lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NCCCN1CCN(c2ccncc2)CC1)c1cc2ccccc2o1
InChIKey: RQSAPWKYJYONRT-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Binding affinity to human D3 receptor expressed in CHO cells assessed as inhibition constant by scintillation counting method
Measurement: Ki > 10 nM (pChEMBL 8)
Descriptors: MW 364.45, ALogP 2.77, HBA 5, HBD 1, PSA 61.61, QED 0.68
Compound (SMILES): Cc1cc(C#Cc2ccccc2NS(=O)(=O)c2c(C)ccc3cccnc23)cnc1C(=O)O
InChIKey: RTMYIDQABONCOX-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Binding affinity to full-length C-terminal GFP-tagged human MCT4 incubated for 1 hrs by fluorescence cross-correlation spectroscopy analysis
Measurement: Ki = 56 nM (pChEMBL 7.25)
Descriptors: MW 457.51, ALogP 4.15, HBA 5, HBD 2, PSA 109.25, QED 0.45
Compound (SMILES): NS(=O)(=O)NCCNC(=O)c1n[nH]nc1/C(=N/O)Nc1ccc(F)c(Br)c1
InChIKey: NWWOQJXJPHGEAC-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human MDA-MB-231 cells
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 465.27, ALogP -0.52, HBA 7, HBD 6, PSA 187.48, QED 0.1
Compound (SMILES): O=C(Nc1cnccc1-c1ccccc1C(F)(F)F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: DFTCADIVUJRTNH-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 426.4, ALogP 4.76, HBA 4, HBD 2, PSA 83.98, QED 0.62
Compound (SMILES): CCc1cnn2c(NCc3ccc[n+]([O-])c3)cc(N3CCCC[C@@H]3CCO)nc12
InChIKey: PIMQWRZWLQKKBJ-GOSISDBHSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 396.5, ALogP 2.28, HBA 7, HBD 2, PSA 92.63, QED 0.47
Compound (SMILES): COC(=O)/C=C/c1ccc(OCCNc2cc3c([nH]c4ccccc43)c(-c3ccc(OC)cc3)n2)c(OC)c1
InChIKey: MTDDYEOOIHJNCQ-OQLLNIDSSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Boc-Lys (Ac)-AMC as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 523.59, ALogP 6.08, HBA 7, HBD 2, PSA 94.7, QED 0.13
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNc2nc(-c3ccccc3)cs2)cc1
InChIKey: KUAJUAAUQILNBN-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 400.51, ALogP 5.26, HBA 5, HBD 3, PSA 80.04, QED 0.39
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CCOCC4)c3)c2n1
InChIKey: DUNLCPJHEDEUQO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 408.47, ALogP 1.38, HBA 8, HBD 1, PSA 105.06, QED 0.7
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N)c2C#N)cc1
InChIKey: AYHXBNNXUXMTKO-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 366.42, ALogP 4.82, HBA 5, HBD 1, PSA 84.82, QED 0.56
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3cccnc3C)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: BLLJUCXNHUVEHL-PMACEKPBSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 2301 nM (pChEMBL 5.639999866485596)
Descriptors: MW 528.59, ALogP 3.81, HBA 8, HBD 3, PSA 126.49, QED 0.33
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C(C)=O)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: HHLHKPYGNVLWFW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 19 Deletion and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR exon 19 deletion and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR exon 19 deletion and T790M mutation. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR E746-A750 deletion and T790M Mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 19 deletion and T790M mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR E746-A750 deletion and T790M Mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR E746-A750 deletion and T790M Mutation (named Ba/F3-EGFR-Del/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR-Del/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 613.72, ALogP 5.2, HBA 11, HBD 2, PSA 130.92, QED 0.16
Compound (SMILES): c1cncc(C[C@@H]2[C@@H](Oc3nnc(-c4ccc5[nH]ccc5c4)s3)C3CCN2CC3)c1
InChIKey: ADPGBLDMLCUZBX-RTWAWAEBSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Binding affinity to alpha3beta4 nAChR (unknown origin) assessed as dissociation constant
Measurement: Ki = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 417.54, ALogP 4.17, HBA 6, HBD 1, PSA 66.93, QED 0.53
Compound (SMILES): CCCN(CCc1cc(O)c(CCN(CCC)[C@H]2CCc3nc(N)sc3C2)cc1O)[C@H]1CCc2nc(N)sc2C1
InChIKey: WLQPRUMGPAOCRW-VXKWHMMOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human D2 receptor expressed in CHO cells assessed as stimulation of [35S]GTPgammaS binding by Perkin elmer analysis
