lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1ccc(Nc2nccc(C(O)c3c(F)cc(-c4ccc(C#N)cc4)cc3F)n2)cc1
InChIKey: RNDOXYPXMIYXSK-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase Y181C mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 125.2 nM (pChEMBL 6.900000095367432)
Descriptors: MW 439.43, ALogP 4.99, HBA 6, HBD 2, PSA 105.62, QED 0.45
Compound (SMILES): CCOC(=O)CC[C@H](Nc1nc2nn(C)cc2c2nc(-c3ccco3)nn12)C(=O)OCC
InChIKey: UCVNXHPZKJNLTN-ZDUSSCGKSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-NECA from human A2A receptor expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 2670 nM (pChEMBL 5.570000171661377)
Descriptors: MW 441.45, ALogP 1.96, HBA 12, HBD 1, PSA 138.67, QED 0.38
Compound (SMILES): FC(F)(F)c1cnc(Nc2ccc3[nH]ncc3c2)nc1NC1CC1
InChIKey: RKMMKIXQLZPDRD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: ULK1 inhibition assay: Gamma-32P assays to measure ULK1 kinase activity were performed as previously described. Briefly, Flag ULK1 was transfected into HEK293T cells and 20 hours later treated as indicated. The immmunoprecipitate was washed in IP buffer 3 times, and washed in kinase buffer (25 mM MOPS, pH 7.5, 1 mM EGTA, 0.1 mM Na3VO4, 15 mM MgCl2,). Hot and cold ATP were added at a 100 μM final concentration. As substrates, GST or the recombinant protein GST-Atg101 purified from E. coli were used at 1 μg for each reaction. Reactions were boiled, run out on SDS page gel. The gel was dried, and imaged using PhosphoImager software. For cold assays to asses ULK1, Flag ULK1 which was transiently overexpressed and immunoprecipited from HEK293T cells. Reactions were then run out on SDS page gel, transferred to PVDF membrane and blotted for total levelsFluorescence MicroscopyVps34flox/flox MEFs were reconstituted with Flag-VPS34 and either p40FX or GFP-DFCP1. 48 hours post infection with adenovirus expressing Cre recombinase (MOI of 100), cells were plated on glass coverslips at a density of 3×105 cells per well in 6-well tissue culture plates. 18 h later, cells were fixed in 4% PFA in PBS for 10 minutes and permeabilized in 0.2% Triton in PBS for 10 minutes. The following primary antibodies were used: mouse anti-Myc epitope and LC3B XP antibody (2276 and 3868 respectively, Cell Signaling Technologies). Secondary antibodies were anti-rabbit Alexa488 and anti-mouse Alexa594 (Molecular Probes, 1:1000. Cells were then fixed and counter stained with DAPI. Coverslips were mounted in FluoromountG (SouthernBiothech). Images were acquired on a Zeiss Axioplan2 epifluorescence microscope coupled to the Openlab software. Confocal images of mitotracker were taken on Zeiss LSM 710 laser scanning confocal microscope. 10 random fields per condition were acquired using the 100× objective and representative images shown. Glass coverslips were mounted directly on plate with FluoromountG and images taken on Zeiss Axioplan2 epifluorescence microscope.
