lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(Nc2cc(-c3cccs3)cc3c2c(=O)[nH]c2ccccc23)cc1
InChIKey: JCAULMHEVXFBGL-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 (104 to 274 residues) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 expressed in Escherichia coli expression system as substrate incubated for 15 mins followed by substrate addition and measured after 2 to 4 hrs by fluorescence based assay
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 398.49, ALogP 6.16, HBA 4, HBD 2, PSA 54.12, QED 0.36
Compound (SMILES): Cl.Nc1ccc(/C(=C(\CCCO)c2ccccc2)c2ccc(C3CCN(C4CC4)CC3)cc2)cc1
InChIKey: PUZIXHQBEURMNU-FJISBNMDSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 452.64, ALogP 6.34, HBA 3, HBD 2, PSA 49.49, QED 0.31
Compound (SMILES): CN(C)C1CCN(c2cc(C(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)ccn2)CC1
InChIKey: DTBDRQJSYYMFRU-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 = 1435 nM (pChEMBL 5.840000152587891)
Descriptors: MW 455.57, ALogP 3.81, HBA 7, HBD 1, PSA 79.18, QED 0.49
Compound (SMILES): CCN1CC2(CCN(CCc3ccccc3)CC2)O[C@H](C)C1=O
InChIKey: NASMRBRQNLMHLZ-MRXNPFEDSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHOK1 cell membranes incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 316.45, ALogP 2.33, HBA 3, HBD 0, PSA 32.78, QED 0.85
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cnc(N)cc2C(F)F)nc(N2CCOCC2(C)C)n1
InChIKey: BIKQHHNLLORGLD-GFCCVEGCSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Binding affinity to wild-type human partial length PIK3CA (R108 to N1068 residues) expressed in HEK293 cells measured after 1 hr by Kinomescan method
Measurement: Kd = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 435.48, ALogP 2.29, HBA 9, HBD 1, PSA 102.52, QED 0.77
Compound (SMILES): CCCCC(=O)Nc1cncc(-c2cc3c(-c4cc5c(-c6cccnc6)ccnc5[nH]4)n[nH]c3cn2)c1
InChIKey: OKQDQCIUZWGVLL-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 9838 nM (pChEMBL 5.010000228881836)
Descriptors: MW 488.56, ALogP 5.75, HBA 6, HBD 3, PSA 125.13, QED 0.26
Compound (SMILES): COc1cccc(COc2ccc3c(CN4CCN(Cc5ccccc5)CC4)cc(=O)oc3c2)c1
InChIKey: YHBBWYZTWCSOGA-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 5570 nM (pChEMBL 5.25)
Descriptors: MW 470.57, ALogP 4.7, HBA 6, HBD 0, PSA 55.15, QED 0.35
Compound (SMILES): CCc1c(C(=O)NCc2c(O)ccc3cccc(O)c23)[nH]c(C)c1C(C)=O
InChIKey: KCGVENSOXCWCNF-UHFFFAOYSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Binding affinity to human His-Tev tagged EP300 expressed in bacterial expression system incubated for 30 mins by isothermal titration calorimetry
Measurement: Kd = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 366.42, ALogP 3.58, HBA 4, HBD 4, PSA 102.42, QED 0.52
Compound (SMILES): COCCn1cc(Nc2cc(-c3cccc(NC(=O)CC#N)c3)ncn2)cn1
InChIKey: VVTLSOHVNNDMFQ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human N-terminal GST-tagged TYK2 cytoplasmic domain (833 to 1187 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 2264 nM (pChEMBL 5.639999866485596)
Descriptors: MW 377.41, ALogP 2.58, HBA 8, HBD 2, PSA 117.75, QED 0.62
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccccc3)c3cccc(O)c3)cc2)CC1.Cl
InChIKey: VCYKHCGHJGYAEB-FJISBNMDSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 455.64, ALogP 6.71, HBA 3, HBD 2, PSA 43.7, QED 0.37
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3C)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: MAWNVWBEHNFLCH-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of recombinant CYP2C9 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 407.5, ALogP 3.67, HBA 9, HBD 1, PSA 82.68, QED 0.54
Compound (SMILES): NC(=O)Cc1cc(N2CCN(CCn3c(=O)sc4c3nc(N)n3nc(-c5ccco5)nc43)CC2)c(F)cc1F
