lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(-c2cc(C(F)(F)F)ccc2[C@H]2CCOc3cc(S(=O)(=O)Nc4ncccn4)ccc32)cn1
InChIKey: HVGAFMZYKBKANC-OAQYLSRUSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells assessed as V1/2 of fast inactivation at 10 Hz frequency at -120 mV holding potential by single pulse protocol based manual patch clamp assay
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 526.54, ALogP 5.58, HBA 6, HBD 1, PSA 94.07, QED 0.36
Compound (SMILES): CC1(C)CN(C(=O)Nc2cc(-c3cn(C4CCOCC4)c4cnccc34)ccn2)C1
InChIKey: WAUJBHZGGVGMME-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG expressed in CHO cells incubated for 90 mins by microbeta scintillation counting method
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 405.5, ALogP 4.32, HBA 5, HBD 1, PSA 72.28, QED 0.7
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](CC(=O)N4CC(Cc5ccccc5)C4)CC3)c12
InChIKey: SXEUSRBRPAJJFS-KESTWPANSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of N-terminal His-tagged human JAK3 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 418.54, ALogP 3.92, HBA 3, HBD 2, PSA 81.85, QED 0.66
Compound (SMILES): CN(C)c1ccccc1-c1cnc2c(c1)C[C@@]1(OCCCc3ccccc3)[C@H]3Cc4ccc(O)c5c4[C@@]1(CCN3CC1CC1)[C@H]2O5
InChIKey: ZSEGEZNFBCYZHP-BPSUTHQGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-diprenorphine from human kappa opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 7.96 nM (pChEMBL 8.100000381469727)
Descriptors: MW 613.8, ALogP 6.88, HBA 6, HBD 1, PSA 58.06, QED 0.21
Compound (SMILES): CCc1nc(N)nc(N)c1-c1ccc(-c2cn(CCCCCC(=O)NO)nn2)cc1
InChIKey: QCVCOCOMJLADHP-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using fluorogenic HDAC substrate class 2A preincubated for 30 mins followed by substrate addition and measured after 15 mins by fluorogenic assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 410.48, ALogP 2.19, HBA 9, HBD 4, PSA 157.86, QED 0.24
Compound (SMILES): COc1cc(/C=C/C(=O)O)ccc1OCc1cn(-c2ccccc2)nn1
InChIKey: XFLHOVXOVHFHQD-CSKARUKUSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human carbonic anhydrase 5A using p-nitrophenyl acetate as substrate by UV-VIS spectrophotometric analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 351.36, ALogP 2.95, HBA 6, HBD 1, PSA 86.47, QED 0.66
Compound (SMILES): C[C@@H](Nc1nc2c(cnn2C2CCCC2)c(=O)n1Cc1ccccc1)c1ccc(Cl)cc1
InChIKey: MALBQEMKPLLDHN-QGZVFWFLSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition of PDE9A (181 to 506 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.97, ALogP 5.58, HBA 6, HBD 1, PSA 64.74, QED 0.42
Compound (SMILES): Cl.Clc1ccc(OC[C@H]2C[C@H]3C[C@H]3N2)cn1
InChIKey: VZIQKVIAFWXNFL-GZJXKWBNSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 12 min in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 32100 nM (pChEMBL 4.489999771118164)
Descriptors: MW 224.69, ALogP 1.86, HBA 3, HBD 1, PSA 34.15, QED 0.8
Compound (SMILES): CC(C)=CCCC1=CC[C@H](C(N)=O)[C@@H](c2ccccc2)C1
InChIKey: BMSQWEZBWQWFAU-ZWKOTPCHSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of Bcl2 (unknown origin)/Bim interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki > 23000 nM (pChEMBL 4.638000011444092)
Descriptors: MW 283.42, ALogP 4.34, HBA 1, HBD 1, PSA 43.09, QED 0.8
Compound (SMILES): CCN(C(=O)c1cccc(C(C)(C)C)c1)c1ccc(C(=O)NO)cc1
InChIKey: BQHABQWCVPOXCG-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of N-terminal His-tagged full length human HDAC8 expressed in baculovirus expression system using FAM-RHKK(TF-Ac)-NH2 substrate incubated for 3 hrs by EMSA method
Measurement: IC50 = 83.5 nM (pChEMBL 7.079999923706055)
Descriptors: MW 340.42, ALogP 3.77, HBA 3, HBD 2, PSA 69.64, QED 0.66
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCCC(C)(C)C(N)=O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: SLLVMGHYDGBTCB-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 690.57, ALogP 4.55, HBA 7, HBD 3, PSA 151.56, QED 0.31
Compound (SMILES): CCOC(=O)Cn1nnc(-c2cc(C(C)C)c(O)cc2O)c1-c1cccc(NS(C)(=O)=O)c1
InChIKey: QQYGMNMVHQBKLR-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Inhibition of GRP94 (unknown origin)
Measurement: IC50 = 209.28 nM (pChEMBL 6.679999828338623)
Descriptors: MW 474.54, ALogP 3.08, HBA 9, HBD 3, PSA 143.64, QED 0.42
