lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CP(C)(=O)c1ccccc1-c1ccc(N2CC(CO)[C@@H](NC(=O)Nc3ccc(Cl)cc3F)C2=O)c(F)c1F
InChIKey: UDKGTLKMPMSTQV-PYFQUHSISA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays: A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 fluorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm. A calibration curve was constructed with an external cAMP standard at concentrations ranging from 1 μM to 0.1 pM by plotting the fluorescent intensity ratio from 665 nm emission to the intensity from the 590 nm emission against cAMP concentrations. The potency and activity of a compound to inhibit cAMP production was then determined by fitting to a 4-parametric logistic equation from a plot of cAMP level versus compound concentrations.
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 565.92, ALogP 4.82, HBA 4, HBD 3, PSA 98.74, QED 0.37
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3ccccc3Cl)C4=O)nn2)cc1
InChIKey: MSUMULVHTXISHH-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human transmembrane carbonic anhydrase 12 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 14.05 nM (pChEMBL 7.849999904632568)
Descriptors: MW 537.94, ALogP 2.73, HBA 9, HBD 1, PSA 154.55, QED 0.29
Compound (SMILES): CNCc1cc(C)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(F)c1
InChIKey: YZXSIGGVKBZQGJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate by LC-MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 350.4, ALogP 3.19, HBA 5, HBD 2, PSA 71.42, QED 0.59
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin)
Measurement: EC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): CC[C@H]1CN(c2nc3ccc(Cl)cc3s2)CCC1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: KDIUXOKNJHLPLN-BHWOMJMDSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 493.46, ALogP 6.55, HBA 5, HBD 1, PSA 62.66, QED 0.39
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(CCN4CCOCC4)c3)c2n1
InChIKey: LSRBAFLNXOUPIC-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 437.51, ALogP 0.36, HBA 9, HBD 1, PSA 108.3, QED 0.61
Compound (SMILES): O=C(Nc1cnccc1C(F)(F)F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: KDUHTFCGEYDKBT-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 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 350.3, ALogP 3.1, HBA 4, HBD 2, PSA 83.98, QED 0.89
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H]1CSC[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(N)=O)NC(=O)CNC(=O)[C@@H](Cc2c[nH]c3ccccc23)C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC1=O)[C@@H](C)CC
InChIKey: AXUOIRLEFGBIDH-YQQUIGGJSA-N
Target: Albumin (SINGLE PROTEIN), Mus musculus
UniProt: P07724
Assay: Binding affinity to mouse albumin assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 2224.53
Compound (SMILES): CCN([C@@H](C(=O)O)C(C)C)S(=O)(=O)c1ccc(-c2nc(-c3ccc(C)s3)no2)cc1
InChIKey: ZVQKPPCVSXIXMD-QGZVFWFLSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of human recombinant MMP-8 (21 to 467 residues) expressed in NS0 cells using (7-methoxycoumarin-4-y1)-acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitropheny1)-L-2,3-diaminopropionyl]-Ala-Arg-NH2 as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 10 mins by fluorescence based analysis
Measurement: IC50 = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 449.55, ALogP 3.89, HBA 7, HBD 1, PSA 113.6, QED 0.55
Compound (SMILES): Cc1ccc2cccnc2c1S(=O)(=O)Nc1ccccc1C#Cc1ccc(C(=O)O)nc1
InChIKey: NZNLHBUIPSPALM-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human SNU-398 cells assessed as inhibition of radioactive lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 443.48, ALogP 3.84, HBA 5, HBD 2, PSA 109.25, QED 0.46
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(OC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: ONOZLVJQXQZLPL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 1039.63
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): O=C(Nc1ccc(-c2ccc(F)cn2)cc1)c1cc2sc(NCCN3CCOCC3)nc2s1
InChIKey: RKMXNTQXGVOORY-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 483.59, ALogP 4.56, HBA 8, HBD 2, PSA 79.38, QED 0.4
Compound (SMILES): O=C(CCCNC(=O)c1cccc(C(=O)NCCCC(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1)NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO
InChIKey: JQLHAXGMYALIFJ-AWSIMMLFSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of human recombinant MMP12 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 1402.83