InChIKey: SGVRZSJMQKGITO-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at adenosine 2A receptor in human peripheral blood lymphocytes assessed as reduction in NECA-stimulated CREB phosphorylation by flow cytometric analysis
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 555.57, ALogP 1.47, HBA 12, HBD 2, PSA 153.81, QED 0.3
Compound (SMILES): NC1CN(c2cc(C(=O)Nc3cc4cc(-c5cnco5)ccc4cn3)ccn2)C1
InChIKey: YUPJLBUUQOSGNF-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 386.42, ALogP 2.68, HBA 7, HBD 2, PSA 110.17, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CSC(=S)N2CCN(C3CCCCC3)CC2)cc1
InChIKey: XGOLETKNUUBXSL-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human erythrocyte CA2 using 4-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 456.66, ALogP 2.24, HBA 6, HBD 2, PSA 95.74, QED 0.66
Compound (SMILES): CCNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(N)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: LSSSJNNPRYIYQE-RGUAOFKASA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 352.78, ALogP -0.52, HBA 8, HBD 4, PSA 139.18, QED 0.54
Compound (SMILES): COC(=O)[C@@H]1C=C(OC(=O)c2ccc(C)cc2)C(=O)[C@H]2[C@@]1(C)CC[C@H]1C(=O)O[C@H](c3ccoc3)C[C@]21C
InChIKey: LRIZBODPEAEWHK-QDBRMXEESA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human mu opiod receptor expressed in CHO-K1 cells assessed as stimulation of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 506.55, ALogP 4.73, HBA 8, HBD 0, PSA 109.11, QED 0.43
Compound (SMILES): N#Cc1ccc(Nc2cc(NCc3cccnc3)nc(-c3ccccc3)n2)cc1
InChIKey: RRKKLAAOYSPQEP-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin) expressed in MDCK-II cells assessed as potentiation of SN-38-induced cytotoxicity measured after 72 hrs by MTT assay
Measurement: EC50 = 44.3 nM (pChEMBL 7.349999904632568)
Descriptors: MW 378.44, ALogP 4.77, HBA 6, HBD 2, PSA 86.52, QED 0.5
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)C2CN(C(=O)C3CC3)Cc3cc(Cl)ccc32)CC1
InChIKey: RLJGVIHFYZJDOY-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human V1a receptor expressed in human 1321N1 cells assessed as decrease in Arg8-vasopressin-stimulated calcium flux by fluorometric calcium assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 437.97, ALogP 3.83, HBA 3, HBD 0, PSA 43.86, QED 0.73
Compound (SMILES): CCCCCCCC/C=C\CCCCCCCC(=O)OCCCCOP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: IFPSMPWJVBKVTN-AXKWSIDASA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 52.48 nM (pChEMBL 7.28000020980835)
Descriptors: MW 521.63, ALogP 5.89, HBA 7, HBD 3, PSA 145.38, QED 0.06
Compound (SMILES): CN1CCC(c2nnc(-c3cnc(Nc4ccc5c(c4)C(C)(C)OC5=O)nc3N[C@H](CO)c3ccccc3)o2)CC1
InChIKey: HZYIMGKDYXEJDM-XMMPIXPASA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in anti-CD3/anti-CD28-stimulated human T-cells assessed as inhibition of SLP76 phosphorylation preincubated for 1 hr followed by anti-CD3/CD28 stimulation for 30 mins by AlphaLISA assay
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 555.64, ALogP 4.63, HBA 11, HBD 3, PSA 138.53, QED 0.26
Compound (SMILES): C[C@H](NC(=O)c1cc(C(F)(F)F)nn1C)c1nc(-c2ccnc(C(F)(F)F)c2)no1
InChIKey: SFSLHKNGLMRBTO-ZETCQYMHSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp analysis
Measurement: IC50 = 11900 nM (pChEMBL 4.920000076293945)
Descriptors: MW 434.3, ALogP 3.39, HBA 7, HBD 1, PSA 98.73, QED 0.63
Compound (SMILES): Cc1cc2c(cc1C(F)(C(F)(F)F)C(F)(F)F)CC[C@H]1N(C(=O)[C@H]3CC[C@H](C(=O)O)CC3)CC[C@@]21S(=O)(=O)c1ccc(F)cc1
InChIKey: ZFVKCNIIMDQMAG-BKNJMBQISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: 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.
