.39, ALogP 3.32, HBA 5, HBD 2, PSA 74.69, QED 0.86
Compound (SMILES): Cl.O=C(NO)c1cnc(N2CCC3(CCN(Cc4c[nH]c5ccccc45)C3)CC2)nc1
InChIKey: CLWKBFQPPQNENW-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using Ac-peptide as substrate preincubated for 15 mins followed by substrate and trypsin addition and further incubated for 60 mins
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 406.49, ALogP 2.57, HBA 6, HBD 3, PSA 97.38, QED 0.46
Compound (SMILES): CO[C@H]1CC[C@H](C(=O)Nc2cc3cc(-c4cnn(C)c4CN4CCCCC4)ccc3cn2)CC1
InChIKey: MCKVVSGRVQMFEY-UILWBTOOSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning). The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission. Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 461.61, ALogP 4.76, HBA 6, HBD 1, PSA 72.28, QED 0.57
Compound (SMILES): C[C@H]1C[C@H](C(=O)O)CC[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3ccccc3)c3cc(F)c(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: ZRBKKZYWZRWOFL-GSDLGJSISA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Inverse agonist activity of PXR (unknown origin)
Measurement: EC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 667.62, ALogP 6.47, HBA 4, HBD 1, PSA 91.75, QED 0.37
Compound (SMILES): Cc1nn(-c2ccncn2)c2c1C(=O)CC(C)(C)C2Br
InChIKey: YVYVDXXWQANVCI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Binding affinity to T7-tagged CDK2 (unknown origin) expressed in bacteriophage infected Escherichia coli BL21 incubated for 30 mins by magnetic beads based qPCR anlaysis
Measurement: Kd = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 335.2, ALogP 3.02, HBA 5, HBD 0, PSA 60.67, QED 0.75
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CCC(N)=O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: HWGGKSUESBGTAA-UMYBCCRSSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 3.96 nM (pChEMBL 8.399999618530273)
Descriptors: MW 445.52, ALogP 0.51, HBA 7, HBD 4, PSA 134.35, QED 0.48
Compound (SMILES): COc1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: YTKAFKXVZBIBGM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 21.5 nM (pChEMBL 7.670000076293945)
Descriptors: MW 428.49, ALogP 0.91, HBA 6, HBD 4, PSA 156.69, QED 0.49
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(C2CCN(C3CC3)CC2)cc1)c1ccccc1
InChIKey: ZYOFNMPBJCPWJW-FJISBNMDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 453.63, ALogP 6.47, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): O=C(O)C1CCCN1C(=O)CCN1CCCc2ccccc21
InChIKey: PJWHESRYVASPCJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 776.25 nM (pChEMBL 6.110000133514404)
Descriptors: MW 302.37, ALogP 1.9, HBA 3, HBD 1, PSA 60.85, QED 0.92
Compound (SMILES): C[C@H](C(=O)Nc1ccc(Cl)cc1)[C@H]1CC[C@]2(CC1)COc1cc(C(F)(F)F)ccc12
InChIKey: WPNANUSCDOZUBH-DFFLPILJSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of TDO in HEK cells
Measurement: IC50 = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 437.89, ALogP 6.45, HBA 2, HBD 1, PSA 38.33, QED 0.6
Compound (SMILES): O=C(O)CSc1ncnc2sc(-c3cc4ccccc4s3)cc12
InChIKey: RRIRDIKTUQVZCW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Inhibition of STK17A (unknown origin) incubated for 90 mins by Kinase seeker split luciferase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCCCC1CO
InChIKey: PFCGTKRNMJTXQP-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 10715.19 nM (pChEMBL 4.96999979019165)
Descriptors: MW 302.42, ALogP 2.2, HBA 3, HBD 1, PSA 43.78, QED 0.93
Compound (SMILES): O=C(CCl)c1ccccc1Nc1cccc(C(F)(F)F)c1
InChIKey: JPVDFGYNLUBCSD-UHFFFAOYSA-N
Target: YAP1-TEAD4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P46937
Assay: Inhibition of N-terminal GST-tagged TEAD4 (217 to 434 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) cells to YAP1 (unknown origin) protein protein interaction preincubated for 24 hrs followed by Fam-YAP(60 to 99) addition by plate reader assay
Measurement: EC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 313.71, ALogP 4.87, HBA 2, HBD 1, PSA 29.1, QED 0.64
Compound (SMILES): CCn1nc(C(F)(F)F)cc1Nc1nc(-c2ccc(-n3cnc(C)c3)c(OC)n2)cs1
InChIKey: UNFVPHNQVGXPKU-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 449.46, ALogP 4.69, HBA 9, HBD 1, PSA 82.68, QED 0.46
