lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC1(F)CC1
InChIKey: PHBYNJGKPFJBPE-NSYGIPOTSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 > 36000 nM (pChEMBL 4.443999767303467)
Descriptors: MW 466.58, ALogP 4.25, HBA 5, HBD 2, PSA 60.08, QED 0.52
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCSc2ccccn2)CC1
InChIKey: CJIJWFWCMIPCCS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in calcium mobilization measured at 2 sec intervals for 180 secs by Fluo-4AM dye based fluorescence assay
Measurement: EC50 = 112.2 nM (pChEMBL 6.949999809265137)
Descriptors: MW 425.93, ALogP 4.2, HBA 4, HBD 1, PSA 45.23, QED 0.53
Compound (SMILES): Cc1cc(-c2ccc3c(c2)-c2nnc(Oc4ccccc4Cl)n2CCO3)ccn1
InChIKey: YFSKKHKIJDECPU-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 404.86, ALogP 5.15, HBA 6, HBD 0, PSA 62.06, QED 0.47
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc3nc(C)ccc3c2)nc1C#N
InChIKey: UJNLAQJFBHIMQO-VPUSJEBWSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 540.71, ALogP 5.62, HBA 6, HBD 2, PSA 114.77, QED 0.3
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3cccc(Cl)c3F)ncnc2cc1OCc1cn(CCC(=O)NO)nn1
InChIKey: HWBDLOPOEYLRKK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) by mobility shift assay
Measurement: IC50 = 0.34 nM (pChEMBL 9.470000267028809)
Descriptors: MW 526.92, ALogP 3.36, HBA 10, HBD 4, PSA 156.18, QED 0.14
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)c3ccc(C(=O)O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: ILYCKBRKVXWUEH-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 466.46, ALogP 3.08, HBA 8, HBD 3, PSA 144.61, QED 0.36
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(CC(=O)n2c3ccccc3c3ccccc32)CC1
InChIKey: FNHZNJFNIFYHIB-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 = 18620.87 nM (pChEMBL 4.730000019073486)
Descriptors: MW 393.49, ALogP 3.99, HBA 5, HBD 0, PSA 54.78, QED 0.66
Compound (SMILES): Nc1nc2sc(CCCc3csc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c3)cc2c(=O)[nH]1
InChIKey: QXWUFUZJYLBZQF-LBPRGKRZSA-N
Target: Bifunctional purine biosynthesis protein ATIC (SINGLE PROTEIN), Homo sapiens
UniProt: P31939
Assay: Inhibition of human full length N-terminal His-tagged ATIC expressed in Chinese Hamster MTXRII-OuaR2-4 R2 cells assessed as reduction in THF formation using 10-CHOTHF as substrate by spectrophotometric method
Measurement: Ki = 19840 nM (pChEMBL 4.699999809265137)
Descriptors: MW 464.53, ALogP 1.85, HBA 8, HBD 5, PSA 175.47, QED 0.3
Compound (SMILES): CN1CCC[C@@H]1COc1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(O)cc2)cc1.Cl
InChIKey: OCAIWVBOBFRZBY-OWEDCIEKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG measured after 4 hrs by fluorescence polarization assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 443.59, ALogP 5.6, HBA 4, HBD 2, PSA 52.93, QED 0.42
Compound (SMILES): C=C(F)COc1ccc2occc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: TYHARJBXULAQSC-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 354.81 nM (pChEMBL 6.449999809265137)
Descriptors: MW 261.3, ALogP 3.36, HBA 3, HBD 1, PSA 48.39, QED 0.9
Compound (SMILES): CN1CCN(c2cc(CC(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)ccn2)CC1
InChIKey: OJYJGFHUQDZCKA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA kinase assay was run using the Ser/Thr 18 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 a ratio of coumarin emission/fluorescein emission. Briefly, recombinant DYRKIA kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was 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 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was 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 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 441.54, ALogP 2.96, HBA 7, HBD 1, PSA 79.18, QED 0.51