Measurement: IC50 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 667.62, ALogP 6.53, HBA 4, HBD 1, PSA 91.75, QED 0.29
Compound (SMILES): CC(C)N1CC=C(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(O)cc3)cc2)CC1.Cl
InChIKey: HTBFUVXJBZTWPQ-FJISBNMDSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 = 1381 nM (pChEMBL 5.860000133514404)
Descriptors: MW 453.63, ALogP 6.62, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): Cn1cc(-c2cc3c(C(=O)Nc4ccc(CN5CCCC5)cc4)n[nH]c3cc2F)cn1
InChIKey: WPENABQDALBNCS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: DYRK1A: Each compound was 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 M to 0.00016 M) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The DYRK1A 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 DYRK1A 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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 418.48, ALogP 3.95, HBA 5, HBD 2, PSA 78.84, QED 0.51
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccc(NC(=O)CCCCC(=O)NO)cc3C2)c(O)cc1O
InChIKey: XQJICAHHMDZSIJ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using RHK-K(Ac)-AMC as substrate by fluorescence based assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 455.51, ALogP 3.38, HBA 6, HBD 5, PSA 139.2, QED 0.23
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](O)[C@]1(C)O
InChIKey: WJRJPWULDYZVOK-CPBVFMMISA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 471.48, ALogP 4.44, HBA 5, HBD 3, PSA 95.34, QED 0.52
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccc2)CC1
InChIKey: DXWRIDGYFFSIIY-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 inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 8.128 nM (pChEMBL 8.09000015258789)
Descriptors: MW 408.88, ALogP 4.09, HBA 3, HBD 1, PSA 41.57, QED 0.7
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CCCCN)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: NKIQDONKAOALDB-FDDRLWOQSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 6.85 nM (pChEMBL 8.15999984741211)
Descriptors: MW 445.56, ALogP 1.37, HBA 7, HBD 4, PSA 117.28, QED 0.44
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2ccccn2c1=O
InChIKey: ZBUAACUFPJCODX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human Ramos B cells assessed as reduction in goat anti human IgM-stimulated calcium flux preincubated for 1 hr followed by goat anti human IgM addition and measured for 180 secs by FLIPR assay
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 518.57, ALogP 4.39, HBA 6, HBD 3, PSA 122.59, QED 0.32
Compound (SMILES): N#Cc1c(-c2ccccc2)nc2c(/N=N/c3ccc(S(N)(=O)=O)cc3)c(N)nn2c1N
InChIKey: CCJFFHRRJCAICV-OCEACIFDSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 39.4 nM (pChEMBL 7.409999847412109)
Descriptors: MW 433.46, ALogP 2.5, HBA 10, HBD 3, PSA 190.9, QED 0.41
Compound (SMILES): Cn1cc(-c2cn3nccc3c(-c3cnn(C4(CC#N)CN(CC#N)C4)c3)n2)cn1
InChIKey: ZEJGQLBINOBMRS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: JAK Caliper Enzyme Assay at 1 mM ATP: Compounds were added to a 384-well plate. Reaction mixtures contained 10 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% BSA, 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAM-KKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20% to 30% phosphorylation. The assays were stopped with 15 μL of 180 mM HEPES, pH 7.4, 20 mM EDTA, and 0.2% Coating Reagent 3. The assay plates were placed on a Caliper Life Science LC3000 instrument, and each well was sampled using appropriate separation conditions to measure the unphosphorylated and phosphorylated peptide.