Compound (SMILES): O=C(NCCc1ccccc1)C(=O)c1ccccc1
InChIKey: KZQQNXZYUPQAQV-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL19
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 253.3, ALogP 2.23, HBA 2, HBD 1, PSA 46.17, QED 0.66
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc([S+]([O-])Cc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: CCGRMLGTKGCLKM-DEQHTHAUSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant human full-length His-tagged CDK9/Cyclin T1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr in presence of Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 = 9220 nM (pChEMBL 5.039999961853027)
Descriptors: MW 541.7, ALogP 4.58, HBA 8, HBD 2, PSA 123.42, QED 0.32
Compound (SMILES): Cc1noc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)ccc(C(F)(F)F)n3n2)n1
InChIKey: CXJQWJBRXYDTFP-GNXNZQSNSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Binding affinity to PIK4CB (unknown origin)
Measurement: Kd > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 491.4, ALogP 3.71, HBA 9, HBD 1, PSA 93.61, QED 0.54
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCOCC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: KQCTYKLPOJQIET-NOZRDPDXSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 518.66, ALogP 5.54, HBA 6, HBD 2, PSA 106.2, QED 0.31
Compound (SMILES): O=C(/C=C/c1nc2cc(F)c(F)cc2[nH]1)c1c(-c2ccc(F)c(F)c2)c2cc(F)ccc2[nH]c1=O
InChIKey: CRSXAJYRKIQUCU-AATRIKPKSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of PKBgamma (unknown origin)
Measurement: IC50 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 481.38, ALogP 5.66, HBA 3, HBD 2, PSA 78.61, QED 0.2
Compound (SMILES): CCCCCC(O)CCc1cccc(=O)n1CCCCCCC(=O)O
InChIKey: BZFMOMUMMMUZDV-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at human EP2 receptor expressed in HEK293 cells by calcium-5 dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.49, ALogP 3.76, HBA 4, HBD 2, PSA 79.53, QED 0.5
Compound (SMILES): Cc1cccc(N2CCN(CCCC(=O)NCn3nc(CC(N)=O)c4ccc(F)cc4c3=O)CC2)c1C
InChIKey: KGPZRSKPAUQQGE-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Displacement of [3H]imipramine from SERT receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 508.6, ALogP 1.86, HBA 7, HBD 2, PSA 113.56, QED 0.46
Compound (SMILES): [O-][S+](CCN1CCN(C[C@@H](O)Cc2ccccc2)CC1)C(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: MACFTPBZAOCTFN-UAJNXHJVSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from Sigma1 receptor in guinea pig cortex membranes incubated for 120 mins by microbeta scintillation counting method
Measurement: Ki = 27.4 nM (pChEMBL 7.559999942779541)
Descriptors: MW 498.64, ALogP 4.02, HBA 4, HBD 1, PSA 49.77, QED 0.43
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5cnccn5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: PICFOVXIBSJPBO-LMUOQGPPSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-diprenorphine from human kappa opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 19.8 nM (pChEMBL 7.699999809265137)
Descriptors: MW 572.71, ALogP 5.6, HBA 7, HBD 1, PSA 80.6, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C(C)C)CC2)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: CTZUZSDLFUWGPJ-IAPPQJPRSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 560.74, ALogP 6.5, HBA 7, HBD 1, PSA 97.56, QED 0.24
Compound (SMILES): CC(C)Nc1cc(Nc2ccc3nonc3c2)ncc1C(=O)NC[C@@H](F)C(C)(C)O
InChIKey: PFQUJAHKZJFXLR-QGZVFWFLSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human whole blood assessed as inhibition of LTA-induced IL-6 production preincubated for 30 mins followed by LTA-stimulation and measured after 5 hrs by ELISA
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 416.46, ALogP 3.02, HBA 8, HBD 4, PSA 125.2, QED 0.44
Compound (SMILES): CC(C)N(C(=O)c1cccc(C(F)(F)F)c1F)c1ccc(C(=O)NO)cc1
InChIKey: DGQMTANDEIDADK-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of N-terminal His-tagged full length human HDAC8 expressed in baculovirus expression system using FAM-RHKK(TF-Ac)-NH2 substrate incubated for 3 hrs by EMSA method
Measurement: IC50 = 88.5 nM (pChEMBL 7.050000190734863)
Descriptors: MW 384.33, ALogP 4.02, HBA 3, HBD 2, PSA 69.64, QED 0.48
Compound (SMILES): COc1ccc(C(=O)N2[C@H](C)CN(C(=O)c3ccc4cc[nH]c4c3)C[C@H]2C)c(F)c1