Compound (SMILES): CC(C)(C(=O)Nc1ccc(-c2cncc(C(F)(F)F)n2)cc1F)c1csc(NS(=O)(=O)C2CC2)n1
InChIKey: OKFGIMQRDHOBOP-UHFFFAOYSA-N
Target: CTP synthase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P70303
Assay: Inhibition of mouse CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 529.54, ALogP 4.58, HBA 7, HBD 2, PSA 113.94, QED 0.43
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)CN(CCCCC3CCN(Cc4ccccc4)CC3)C(=O)c3cc(=O)c4ccccc4o3)c2c1
InChIKey: LHSUEACWFJGZKG-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B using kynuramine as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by spectroscopic analysis
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 648.8, ALogP 6.17, HBA 6, HBD 2, PSA 107.88, QED 0.14
Compound (SMILES): COc1c(CC=C(C)C)c(=O)[nH]c2c(OC)c(O)ccc12
InChIKey: AZFKJXQYMUMVEP-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at GST-tagged PPAR-gamma ligand binding domain (unknown origin) assessed as recruitment of fluorescein-labeled PRIP/RAP250 coactivator peptide by LanthaScreen TR-FRET Coactivator assay
Measurement: EC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 289.33, ALogP 2.76, HBA 4, HBD 2, PSA 71.55, QED 0.85
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OCC)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: FCZMHSXKERLEIN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 21 L858R and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR L858R and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR L858R and T790M double mutations. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR L858R and T790M double mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR L858R and T790M double 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 L858R and T790M double mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR L858R and T790M double mutation (named Ba/F3-EGFR L858R/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR L858R/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 571.68, ALogP 4.69, HBA 10, HBD 2, PSA 113.85, QED 0.18
Compound (SMILES): COc1cc(CCc2ccccc2)c(C(=O)O)c(O)c1C/C=C(\C)CC=C(C)C
InChIKey: WNQYHTVUADEJHB-LDADJPATSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Binding affinity to PPARalpha (unknown origin)
Measurement: Ki = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 394.51, ALogP 5.73, HBA 3, HBD 2, PSA 66.76, QED 0.53
Compound (SMILES): C#CCO[C@@H]1[C@H](C)[C@@H](COC(=O)c2ccc(S(=O)(=O)F)cc2)O[C@H]1n1nc(-c2ccc(C)cc2)c2c(N)ncnc21
InChIKey: VCIZYTQJDGPPDJ-CLQHIKNWSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin)
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 579.61, ALogP 3.45, HBA 11, HBD 1, PSA 148.52, QED 0.19
Compound (SMILES): CNCCNCc1cccc(-c2nc(Nc3ccccc3)c(C)c(-c3c(C)noc3C)n2)c1
InChIKey: DVIUIRPCVXVFSX-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) incubated for 15 mins measured after 60 min by AlphaLISA assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 442.57, ALogP 4.78, HBA 7, HBD 3, PSA 87.9, QED 0.32
Compound (SMILES): CCCCNNC(=O)c1ccc(F)cc1
InChIKey: YRLLWXIGAGZKFP-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
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 = 4769 nM (pChEMBL 5.320000171661377)
Descriptors: MW 210.25, ALogP 1.86, HBA 2, HBD 2, PSA 41.13, QED 0.58
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(CC)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: FDTGYJGRULJHQZ-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 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 599.74, ALogP 5.56, HBA 10, HBD 2, PSA 113.85, QED 0.15
Compound (SMILES): O=C(CNc1cc(Cl)cc(Cl)c1)N1CC[C@H]2CCN(c3ncnc4[nH]ccc34)[C@H]2C1
InChIKey: ZJKAMIGVAPQVOU-UGSOOPFHSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 15 mins in the presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.35, ALogP 3.8, HBA 5, HBD 2, PSA 77.15, QED 0.64
Compound (SMILES): O=C([O-])CNC(=O)c1ccc(S(=O)(=O)N2CCC(c3ccc(Cl)cc3)CC2)cn1.[K+]
InChIKey: DJLPNUNUNPABGA-UHFFFAOYSA-M
Target: Ubiquitin carboxyl-terminal hydrolase 16 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5T5
Assay: Binding affinity to biotinylated USP16 zinc finger ubiquitin binding domain (25 to 185 residues) (unknown origin) expressed in Escherichia coli incubated for 120 secs by Biolayer Interferometry assay
Measurement: Kd > 100000 nM (pChEMBL 4)