Measurement: EC50 = 34.37 nM (pChEMBL 7.460000038146973)
Descriptors: MW 584.86, ALogP 4.8, HBA 10, HBD 4, PSA 124.76, QED 0.22
Compound (SMILES): O=C(NO)c1ccc(CN2CC(=O)N(Cc3cccc(Cl)c3)[C@H](Cc3ccccc3)C2=O)cc1
InChIKey: GUNBRUHPJCKSKN-HSZRJFAPSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 477.95, ALogP 3.44, HBA 4, HBD 2, PSA 89.95, QED 0.4
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)CC1
InChIKey: CTYFJJGDZUXTIC-RRPNLBNLSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 602.68, ALogP 3.67, HBA 7, HBD 2, PSA 105.9, QED 0.33
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(C5CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: IBFWZLVKHAJJDH-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 528.66, ALogP 3.82, HBA 10, HBD 2, PSA 104.34, QED 0.39
Compound (SMILES): CCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1)C(=O)C(=O)NCc1ccccn1
InChIKey: PLVWMBFPIAQRHK-VXKWHMMOSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of 6his/TEV-fused GST tagged SARS-CoV-2 MPro (1 to 306 residues) expressed in Escherichia coli RIL cells using 5-FAM-AVLQSGFR-Lys-(Dabcyl)-K-amide as substrate assessed as substrate cleavage preincubated for 30 mins followed by substrate addition and measured every 30 sec for 60 cycles by FRET based assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 482.58, ALogP 2.89, HBA 6, HBD 3, PSA 126.49, QED 0.38
Compound (SMILES): Clc1cc(Nc2nc(-c3nccs3)cs2)cc(Cl)c1Cl
InChIKey: KHOPUVQYPHBWKK-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 482.9 nM (pChEMBL 6.320000171661377)
Descriptors: MW 362.69, ALogP 5.97, HBA 5, HBD 1, PSA 37.81, QED 0.58
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CCn1cc(CNC(=O)c2cc3ccccc3[nH]2)nn1
InChIKey: ZCKIEICGPWNFBV-KSFYIVLOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylscopolamine from human dopamine D2 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 32300 nM (pChEMBL 4.489999771118164)
Descriptors: MW 460.54, ALogP 2.13, HBA 8, HBD 3, PSA 126.98, QED 0.39
Compound (SMILES): CN1CCC(n2cc(Nc3nc(OC4(C)CC4)c4nc(-c5cnn(C)c5)ccc4n3)cn2)CC1
InChIKey: WGMWEVJCHUDPID-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) in presence of 600 uM ATP
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 459.56, ALogP 3.56, HBA 10, HBD 1, PSA 98.81, QED 0.47
Compound (SMILES): OCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: FJLDXKYVYZQADI-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 426.37, ALogP 4.28, HBA 6, HBD 1, PSA 77.61, QED 0.41
Compound (SMILES): CCOC(=O)Nc1nc2ccc(-c3cc(Cc4n[nH]c(=O)c5ccccc45)ccc3F)cc2[nH]1
InChIKey: DCSUGHIXMFUMOQ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin)
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 457.47, ALogP 4.76, HBA 5, HBD 3, PSA 112.76, QED 0.35
Compound (SMILES): CN1CCC[C@@H]1Cc1c[nH]c2cccc(F)c12
InChIKey: ZXGSXBKTNNCUFJ-LLVKDONJSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: i. Prepare the assay buffer following the table below;Reagent ConcentrationTris 50 mMCaCl2  4 mMBSA 0.1% (w/v)Adjust pH to 7.4 followed by 0.2 μM sterile filtrationii. Preparation of 8 doses of reference and exemplary test compounds starting from 10 mM stock solution as requested by 5-fold serial dilutions with 100%;iii. Prepare (v/v) DMSO: a. Add 50 μl/well of 0.5% (v/v) PEI to UniFilter-96 GF/B plates. Seal the plates and incubate at 4° C. for 3 hrs; b. After incubation, wash the plates 3 times with ice-cold wash buffer (50 mM Tris, pH7.4);iv. Preparation of assay plates: a. Dilute cell membrane with assay buffer and add 330 μl/well to 96 round deep well plates to reach a concentration of 20 μg/well; b. Prepare 8 concentrations of reference or exemplary test compounds and add 110 μl/well to 96 round deep well plates; c. Dilute [3H]-ketanserin with assay buffer to 5 nM (5× final concentration) and add 110 μl/well to 96 round deep well plates.v. Centrifuge the plate at 1000 rpm for 30 secs and then agitate at 600 rpm, R.T. for 5 min.vi. Seal the plates and incubate the plate at 27° C. for 90 min.vii. Stop the incubation by vacuum filtration onto GF/B filter plates followed by 4 times washing with ice-cold wash buffer (50 mM Tris, pH7.4).vii. Dry the plates at 37° C. for 45 min.ix. Seal the filter plates and add 40 μl/well of scintillation cocktail.x. Read the plate by using a Microbeta2 microplate counter.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 232.3, ALogP 2.94, HBA 1, HBD 1, PSA 19.03, QED 0.84