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 334.31, ALogP 3.69, HBA 5, HBD 3, PSA 78.52, QED 0.68
Compound (SMILES): Cc1cc(-c2ccc(C#N)cc2)ccc1[C@@H](O)c1ccnc(Nc2ccc(C#N)cc2)n1
InChIKey: SVMKVGLWWWVHNE-RUZDIDTESA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase Y181C mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 742.6 nM (pChEMBL 6.130000114440918)
Descriptors: MW 417.47, ALogP 5.02, HBA 6, HBD 2, PSA 105.62, QED 0.47
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1Cc2cn(nn2)CCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: GJFLVESIDOAAJH-MREPYCEBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as reduction in alpha-MSH-induced cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: IC50 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 1098.28
Compound (SMILES): O=C1CC(c2ccc(OCCCCN3CCc4ccccc4C3)cc2)Oc2cc(OCCCCN3CCc4ccccc4C3)cc(O)c21
InChIKey: CERDJUBMBLYNCC-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE by Ellman's method
Measurement: IC50 = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 646.83, ALogP 7.53, HBA 7, HBD 1, PSA 71.47, QED 0.15
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc(F)cc(F)c2OC)[nH]1
InChIKey: KMKZXUFHLBKPAD-VWNXMTODSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 530.66, ALogP 5.57, HBA 5, HBD 2, PSA 87.32, QED 0.33
Compound (SMILES): CCCCNc1cc(-c2ccccc2)cc2c1c(=O)[nH]c1ccccc12
InChIKey: WKOPCECKRFIMLX-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 (107 to 449 residues) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 expressed in Escherichia coli expression system as substrate incubated for 15 mins followed by substrate addition and measured after 2 to 4 hrs by fluorescence based assay
Measurement: IC50 = 99500 nM (pChEMBL 4)
Descriptors: MW 342.44, ALogP 5.56, HBA 2, HBD 2, PSA 44.89, QED 0.37
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PCEMPIMHMWVATP-OONSMZQZSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of alphavbeta3 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 835.98, ALogP 1.7, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC(Nc3ncc4ccccc4n3)C2)cc1
InChIKey: OPOLXEPGMNZIEN-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 373.42, ALogP 2.69, HBA 5, HBD 2, PSA 87.22, QED 0.67
Compound (SMILES): COc1cccc(-c2cncc3[nH]c(-c4n[nH]c5ccc(-c6cn[nH]c6)nc45)nc23)c1
InChIKey: HFNPLLLTCPMMPT-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.43, ALogP 3.96, HBA 6, HBD 3, PSA 121.05, QED 0.41
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2sc(CN3CCC4(C=Cc5ccccc54)CC3)nc2C)cc1
InChIKey: IBBXYPXDPQQROL-VWLOTQADSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full-length Prolink-tagged GPR40 fused with EA-tagged beta-arrestin expressed in human HEK293 cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 512.68, ALogP 6.17, HBA 5, HBD 1, PSA 62.66, QED 0.37
Compound (SMILES): O=C(NCC1(O)CC1)[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: CKLLZSBEJCDVBN-NHCICSSKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 611.55, ALogP 5.4, HBA 4, HBD 2, PSA 83.47, QED 0.34
Compound (SMILES): O=C(Nc1ccc(Nc2ncnc3c2OCCN3)cc1)Nc1cccs1
InChIKey: FPHGQHCCOGVUPR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of recombinant human RET using KKKSPGEYVNIEFG as substrate incubated for 15 mins followed by Mg/ATP addition and measured after 40 mins by [gamma-33P]-ATP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 368.42, ALogP 3.73, HBA 7, HBD 4, PSA 100.2, QED 0.56
Compound (SMILES): Fc1cc(CNc2ccc3[nH]nc(/C=C/c4ccccn4)c3c2)cc(C(F)(F)F)c1
InChIKey: DNFPFLPJDNMARR-GQCTYLIASA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TrkC (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay
Measurement: IC50 = 160.4 nM (pChEMBL 6.789999961853027)
Descriptors: MW 412.39, ALogP 5.9, HBA 3, HBD 2, PSA 53.6, QED 0.4
Compound (SMILES): O=C(NO)c1ccc(CNC(=O)c2ccc(-c3csc(N4N=C(c5ccccc5)/C(=N/Nc5nccs5)C4=O)n3)cc2)cc1
InChIKey: QQRFMJJLLFBVLU-NQUVTRGKSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) in using Boc-Lys(acetyl)-AMC or Boc-Lys (triflouroacetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 622.69, ALogP 4.53, HBA 11, HBD 4, PSA 161.27, QED 0.14
Compound (SMILES): Cc1n[nH]c2ccc(-c3cncc(N4CCC[C@H](N)C4)n3)cc12
InChIKey: ZFNPZIHAKBWOMC-ZDUSSCGKSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 8008 nM (pChEMBL 5.099999904632568)
Descriptors: MW 308.39, ALogP 2.26, HBA 5, HBD 2, PSA 83.72, QED 0.76
Compound (SMILES): COc1ccc(Nc2ncnc3c2c(-c2ccc(Cl)cc2)cn3-c2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: DPWJXZSJOPCILT-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 66.1 nM (pChEMBL 7.179999828338623)
Descriptors: MW 505.99, ALogP 5.14, HBA 7, HBD 2, PSA 112.13, QED 0.33