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCF)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: FTHWMXAAFNYFAB-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 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 439.52, ALogP 4.11, HBA 9, HBD 1, PSA 82.68, QED 0.47
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cnc3cccnc3c2)[nH]1
InChIKey: DHWPAUZGRCCDDS-VWNXMTODSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 502.66, ALogP 4.84, HBA 6, HBD 2, PSA 103.87, QED 0.36
Compound (SMILES): Cc1ccc(C(=O)/C=C/C(=O)N2CCc3cc(Nc4ncc(C)c(-c5cnn(C(C)C)c5)n4)ccc3C2)cc1
InChIKey: GHWJXBANKVFCJG-VAWYXSNFSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808 to end residues) KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCc3ccccc3C2)ccc1OC(=O)N(C)C
InChIKey: SCZIJKUJAHPGAK-PKNBQFBNSA-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 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 380.44, ALogP 3.35, HBA 4, HBD 0, PSA 59.08, QED 0.76
Compound (SMILES): Cc1c(F)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: JVXRSOAAKCNGDD-UHFFFAOYSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of human ABHD6 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 374.43, ALogP 3.94, HBA 3, HBD 1, PSA 51.1, QED 0.82
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCCC1CO
InChIKey: SHOIGSCXAHSRKT-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 = 19054.61 nM (pChEMBL 4.71999979019165)
Descriptors: MW 288.39, ALogP 1.81, HBA 3, HBD 1, PSA 43.78, QED 0.92
Compound (SMILES): O=C(Nc1cc2cc(-c3cncs3)ccc2cn1)c1ccc2c(c1)CNCC2
InChIKey: UHRGOZSADKOBED-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA kinase assay was run using the Ser/Thr 18 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 a ratio of coumarin emission/fluorescein emission. Briefly, recombinant DYRKIA kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was 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 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was 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 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 386.48, ALogP 4.26, HBA 5, HBD 2, PSA 66.91, QED 0.55
Compound (SMILES): CN[C@@H]1CC[C@H](N2CC[C@H](Nc3ncnc4ccc(C(F)(F)F)cc34)C2=O)[C@H](NC(C)=O)C1
InChIKey: XAEGFERQJKCQQO-FDPIWHGQSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 464.49, ALogP 2.31, HBA 6, HBD 3, PSA 99.25, QED 0.63
Compound (SMILES): CCc1nc2c(N3CCNCC3)nccc2n1S(=O)(=O)c1cccc(F)c1
InChIKey: UXDZDQRAGSHUBW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5HT7b expressed in HEK293 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 389.46, ALogP 1.78, HBA 7, HBD 1, PSA 80.12, QED 0.73
Compound (SMILES): O=C(O)c1ccc(Oc2ccc(Cl)cc2NS(=O)(=O)c2ccc(Cl)c(Cl)c2)cc1
InChIKey: SEXCSTOTDUMWPC-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Displacement of [3H]-CCR2-RA-(R) from human CCR2b expressed in human U2OS cell membranes pre-incubated for 4 hrs before radio ligand addition and measured after 20 mins by scintillation counting method
Measurement: Ki = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 472.73, ALogP 5.94, HBA 4, HBD 2, PSA 92.7, QED 0.46
Compound (SMILES): CC1CCCC(C)N1C(=O)CCN1CCCc2ccccc21
InChIKey: ZJKKWZMKWAJTKP-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 = 21877.62 nM (pChEMBL 4.659999847412109)
Descriptors: MW 300.45, ALogP 3.62, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CC(N)=O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: VJFNAJWMIIUIKO-YQSLKQGWSA-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 = 3.18 nM (pChEMBL 8.5)