Measurement: IC50 = 6682 nM (pChEMBL 5.170000076293945)
Descriptors: MW 398.43, ALogP 1.44, HBA 10, HBD 0, PSA 116.65, QED 0.47
Compound (SMILES): FC(F)(F)c1cnc(Nc2ccc3nc[nH]c3c2)nc1NC1CC1
InChIKey: HTSMUTPVZNMYSW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IYT8
Assay: Inhibition of ULK2 (unknown origin) expressed in HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 703 nM (pChEMBL 6.150000095367432)
Descriptors: MW 334.31, ALogP 3.69, HBA 5, HBD 3, PSA 78.52, QED 0.68
Compound (SMILES): CN1CCC(c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)CC1
InChIKey: BWUOLNXJAQPJKF-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human recombinant CLK4 using YRRAAVPPSPSLS substrate by radiometric scintillation assay
Measurement: IC50 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 372.47, ALogP 4.7, HBA 5, HBD 0, PSA 47.09, QED 0.52
Compound (SMILES): CNC(=O)c1cn(C[C@H](F)CCc2ccc(NC(=O)Cc3cc(OC4CC(F)(F)C4)cc(C)n3)nn2)nn1
InChIKey: GEHZIZWHNLQFAS-OAHLLOKOSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 532.53, ALogP 2.46, HBA 9, HBD 2, PSA 136.81, QED 0.38
Compound (SMILES): COc1ccccc1C1c2c(CCO)n[nH]c2C(=O)N1c1ccc(-c2ccon2)cc1
InChIKey: APFUKKWTUFRERG-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 416.44, ALogP 3.36, HBA 6, HBD 2, PSA 104.48, QED 0.5
Compound (SMILES): COc1cc(SCc2ccc(CN3CCCC3)o2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: QOEFDQQUMQBVOB-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of recombinant human N-terminal GST-tagged ROS1 (1883 to 2347 residues) expressed in baculovirus expression system using IRS1 as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 615.18, ALogP 6.48, HBA 10, HBD 3, PSA 121.62, QED 0.15
Compound (SMILES): C#CCN(C)Cc1ccc(OCCCCCN2CCN(c3cccc4c3ccn4S(=O)(=O)c3ccccc3)CC2)cc1
InChIKey: CUFJQHNVDRIQJL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from human 5HT2A receptor expressed in CHOK1 cells incubated at 27 degree C for 1 hr by microbeta plate reader analysis
Measurement: Ki = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 584.79, ALogP 5.31, HBA 7, HBD 0, PSA 58.02, QED 0.16
Compound (SMILES): CC[C@@H](C)n1c(=O)c(NCc2ccc(S(=O)(=O)CC)cn2)nc2cnc(-c3c(OC)ncnc3C3CC3)nc21
InChIKey: DCSACVSUKUQBSN-OAHLLOKOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at GAL4 DBD-fused human RORgamma LBD expressed in pGL4.3 luc2P/GAL4UAS/hygro and pBIND transfected HEK293 cells assessed as inhibition of RORgamma driven transcriptional activity incubated for 20 to 24 hrs by Bright-Glo luciferase assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 550.65, ALogP 3.3, HBA 12, HBD 1, PSA 154.74, QED 0.31
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(N)=O)C(C)C
InChIKey: ILQNQNXHECHYOX-RBAYCRCTSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.6 expressed in HEK293 cells incubated for 30 mins by FLIPRTetra fluorescent membrane potential assay
Measurement: EC50 = 15.8 nM (pChEMBL 7.800000190734863)
Descriptors: MW 7596.8
Compound (SMILES): CCC(=O)CCCCCC(NC(=O)c1cncs1)c1[nH]c(-c2ccccc2)nc1C(N)=O
InChIKey: IWHILOQIJOWDKF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 < 1.5 nM (pChEMBL 8.824000358581543)
Descriptors: MW 453.57, ALogP 4.03, HBA 6, HBD 3, PSA 130.83, QED 0.36
Compound (SMILES): CC(C)c1cc(-c2cnn3ccc(-c4cc5c(c(C(F)(F)F)c4)C(=O)N([C@@H](C)C4CC4)C5)nc23)ccc1C(=O)O