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](C)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: ZDYOGHURRMOUMQ-QYYSHDEWSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.72
Compound (SMILES): O=c1cc(-c2cccc(O)c2)oc2c1ccc1occc12
InChIKey: DPEBAAUPCCEJDT-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin)
Measurement: IC50 = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 278.26, ALogP 3.91, HBA 4, HBD 1, PSA 63.58, QED 0.57
Compound (SMILES): CN[C@@H]1C[C@H]2O[C@@](C)([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4=O
InChIKey: POTTVLREWUNNRO-UGZRAAABSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of N-terminal His10-StrepII tagged human ROCK2 catalytic domain (1 to 553 residues) expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 480.52, ALogP 3.99, HBA 7, HBD 2, PSA 86.52, QED 0.37
Compound (SMILES): COc1cc(Nc2ncc(CCc3c(F)c(OC)cc(OC)c3F)cn2)ccc1N1CCC(N2CCN(C)CC2)CC1
InChIKey: ZUURNUDMSWVVCL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human N-terminal GST-tagged VEGFR2 (790 to end residues) expressed in baculovirus expression system using CSKtide as substrate incubated for 30 mins in presence of ATP by off-chip mobility shift assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 582.7, ALogP 4.53, HBA 9, HBD 1, PSA 75.22, QED 0.37
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1cccnc1
InChIKey: FQJBNNUXCQXZSV-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in antiIgM/CD40L-induced human B cells assessed as reduction in cell viability preincubated for 30 mins followed by antiIgM/CD40L addition and measured after 72 hrs by [3H]-thymidine incorporation assay
Measurement: IC50 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 374.38, ALogP 2.98, HBA 8, HBD 2, PSA 118.33, QED 0.56
Compound (SMILES): Nc1nccc(COc2cc(F)c3nc(N[C@@H]4CCCC[C@H]4O)sc3c2)c1Cl
InChIKey: KTRYEZRTYBBSHL-ZIAGYGMSSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-TetR cells incubated for 1 hr followed by PDGF-DD stimulation and measured after 5 mins by HTRF assay
Measurement: IC50 = 1339 nM (pChEMBL 5.869999885559082)
Descriptors: MW 422.91, ALogP 4.36, HBA 7, HBD 3, PSA 93.29, QED 0.57
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(-c3nc4ccccc4c(=O)n3-c3ccc(C)cc3)s2)cc1
InChIKey: WOGMWVBGNNNFPL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 544.64, ALogP 6.75, HBA 7, HBD 1, PSA 86.11, QED 0.25
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2cc(F)ccc2n1-c1cccc(S(C)(=O)=O)c1
InChIKey: NECJQZONAPGIJP-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in antiIgM/CD40L-induced human B cells assessed as reduction in cell viability preincubated for 30 mins followed by antiIgM/CD40L addition and measured after 72 hrs by [3H]-thymidine incorporation assay
Measurement: IC50 = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 451.49, ALogP 2.99, HBA 9, HBD 2, PSA 139.58, QED 0.47
Compound (SMILES): N#CCCN1C(=O)CC[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: XDDWLXGEQFTMIY-PPJWLVRDSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: General RORgamma SPA binding assay : The binding of potential ligands to RORγ is measured by competition with [3H]25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA). The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 μg/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 μM to 0.28 nM, for 10 min at rt in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% glycerol (Sigma Cat#G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat # RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce [3H] 25-hydroxycholesterol specific binding by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 663.59, ALogP 5.24, HBA 5, HBD 0, PSA 98.55, QED 0.31
Compound (SMILES): CSc1ccccc1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: IBVNIPPBTCWYJG-DEOSSOPVSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli using BML-KI178 as substrate and SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 555.73, ALogP 6.48, HBA 6, HBD 3, PSA 99.77, QED 0.13
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@H]4CC[C@H](CO)CC4)nc32)cc1
InChIKey: ZHURSLXNNAPMNU-JOCQHMNTSA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Inhibition of recombinant His6-GST fusion tagged ERK3 (1 to 471 residues) (unknown origin) expressed in Sf21 insect cells using MK5 K51A mutant as substrate by ADP-Glo assay