Descriptors: MW 431.49, ALogP 0.12, HBA 7, HBD 4, PSA 134.35, QED 0.5
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)c1cncs1)c1[nH]c(-c2ccc(F)cc2)nc1C#N
InChIKey: CVDCDYPZZIBFOG-SFHVURJKSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 453.54, ALogP 4.94, HBA 6, HBD 2, PSA 111.53, QED 0.4
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccc2F)CC1
InChIKey: FRPYDYUBDGOHLI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 24.55 nM (pChEMBL 7.610000133514404)
Descriptors: MW 426.87, ALogP 4.23, HBA 3, HBD 1, PSA 41.57, QED 0.67
Compound (SMILES): Cc1ncnc(C2CC2)c1-c1ncc2nc(NCc3ccc(S(C)(=O)=O)cn3)c(=O)n([C@@H](C)C3CC3)c2n1
InChIKey: HVVHIBHBDCYLDI-HNNXBMFYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells assessed as reduction in channel tail current by whole cell patch clamp assay
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 532.63, ALogP 3.21, HBA 11, HBD 1, PSA 145.51, QED 0.36
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccc([N+](=O)[O-])cc2)cc1
InChIKey: UMYGCMORXGSBRC-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 = 230.8 nM (pChEMBL 6.639999866485596)
Descriptors: MW 443.46, ALogP 0.81, HBA 7, HBD 4, PSA 190.6, QED 0.34
Compound (SMILES): O[C@@H]1[C@H](O)CO[C@H]1Cn1cnc2c(NCc3cccc(I)c3)nc(Cl)nc21
InChIKey: YNJLPUNKRNXONY-MBNYWOFBSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Binding affinity to PPARdelta (unknown origin) by TR-FRET based LanthaScreen competitive binding assay
Measurement: Ki = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 501.71, ALogP 1.82, HBA 8, HBD 3, PSA 105.32, QED 0.36
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(F)F
InChIKey: IVBCTFVBWGUGKC-DXPJPUQTSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluormone ES2 green reagent from human GST-tagged ERalpha LBD (282 to 595 residues) expressed in baculovirus infected insect cells incubated for 1 hrs by TR-FRET Lanthascreen assay
Measurement: IC50 = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 487.57, ALogP 4.63, HBA 5, HBD 2, PSA 56.42, QED 0.46
Compound (SMILES): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: QKNTUQSKNADJQQ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29276
Assay: Displacement of [3H]PSB-603 from rat adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 504.57, ALogP 6.33, HBA 7, HBD 1, PSA 90.02, QED 0.3
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)nc1
InChIKey: RVJLYMOGPFRCQZ-QGZVFWFLSA-N
Target: Cyclin-dependent kinase 13/Cyclin-K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of human recombinant CDK13/CyclinK assessed as reduction in substrate phosphorylation using His-c-Myc as substrate preincubated with enzyme for 5 mins followed by substrate addition for 15 mins in presence of [gamma 32P-ATP] by radioactive kinase assay
Measurement: IC50 = 798.9 nM (pChEMBL 6.099999904632568)
Descriptors: MW 501.98, ALogP 4.51, HBA 6, HBD 3, PSA 115.9, QED 0.33
Compound (SMILES): CN(C)c1nc(-c2ccc(S(N)(=O)=O)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: SMRAUEYCFQUGMY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 6729 nM (pChEMBL 5.170000076293945)
Descriptors: MW 410.46, ALogP 1.26, HBA 8, HBD 1, PSA 115.59, QED 0.54
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCC2CC2)ccc2c1CCO2
InChIKey: AJMUJJINXBRVEL-YLAFAASESA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 754 nM (pChEMBL 6.119999885559082)
Descriptors: MW 259.35, ALogP 2.47, HBA 3, HBD 1, PSA 44.48, QED 0.88
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)CCN1Cc2ccccc2C[C@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](N)Cc2c(C)cc(O)cc2C)C1=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C