InChIKey: VHCSLWRCKYDLOT-INIZCTEOSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 459 nM (pChEMBL 6.340000152587891)
Descriptors: MW 548.57, ALogP 6.66, HBA 5, HBD 1, PSA 87.8, QED 0.29
Compound (SMILES): CC(Nc1c(Cl)cnc2ccc(-c3cnc(C(C)(C)O)nc3)nc12)c1ccccc1F
InChIKey: JGVFDTLFVROGOH-UHFFFAOYSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Inhibition of exogenous human TNFalpha in HEK-Blue-CD40L cells assessed as reduction in TNF-alpha-induced NFkappaB activation incubated for 18 hrs by quanti-blue based SEAP assay
Measurement: IC50 = 753 nM (pChEMBL 6.119999885559082)
Descriptors: MW 437.91, ALogP 5.28, HBA 6, HBD 2, PSA 83.82, QED 0.44
Compound (SMILES): Cn1cc(-c2ccccc2Oc2ccccc2)c2cc(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)[nH]c2c1=O
InChIKey: BXNOLMGJPGBWLA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 18.7 nM (pChEMBL 7.730000019073486)
Descriptors: MW 583.65, ALogP 6.09, HBA 6, HBD 4, PSA 131.24, QED 0.16
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccnc2)CC1
InChIKey: XGRYGIWQWQUCIB-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 inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 47.86 nM (pChEMBL 7.320000171661377)
Descriptors: MW 409.86, ALogP 3.49, HBA 4, HBD 1, PSA 54.46, QED 0.71
Compound (SMILES): O=C(Nc1nc2ccccc2s1)C(c1ccccc1)S(=O)(=O)O
InChIKey: VEVZMUHLTRGYHA-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P35236
Assay: Inhibition of His-tagged HePTP (unknown origin) expressed in Escherichia coli BL21 cells using para-nitrophenyl phosphate as substrate incubated for 5 to 10 mins by microplate reader based spectrophotometric analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 348.41, ALogP 2.86, HBA 5, HBD 2, PSA 96.36, QED 0.71
Compound (SMILES): CNc1ccccc1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: DMLMKQIHOFYZPV-VWLOTQADSA-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 538.68, ALogP 5.8, HBA 6, HBD 4, PSA 111.8, QED 0.16
Compound (SMILES): O=C(c1cccc(F)c1-c1ncccn1)N1C2CCC1C(Oc1ccc(C(F)(F)F)cn1)C2
InChIKey: FPUDTUWRAHVTMS-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Rat and Human Orexin 1 Receptor Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat #SH30022), 10% FBS, 1× Pen/Strep, 1× sodium pyruvate, 10 mM HEPES, 600 μg/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat #SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −800 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-(1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Moraveck Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-(1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 458.42, ALogP 4.52, HBA 5, HBD 0, PSA 68.21, QED 0.54
Compound (SMILES): CONC(=O)c1ccccc1Nc1cc(Nc2cc(C)nn2C(C)C)ncc1Cl
InChIKey: BVAHPPKGOOJSPU-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin)
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 414.9, ALogP 4.6, HBA 7, HBD 3, PSA 93.1, QED 0.49
Compound (SMILES): C[C@@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-DYVFJYSZSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Mus musculus
UniProt: Q91XA9
Assay: Inhibition of full-length C-terminal his-tagged mouse AMCase expressed in expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N'-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): O=c1[nH]c2ccccc2c2cc(-c3ccco3)cc(Nc3ccccc3)c12