Compound (SMILES): OCCOCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: KBRMRLCSXVNEMV-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 470.42, ALogP 4.3, HBA 7, HBD 1, PSA 86.84, QED 0.31
Compound (SMILES): OCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: MHXTXRZADPVWNK-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 382.31, ALogP 4.26, HBA 5, HBD 1, PSA 68.38, QED 0.65
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1CCCCN1CCN(Cc2ccccc2)CC1
InChIKey: DXQPJYSXJVUZSK-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 756 nM (pChEMBL 6.119999885559082)
Descriptors: MW 436.63, ALogP 3.84, HBA 5, HBD 0, PSA 39.15, QED 0.62
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc5ccccc5c4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: TXPWCFRRRKKLCN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P28593
Assay: Inhibition of HIS-tagged recombinant Trypanosoma cruzi TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 596.78, ALogP 4.44, HBA 7, HBD 2, PSA 102.18, QED 0.15
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(C)c3)cc2)nc2cnccc12)C(N)=O
InChIKey: SGGAMBTYCITZTQ-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 2680 nM (pChEMBL 5.570000171661377)
Descriptors: MW 421.5, ALogP 4.82, HBA 5, HBD 2, PSA 104.69, QED 0.46
Compound (SMILES): CCOc1ccc2c(c1)OC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)CC2=O
InChIKey: ZZZIMIPHNKMIDC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 2653.5 nM (pChEMBL 5.579999923706055)
Descriptors: MW 461.5, ALogP 2.65, HBA 8, HBD 1, PSA 142.07, QED 0.53
Compound (SMILES): COCCCOc1cc2c(cc1Cl)-c1cc(=O)c(C(=O)O)cn1[C@H](C(C)C)CO2
InChIKey: HVBMZIVDVKAMGA-KRWDZBQOSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Reversible inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate pre-incubated for 30 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 421.88, ALogP 3.87, HBA 6, HBD 1, PSA 86.99, QED 0.68
Compound (SMILES): CCc1cnn2c(NCc3ccc[n+]([O-])c3)cc(N3CCCC[C@@H]3CCO)nc12
InChIKey: PIMQWRZWLQKKBJ-GOSISDBHSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of CDK5 (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 396.5, ALogP 2.28, HBA 7, HBD 2, PSA 92.63, QED 0.47
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNc2nc(-c3ccccc3)cs2)cc1
InChIKey: KUAJUAAUQILNBN-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 400.51, ALogP 5.26, HBA 5, HBD 3, PSA 80.04, QED 0.39
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CCOCC4)c3)c2n1
InChIKey: DUNLCPJHEDEUQO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: Phosphorylated (P): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including phosphorylated (P)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 408.47, ALogP 1.38, HBA 8, HBD 1, PSA 105.06, QED 0.7
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3cccnc3C)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: BLLJUCXNHUVEHL-PMACEKPBSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12851
Assay: Inhibition of MAP4K2 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 819 nM (pChEMBL 6.090000152587891)
Descriptors: MW 528.59, ALogP 3.81, HBA 8, HBD 3, PSA 126.49, QED 0.33
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C(C)=O)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: HHLHKPYGNVLWFW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: HER2 Exon 20 YVMA Insertion Mutation: A compound's ability in selectively inhibiting Her2 exon 20 YVMA insertion mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with Her2 Exon20 YVMA insertions. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR exon 20 insertions YVMA (A775_G776ins YVMA), was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 20 insertions. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR Exon20 virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing Her2 Exon20 YVMA insertions (named Ba/F3-Her2 Exon20 YVMA) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-Her2 Exon20 YVMA cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 613.72, ALogP 5.2, HBA 11, HBD 2, PSA 130.92, QED 0.16