InChIKey: RUHXXMOCSLYNBV-YRHYFRTJSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR stably expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding incubated for 1 hr by liquid scintillation counting assay
Measurement: EC50 = 48.7 nM (pChEMBL 7.309999942779541)
Descriptors: MW 1366.72
Compound (SMILES): CS(=O)(=O)N1C[C@@H](NS(=O)(=O)c2ccc(-c3ccccc3)cc2)C[C@@H]1C(=O)NO
InChIKey: BZIYLYICROTDCU-DOTOQJQBSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 439.52, ALogP 0.54, HBA 6, HBD 3, PSA 132.88, QED 0.44
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCc1cn(CCCCC(=O)NO)nn1
InChIKey: SSAKQDBVDKDWIF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R (unknown origin) by mobility shift assay
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 661.09, ALogP 5.72, HBA 11, HBD 4, PSA 165.41, QED 0.05
Compound (SMILES): CC1(C)C(=O)Nc2nc(-n3nc(CCC(F)(F)F)c4cc(Cl)ccc43)nc(N)c21
InChIKey: RMQPTENEQUQKPM-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 424.81, ALogP 3.78, HBA 6, HBD 2, PSA 98.72, QED 0.67
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCc1cn(CCC(=O)NO)nn1
InChIKey: WUOFCZPJKYPFBV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R (unknown origin) by mobility shift assay
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 633.04, ALogP 4.94, HBA 11, HBD 4, PSA 165.41, QED 0.08
Compound (SMILES): Cn1cncc1-c1ccc2cnc(NC(=O)c3ccnc(N4CCN(C5CC5)CC4)c3)cc2c1
InChIKey: JMMFCWMGIQZGQW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSK3 beta kinase assay: 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%)))].
Measurement: EC50 = 1853 nM (pChEMBL 5.730000019073486)
Descriptors: MW 453.55, ALogP 3.57, HBA 7, HBD 1, PSA 79.18, QED 0.5
Compound (SMILES): Cc1ccc(-c2ccnc3c(/N=N/c4ccc(S(N)(=O)=O)cc4)c(N)nn23)cc1
InChIKey: KJDLSZXXWPOVFP-WCWDXBQESA-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 407.46, ALogP 3.35, HBA 8, HBD 2, PSA 141.09, QED 0.5
Compound (SMILES): N#Cc1ccc(C(=O)N(Cc2cccs2)C2CC2)cc1
InChIKey: WYAGGMZTARRIDX-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZ95
Assay: Binding affinity to NSD3 (unknown origin) assessed as dissociation constant
Measurement: Kd = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 282.37, ALogP 3.42, HBA 3, HBD 0, PSA 44.1, QED 0.86
Compound (SMILES): CC(Sc1nc2ncccc2n1-c1ccc(C2CC2)c2ccccc12)C(=O)O
InChIKey: CGDNIBCXZXFIFY-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsome using probe substrate measured after 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 389.48, ALogP 5.02, HBA 5, HBD 1, PSA 68.01, QED 0.49
Compound (SMILES): O=C(NO)[C@H]1C[C@H](NS(=O)(=O)c2ccc(-c3ccccc3)cc2)CN1S(=O)(=O)c1ccc(-c2ccccc2)cc1
InChIKey: QAOSFIACYHTRMI-LBNVMWSVSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 8820 nM (pChEMBL 5.050000190734863)
Descriptors: MW 577.68, ALogP 3.64, HBA 6, HBD 3, PSA 132.88, QED 0.22
Compound (SMILES): Cc1ccc(S(=O)(=O)n2cc(-c3ccsc3)c3ccc(CO[C@H](C(=O)O)[C@H](N)C(=O)O)cc32)cc1.O=C(O)C(F)(F)F
InChIKey: VMPFGBKJPICYPD-VROPFNGYSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of human EAAT2 transfected in HEK293 cells assessed as inhibition of [3H]-D-aspartate uptake incubated for 4 mins by TopCount scintillation counting analysis
Measurement: IC50 = 208.93 nM (pChEMBL 6.679999828338623)
Descriptors: MW 514.58, ALogP 3.3, HBA 8, HBD 3, PSA 148.92, QED 0.31
Compound (SMILES): Nc1nccc(COc2ccc3nc(N[C@@H]4CCCC[C@H]4O)sc3c2)c1Cl
InChIKey: NGKALCMOLVCFHL-UKRRQHHQSA-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 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 404.92, ALogP 4.22, HBA 7, HBD 3, PSA 93.29, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(S(=O)(=O)N(C[C@H](O)[C@@H](N)c2ccc(OC(F)(F)F)cc2)C2CCC2)cc1