InChIKey: WTXZRSDVMFYIFC-HUUCEWRRSA-N
Target: Multifunctional protein CAD (SINGLE PROTEIN), Homo sapiens
UniProt: P27708
Assay: Inhibition of CAD (unknown origin) CSP2 activity expressed in Escherichia coli BL21 (DE3) preincubated for 20 mins followed by ATP addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 >= 100000 nM (pChEMBL 4)
Descriptors: MW 409.46, ALogP 3.69, HBA 3, HBD 1, PSA 65.64, QED 0.72
Compound (SMILES): CCCCCC(=O)N[C@H](C(=O)NCc1ccc(NC(=N)N)cc1)c1ccc(OCc2ccccc2)cc1.O=C(O)C(F)(F)F
InChIKey: RMLDGSREBIUICI-YCBFMBTMSA-N
Target: Genome polyprotein (SINGLE PROTEIN), West Nile virus
UniProt: P06935
Assay: Inhibition of West Nile virus NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Gly-Leu-Lys-Arg-Gly-Gly-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition measured for 15 mins by fluorimetric analysis
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 501.63, ALogP 4.62, HBA 4, HBD 5, PSA 129.33, QED 0.13
Compound (SMILES): CCCCCCCCCC(=O)N[C@H](C(=O)NCc1ccc(NC(=N)N)cc1)c1ccc(OCc2ccccc2)cc1.O=C(O)C(F)(F)F
InChIKey: AQZURVGRGWWYRK-YNMZEGNTSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of Dengue virus serotype 2 NS2B-NS3 protease transfected in human HeLa cells measured after 24 hrs by Renilla-luciferase reporter gene assay
Measurement: EC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 557.74, ALogP 6.19, HBA 4, HBD 5, PSA 129.33, QED 0.08
Compound (SMILES): C[N+](C)(C)C[C@@H]1COC[C@H](c2ccc(S(=O)(=O)c3ccccc3)cc2)O1.[I-]
InChIKey: FPYOERQVOVHGLH-OGPPPPIKSA-M
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M3 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 376.5, ALogP 2.68, HBA 4, HBD 0, PSA 52.6, QED 0.75
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccc(Oc2ccc(C(F)(F)F)nc2)cc1
InChIKey: DSDXBNSGGMWCKX-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL19
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 456.46, ALogP 5.14, HBA 4, HBD 1, PSA 68.29, QED 0.43
Compound (SMILES): C[C@@H]1CN(c2nc(-c3cnn(C)c3)cnc2C#N)CCN1C(=O)C1CC1
InChIKey: GLCGTMKCHJYJFD-GFCCVEGCSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: The PI3-Kinase biochemical assay was optimized using the HTRF kit provided by Upstate (Millipore). The assay kit contains six reagents: 1) 4×Reaction Buffer; 2) native PIP2 (substrate); 3) Stop (EDTA); 4) Detection Mix A (Streptavidin-APC); 5) Detection Mix B (Eu-labeled Anti-GST plus GST-tagged PH-domain): 6) Detection Mix C. In addition, the following items were obtained or purchased; PI3Kinase (catalog #'s alpha 14-602, beta 14-603, gamma 14-558 and delta 14-604 from Upstate Biotechnology now EMD Millipore, Mahopac, N.Y., USA), dithiothreitol (Sigma-Aldrich Corp. (St. Louis, Mo., USA) Catalog #D-5545), Adenosine-5′ triphosphate (InVitrogen (Waltham, Mass., USA), Cat#AS001 Å), native PIP3 (PI(3,4,5)P3, diC8, H+, CELLSIGNALS, INC., (Columbus, Ohio, USA) Cat #907) DMSO ((Sigma-Aldrich Corp. (St. Louis. Mo., USA) Catalog #472301).PI3Kinase Reaction Buffer is prepared by dilution the stock 1:4 with de-ionized water. DTT (DL-Dithiothreitol), phosphatidylinositol 4,5-bisphosphate (PIP2) and Biotin-PIP3 were added to 1536 assay plate at a final concentration of 5 mM, 5 mM and 25 nM on the day of use. Enzyme addition and compound pre-incubation are initiated by the addition of 1.25 ul of PI3K (at twice its final concentration) in the 1× reaction buffer to all wells using a BioRaptor. Plates are incubated at room temperature for 15 minutes. Reactions are initiated by addition of 1.25 ul of 2× substrate solution (PIP2 and ATP in 1× reaction buffer) using BioRaptor. Plates are incubated in humidified chamber at room temperature for one hour. Reactions are quenched by addition of 0.625 uL of stop solution to all wells using the BioRaptor. The quenched reactions are then processed to detect product formation by adding 0.625 uL of Detection Solution to all wells using the BioRaptor (Detection mix C, Detection Mix A and Detection Mix B combined together in an 18:1:1 ratio prepared 2 hours prior to use). Following a one hour incubation in the dark, the HTRF signal is measured on the Envision plate reader set for 330 nm excitation and dual emission detection at 620 nM (Eu) and 665 nM (APC).