InChIKey: ZAPNBHGFIWFOTQ-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 (104 to 274 residues) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 expressed in Escherichia coli expression system as substrate incubated for 15 mins followed by substrate addition and measured after 2 to 4 hrs by fluorescence based assay
Measurement: IC50 = 41700 nM (pChEMBL 4.380000114440918)
Descriptors: MW 352.39, ALogP 5.68, HBA 3, HBD 2, PSA 58.03, QED 0.41
Compound (SMILES): CCCCCCCCCCCCCC(=O)NCCOCCOCCNC(=O)CCOCCOCCNC(=O)[C@H]1CCCNC(=O)CSC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCCNC(=N)N)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)CSCC(=O)N1
InChIKey: OPCICTJVPFTEFT-IYTQQNEGSA-N
Target: Prolactin-releasing peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P49683
Assay: Activation of human GPR10 overexpressed in CHO-K1 cells assessed as increase in beta arrestin recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 4274.02
Compound (SMILES): CN(C)CCN1C(=O)c2ccccc2N(C)C(=O)c2ccccc21
InChIKey: JRBXXARYECIAQB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to 5HT1A receptor (unknown origin)
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 323.4, ALogP 2.49, HBA 3, HBD 0, PSA 43.86, QED 0.87
Compound (SMILES): COc1ccc(-c2nnc(-c3ccccc3)o2)cc1S(N)(=O)=O
InChIKey: UWJJFDNYKXWCBH-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of recombinant human carbonic anhydrase 13 by stopped flow CO2 hydrase assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 331.35, ALogP 2.06, HBA 6, HBD 1, PSA 108.31, QED 0.78
Compound (SMILES): CC(=O)N1CCC(C(=O)N2C[C@@H](c3ccc(C(O)(C(F)(F)F)C(F)(F)F)cc3)[C@@](C)(c3ccc(F)cc3)C2)CC1
InChIKey: PLEBLNIHUKCNPF-UKILVPOCSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: 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) binding assay. 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 room temperature 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.
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 574.54, ALogP 5.28, HBA 3, HBD 1, PSA 60.85, QED 0.51
Compound (SMILES): COc1ccc(N2CCN(Cc3cc(=O)oc4cc(OCc5ccc(Br)cc5)ccc34)CC2)cc1
InChIKey: KSPFBVXXXSEPCT-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 3440 nM (pChEMBL 5.460000038146973)
Descriptors: MW 535.44, ALogP 5.47, HBA 6, HBD 0, PSA 55.15, QED 0.29
Compound (SMILES): CC(C)(C)c1ccc(NC(=O)c2ccc(C(=O)NO)cc2)cc1
InChIKey: GYMSRUYUXJKIQR-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 447 nM (pChEMBL 6.349999904632568)
Descriptors: MW 312.37, ALogP 3.36, HBA 3, HBD 3, PSA 78.43, QED 0.6
Compound (SMILES): CCCCNNC(=O)c1ccc2ccccc2c1
InChIKey: KAROTAWAKPGPJD-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 5920 nM (pChEMBL 5.230000019073486)
Descriptors: MW 242.32, ALogP 2.87, HBA 2, HBD 2, PSA 41.13, QED 0.62
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(C)C)CSSC[C@H](N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)O)CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)O)NC1=O
InChIKey: PLBJQXYTEQHUPH-LSTQPPRASA-N
Target: Relaxin-3 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU9
Assay: Agonist activity at human RXFP4 expressed in CHO-K1 cells assessed as reduction in forskolin-induced cAMP production by pCRE beta-galactosidase reporter assay
Measurement: EC50 = 15.13 nM (pChEMBL 7.820000171661377)
Descriptors: MW 4370.16
Compound (SMILES): CC(C)C(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: RWOHIVZSQHNUEH-NRFANRHFSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 442.52, ALogP 0.38, HBA 10, HBD 3, PSA 142.62, QED 0.57