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)CC2CC(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: KQQPMJPLUTYQMW-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Antagonist activity at alphaVbeta3 in human SK-MEL-24 cells assessed as reduction in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 = 71.7 nM (pChEMBL 7.139999866485596)
Descriptors: MW 277.28, ALogP 0.55, HBA 4, HBD 3, PSA 112.73, QED 0.55
Compound (SMILES): O=C(NO)c1ccc(COC(=O)N2CCC3(CC2)CN(Cc2ccccc2)c2ccccc23)cc1
InChIKey: KJFQCAJLBHHVPB-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli using Fluor de Lys substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 3190 nM (pChEMBL 5.5)
Descriptors: MW 471.56, ALogP 4.5, HBA 5, HBD 2, PSA 82.11, QED 0.42
Compound (SMILES): Cc1c(NC(=O)NCCc2ccc(S(N)(=O)=O)cc2)sc2nc3ccccc3n12
InChIKey: BIPDFKKKCULZPA-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 29.7 nM (pChEMBL 7.53000020980835)
Descriptors: MW 429.53, ALogP 2.87, HBA 6, HBD 3, PSA 118.59, QED 0.45
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1cc2ccc(F)cn2c(=O)c1-c1ccccc1
InChIKey: SSHWKFPRWQRASS-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHG7
Assay: Inhibition of PI3Kgamma in mouse RAW 264.7 cells assessed as reduction in phosphorylation of AKT at 473 measured after 2 hr by alpha screen assay
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 415.43, ALogP 3.1, HBA 8, HBD 3, PSA 135.12, QED 0.47
Compound (SMILES): C[C@]1(c2ccccc2)CN(CC(N)=O)C[C@H]1c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: NANKRNOZMVMNLJ-PKOBYXMFSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 460.42, ALogP 3.84, HBA 3, HBD 2, PSA 66.56, QED 0.67
Compound (SMILES): CCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1CCCCC1)C(=O)N1CCC[C@H]1C(=O)O)C(C)C
InChIKey: DVPWMZAKJYXXEG-BQBSFLCNSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells co-expressing PDZ-Rho-Gef-RLucll assessed as induction of Galpha12 effector (PDZ-RhoGEF) to the cell membrane incubated for 5 mins by BRET assay
Measurement: EC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 1168.45
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCCC(Nc3ncc(CCc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: NXZXWOASWYOLBZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 507.66, ALogP 5.06, HBA 7, HBD 2, PSA 100.36, QED 0.41
Compound (SMILES): OC1CCC(c2cccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c23)CC1
InChIKey: XZXJVMPFESCWIA-PCKAHOCUSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 459.52, ALogP 4.83, HBA 5, HBD 4, PSA 85.86, QED 0.45
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2n[nH]c3ncc(-c4ccc(OC)cc4Cl)cc23)c1F
InChIKey: HIFSUIBXPYGBLF-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P45985
Assay: Inhibition of MEKK2 (unknown origin) using casein as substrate in presence of [gamma-33P]-ATP by scintillation counter assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 520.95, ALogP 4.95, HBA 6, HBD 2, PSA 114.04, QED 0.32
Compound (SMILES): COc1ccc(N2Cc3ccc(O)cc3OC2=O)cc1OC
InChIKey: ZZMRAJIUHSPJIQ-UHFFFAOYSA-N
Target: Macrophage migration inhibitory factor (SINGLE PROTEIN), Homo sapiens
UniProt: P14174
Assay: Displacement of 4'-(7-Hydroxy-2-oxo-2H-chromen-3-yl)-[1,1'-biphenyl]-4-carboxylic acid from C-terminal His-tagged recombinant human MIF expressed in Escherichia coli BL21 (DE3) preincubated for 10 mins followed by probe addition and measured after 10 mins by fluorescence assay
Measurement: Kd = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 301.3, ALogP 2.93, HBA 5, HBD 1, PSA 68.23, QED 0.94
Compound (SMILES): Fc1cc2[nH]cc(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c2cc1F
InChIKey: WMWJOZFPAJCSFJ-VIFPVBQESA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 363.8, ALogP 3.72, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): Cc1nc(NC(=O)CN2CCN(C)CC2)sc1-c1ccc2c(/C=C/c3ccccn3)n[nH]c2c1
InChIKey: CHLFFSKXUJQLQO-VQHVLOKHSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of human KIT by Z-LYTE or ADP-Glo assay
Measurement: IC50 = 2167 nM (pChEMBL 5.659999847412109)
Descriptors: MW 473.61, ALogP 3.75, HBA 7, HBD 2, PSA 90.04, QED 0.44
Compound (SMILES): Fc1ccc(CN2CCC(NCCSC(c3ccc(F)cc3)c3ccc(F)cc3)CC2)cc1
InChIKey: JZQOJABCZMOQTR-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma 1 receptor in guinea pig brain cortex membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 470.6, ALogP 6.18, HBA 3, HBD 1, PSA 15.27, QED 0.38
Compound (SMILES): COC(=O)c1nc([C@@H]2CC[C@@H](C)N(C(=O)c3ccccc3-n3nccn3)C2)oc1-c1ccccc1
InChIKey: AZIMZRYVUDARIJ-IEBWSBKVSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: FLIPR Ca2+ Flux Assay: For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 μg/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 μl assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 μl assay buffer containing 1 μM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 μl assay buffer. 30 μl of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 μl, incubated for 5 min and finally 25 μl of agonist is added.