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 351.41, ALogP 1.2, HBA 7, HBD 0, PSA 90.94, QED 0.83
Compound (SMILES): Cc1cnc(-c2ccc(OC(F)(F)F)cc2)n1Cc1ccccc1OCCC[C@@H](C)CC(=O)O
InChIKey: GYNMVDMBFKGCCR-QGZVFWFLSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Modulator activity at GAL4-fused human PPARgamma LBD (unknown origin) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.5, ALogP 6.08, HBA 5, HBD 1, PSA 73.58, QED 0.34
Compound (SMILES): O=C(CN1CN(c2ccccc2)C2(CCN(C(=O)c3cnc4[nH]ncc4c3)CC2)C1=O)NCC(F)(F)F
InChIKey: SYDKMYUOXNXPAU-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Inhibition of recombinant GST-tagged human DDR2 by FRET assay
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 515.5, ALogP 1.92, HBA 6, HBD 2, PSA 114.53, QED 0.54
Compound (SMILES): CCCC(=O)Nc1ccc2c(c1)-c1c(OC)c(OC)cc3c1C(C2)N(C)CC3
InChIKey: WMYHWQZCZLJFGR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expresssed in stable HEK cell membrane incubated for 90 mins by microbeta counting method
Measurement: Ki = 356 nM (pChEMBL 6.449999809265137)
Descriptors: MW 380.49, ALogP 4.19, HBA 4, HBD 1, PSA 50.8, QED 0.84
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3cccc(F)c3)CC2)cc1
InChIKey: YBCUNRWDUZQOAB-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human CA7 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 66.1 nM (pChEMBL 7.179999828338623)
Descriptors: MW 391.42, ALogP 1.07, HBA 4, HBD 1, PSA 100.78, QED 0.85
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: UQTCOSRFOINFNG-FSJACQRISA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells
Measurement: Ki > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 925.11, ALogP -3.04, HBA 12, HBD 18, PSA 440.77, QED 0.02
Compound (SMILES): Oc1ccc(-c2cc3c(s2)CCC(NCCCc2ccccc2)CC3)cc1
InChIKey: AXGBTJWSECLUHH-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor in rat liver membranes incubated for 120 mins in the presence of sigma1 receptor ligand (+)-pentazocine by scintillation counting method
Measurement: Ki = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 377.55, ALogP 5.59, HBA 3, HBD 2, PSA 32.26, QED 0.43
Compound (SMILES): O=C(CCc1ccccc1)N1CC[C@]23Cc4nc5ccccc5cc4C[C@@]2(O)[C@H]1Cc1ccc(O)cc13
InChIKey: PJCSQJTYHDBALX-AFEGNUHBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human delta opioid receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assay
Measurement: EC50 = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 490.6, ALogP 4.5, HBA 4, HBD 2, PSA 73.66, QED 0.44
Compound (SMILES): CCOc1cc(Cl)c(C(=O)Nc2nc3ccc(S(=O)(=O)CCCN4CCN(C)CC4)cc3s2)cc1N1CCO[C@H](C)C1
InChIKey: CGNPOKNBKXLUSH-HXUWFJFHSA-N
Target: Hydroxycarboxylic acid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDS4
Assay: Agonist activity at human GPR109A receptor
Measurement: EC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 636.24, ALogP 4.24, HBA 10, HBD 1, PSA 104.31, QED 0.35
Compound (SMILES): O=C(CSc1nccc(Nc2ccc(S(=O)(=O)Nc3ccccn3)cc2)n1)c1ccccc1
InChIKey: MXIKGRZQLQIJMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 477.57, ALogP 4.39, HBA 8, HBD 2, PSA 113.94, QED 0.21
Compound (SMILES): C=CCOc1c(OC)cc2c3c1-c1cc(N)ccc1CC3N(C)CC2
InChIKey: WVHMHWPHKVTXSC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to human 5HT2A receptor
Measurement: Ki = 234 nM (pChEMBL 6.630000114440918)
Descriptors: MW 336.44, ALogP 3.59, HBA 4, HBD 1, PSA 47.72, QED 0.68
Compound (SMILES): CCN1CCN(c2ccc(Nc3nc(-c4ccc5cn[nH]c5c4)cn4ccnc34)cc2)CC1
InChIKey: ZOAWTCISMWOTGW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human whole blood assessed as reduction in anti-FCepsilonR1 mAb-induced basophil activation by measuring decrease in CD63 surface expression incubated for 60 mins followed by anti-FCepsilonR1 mAb stimulation for 20 mins by flow cytometry analysis
Measurement: EC50 = 456 nM (pChEMBL 6.340000152587891)
Descriptors: MW 438.54, ALogP 4.16, HBA 7, HBD 2, PSA 77.38, QED 0.43
Compound (SMILES): O=C(CCc1ccccc1)C(=O)NCCc1ccccc1
InChIKey: JRCFFCLOAWGFFS-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL19
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 281.36, ALogP 2.55, HBA 2, HBD 1, PSA 46.17, QED 0.79
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3nnc(SCc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: ZGTBRXCHDKWPQT-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 526.69, ALogP 4.96, HBA 9, HBD 2, PSA 113.25, QED 0.31
Compound (SMILES): O=C1C[C@H](Nc2ncnc3[nH]cnc23)CN1Cc1ccccc1
InChIKey: HUWOMAVUXTXEKT-LBPRGKRZSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Binding affinity to recombinant TNFalpha (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as Kd for TNF-alpha-TNFR1 binding at 10 uM pe-incubated for 15 mins before TNFR1 addition and measured after 15 mins by MST assay (Rvb = 0.23 uM)