InChIKey: KEEHEUGOPCFXAV-VXKWHMMOSA-N
Target: Signal peptide peptidase-like 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TCT7
Assay: Inhibition of SPPL2b in human U2OS cells cotransfected with EGFP-labeled TNFalpha (1 to 76 residues)-NTF incubated for 24 hrs by Hoechst staining based Cellomics ArrayScan analysis
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 500.58, ALogP 4.49, HBA 5, HBD 2, PSA 92.86, QED 0.56
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCc1cn(CCCC(=O)NO)nn1
InChIKey: NYYMSVYTUYTODA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R (unknown origin) by mobility shift assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 540.94, ALogP 3.75, HBA 10, HBD 4, PSA 156.18, QED 0.13
Compound (SMILES): CC(=O)NC1CCCC(C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(Cl)cn2)C1
InChIKey: AVIWDYSJSPOOAR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MV4-11 cells assessed as induction of caspase-3/7 activation measured after 6 hrs followed by Caspase-glo reagent based assay
Measurement: EC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 429.95, ALogP 3.81, HBA 5, HBD 2, PSA 88.91, QED 0.77
Compound (SMILES): CSCC[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: WXXIHVNTCSDRKD-LEFBFSETSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 114.82 nM (pChEMBL 6.940000057220459)
Descriptors: MW 1172.38
Compound (SMILES): Fc1ccc(-c2nnc(N3CCN(c4ccccn4)CC3)o2)c(F)c1
InChIKey: JDYATWHUSHCNRV-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Mixed type inhibition of human erythrocytes AChE using varying levels of acetylthiocholine iodide substrate by Dixon plot analysis
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 343.34, ALogP 2.74, HBA 6, HBD 0, PSA 58.29, QED 0.73
Compound (SMILES): CC(C)Oc1ccc2occc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: HAIVDRAVZBKQDP-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 298 nM (pChEMBL 6.53000020980835)
Descriptors: MW 245.32, ALogP 3.28, HBA 3, HBD 1, PSA 48.39, QED 0.9
Compound (SMILES): CN(C)c1ccc(CC(=O)N[C@@H]2CNC[C@H]2c2ccc(C(C)(F)F)cc2)cc1
InChIKey: WQTOGFREMHSJJS-VQTJNVASSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of Tracer Red from human ERG incubated for 2 hrs by fluorescence polarization assay
Measurement: IC50 = 2809 nM (pChEMBL 5.550000190734863)
Descriptors: MW 387.47, ALogP 3.28, HBA 3, HBD 2, PSA 44.37, QED 0.8
Compound (SMILES): COc1cc(C#Cc2sc(NC(=O)NCCOCC3CC3)nc2C)cnc1OC
InChIKey: NXINHUNNPLATCI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin)
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 416.5, ALogP 2.81, HBA 7, HBD 2, PSA 94.6, QED 0.51
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@H]4CC[C@H](N)CC4)nc32)cc1
InChIKey: OYCSZJFCBXZCDD-HAQNSBGRSA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Inhibition of recombinant full length His6-GST fusion tagged ERK3 (1 to 721 residues) (unknown origin) using MK5 K51A mutant as substrate by ADP-Glo assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 339.4, ALogP 1.9, HBA 8, HBD 2, PSA 103.77, QED 0.75
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCC(Cc3ccccc3)CC2)ccc1OC(=O)N(c1ccccc1)c1ccccc1
InChIKey: GKLOQGGYHKLMHI-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 = 88300 nM (pChEMBL 4.050000190734863)
Descriptors: MW 546.67, ALogP 7.53, HBA 4, HBD 0, PSA 59.08, QED 0.21
Compound (SMILES): CC(C)n1cnnc1-c1cccc(NC(=O)C2CCCCO2)n1
InChIKey: ZKCUEAJARGYWOA-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET (unknown origin)
Measurement: IC50 > 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 315.38, ALogP 2.43, HBA 6, HBD 1, PSA 81.93, QED 0.94