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N2Cc3ccc(O)cc3C[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: HSTHLZHYPGORFI-IZFFCAOBSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]-neurotensin from human recombinant NTS1 stably expressed in CHO-K1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 4710 nM (pChEMBL 5.329999923706055)
Descriptors: MW 1406.7
Compound (SMILES): O=C1CCC(N2Cc3cc(CNC(=O)C(F)(F)c4ccc(Cl)cc4)ccc3C2=O)C(=O)N1
InChIKey: PWBHUSLMHZLGRN-UHFFFAOYSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to human CRBN by HTRF method
Measurement: IC50 = 432 nM (pChEMBL 6.369999885559082)
Descriptors: MW 461.85, ALogP 2.51, HBA 4, HBD 2, PSA 95.58, QED 0.67
Compound (SMILES): O=C(CCCCCNC(=O)COc1ccc(/C=C/C2=[N+]3C(=Cc4ccc(-c5cccs5)n4[B-]3(F)F)C=C2)cc1)NCCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: WRUQALAONUATIE-OIWVIQBMSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M4 expressed in CHO-K9 cell membranes measured after 3 hrs by radioligand competition binding assay
Measurement: Ki = 0.4169 nM (pChEMBL 9.380000114440918)
Descriptors: MW 1117.15
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CCC4CC4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: QWBQEGAXRGYISD-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 608.69, ALogP 5.31, HBA 7, HBD 2, PSA 128.17, QED 0.25
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1N[C@@H]1CCN(Cc2cccc(OC)c2)C[C@H]1F
InChIKey: QYCQCEJRCQDCKL-RTBURBONSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 696 nM (pChEMBL 6.159999847412109)
Descriptors: MW 411.48, ALogP 2.96, HBA 5, HBD 3, PSA 82.28, QED 0.58
Compound (SMILES): COc1ccc2c(c1)c(CCNC(C)=O)cn2C(=O)c1ccc(Cl)cc1
InChIKey: NDAAJXSISJLIBF-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of AKR1C3 (unknown origin) using 9,10-phenanthrenequinone as substrate
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 370.84, ALogP 3.67, HBA 4, HBD 1, PSA 60.33, QED 0.75
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CCC[C@@H]2CO)cc1)c1ccccc1
InChIKey: PUUZQGFZAABHAA-VSNNFTROSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to GST-tagged ERalpha LBD (unknown origin) using fluorescein PGC1alpha as coactivator incubated for 1 hr by LanthaScreen TR-FRET co-regulator assay
Measurement: IC50 = 408 nM (pChEMBL 6.389999866485596)
Descriptors: MW 473.61, ALogP 4.96, HBA 5, HBD 3, PSA 73.16, QED 0.34
Compound (SMILES): CC(C)c1nc2c(N3CCNCC3)nccc2n1S(=O)(=O)c1cccc(Cl)c1
InChIKey: QWMKBPOOVMOXIR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT2A expressed in HEK293 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 239 nM (pChEMBL 6.619999885559082)
Descriptors: MW 419.94, ALogP 2.85, HBA 7, HBD 1, PSA 80.12, QED 0.7
Compound (SMILES): Cc1cc(-c2ccc3nc(NC(=O)C(C)C)cn3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: MIOGYNUMVQFNOQ-HNNXBMFYSA-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 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 417.51, ALogP 4.05, HBA 5, HBD 1, PSA 79.6, QED 0.68
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NC1CCN(Cc2ccc(Cl)cc2)C1
InChIKey: RHHJOBKVURZMHE-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 657.7 nM (pChEMBL 6.179999828338623)
Descriptors: MW 383.88, ALogP 3.26, HBA 4, HBD 3, PSA 73.05, QED 0.63
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(CN3CCN(S(N)(=O)=O)CC3)cc2)nc2ccsc12