Measurement: Kd = 4260 nM (pChEMBL 5.369999885559082)
Descriptors: MW 308.35, ALogP 1.57, HBA 5, HBD 2, PSA 86.8, QED 0.76
Compound (SMILES): Cc1cccc(C)c1-c1cnc2c(c1)C[C@@]1(OCCCc3ccccc3)[C@H]3Cc4ccc(O)c5c4[C@@]1(CCN3CC1CC1)[C@H]2O5
InChIKey: HHPBPMMGXGLFBZ-GYVZUEEYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-diprenorphine from human kappa opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 598.79, ALogP 7.43, HBA 5, HBD 1, PSA 54.82, QED 0.21
Compound (SMILES): Cc1nsc(N2CC3CCC(C2)C3Nc2nc3c(-c4ccc(F)c(F)c4F)cccn3n2)n1
InChIKey: IAINSZMFDDIZGX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Binding affinity to PIK4CB (unknown origin)
Measurement: Kd = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 471.51, ALogP 4.3, HBA 8, HBD 1, PSA 71.24, QED 0.45
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc(OC(F)(F)F)cc2)cc1
InChIKey: RMIKMESCOHMNMH-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 349.26, ALogP 3.01, HBA 3, HBD 2, PSA 75.63, QED 0.65
Compound (SMILES): N#Cc1ccc(C#Cc2ccc(NC(=O)C(=O)O)cc2)cc1
InChIKey: DREKYVXEUFPNQZ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 290.28, ALogP 1.98, HBA 3, HBD 2, PSA 90.19, QED 0.62
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CCN(S(=O)(=O)C4CC4)C[C@@H]3C(=O)NCCN(C)C)cc2c1
InChIKey: PKTCAWOZYIDOCG-ICSRJNTNSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 475.62, ALogP 1.07, HBA 5, HBD 3, PSA 114.61, QED 0.53
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(CC(C)(C)C(=O)O)nc2CC2CCC2)c(Cl)c1)C(F)(F)F
InChIKey: VHUBIAFBCJTTBS-SFHVURJKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as reduction in IL-17a production
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 553.07, ALogP 6.08, HBA 5, HBD 2, PSA 96.36, QED 0.37
Compound (SMILES): CC(C)N(C(=O)c1cccc(OC(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: JTLGBSYAFABUCJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of N-terminal His-tagged full length human HDAC8 expressed in baculovirus expression system using FAM-RHKK(TF-Ac)-NH2 substrate incubated for 3 hrs by EMSA method
Measurement: IC50 = 65.5 nM (pChEMBL 7.179999828338623)
Descriptors: MW 382.34, ALogP 3.76, HBA 4, HBD 2, PSA 78.87, QED 0.61
Compound (SMILES): CC(C)Nc1cc(Nc2ccc3ncsc3c2)ncc1C(=O)NCCC(C)(C)O
InChIKey: NHLXRGNIXZDNBK-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μL prepared from 15 μL additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.2, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of IRAK4 with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentrations of reagents in the assays are ATP, 500 μM; FL-IPTSPITTTYFFFKKK peptide 1.5 μM; IRAK4, 0.6 nM; and DMSO, 1.6%.
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 413.55, ALogP 4.15, HBA 7, HBD 4, PSA 99.17, QED 0.44
Compound (SMILES): CCN(C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl)C12CC(C1)C2
InChIKey: DFUYWGXFDKATDI-HGTVVZKYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 657.56, ALogP 4.86, HBA 7, HBD 3, PSA 128.7, QED 0.34
Compound (SMILES): O=C(CCc1ccc(C(F)(F)F)cc1)C(=O)NCCc1ccccc1
InChIKey: RUTQOCJMJDUBEK-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL19
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT4 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 349.35, ALogP 3.57, HBA 2, HBD 1, PSA 46.17, QED 0.78
Compound (SMILES): CC(C)NCc1ccc(C[C@@H]2NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H]3CCC(=O)NCCCC(=O)NCC[C@@H](NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)N[C@H](CCCCN)C(=O)N[C@H](Cc2ccccc2)C(=O)N3)cc1
InChIKey: DMUOHDWFEHIXQJ-SFYPIHDGSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Inhibition of 125I-[Leu8,D-Trp22,Tyr25]SRIF-28 binding to human somatostatin receptor type 3
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1697.02
Compound (SMILES): CC(C)NCc1ccc(C[C@@H]2NC(=O)[C@@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H]3CCC(=O)NCCCCCC[C@@H](NC(=O)[C@@H](Cc4ccccc4)NC(=O)[C@@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)N[C@H](CCCCN)C(=O)N[C@H](Cc2ccccc2)C(=O)N3)cc1
InChIKey: PWNGKIWHLMJETN-BDRBHZDKSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Inhibition of 125I-[Leu8,D-Trp22,Tyr25]SRIF-28 binding to human somatostatin receptor type 3
Measurement: IC50 = 772 nM (pChEMBL 6.110000133514404)
Descriptors: MW 1668.02
Compound (SMILES): CO[C@@]12C=C[C@]34C[C@]1(C)[C@@H](c1ccccc1)N[C@H]2[C@@]31CCN(C)[C@@H]4Cc2ccc(O)cc21