Compound (SMILES): CCCCN(Cc1ccc(C(=O)NO)cc1)C(=O)Nc1ccc(CN)cc1
InChIKey: GESBEDAZDXKNGG-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of human HDAC5 expressed in HEK293/T17 cells pre-incubated for 10 mins before Boc-Lys(TFA)-AM substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 10100 nM (pChEMBL 5)
Descriptors: MW 370.45, ALogP 3.1, HBA 4, HBD 4, PSA 107.69, QED 0.42
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(F)(F)F
InChIKey: JUMJODAYGHYIAH-CPJLOUKISA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 505.56, ALogP 4.93, HBA 5, HBD 2, PSA 56.42, QED 0.43
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCSc2ccccn2)CC1
InChIKey: CJIJWFWCMIPCCS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Receptor Binding Assay: 5-HT1A: Radioligand binding was performed using membranes from CHO-K1 cells stably transfected with the human 5-HT1A receptor. All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-8-OH-DPAT (final concentration 1 nM, Kd 0.8 nM) and 150 μL diluted membranes (10 μg protein per well) prepared in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 0.1 mM EDTA, 0.1% ascorbic acid) were transferred to polypropylene 96-well microplate using 96-wells pipetting station Rainin Liquidator (MettlerToledo). Serotonin (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 60 minutes at 27° C. The reaction was terminated by rapid filtration through GF/C filter mate presoaked with 0.3% polyethyleneimine for 30 minutes. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.4) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and then solid scintillator MeltiLex was melted on filter mates at 90° C. for 5 minutes. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (GraphPad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 425.93, ALogP 4.2, HBA 4, HBD 1, PSA 45.23, QED 0.53
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3cccc(Cl)c3F)ncnc2cc1OCc1cn(CCC(=O)NO)nn1
InChIKey: HWBDLOPOEYLRKK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R (unknown origin) by mobility shift assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 526.92, ALogP 3.36, HBA 10, HBD 4, PSA 156.18, QED 0.14
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)c3ccc(C(=O)O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: ILYCKBRKVXWUEH-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 466.46, ALogP 3.08, HBA 8, HBD 3, PSA 144.61, QED 0.36
Compound (SMILES): C=C(F)COc1ccc2occc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: TYHARJBXULAQSC-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 358 nM (pChEMBL 6.449999809265137)
Descriptors: MW 261.3, ALogP 3.36, HBA 3, HBD 1, PSA 48.39, QED 0.9
Compound (SMILES): CN1CCN(c2cc(CC(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)ccn2)CC1
InChIKey: OJYJGFHUQDZCKA-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.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 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 441.54, ALogP 2.96, HBA 7, HBD 1, PSA 79.18, QED 0.51
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCF)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: FTHWMXAAFNYFAB-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 439.52, ALogP 4.11, HBA 9, HBD 1, PSA 82.68, QED 0.47
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cnc3cccnc3c2)[nH]1
InChIKey: DHWPAUZGRCCDDS-VWNXMTODSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 502.66, ALogP 4.84, HBA 6, HBD 2, PSA 103.87, QED 0.36
Compound (SMILES): Cc1ccc(C(=O)/C=C/C(=O)N2CCc3cc(Nc4ncc(C)c(-c5cnn(C(C)C)c5)n4)ccc3C2)cc1