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 354.41, ALogP 2.18, HBA 8, HBD 2, PSA 97.98, QED 0.72
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)c(C(=O)c2ccc(Cl)cc2)s1)c1ccccc1
InChIKey: NJTBKCWDDYQTJT-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 418.91, ALogP 5.95, HBA 4, HBD 1, PSA 59.06, QED 0.41
Compound (SMILES): CN1CCN(C(=S)SCC(=O)Nc2ccc(S(N)(=O)=O)cc2)CC1
InChIKey: SMLRBEBCNCWDHG-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant preincubated for 15 mins and measured for 10 to 100 sec by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 65.6 nM (pChEMBL 7.179999828338623)
Descriptors: MW 388.54, ALogP 0.54, HBA 6, HBD 2, PSA 95.74, QED 0.73
Compound (SMILES): C=CC(=O)N[C@@H]1COC[C@@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)c(=O)n(C)c2n1
InChIKey: ZIJVLVUPDVUSMA-KGLIPLIRSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) expressed in human Huh7 cells assessed as autophosphorylation after 1 hr incubation measured by Mesoscale discovery (MSD) assay
Measurement: IC50 = 2212 nM (pChEMBL 5.659999847412109)
Descriptors: MW 520.37, ALogP 2.8, HBA 9, HBD 2, PSA 116.6, QED 0.46
Compound (SMILES): Cc1cc(-c2ccc3nc(N)cn3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: HXPFZIAXUXSSNV-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 347.42, ALogP 3.04, HBA 5, HBD 1, PSA 76.52, QED 0.79
Compound (SMILES): CN1CCN(c2ccc(C(=O)N3CCN(c4cc(C(=O)Nc5cc6cc(-c7cnn(C)c7)ccc6cn5)ccn4)CC3)cn2)CC1
InChIKey: PEENWSBWWBNUKY-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 3051 nM (pChEMBL 5.519999980926514)
Descriptors: MW 616.73, ALogP 3.39, HBA 10, HBD 1, PSA 115.62, QED 0.31
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CN(C)CC4)c(Cl)cn2)C1
InChIKey: CFOMPAUTQPTGQD-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 430.94, ALogP 2.68, HBA 6, HBD 2, PSA 92.15, QED 0.78
Compound (SMILES): c1cncc(-c2cc3c(-c4nc5ccccc5[nH]4)n[nH]c3cn2)c1
InChIKey: CWRRGHCIIWHSGO-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: TGF-beta 1 Assay: Compound Screening: Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:2, 11-point dose-response curves from 10 μM to 1.87 nM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well clear bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. LL29 cells were plated at 1,500 cells/well in 80 μl/well F12 medium supplemented with 1% Fetal Bovine Serum. One hour after addition of the cells, TGF-β1 (Peprotech; 20 ng/mL) was added to the plates to induce fibrosis (ref. 1 and 2 above). Wells treated with TGF-β1 and containing DMSO were used as controls. Cells were incubated at 37° C. and 5% CO2 for 4 days. Following incubation for 4 days, SYTOX green nucleic acid stain (Life Technologies [Thermo Fisher Scientific]) was added to the wells at a final concentration of 1 uM and incubated at room temperature for 30 min. Cells were then fixed using 4% formaldehyde (Electron Microscopy Sciences), washed 3 times with PBS followed by blocking and permeabilization using 3% Bovine Serum Albumin (BSA; Sigma) and 0.3% Triton X-100 (Sigma) in PBS. Cells were then stained with antibody specific to α-smooth muscle actin (aSMA; Abcam) (ref. 1 and 2 above) in 3% Bovine Serum Albumin (BSA; Sigma) and 0.3% Triton X-100 (Sigma) in PBS, and incubated overnight at 4° C. Cells were then washed 3 times with PBS, followed by incubation with Alexa Flor-647 conjugated secondary antibody (Life Technologies [Thermo Fisher Scientific]) and DAPI at room temperature for 1 hour. Cells were then washed 3 times with PBS and plates were sealed for imaging. αSMA staining was imaged by excitation at 630 nm and emission at 665 nm and quantified using the Compartmental Analysis program on the CellInsight CX5 (Thermo Scientific). Dead or apoptotic cells were excluded from analysis based on positive SYTOX green staining. % of total cells positive for αSMA were counted in each well and normalized to the average of 11 wells treated with TGF-β1 on the same plate using Dotmatics' Studies Software. The normalized averages (fold change over untreated) of 3 replicate wells for each compound concentration were used to create dose-responses curves and EC50 values were calculated using non-linear regression curve fit in the Dotmatics' Studies Software.