InChIKey: MFLAVNPTRFOLPB-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 575.72, ALogP 4.7, HBA 9, HBD 2, PSA 137.47, QED 0.29
Compound (SMILES): Cn1ccc2c(S(=O)(=O)N[C@@H]3CCN(CCCc4noc5ccccc45)C3)cccc21
InChIKey: RDXPMJJNBGHREI-QGZVFWFLSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from recombinant human D2 receptor expressed in CHOK1 cell membranes measured after 60 mins by microbeta counting method
Measurement: Ki = 9.12 nM (pChEMBL 8.039999961853027)
Descriptors: MW 438.55, ALogP 3.3, HBA 6, HBD 1, PSA 80.37, QED 0.48
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC1(F)CC1
InChIKey: YZMMWVWLDOCLCK-CLYVBNDRSA-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 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 495.62, ALogP 4.87, HBA 5, HBD 2, PSA 56.42, QED 0.44
Compound (SMILES): Cl.Oc1ccc(C2NCCc3c2[nH]c2ccc(Cl)cc32)cc1
InChIKey: ZOZXHFMUDIUESR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 104.71 nM (pChEMBL 6.980000019073486)
Descriptors: MW 298.77, ALogP 3.76, HBA 2, HBD 3, PSA 48.05, QED 0.64
Compound (SMILES): C[C@@H](OCc1ccccc1)[C@@H](C#N)NC(=O)[C@H](Cc1cccc(Br)c1)NC(=O)Cc1ccc(-c2ccccc2)cc1
InChIKey: GHXSRNDWXMXOLF-AVCZWDQHSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of human cathepsin S
Measurement: Ki = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 610.55, ALogP 6, HBA 4, HBD 2, PSA 91.22, QED 0.21
Compound (SMILES): COc1cc(OC)c(Cl)c(COc2cnc(Nc3c(C)cccc3NCC=O)nc2)c1Cl
InChIKey: JOHIKBITJWWHQQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human His-tagged FGFR3 (399 to 806 residues) cytoplasmic domain expressed in baculovirus expression system using Tyr 04 peptide as substrate after 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 477.35, ALogP 5.04, HBA 8, HBD 2, PSA 94.6, QED 0.39
Compound (SMILES): Cc1cccn2c(-c3ccc(O)cc3)c(N)nc12
InChIKey: BPUGMMFDXGULNQ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: P54578
Assay: Inhibition of USP14 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 239.28, ALogP 2.6, HBA 4, HBD 2, PSA 63.55, QED 0.69
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(C5CNCCN5)cc4)ccn23)c2ccccc2n1
InChIKey: UQEFQNWFVJXGDE-UHFFFAOYSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: Inhibition of human ALK4 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 192 nM (pChEMBL 6.71999979019165)
Descriptors: MW 419.53, ALogP 4.76, HBA 5, HBD 2, PSA 54.25, QED 0.44
Compound (SMILES): CC[C@]1(O)[C@H](O)C[C@H](c2ccncc2NC(=O)c2nc(-c3ncccc3F)ccc2N)C[C@@H]1C
InChIKey: JXVXKOPUJQFJEO-IBUDROQVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 465.53, ALogP 3.53, HBA 7, HBD 4, PSA 134.25, QED 0.45
Compound (SMILES): COc1cccc(Cn2cnc3ccc(-c4cn[nH]c4)cc3c2=O)c1
InChIKey: QQJKCGXOHWHBQV-UHFFFAOYSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P34947
Assay: Inhibition of human GRK5
Measurement: IC50 = 4497 nM (pChEMBL 5.349999904632568)
Descriptors: MW 332.36, ALogP 2.84, HBA 5, HBD 1, PSA 72.8, QED 0.62
Compound (SMILES): Cc1cc(F)cnc1N1CCN(C(=O)CCCc2cccc3ncccc23)[C@@H](C)C1
InChIKey: OIZGGNJJLMUGKL-SFHVURJKSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human recombinant muscarinic receptor M1 expressed in CHO-K1 cells assessed as EC80 acetylcholine-induced calcium flux incubated for 30 mins
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 406.51, ALogP 4.14, HBA 4, HBD 0, PSA 49.33, QED 0.64