InChIKey: GHWJXBANKVFCJG-VAWYXSNFSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 (781 to end residues) using GGEEEEYFELVKKKK as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCc3ccccc3C2)ccc1OC(=O)N(C)C
InChIKey: SCZIJKUJAHPGAK-PKNBQFBNSA-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 = 26800 nM (pChEMBL 4.570000171661377)
Descriptors: MW 380.44, ALogP 3.35, HBA 4, HBD 0, PSA 59.08, QED 0.76
Compound (SMILES): Cc1c(F)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: JVXRSOAAKCNGDD-UHFFFAOYSA-N
Target: Lysophosphatidylserine lipase ABHD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N2K0
Assay: Inhibition of human ABHD12 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 374.43, ALogP 3.94, HBA 3, HBD 1, PSA 51.1, QED 0.82
Compound (SMILES): O=C(Nc1cc2cc(-c3cncs3)ccc2cn1)c1ccc2c(c1)CNCC2
InChIKey: UHRGOZSADKOBED-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.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 = 346 nM (pChEMBL 6.460000038146973)
Descriptors: MW 386.48, ALogP 4.26, HBA 5, HBD 2, PSA 66.91, QED 0.55
Compound (SMILES): CN[C@@H]1CC[C@H](N2CC[C@H](Nc3ncnc4ccc(C(F)(F)F)cc34)C2=O)[C@H](NC(C)=O)C1
InChIKey: XAEGFERQJKCQQO-FDPIWHGQSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 464.49, ALogP 2.31, HBA 6, HBD 3, PSA 99.25, QED 0.63
Compound (SMILES): CCc1nc2c(N3CCNCC3)nccc2n1S(=O)(=O)c1cccc(F)c1
InChIKey: UXDZDQRAGSHUBW-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L expressed in CHO-K1 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 689 nM (pChEMBL 6.159999847412109)
Descriptors: MW 389.46, ALogP 1.78, HBA 7, HBD 1, PSA 80.12, QED 0.73
Compound (SMILES): O=C(O)c1ccc(Oc2ccc(Cl)cc2NS(=O)(=O)c2ccc(Cl)c(Cl)c2)cc1
InChIKey: SEXCSTOTDUMWPC-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Displacement of [3H]-CCR2-RA-(R) from human CCR2b expressed in human U2OS cell membranes pre-incubated for 4 hrs before radio ligand addition and measured after 20 mins by scintillation counting method
Measurement: Ki = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 472.73, ALogP 5.94, HBA 4, HBD 2, PSA 92.7, QED 0.46
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CC(N)=O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: VJFNAJWMIIUIKO-YQSLKQGWSA-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 = 923 nM (pChEMBL 6.039999961853027)
Descriptors: MW 431.49, ALogP 0.12, HBA 7, HBD 4, PSA 134.35, QED 0.5
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccc2F)CC1
InChIKey: FRPYDYUBDGOHLI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 151.36 nM (pChEMBL 6.820000171661377)
Descriptors: MW 426.87, ALogP 4.23, HBA 3, HBD 1, PSA 41.57, QED 0.67
Compound (SMILES): Cc1ncnc(C2CC2)c1-c1ncc2nc(NCc3ccc(S(C)(=O)=O)cn3)c(=O)n([C@@H](C)C3CC3)c2n1
InChIKey: HVVHIBHBDCYLDI-HNNXBMFYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human whole blood derived CD4-positive T cells assessed as inhibition of IL-17 secretion from differentiated Th17 cells preincubated for 1 hr and measured after 48 hrs
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 532.63, ALogP 3.21, HBA 11, HBD 1, PSA 145.51, QED 0.36
Compound (SMILES): O[C@@H]1[C@H](O)CO[C@H]1Cn1cnc2c(NCc3cccc(I)c3)nc(Cl)nc21
InChIKey: YNJLPUNKRNXONY-MBNYWOFBSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Antagonist activity at PPARdelta (unknown origin) by TR-FRET assay
Measurement: EC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 501.71, ALogP 1.82, HBA 8, HBD 3, PSA 105.32, QED 0.36
Compound (SMILES): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: QKNTUQSKNADJQQ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki = 25.4 nM (pChEMBL 7.590000152587891)
Descriptors: MW 504.57, ALogP 6.33, HBA 7, HBD 1, PSA 90.02, QED 0.3