Measurement: EC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 312.34, ALogP 3.56, HBA 4, HBD 2, PSA 83.14, QED 0.52
Compound (SMILES): N=C(N)NCCCCNC(=O)NC[C@H](NC(=O)[C@@H]1CCCN1S(=O)(=O)c1ccccc1)C(=O)O
InChIKey: IUFCIFVCEOUHLU-HOTGVXAUSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Cell adhesion assay to Hamster Ovary: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alphavbeta1 (adhesion of Chinese Hamster Ovary cells transfected with human alphav to the latency associated peptide of transforming growth factor beta, a response that is entirely dependent on binding of alphavbeta1 to LAP).
Measurement: IC50 = 5050 nM (pChEMBL 5.300000190734863)
Descriptors: MW 497.58, ALogP -1.03, HBA 6, HBD 7, PSA 206.81, QED 0.11
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(c5nnc(-c6ccc(F)cc6)o5)CC4)cc3F)ccnc2cc1OCCCN1CCCCC1
InChIKey: IRBBFXPKIBQFKT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human N-terminal GST-fused FLT3 cytoplasmic domain (564 to 993 residues) expressed in baculovirus expression system using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 655.7, ALogP 7.29, HBA 9, HBD 1, PSA 111.84, QED 0.14
Compound (SMILES): C=CC(=O)N(C)Cc1c[nH]c2ncnc(-c3cccc(NC(=O)c4ccc(C(C)(C)C)cc4)c3C)c12
InChIKey: JMPKWKAQXXADIE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 481.6, ALogP 5.63, HBA 4, HBD 2, PSA 90.98, QED 0.35
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: GTMHRCTXZNYSIX-IVIUVZLUSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Antagonist activity at human KOR expressed in CHO cell membranes assessed as reduction in U50,488 induced response incubated for 1 hr by liquid scintillation counting based [35S]GTP-gamma-S assay
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 1245.54
Compound (SMILES): C=C(C)[C@@H]1CCC(C)=C[C@H]1c1c(O)cc(CCCCC)c(Cc2c(CCCCC)cc(O)c([C@@H]3C=C(C)CC[C@H]3C(=C)C)c2O)c1O
InChIKey: UMJIRNQSAUOZKO-HEZKMHOLSA-N
Target: Heat sensitive channel TRPV3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q4QYD9
Assay: Antagonist activity at rat TRPV3 expressed in HEK293 cells assessed as inhibition of thymol-induced Ca2+ response preincubated for 5 mins followed by thymol addition by Fluo-4AM dye based fluorescence assay
Measurement: IC50 = 11800 nM (pChEMBL 4.929999828338623)
Descriptors: MW 640.95, ALogP 11.6, HBA 4, HBD 4, PSA 80.92, QED 0.12
Compound (SMILES): CCCCCCCCCCCCCC(=S)NCCCC[C@H](NC(=O)CCOCCOCCOCCOCCNc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O)C(=O)Nc1ccccc1
InChIKey: CYVGGMWMJPYYNF-DYJLHVNUSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of human SIRT3 deacetylation activity using H3K9Ac as substrate preincubated for 15 mins in presence of NAD+ followed by substrate addition by HPLC analysis
Measurement: IC50 > 83000 nM (pChEMBL 4.080999851226807)
Descriptors: MW 951.24, ALogP 6.87, HBA 12, HBD 5, PSA 202.73, QED 0.03
Compound (SMILES): CCN(Cc1ccccc1)C(=O)/C=C/c1ccc(OC(=O)N(c2ccccc2)c2ccccc2)c(OC)c1
InChIKey: KOURHYYDCUECQR-LSDHQDQOSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 18900 nM (pChEMBL 4.71999979019165)
Descriptors: MW 506.6, ALogP 7.09, HBA 4, HBD 0, PSA 59.08, QED 0.23
Compound (SMILES): Nc1nn2c(-c3cccs3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: TWLBRDPBOUDNES-QZQOTICOSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human full-length N-terminal GST/His6-tagged CDK9 (1 to 372 residues)/His6-tagged Cyclin-T1 (1 to 726 residues) expressed in sf9 cells using (YSPTSPS)2KK peptide as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 399.46, ALogP 3.1, HBA 9, HBD 2, PSA 141.09, QED 0.51