Measurement: IC50 = 1173 nM (pChEMBL 5.929999828338623)
Descriptors: MW 471.52, ALogP 4.12, HBA 8, HBD 0, PSA 103.35, QED 0.4
Compound (SMILES): COc1ccc(C(=O)N(CC(C)(C)C)c2cccc(C)n2)c(N2CCC(COc3cc([C@@H](CC(=O)O)C4CC4)ccn3)CC2)c1
InChIKey: VVRXREQIOCYUKN-PMERELPUSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at GPR40 (unknown origin) expressed in HEK293 cells assessed as intracellular cAMP level incubated for 30 mins by LANCE Ultra cAMP kit based multiplate reader analysis
Measurement: EC50 = 87.9 nM (pChEMBL 7.059999942779541)
Descriptors: MW 614.79, ALogP 6.75, HBA 7, HBD 1, PSA 105.09, QED 0.24
Compound (SMILES): Cc1ccc(Cl)c(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)c1
InChIKey: ZXZHTJNNFHZERH-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 921.6 nM (pChEMBL 6.039999961853027)
Descriptors: MW 446.94, ALogP 1.86, HBA 5, HBD 4, PSA 147.46, QED 0.51
Compound (SMILES): COc1ccc(/C=C/C(=O)Nc2ccc3oc(=O)ccc3c2)cc1
InChIKey: QCYPXBSJTHOSNZ-ONNFQVAWSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 883.7 nM (pChEMBL 6.050000190734863)
Descriptors: MW 321.33, ALogP 3.45, HBA 4, HBD 1, PSA 68.54, QED 0.59
Compound (SMILES): CNc1nc(Nc2ccc(-n3cnc(Cl)c3)c(OC)c2)nc2c1CC[C@H]2c1ccccc1
InChIKey: KXPNLMZWAKJGRB-KRWDZBQOSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Inhibition of OATP1B1 (unknown origin)
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 446.94, ALogP 5.19, HBA 7, HBD 2, PSA 76.89, QED 0.42
Compound (SMILES): C[C@](O)(Cn1cc(Br)c(F)n1)C(=O)Nc1cnc(C#N)c(C(F)(F)F)c1
InChIKey: GLFIPMYNFOOFOV-ZDUSSCGKSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Affinity Assay: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone. The results of this assay are reported as Ki values (nM) in Table 1 in the column labeled wt AR Binding (Ki(left)). As discussed above and is apparent from Table 1, there is a poor correlation between AR-LBD affinity and SARD activity. E.g., see in vitro SARD activity for 1002, 1005, 1015, 1019, 1020, and 1022 despite no binding affinity for the LBD.