Descriptors: MW 437.91, ALogP 2.12, HBA 5, HBD 2, PSA 116.67, QED 0.71
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using (S)-mephenytoin as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 23300 nM (pChEMBL 4.630000114440918)
Descriptors: MW 1439.82
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3c(C)nn(C)c3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: YXFNNHJWPFANTQ-OALUTQOASA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human whole blood assessed as reduction in SLP76 phosphorylation incubated for 1 hr by HTRF assay
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 556.6, ALogP 3.02, HBA 10, HBD 3, PSA 155.21, QED 0.31
Compound (SMILES): Cc1cc(OC(F)F)ccc1NC(=O)c1cc(C(=O)NCc2ccc(F)cc2)c(F)cc1Cl
InChIKey: NFAGOVIQVGGRKR-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Inverse agonist activity at human PPARdelta expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 480.85, ALogP 5.71, HBA 3, HBD 2, PSA 67.43, QED 0.43
Compound (SMILES): CP(C)(=O)c1ccccc1-c1ccc(N2CC(CO)[C@@H](NC(=O)Nc3ccc(Cl)cc3F)C2=O)c(F)c1F
InChIKey: UDKGTLKMPMSTQV-PYFQUHSISA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays: A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 fluorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm. A calibration curve was constructed with an external cAMP standard at concentrations ranging from 1 μM to 0.1 pM by plotting the fluorescent intensity ratio from 665 nm emission to the intensity from the 590 nm emission against cAMP concentrations. The potency and activity of a compound to inhibit cAMP production was then determined by fitting to a 4-parametric logistic equation from a plot of cAMP level versus compound concentrations.
Measurement: EC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 565.92, ALogP 4.82, HBA 4, HBD 3, PSA 98.74, QED 0.37
Compound (SMILES): CNCc1cc(C)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(F)c1
InChIKey: YZXSIGGVKBZQGJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Binding affinity to recombinant human HPK1 (1 to 346 residues) expressed sf9 cells incubated for 1 hr by LanthaScreen assay
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 350.4, ALogP 3.19, HBA 5, HBD 2, PSA 71.42, QED 0.59
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin)
Measurement: EC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): CC[C@H]1CN(c2nc3ccc(Cl)cc3s2)CCC1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: KDIUXOKNJHLPLN-BHWOMJMDSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Agonist activity at Gal4-fused mouse PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 493.46, ALogP 6.55, HBA 5, HBD 1, PSA 62.66, QED 0.39
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(CCN4CCOCC4)c3)c2n1
InChIKey: LSRBAFLNXOUPIC-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 437.51, ALogP 0.36, HBA 9, HBD 1, PSA 108.3, QED 0.61
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H]1CSC[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(N)=O)NC(=O)CNC(=O)[C@@H](Cc2c[nH]c3ccccc23)C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC1=O)[C@@H](C)CC
InChIKey: AXUOIRLEFGBIDH-YQQUIGGJSA-N
Target: Albumin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P02770
Assay: Binding affinity to rat albumin assessed as dissociation constant
Measurement: Kd = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 2224.53
Compound (SMILES): CCN([C@@H](C(=O)O)C(C)C)S(=O)(=O)c1ccc(-c2nc(-c3ccc(C)s3)no2)cc1
InChIKey: ZVQKPPCVSXIXMD-QGZVFWFLSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of human recombinant MMP-13 (20 to 471 residues) expressed in NS0 cells using (7-methoxycoumarin-4-y1)-acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitropheny1)-L-2,3-diaminopropionyl]-Ala-Arg-NH2 as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 10 mins by fluorescence based analysis
Measurement: IC50 = 252 nM (pChEMBL 6.599999904632568)
Descriptors: MW 449.55, ALogP 3.89, HBA 7, HBD 1, PSA 113.6, QED 0.55
Compound (SMILES): Cc1ccc2cccnc2c1S(=O)(=O)Nc1ccccc1C#Cc1ccc(C(=O)O)nc1
InChIKey: NZNLHBUIPSPALM-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human SNU-398 cells assessed as inhibition of lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 443.48, ALogP 3.84, HBA 5, HBD 2, PSA 109.25, QED 0.46
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Agonist activity at human SST5 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): O=C(Nc1ccc(-c2ccc(F)cn2)cc1)c1cc2sc(NCCN3CCOCC3)nc2s1