Compound (SMILES): C=CC(=O)NCc1ccc(-c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2)cc1
InChIKey: ZIAQTARFHIBGJS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) assessed as reduction in ATP-dependent phosphorylation of ULight-myelin basic protein substrate peptide incubated for 60 mins by LANCE TR-FRET assay
Measurement: IC50 = 2118 nM (pChEMBL 5.670000076293945)
Descriptors: MW 414.51, ALogP 4.5, HBA 3, HBD 3, PSA 86.88, QED 0.47
Compound (SMILES): CN(C)C(=O)c1ccc(-c2cc(C(=O)N(C)C3CCCC3)no2)cc1O
InChIKey: CKEICVFLYGXFOP-UHFFFAOYSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000732a MLLT3
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 357.41, ALogP 2.76, HBA 5, HBD 1, PSA 86.88, QED 0.91
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCN(Cc3ccccc3)CC2)ccc1OC(=O)N(c1ccccc1)c1ccccc1
InChIKey: ICKSGIYUZRTUTJ-CZIZESTLSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 89800 nM (pChEMBL 4.050000190734863)
Descriptors: MW 547.66, ALogP 6.39, HBA 5, HBD 0, PSA 62.32, QED 0.24
Compound (SMILES): OCCCNc1ccnc2c1nc(-c1ccco1)n2C1CCCC1
InChIKey: CXELNJALEVTKCV-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of human recombinant PDE3A using cAMP as substrate incubated for 20 mins measured by Kinase Glo reagent based microplate reader assay
Measurement: IC50 = 47280 nM (pChEMBL 4.329999923706055)
Descriptors: MW 326.4, ALogP 3.6, HBA 6, HBD 2, PSA 76.11, QED 0.68
Compound (SMILES): O=c1[nH]cc(C2CCCCC2)c2nccn12
InChIKey: IRDDESQGXYVSBF-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Binding affinity to CDK2 (unknown origin) by isothermal titration calorimetry
Measurement: Kd = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 217.27, ALogP 2.07, HBA 3, HBD 1, PSA 50.16, QED 0.79
Compound (SMILES): COc1cc(OCc2ccnc(N)n2)cc2sc(N[C@H]3CCCC[C@@H]3O)nc12
InChIKey: QPANAVQRQRUDJJ-KBPBESRZSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R phosphorylation in M-CSF induced human THP1 cells incubated for 30 mins by ELISA assay
Measurement: IC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 401.49, ALogP 2.97, HBA 9, HBD 3, PSA 115.41, QED 0.58
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccccc23)cc1
InChIKey: HYCPLKOVNZFNAS-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of amyloid beta (1 to 42) (unknown origin) self aggregation after 24 hrs by thioflavin-T fluorescence method
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 329.36, ALogP 4.25, HBA 4, HBD 3, PSA 74.25, QED 0.3
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4cccc(-c5cc[nH]n5)c4)c3n2)cn1
InChIKey: MEZZCEDCBNWCRR-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human full length recombinant DYRK1B using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 = 1894 nM (pChEMBL 5.71999979019165)
Descriptors: MW 341.37, ALogP 4.29, HBA 5, HBD 1, PSA 72.53, QED 0.53
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)c(N3CCN(C)CC3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: DXEYGTAOOLIULQ-ZCXCRYNXSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 2a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.143 nM (pChEMBL 9.850000381469727)
Descriptors: MW 843, ALogP 4.76, HBA 10, HBD 4, PSA 181.12, QED 0.16
Compound (SMILES): CN1C(=O)c2c(F)cccc2Oc2cc(N[C@H]3CC[C@H](O)CC3)ncc21