Measurement: Ki = 566 nM (pChEMBL 6.25)
Descriptors: MW 436.16, ALogP 2.46, HBA 6, HBD 2, PSA 103.83, QED 0.72
Compound (SMILES): Cc1c(N2CCC3(CC2)Cc2ncccc2[C@@H]3N)nc(C)n(-c2cccc(Cl)c2Cl)c1=O
InChIKey: PUAFKERZWLWHED-NRFANRHFSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Biochemical Assay: The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2,E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 470.4, ALogP 4.39, HBA 6, HBD 1, PSA 77.04, QED 0.6
Compound (SMILES): CC(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O
InChIKey: HSJMNXXZYVFSJQ-HVRNLMOBSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse melanocortin receptor 5 expressed in HEK293 cells assessed as stimulation of cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay
Measurement: EC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 734.86, ALogP 1.04, HBA 7, HBD 8, PSA 241.28, QED 0.05
Compound (SMILES): O=C(NC1CCN(C2CCCCC2)CC1)c1cc(-c2ccc(F)cc2F)on1
InChIKey: XJCSHBIFSXBNBN-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at -40 mV holding potential by Q-patch clamp assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 389.45, ALogP 4.15, HBA 4, HBD 1, PSA 58.37, QED 0.85
Compound (SMILES): COc1cc2ncnc(Oc3ccc(Nc4nccc5[nH]cc(-c6ccc(F)cc6)c(=O)c45)cc3F)c2cc1OC
InChIKey: QOMGQLZYIUPQLG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant VEGFR2 kinase domain (unknown origin)
Measurement: IC50 = 267.3 nM (pChEMBL 6.570000171661377)
Descriptors: MW 553.53, ALogP 6.36, HBA 8, HBD 2, PSA 111.25, QED 0.23
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccc(Cl)cc2)cc1
InChIKey: LROWEQWLRCXFQZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 162.2 nM (pChEMBL 6.789999961853027)
Descriptors: MW 432.91, ALogP 1.55, HBA 5, HBD 4, PSA 147.46, QED 0.52
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCCCCCCC(=O)NO)cc12
InChIKey: OEMGJZQIDXYGFV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 1 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 368.7 nM (pChEMBL 6.429999828338623)
Descriptors: MW 606.7, ALogP 5.49, HBA 7, HBD 5, PSA 145.68, QED 0.08
Compound (SMILES): COc1ccc(C(C)C)c2c1C(=O)C(O)(O)C2=O
InChIKey: PXHQIRFPVXVSCM-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 250.25, ALogP 0.88, HBA 5, HBD 2, PSA 83.83, QED 0.6
Compound (SMILES): CCC(=O)Nc1ccc(Oc2ccc(Cl)c3ccccc23)c(Cl)c1
InChIKey: MQIIVYOAOLYJSB-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at full-length PPARgamma (unknown origin) expressed in MG63 cells assessed as transcriptional activation incubated for 18 hrs by dual-Glo luciferase assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 360.24, ALogP 6.29, HBA 2, HBD 1, PSA 38.33, QED 0.59
Compound (SMILES): COc1ccc(C(=O)CC2CC(=O)N(c3ccc(S(N)(=O)=O)cc3)C2=O)cc1
InChIKey: OSRMMDIQMSUNFC-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5LOX expressed in baculovirus infected Sf insect cells using linoleic acid as substrate preincubated for 5 mins followed by substrate addition
Measurement: IC50 = 4740 nM (pChEMBL 5.320000171661377)
Descriptors: MW 402.43, ALogP 1.5, HBA 6, HBD 1, PSA 123.84, QED 0.58
Compound (SMILES): C[C@@H](CNc1ccc(Cl)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: NQGXTYTUMOTTJU-OKZBNKHCSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells preincubated for 2 hrs followed by IFNgamma stimulation and measured after 18 hrs by
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 396.94, ALogP 7.05, HBA 2, HBD 1, PSA 24.92, QED 0.5
Compound (SMILES): Cl.N=C(N)N/N=C/c1ccc(Cl)c(C(F)(F)F)c1
InChIKey: OMYOUCJVJYJITH-CQCNNJTASA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293T cells harboring EP2 incubated for 15 mins by cAMP assay
Measurement: EC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 264.64, ALogP 2.18, HBA 2, HBD 3, PSA 74.26, QED 0.44
Compound (SMILES): Cc1nnn(Cc2cc(C(F)(F)F)ccc2/C=C/C(=O)N2CCC(c3nnc(C)o3)CC2)n1