InChIKey: RGJHUVJQGAAZLK-BZGZDSDCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Compound was tested for its ability to displace [3H]U-69593 from Opioid receptor kappa 1 in hartley guinea pig brain membrane in the presence of 100 nM of U-69,593
Measurement: IC50 = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 428.58, ALogP 3.95, HBA 4, HBD 2, PSA 44.73, QED 0.71
Compound (SMILES): C[C@H](Nc1ccc2c(c1)OCCn1cc(N3C(=O)OC[C@H]3C(F)F)nc1-2)C(N)=O
InChIKey: SGEUNORSOZVTOL-CABZTGNLSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 407.38, ALogP 1.82, HBA 7, HBD 2, PSA 111.71, QED 0.78
Compound (SMILES): CO[C@]1(CN2CCN3CCCC[C@@H]3C2)/C=C/C[C@H](C)[C@@H](C)S(=O)(=O)NC(=O)c2ccc3c(c2)N(C[C@@H]2CC[C@H]21)C[C@@]1(CCCc2cc(Cl)ccc21)CO3
InChIKey: BJTFTQIBRVBSBH-VCQPVEJUSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of recombinant His6-tagged human Bcl-xL (1 to 196 residues) expressed in Escherichia coli using biotinylated Bim BH3 peptide as substrate incubated for 60 mins by TR-FRET analysis
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 765.46, ALogP 6.44, HBA 8, HBD 1, PSA 91.42, QED 0.36
Compound (SMILES): C=CC(=O)N[C@H]1C=C(C)c2c(-c3cnc4ccccc4c3)c3c(N)ncnc3n2C1
InChIKey: MKCYPWYURWOKST-INIZCTEOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR-D770-N771insNPG mutant (unknown origin) phosphorylation
Measurement: IC50 = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 396.45, ALogP 3.32, HBA 6, HBD 2, PSA 98.72, QED 0.52
Compound (SMILES): CCCNc1nc(Nc2ccc(C#N)cc2)ncc1C#CCCCNC(=O)[C@H](C)N(C)C(=O)/C=C/CN(C)C
InChIKey: HJFSVYUFOXAVAA-YUAYGMJFSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin) using MBP as substrate incubated for 2 hrs by ADP-Glo assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 530.68, ALogP 3.13, HBA 8, HBD 3, PSA 126.28, QED 0.2
Compound (SMILES): O=C1Nc2cc3[nH]nc(-c4ccncc4)c3cc2CN1Cc1ccccc1
InChIKey: ODIUJYZERXVGEI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Z′-LYTE Kinase Assay: The inhibition of ERK activity by the compounds disclosed herein was determined using the Z′-LYTE kinase assay kit (Life Technologies) with a Ser/Thr 3 peptide substrate (Life Technologies) according to manufacturers' instructions. The assay was run with an ERK2 enzyme (Life Technologies) concentration of 0.47 ng/μL at 100 μM ATP (approximately the ATP Km for ERK2). The IC50 values for the compounds were determined with 3-fold serial dilutions in duplicate. The compounds were first diluted in 1:3 dilutions in 100% DMSO at 100× the desired concentration, and then further diluted (1:25) in 20 mM HEPES buffer (Invitrogen) to make 4× solutions prior to adding to the enzyme solution. The final DMSO concentration in the assay was 1%. Final reaction volume was 20 μL/well in 384-well plates. Kinase reactions were conducted or 1 hour followed by the assay development reaction (1 hour) in a 20 ul/well in a 384 well plate format.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 355.4, ALogP 4.17, HBA 3, HBD 2, PSA 73.91, QED 0.58
Compound (SMILES): Cn1nccc1Nc1nccc(-c2cc3c(s2)C(C)(C)N(CCN2CCOCC2)C3=O)n1
InChIKey: JNPRPMBJODOFEC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27361
Assay: Inhibition of ERK1 (unknown origin)
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 453.57, ALogP 2.71, HBA 9, HBD 1, PSA 88.41, QED 0.61
Compound (SMILES): Nc1nn2cc(F)cnc2c1C(=O)Nc1cncc(F)c1N1CCC(C(=O)N2CCN(C3COC3)CC2)CC1
InChIKey: QAYHKBLKSXWOEO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR (unknown origin)-driven CHK1 phosphorylation
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 541.56, ALogP 1, HBA 10, HBD 2, PSA 134.22, QED 0.49
Compound (SMILES): C[C@H](Oc1cc2cc(F)ccc2nc1N)c1[nH]c(=O)ccc1-n1cccn1
InChIKey: CLEFVPILGAPOTG-NSHDSACASA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 21800 nM (pChEMBL 4.659999847412109)
Descriptors: MW 365.37, ALogP 2.97, HBA 6, HBD 2, PSA 98.82, QED 0.58
Compound (SMILES): O=C(O)CNC(=O)c1c(O)c2ccccc2n(OCC2CC2)c1=O
InChIKey: IKRKQQLJYBAPQT-UHFFFAOYSA-N
Target: Aspartyl/asparaginyl beta-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: Q12797
Assay: Inhibition of AspH (unknown origin)
Measurement: IC50 = 9900 nM (pChEMBL 5)
Descriptors: MW 332.31, ALogP 0.36, HBA 6, HBD 3, PSA 117.86, QED 0.7
Compound (SMILES): C[C@@H]1Cc2c([nH]c3ccccc23)[C@@H](c2c(F)cc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)CO
InChIKey: GQCXHIKRWBIQMD-AKJBCIBTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Reversible inhibition of CYP3A4 in human liver microsomes at 10 uM using midazolam as substrate preincubated for 10 mins followed by NADPH addition by LC/MS/MS analysis
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 522.56, ALogP 4.87, HBA 4, HBD 3, PSA 54.53, QED 0.35