InChIKey: GFDDTDKCZCGJLM-HAQNSBGRSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG stably expressed in CHO cells at holding potential of -80 mV incubated for 12 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 357.39, ALogP 3.32, HBA 5, HBD 2, PSA 74.69, QED 0.86
Compound (SMILES): Cl.O=C(NO)c1cnc(N2CCC3(CCN(Cc4c[nH]c5ccccc45)C3)CC2)nc1
InChIKey: CLWKBFQPPQNENW-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of human C-terminal His-tagged SIRT2 (50 to 356 residues) expressed in Escherichia coli using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and incubated for 240 mins followed by trypsin addition and further incubated for 120 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 406.49, ALogP 2.57, HBA 6, HBD 3, PSA 97.38, QED 0.46
Compound (SMILES): CO[C@H]1CC[C@H](C(=O)Nc2cc3cc(-c4cnn(C)c4CN4CCCCC4)ccc3cn2)CC1
InChIKey: MCKVVSGRVQMFEY-UILWBTOOSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. response-variable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 471 nM (pChEMBL 6.329999923706055)
Descriptors: MW 461.61, ALogP 4.76, HBA 6, HBD 1, PSA 72.28, QED 0.57
Compound (SMILES): C[C@H]1C[C@H](C(=O)O)CC[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3ccccc3)c3cc(F)c(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: ZRBKKZYWZRWOFL-GSDLGJSISA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Inverse agonist activity of LXRalpha (unknown origin)
Measurement: EC50 > 12000 nM (pChEMBL 4.921000003814697)
Descriptors: MW 667.62, ALogP 6.47, HBA 4, HBD 1, PSA 91.75, QED 0.37
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CCC(N)=O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: HWGGKSUESBGTAA-UMYBCCRSSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 1410 nM (pChEMBL 5.849999904632568)
Descriptors: MW 445.52, ALogP 0.51, HBA 7, HBD 4, PSA 134.35, QED 0.48
Compound (SMILES): COc1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: YTKAFKXVZBIBGM-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 33.2 nM (pChEMBL 7.480000019073486)
Descriptors: MW 428.49, ALogP 0.91, HBA 6, HBD 4, PSA 156.69, QED 0.49
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(C2CCN(C3CC3)CC2)cc1)c1ccccc1
InChIKey: ZYOFNMPBJCPWJW-FJISBNMDSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Inverse agonist activity at ERRgamma (unknown origin) by luciferase reporter gene assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 453.63, ALogP 6.47, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): C[C@H](C(=O)Nc1ccc(Cl)cc1)[C@H]1CC[C@]2(CC1)COc1cc(C(F)(F)F)ccc12
InChIKey: WPNANUSCDOZUBH-DFFLPILJSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human SKOV3 cells
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 437.89, ALogP 6.45, HBA 2, HBD 1, PSA 38.33, QED 0.6
Compound (SMILES): O=C(O)CSc1ncnc2sc(-c3cc4ccccc4s3)cc12
InChIKey: RRIRDIKTUQVZCW-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NE63
Assay: Binding affinity to human HIPK4 by KINOMEscan scanMAX assay
Measurement: Kd = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): CCn1nc(C(F)(F)F)cc1Nc1nc(-c2ccc(-n3cnc(C)c3)c(OC)n2)cs1
InChIKey: UNFVPHNQVGXPKU-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant CYP2D6 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 449.46, ALogP 4.69, HBA 9, HBD 1, PSA 82.68, QED 0.46
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](C)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: ZDYOGHURRMOUMQ-QYYSHDEWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 392 nM (pChEMBL 6.409999847412109)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.72