InChIKey: YFDNXWTWDPWCOC-GQCTYLIASA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: ATX Assay: Reagents LPC (oleoyl (18:1)) was purchased from Avanti Polar Lipids (Alabaster, Ala.) and solubilized in methanol to 20 mM. Amplex Red was obtained from Invitrogen Life Technologies (Paisley, UK) and dissolved in DMSO to 10 mM. Choline oxidase and horseradish peroxidase (HRP) were obtained from Sigma Aldrich (Dorset, UK) and dissolved in HBSS to 20 U/ml and 200 U/ml respectively. All reagents were stored at −20° C. in single use aliquots. All experimental measurements were performed in assay buffer made up immediately prior to use (HBSS, 0.01% BSA essentially fatty acid free).Protein Recombinant human ATX was prepared at Novartis (Basel, CH) in a human embryonic kidney (HEK) cell preparation, and stored in single use aliquots of 26 mg/ml (26 μM) stocks stored at −80° C.Method All experimental measurements were performed in black 384 well polystyrene (low volume, round bottom, Corning (3676)) plates. PerkinElmer EnVision (Fluorescence Intensity/Absorbance Monochromator) or Tecan Infinite 200 PRO series plate reader was used to detect change in fluorescent intensity.Assessing ATX inhibition ATX activity was determined by measurement of released choline in reactions containing ATX (10 nM), choline oxidase (0.1 U/ml), HRP (100 U/ml), amplex red (50 μM) and LPC 18:1 (10 μM). Compounds of the invention were prepared as 10 point serial dilutions from 1 μM in duplicate and pre-incubated with ATX at 37° C. for 20 minutes prior to the addition of remaining reagents. The liberated choline was measured from changes in fluorescence intensity (λex 530 nm, λem 590 nm) of the product resurofin at 37° C. every 2 minutes over a 40-minute period. ATX activity was measured as a slope of the linear portion of the progress curve, typically between 14 to 24 minutes.Data analysis Slope data was exported to Graphpad prism (Graphpad software, San Diego, Calif.)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 461.45, ALogP 3.16, HBA 8, HBD 0, PSA 102.83, QED 0.54
Compound (SMILES): CCOc1nc(Nc2ccc(C(=O)N3CCOCC3)cc2OC)nc2[nH]ccc12
InChIKey: OTTOCUYGSZUQOI-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of LRRK2 in human AHE cells assessed as reduction in Ser935 phosphorylation
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 397.44, ALogP 2.58, HBA 7, HBD 2, PSA 101.6, QED 0.66
Compound (SMILES): CC(C)[C@@H]1N(C(=O)OC(C)(C)C)CC[C@@]12C(=O)N(c1cccc(-c3ccc(CO)c(S(C)(=O)=O)c3)c1)c1ccccc12
InChIKey: ZWVQGRNZPMCKOJ-ZQAZVOLISA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Inverse agonist activity at human LXRbeta transfected in human HEK293T cells co-transfected with pSG5 and pGL3/(DR-4)-c-fos-FF-luc/pCMV/Renilla-luc assessed as receptor transactivation incubated for 20 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 590.74, ALogP 5.83, HBA 6, HBD 1, PSA 104.22, QED 0.4
Compound (SMILES): Nc1ncnc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(C(=O)NC3CC3(F)F)C[C@H]12
InChIKey: SLINDUCBZWRWNA-VOXIZFLGSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Kd > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 366.33, ALogP -0.78, HBA 8, HBD 4, PSA 139.18, QED 0.56
Compound (SMILES): Cc1nc(Cl)cc(Nc2c[nH]nc2-c2nc(-c3ccc(CN4CCOCC4)cc3)c[nH]2)n1
InChIKey: JCGXVWCLMLBCHZ-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) incubated for 40 mins in presence of ATP by Kinase-glo luminescence assay
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 450.93, ALogP 3.79, HBA 7, HBD 3, PSA 107.64, QED 0.38
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCc1cn(CCCC(=O)NO)nn1
InChIKey: RXCJZPBISMXQDN-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 647.07, ALogP 5.33, HBA 11, HBD 4, PSA 165.41, QED 0.07
Compound (SMILES): CC/C(=C(/c1ccc(O)cc1)c1ccc(/C=C/C(=O)NCCNC(=O)/C=C/c2ccc(/C(=C(\CC)c3ccccc3)c3ccc(O)cc3)cc2)cc1)c1ccccc1
InChIKey: GZSBAXVVAPODNV-WDYVLNGVSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha (unknown origin) expressed in human U2OS cells assessed as inhibition of E2-induced transactivation measured after 21 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 764.97, ALogP 10.79, HBA 4, HBD 4, PSA 98.66, QED 0.05
Compound (SMILES): CCNC(=O)N1CCc2cc(OC)c(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)cc2C1