Compound (SMILES): COc1nc(C(=O)NC[C@](C)(O)C(F)(F)F)c(N)cc1C(F)(F)F
InChIKey: USHQRIKZLHNPQR-JTQLQIEISA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Potentiation of CFTR F508del mutant (unknown origin) expressed in CHO cells assessed as chloride transport by measuring membrane potential incubated for 5 to 30 mins in presence of forskolin by Quattro assay
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 361.24, ALogP 1.73, HBA 5, HBD 3, PSA 97.47, QED 0.71
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: AZSRSNUQCUDCGG-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/C797S mutant (unknown origin) using TK-substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 20 mins by HTRF assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 585.71, ALogP 5.08, HBA 10, HBD 2, PSA 113.85, QED 0.17
Compound (SMILES): C=CC(=O)N1CCC(c2ccc(C(N)=O)c(-c3ccc(Oc4ccccc4)cc3)n2)CC1
InChIKey: MZPVEMOYADUARK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR autophosphorylation at Tyr1068 residue in EGFR-amplified human A-431 cells preincubated with compound for 1 hrs followed by stimulation with human recombinant EGF and measured after 10 mins by HTRF-based analysis
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 427.5, ALogP 4.53, HBA 4, HBD 1, PSA 85.52, QED 0.59
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)nccc32)C1
InChIKey: KOEUOFPEZFUWRF-LJQANCHMSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 455.52, ALogP 3.91, HBA 7, HBD 1, PSA 95.38, QED 0.46
Compound (SMILES): Cc1c(-c2[nH]c3ccc(C4CCN(CC(N)=O)CC4)cc3c2C(C)C)cn2ncnc2c1C
InChIKey: SNFVHLQYHFQOEP-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: TLR7/8/9 Inhibition Reporter Assay: HEK-Blue-cells (Invivogen) overexpressing human TLR7, TLR8 or TLR9 receptors were used for screening inhibitors of these receptors using an inducible SEAP (secreted embryonic alkaline phosphatase) reporter gene under the control of the IFN-β minimal promoter fused to five NF-κB and AP-1-binding sites. Briefly, cells are seeded into Greiner 384 well plates (15000 cells per well for TLR7, 20,000 for TLR8 and 25,000 for TLR9) and then treated with test compounds in DMSO to yield a final dose response concentration range of 0.05 nM-50 μM. After a 30 minute compound pre-treatment at room temperature, the cells are then stimulated with a TLR7 ligand (gardiquimod at a final concentration of 7.5 μM), TLR8 ligand (R848 at a final concentration of 15.9 μM) or TLR9 ligand (ODN2006 at a final concentration of 5 nM) to activate NF-κB and AP-1 which induce the production of SEAP. After a 22 hour incubation at 37° C., 5% CO2, SEAP levels are determined with the addition of HEK-Blue Detection reagent (Invivogen), a cell culture medium that allows for detection of SEAP, according to manufacturer's specifications. The percent inhibition is determined as the % reduction in the HEK-Blue signal present in wells treated with agonist plus DMSO alone compared to wells treated with a known inhibitor.
Measurement: IC50 = 5113 nM (pChEMBL 5.289999961853027)
Descriptors: MW 444.58, ALogP 4.28, HBA 5, HBD 2, PSA 92.31, QED 0.48
Compound (SMILES): C[C@H]1CN(C(=O)CC[C@@]2(C3CC3)NC(=O)NC2=O)CCN1c1cc(F)cc(F)c1
InChIKey: CMLVKUWQFZQPPS-YUNKPMOVSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O75173
Assay: Inhibition of human recombinant ADAMTS-4 (AA1 to 520) assessed as cleavage of fluorescent substrate using as TBIS-1 substrate incubated for 180 mins by biochemical assay
Measurement: IC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 406.43, ALogP 1.77, HBA 4, HBD 2, PSA 81.75, QED 0.73
Compound (SMILES): CNC[C@@H]1OCCc2ccsc21
InChIKey: ABDDQTDRAHXHOC-QMMMGPOBSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at human TAAR1 extracted from CHO-K1 cell membrane coexpressing AGTRL1/Gi by cAMP assay
Measurement: EC50 = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 183.28, ALogP 1.58, HBA 3, HBD 1, PSA 21.26, QED 0.75
Compound (SMILES): COC(=O)N1CCC[C@H](NS(C)(=O)=O)[C@@H]1CO[C@H]1CC[C@@H](c2ccccc2)CC1
InChIKey: UXZAJSZFFARTEI-YRPNKDGESA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Agonist activity at human OX1R expressed in CHO-K1 cells by FLIPR calcium flux assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 424.56, ALogP 2.88, HBA 5, HBD 1, PSA 84.94, QED 0.76
Compound (SMILES): Cc1cc(Nc2cc3ncccc3c(N[C@@H]3C[C@H]4CC[C@@H](C3)N4CCC#N)n2)n[nH]1