Compound (SMILES): CCCN(CCc1cc(O)c(CCN(CCC)[C@H]2CCc3nc(N)sc3C2)cc1O)[C@H]1CCc2nc(N)sc2C1
InChIKey: WLQPRUMGPAOCRW-VXKWHMMOSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human D3 receptor expressed in CHO cells assessed as stimulation of [35S]GTPgammaS binding by Perkin elmer analysis
Measurement: EC50 = 5.36 nM (pChEMBL 8.270000457763672)
Descriptors: MW 584.86, ALogP 4.8, HBA 10, HBD 4, PSA 124.76, QED 0.22
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)CC1
InChIKey: CTYFJJGDZUXTIC-RRPNLBNLSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 602.68, ALogP 3.67, HBA 7, HBD 2, PSA 105.9, QED 0.33
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CCn1cc(CNC(=O)c2cc3ccccc3[nH]2)nn1
InChIKey: ZCKIEICGPWNFBV-KSFYIVLOSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylscopolamine from human dopamine D3 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 2780 nM (pChEMBL 5.559999942779541)
Descriptors: MW 460.54, ALogP 2.13, HBA 8, HBD 3, PSA 126.98, QED 0.39
Compound (SMILES): OCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: FJLDXKYVYZQADI-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95977
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 426.37, ALogP 4.28, HBA 6, HBD 1, PSA 77.61, QED 0.41
Compound (SMILES): OCCOCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: KBRMRLCSXVNEMV-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95977
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 470.42, ALogP 4.3, HBA 7, HBD 1, PSA 86.84, QED 0.31
Compound (SMILES): OCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: MHXTXRZADPVWNK-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95977
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 382.31, ALogP 4.26, HBA 5, HBD 1, PSA 68.38, QED 0.65
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc5ccccc5c4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: TXPWCFRRRKKLCN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma congolense
UniProt: P13110
Assay: Inhibition of HIS-tagged recombinant Trypanosoma congolense TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 596.78, ALogP 4.44, HBA 7, HBD 2, PSA 102.18, QED 0.15
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(C)c3)cc2)nc2cnccc12)C(N)=O
InChIKey: SGGAMBTYCITZTQ-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 421.5, ALogP 4.82, HBA 5, HBD 2, PSA 104.69, QED 0.46
Compound (SMILES): COCCCOc1cc2c(cc1Cl)-c1cc(=O)c(C(=O)O)cn1[C@H](C(C)C)CO2
InChIKey: HVBMZIVDVKAMGA-KRWDZBQOSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Reversible inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate pre-incubated for 30 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 421.88, ALogP 3.87, HBA 6, HBD 1, PSA 86.99, QED 0.68
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CCOCC4)c3)c2n1
InChIKey: DUNLCPJHEDEUQO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 408.47, ALogP 1.38, HBA 8, HBD 1, PSA 105.06, QED 0.7
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3cccnc3C)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: BLLJUCXNHUVEHL-PMACEKPBSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of STK4 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 528.59, ALogP 3.81, HBA 8, HBD 3, PSA 126.49, QED 0.33
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C(C)=O)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: HHLHKPYGNVLWFW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGR-induced EGFR phosphorylation in human A549 cells pretreated for 2 hrs followed by EGF stimulation by immune assay
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 613.72, ALogP 5.2, HBA 11, HBD 2, PSA 130.92, QED 0.16
Compound (SMILES): OCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: FJLDXKYVYZQADI-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 426.37, ALogP 4.28, HBA 6, HBD 1, PSA 77.61, QED 0.41
Compound (SMILES): OCCOCCOCc1ccc(-c2noc(-c3ccc(OCCF)c(C(F)(F)F)c3)n2)cc1
InChIKey: KBRMRLCSXVNEMV-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 470.42, ALogP 4.3, HBA 7, HBD 1, PSA 86.84, QED 0.31