InChIKey: RKMXNTQXGVOORY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 = 27600 nM (pChEMBL 4.559999942779541)
Descriptors: MW 483.59, ALogP 4.56, HBA 8, HBD 2, PSA 79.38, QED 0.4
Compound (SMILES): O=C(CCCNC(=O)c1cccc(C(=O)NCCCC(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1)NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO
InChIKey: JQLHAXGMYALIFJ-AWSIMMLFSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of human recombinant MMP14 catalytic domain using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 57000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 1402.83
Compound (SMILES): CC(C)(C(=O)Nc1ccc(-c2cncc(C(F)(F)F)n2)cc1F)c1csc(NS(=O)(=O)C2CC2)n1
InChIKey: OKFGIMQRDHOBOP-UHFFFAOYSA-N
Target: CTP synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P70698
Assay: Inhibition of mouse CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 529.54, ALogP 4.58, HBA 7, HBD 2, PSA 113.94, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OCC)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: FCZMHSXKERLEIN-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 571.68, ALogP 4.69, HBA 10, HBD 2, PSA 113.85, QED 0.18
Compound (SMILES): COc1cc(CCc2ccccc2)c(C(=O)O)c(O)c1C/C=C(\C)CC=C(C)C
InChIKey: WNQYHTVUADEJHB-LDADJPATSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Binding affinity to PPARdelta (unknown origin)
Measurement: Ki = 1800 nM (pChEMBL 5.75)
Descriptors: MW 394.51, ALogP 5.73, HBA 3, HBD 2, PSA 66.76, QED 0.53
Compound (SMILES): C#CCO[C@@H]1[C@H](C)[C@@H](COC(=O)c2ccc(S(=O)(=O)F)cc2)O[C@H]1n1nc(-c2ccc(C)cc2)c2c(N)ncnc21
InChIKey: VCIZYTQJDGPPDJ-CLQHIKNWSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin)
Measurement: IC50 = 475 nM (pChEMBL 6.320000171661377)
Descriptors: MW 579.61, ALogP 3.45, HBA 11, HBD 1, PSA 148.52, QED 0.19
Compound (SMILES): CNCCNCc1cccc(-c2nc(Nc3ccccc3)c(C)c(-c3c(C)noc3C)n2)c1
InChIKey: DVIUIRPCVXVFSX-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NVM4
Assay: Inhibition of PRMT7 (unknown origin) by radioisotope based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 442.57, ALogP 4.78, HBA 7, HBD 3, PSA 87.9, QED 0.32
Compound (SMILES): O=C(CNc1cc(Cl)cc(Cl)c1)N1CC[C@H]2CCN(c3ncnc4[nH]ccc34)[C@H]2C1
InChIKey: ZJKAMIGVAPQVOU-UGSOOPFHSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 15 mins in the presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.35, ALogP 3.8, HBA 5, HBD 2, PSA 77.15, QED 0.64
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using bufuralol as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 21900 nM (pChEMBL 4.659999847412109)
Descriptors: MW 1439.82
Compound (SMILES): Cc1cc(OC(F)F)ccc1NC(=O)c1cc(C(=O)NCc2ccc(F)cc2)c(F)cc1Cl
InChIKey: NFAGOVIQVGGRKR-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Inverse agonist activity at human FXR expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 480.85, ALogP 5.71, HBA 3, HBD 2, PSA 67.43, QED 0.43
Compound (SMILES): CNCc1cc(C)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(F)c1
InChIKey: YZXSIGGVKBZQGJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human Jurkat cells assessed as reduction in SLP76 phosphorylation incubated for 1 hr by HTRF assay
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 350.4, ALogP 3.19, HBA 5, HBD 2, PSA 71.42, QED 0.59
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(CCN4CCOCC4)c3)c2n1
InChIKey: LSRBAFLNXOUPIC-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 437.51, ALogP 0.36, HBA 9, HBD 1, PSA 108.3, QED 0.61
Compound (SMILES): CCN([C@@H](C(=O)O)C(C)C)S(=O)(=O)c1ccc(-c2nc(-c3ccc(C)s3)no2)cc1
InChIKey: ZVQKPPCVSXIXMD-QGZVFWFLSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of human recombinant MMP-12 (17 to 470 residues) Val97Leu mutant expressed in NS0 cells using (7-methoxycoumarin-4-y1)-acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitropheny1)-L-2,3-diaminopropionyl]-Ala-Arg-NH2 as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 10 mins by fluorescence based analysis
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 449.55, ALogP 3.89, HBA 7, HBD 1, PSA 113.6, QED 0.55
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG by patch clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): O=C(CCCNC(=O)c1cccc(C(=O)NCCCC(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1)NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO
InChIKey: JQLHAXGMYALIFJ-AWSIMMLFSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O14672
Assay: Inhibition of human recombinant ADAM10 expressed in baculovorus-infected Sf21 cells using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 30600 nM (pChEMBL 4.510000228881836)
Descriptors: MW 1402.83
Compound (SMILES): O=C(CNc1cc(Cl)cc(Cl)c1)N1CC[C@H]2CCN(c3ncnc4[nH]ccc34)[C@H]2C1
InChIKey: ZJKAMIGVAPQVOU-UGSOOPFHSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 30 mins in the presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.35, ALogP 3.8, HBA 5, HBD 2, PSA 77.15, QED 0.64
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 2E1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05181
Assay: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 30900 nM (pChEMBL 4.510000228881836)
Descriptors: MW 1439.82
Compound (SMILES): Cc1cc(OC(F)F)ccc1NC(=O)c1cc(C(=O)NCc2ccc(F)cc2)c(F)cc1Cl
InChIKey: NFAGOVIQVGGRKR-UHFFFAOYSA-N
Target: Thyroid hormone receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10827
Assay: Inverse agonist activity at human THRA expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 480.85, ALogP 5.71, HBA 3, HBD 2, PSA 67.43, QED 0.43
Compound (SMILES): CNCc1cc(C)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(F)c1
InChIKey: YZXSIGGVKBZQGJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 350.4, ALogP 3.19, HBA 5, HBD 2, PSA 71.42, QED 0.59
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 expressed in insect cell microsomes in presence of NADP+ by fluorescence based analysis
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): O=C(CCCNC(=O)c1cccc(C(=O)NCCCC(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1)NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO
InChIKey: JQLHAXGMYALIFJ-AWSIMMLFSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P78325
Assay: Inhibition of ADAM8 (unknown origin) expressed in HEK293 cells assessed as inhibition of CD23 shedding by measuring reduction of soluble CD23 release in cell supernatants incubated for 24 hrs by ELISA
Measurement: IC50 > 1500 nM (pChEMBL 5.823999881744385)
Descriptors: MW 1402.83
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 1439.82
Compound (SMILES): Cc1cc(OC(F)F)ccc1NC(=O)c1cc(C(=O)NCc2ccc(F)cc2)c(F)cc1Cl
InChIKey: NFAGOVIQVGGRKR-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Inverse agonist activity at human THRB expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 480.85, ALogP 5.71, HBA 3, HBD 2, PSA 67.43, QED 0.43
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in insect cell microsomes in presence of NADP+ by fluorescence based analysis
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 18800 nM (pChEMBL 4.730000019073486)
Descriptors: MW 1439.82
Compound (SMILES): Cc1cc(OC(F)F)ccc1NC(=O)c1cc(C(=O)NCc2ccc(F)cc2)c(F)cc1Cl
InChIKey: NFAGOVIQVGGRKR-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Inverse agonist activity at PPARgamma in mouse 3T3-L1 adipocytes assessed as inhibition of adipogenesis by measuring lipid droplet staining by BODIPY 495 incubated for 6 days by fluorescence based assay
Measurement: IC50 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 480.85, ALogP 5.71, HBA 3, HBD 2, PSA 67.43, QED 0.43
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in insect cell microsomes in presence of NADP+ by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using as phenacetin substrate assessed as reduction in O-deethylation of phenacetin incubated for 30 mins in presence of beta-NADPH by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 1439.82
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in insect cell microsomes in presence of NADP+ by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 2A6 (SINGLE PROTEIN), Homo sapiens
UniProt: P11509
Assay: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate assessed as reduction in substrate hydroxylation incubated for 30 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 26300 nM (pChEMBL 4.579999923706055)
Descriptors: MW 1439.82
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCCCC3c2ccccc2)cc1
InChIKey: MIJWCIIAFVQEQD-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 516.61, ALogP 6.79, HBA 5, HBD 3, PSA 104.82, QED 0.24
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30680
Assay: Agonist activity at rat SST2 receptor
Measurement: EC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43