InChIKey: DADAEARVGOQWHV-OSYLJGHBSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Biochemical JAK Assay: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies.Serially diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for lh. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for lh before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.For dose-response analysis, percent inhibition data were plotted vs. compound concentrations, and IC50 values were determined from a 4-parameter robust fit model with the Prism software (GraphPad Software). Results were expressed as pIC50 (negative logarithm of IC50) and subsequently converted to pKi (negative logarithm of dissociation constant, Ki) using the Cheng-Prusoff equation.Test compounds having a higher pKi value in each of the four JAK assays show greater inhibition of JAK activity. Compounds of the invention tested in this assay typically exhibited pKi values between about 7 and about 10.3
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 402.51, ALogP 3.73, HBA 7, HBD 3, PSA 105.55, QED 0.58
Compound (SMILES): CC(C)n1ccc(S(=O)(=O)NC(=O)Nc2c3c(cc4c2CCC4)CCC3)n1
InChIKey: MTOUOUSKXWSTAX-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Antagonist activity against NLRP3 in PMA-primed human THP-1 cells assessed as inhibition of gramicidin-induced IL-1beta release measured after 1 hr incubation by HTRF analysis
Measurement: IC50 = 1740 nM (pChEMBL 5.760000228881836)
Descriptors: MW 388.49, ALogP 2.95, HBA 5, HBD 2, PSA 93.09, QED 0.84
Compound (SMILES): COc1ccc(-c2c(-c3ccc(C#N)c(F)c3)nc(N3CCC(N)CC3)n(C)c2=O)cc1F.O=S(=O)(O)c1ccccc1
InChIKey: AWZCBGWZNHQCIZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells by patch clamp assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 451.48, ALogP 3.2, HBA 7, HBD 1, PSA 97.17, QED 0.65
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)(F)F
InChIKey: WDHOIABIERMLGY-CMJOXMDJSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 476.52, ALogP 4.31, HBA 5, HBD 2, PSA 60.08, QED 0.5
Compound (SMILES): COc1ccc(F)cc1C(=O)NCc1ccc(-c2nn([C@@H](C)C(F)(F)F)c(N)c2C(N)=O)cc1
InChIKey: FWZAWAUZXYCBKZ-NSHDSACASA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of wild type BTK in human CLL cells assessed as
Measurement: IC50 = 3.68 nM (pChEMBL 8.430000305175781)
Descriptors: MW 479.43, ALogP 3.43, HBA 6, HBD 3, PSA 125.26, QED 0.45
Compound (SMILES): C[C@@H]1OCC2(CCN(c3cnc(Sc4ccnc(N)c4Cl)c(N)n3)CC2)[C@@H]1N
InChIKey: UCJZOKGUEJUNIO-IINYFYTJSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of human SHP2 in human KYSE-520 cells assessed as reduction in ERK1/2 phosphorylation by fluorescence based assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 421.96, ALogP 2.17, HBA 9, HBD 3, PSA 129.2, QED 0.68
Compound (SMILES): Cc1ccc2nc(-c3ccc([N+](=O)[O-])cc3)oc2c1
InChIKey: XIKITIBPZYVXQL-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 catalytic domain (Tyr104 to Asn274 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 254.25, ALogP 3.71, HBA 4, HBD 0, PSA 69.17, QED 0.52
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC[C@@H]2CF)c(Cl)c1Cl)C(F)(F)F
InChIKey: JOBFZMGKEFCXAH-NWDGAFQWSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Binding affinity to human RORbeta by thermofluor assay
Measurement: Kd = 74000 nM (pChEMBL 4.130000114440918)
Descriptors: MW 649.52, ALogP 4.42, HBA 7, HBD 3, PSA 128.7, QED 0.35
Compound (SMILES): Nc1nc(N2CCC(N3Cc4ccncc4OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n[nH]1
InChIKey: OCSUHJZRJCUEHY-IBGZPJMESA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Human AMCase Activity Assay: An enzymatic assay with recombinant human AMCase was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-Methylumbelliferyl B-D-N,N′-diacetylchitobioside hydrate was used as a substrate for the enzyme. Upon hydrolysis by AMCase, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of hAMCase recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Buffer (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 439.95, ALogP 2.91, HBA 7, HBD 2, PSA 96.19, QED 0.64
Compound (SMILES): CN1CCN(CCOc2ccc(-c3cn4c(=O)n(-c5ccccc5)nc4c(N)n3)cc2)CC1
InChIKey: QFMDFBRPJRPXLV-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity against human A2B adenosine receptor expressed in CHO cells assessed as inhibition of NECA-induced adenylyl cylase activity
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 445.53, ALogP 1.76, HBA 9, HBD 1, PSA 93.92, QED 0.48
Compound (SMILES): C[Si]1(C)C[C@@H]2C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](Cc3ccccc3)C(=O)N2C1.O=C(O)C(F)(F)F
InChIKey: PGOCUMIEUZYJSO-GSWLFNFOSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of latency-associated peptide/TGF-beta binding to recombinant human integrin alphaV (Phe31 to Val992 residues) beta6 (Gly22 to Asn707 residues) expressed in CHO cells by ELISA based solid phase binding assay
Measurement: IC50 = 178 nM (pChEMBL 6.75)
Descriptors: MW 616.75