InChIKey: UCBFFSCNFDWWSG-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 559.09, ALogP 4.9, HBA 8, HBD 3, PSA 125.55, QED 0.36
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@H]4CC[C@H](C(N)=O)CC4)nc32)cc1
InChIKey: JDUQEHFYOAZGKI-HAQNSBGRSA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Binding affinity to LPP-dephosphorylated recombinant wild-type ERK3 (9 to 327 residues) (unknown origin) expressed in Escherichia coli by microscale thermophoresis assay
Measurement: Kd = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 367.41, ALogP 1.68, HBA 8, HBD 2, PSA 120.84, QED 0.7
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c([S+]([O-])O)cccc12
InChIKey: QSQRFECBUPREPJ-ZDUSSCGKSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 385.49, ALogP 2.93, HBA 6, HBD 4, PSA 108.92, QED 0.5
Compound (SMILES): FC(F)(F)Cc1cnc(N[C@H]2CCCNC2)nc1-c1n[nH]c2ccccc12
InChIKey: SELGYLPDJDLPJJ-LBPRGKRZSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 376.39, ALogP 3.29, HBA 5, HBD 3, PSA 78.52, QED 0.65
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(N)ncnc31)[C@H](O)[C@@H]2O
InChIKey: PBLIHKYNMUXZRL-XEMBYONJSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Kd > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 304.31, ALogP -1.56, HBA 8, HBD 4, PSA 139.18, QED 0.53
Compound (SMILES): CC#CC(=O)N1CCC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)C1
InChIKey: HMZGUBXDLSCJRA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using ULight -mylein basic protein as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 2190 nM (pChEMBL 5.659999847412109)
Descriptors: MW 403.49, ALogP 3.06, HBA 4, HBD 2, PSA 90.98, QED 0.75
Compound (SMILES): C[C@@H]1CN(c2ccc(NC(=O)c3n[nH]c4ccc(-c5cncc(CN6CCCCC6)c5)cc34)cn2)C[C@H](C)O1
InChIKey: GUGHZLAJQJKGHH-OYRHEFFESA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 525.66, ALogP 4.87, HBA 7, HBD 2, PSA 99.27, QED 0.37
Compound (SMILES): COc1cccc2c1C(=O)N1CCc3c([nH]c4cccc(OC)c34)[C@H]1N2C
InChIKey: FFAIVCGLKMKWII-FQEVSTJZSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q01064
Assay: Inhibition of human PDE1B (10-487 residues) expressed in Sf9 cells incubated for 15 mins using [3H]-cGMP as substrate by liquid scintillation counting method
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 363.42, ALogP 3.33, HBA 4, HBD 1, PSA 57.8, QED 0.76
Compound (SMILES): COc1nc(-c2csc(Nc3cc(C(C)(C)C)nn3C(C)C)n2)ccc1-n1cnc(C)c1
InChIKey: PVYMEWFIIZLAAI-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant CYP1A2 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 451.6, ALogP 5.53, HBA 9, HBD 1, PSA 82.68, QED 0.42
Compound (SMILES): N#Cc1ccc(Nc2cc(NCc3ccncc3)nc(-c3ccccc3)n2)cc1
InChIKey: PXHGGTUWGFIZHB-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin) expressed in MDCK-II cells assessed as potentiation of SN-38-induced cytotoxicity measured after 72 hrs by MTT assay
Measurement: EC50 = 72.5 nM (pChEMBL 7.139999866485596)
Descriptors: MW 378.44, ALogP 4.77, HBA 6, HBD 2, PSA 86.52, QED 0.5
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CCO)C(=O)NCc1ccccc1Cl)c1sccc1C
InChIKey: IJIMBHRRVMFBCK-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GAT1 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 13803.84 nM (pChEMBL 4.860000133514404)
Descriptors: MW 503.13, ALogP 5.9, HBA 5, HBD 2, PSA 52.57, QED 0.34
Compound (SMILES): CN(C)c1ccc(/C=N/Nc2ncnc3c2c(-c2ccc(Cl)cc2)cn3-c2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: HYSWJWUKPITTJW-VWJSQJICSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 3031.1 nM (pChEMBL 5.519999980926514)
Descriptors: MW 546.06, ALogP 4.9, HBA 8, HBD 2, PSA 118.5, QED 0.22
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCN(C5CC5)C4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: NWLLJGVSVSXYSN-ZDUSSCGKSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 479.53, ALogP 4.09, HBA 6, HBD 2, PSA 90.98, QED 0.57
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CCC4CCCO4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: XNKXKMIABXRUNJ-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 937 nM (pChEMBL 6.03000020980835)
Descriptors: MW 638.72, ALogP 5.08, HBA 8, HBD 2, PSA 137.4, QED 0.24
Compound (SMILES): COc1ccc(CNC(=O)N2C[C@@H](c3ccc(C(O)(C(F)(F)F)C(F)(F)F)cc3)[C@@](C)(c3ccc(F)cc3)C2)cc1
InChIKey: ZJWOHCMGUADUFY-AZGAKELHSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 584.53, ALogP 6.41, HBA 3, HBD 2, PSA 61.8, QED 0.33
Compound (SMILES): N[C@@H]1CCCN(c2cc(Nc3cc(Cl)ccn3)n3nccc3n2)C1
InChIKey: KTBUQJNYPCXMFT-GFCCVEGCSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 343.82, ALogP 2.45, HBA 7, HBD 2, PSA 84.37, QED 0.76
Compound (SMILES): NC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCCC1CCN(Cc2ccccc2)CC1
InChIKey: ZUWQNIVETLIDSE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholineiodide as substrate incubated for 10 mins by Ellman's method
Measurement: IC50 = 20600 nM (pChEMBL 4.690000057220459)
Descriptors: MW 519.67, ALogP 4.72, HBA 7, HBD 2, PSA 110.44, QED 0.35
Compound (SMILES): CC(C)Cc1ccc(-c2coc3ccc(-c4cn[nH]c4)nc23)cc1
InChIKey: CIUGVTHIGIBJMT-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of human full length recombinant CLK3 using ERMRPRKRQGSVR substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 317.39, ALogP 5.08, HBA 3, HBD 1, PSA 54.71, QED 0.57
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2cc(-c3cc[nH]n3)ccc12
InChIKey: HOWNBGZWAXBZST-ZDUSSCGKSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 427.43, ALogP 4.2, HBA 5, HBD 4, PSA 94.31, QED 0.39
Compound (SMILES): Cc1cc(-c2ccc3nc(NS(C)(=O)=O)cn3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: OVOIHWKNZQREEB-ZDUSSCGKSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.51, ALogP 2.83, HBA 6, HBD 1, PSA 96.67, QED 0.68
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(SCC(=O)Nc3cccc(Cl)c3)o2)cc1
InChIKey: KSJFCHKRVINFCW-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 50.8 nM (pChEMBL 7.289999961853027)
Descriptors: MW 424.89, ALogP 2.77, HBA 7, HBD 2, PSA 128.18, QED 0.58
Compound (SMILES): COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n([C@H](C)C2CCN(CC(C)(F)F)CC2)c2ccccc12
InChIKey: PNEFSJHJVDPVFV-GOSISDBHSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 in human HeLa cells assessed as inhibition of trimethylation of H3K27 after 72 hrs by AlphaLISA assay
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 514.62, ALogP 4.81, HBA 5, HBD 2, PSA 79.36, QED 0.45
Compound (SMILES): CNc1nnc(CCc2c[nH]c3ccc(OC)cc23)o1
InChIKey: BQFCFEKFFSVPDO-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human MAO-A using p-tyramine as substrate by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 272.31, ALogP 2.39, HBA 5, HBD 2, PSA 75.97, QED 0.75
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cccc(C(F)(F)F)c2OC)[nH]1
InChIKey: VYVFFMPROFRJGV-RPWUZVMVSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 562.68, ALogP 6.31, HBA 5, HBD 2, PSA 87.32, QED 0.28
Compound (SMILES): CCNc1ncc2c(n1)N(C)CCN(c1cccc(O[C@H](CCNC)c3ccccc3)c1)C2=O
InChIKey: MGGCXTKDCMPNFI-HSZRJFAPSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of human NET expressed in HEK293 cells assessed as reduction in ASP+ uptake incubated for 20 mins before ASP+ addition and measured after 90 mins by scintillation counting method
Measurement: IC50 = 203 nM (pChEMBL 6.690000057220459)
Descriptors: MW 460.58, ALogP 3.73, HBA 7, HBD 2, PSA 82.62, QED 0.5
Compound (SMILES): O=C(Nc1ccc(Br)cc1)Nc1ccc(Nc2ncnc3c2OCCN3)cc1
InChIKey: DDLMFJBQTCPFPD-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of recombinant human RET using KKKSPGEYVNIEFG as substrate incubated for 15 mins followed by Mg/ATP addition and measured after 40 mins by [gamma-33P]-ATP assay
Measurement: IC50 = 2223 nM (pChEMBL 5.650000095367432)
Descriptors: MW 441.29, ALogP 4.43, HBA 6, HBD 4, PSA 100.2, QED 0.48
Compound (SMILES): CC(C)C[C@H](CC(=O)NO)C(=O)N[C@@H](Cc1ccc(OCCNC(=O)c2ccc(NN)nc2)cc1)C(=O)O
InChIKey: COWAOBZJUFXZPY-QUCCMNQESA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP9 using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by spectrophotometry
Measurement: Ki = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 530.58, ALogP 0.85, HBA 9, HBD 7, PSA 205, QED 0.07