lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)c1cc2c(c(O)c1O)[C@@]1(c3nnc([C@H](C)NCO)o3)CCCC(C)(C)[C@@H]1CC2
InChIKey: RBPXDDKOZBAQRF-ZSCHSRKISA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged GGPPS expressed in Escherichia coli BL21 (DE3) using FPP and [14C] IPP as substrate preincubated for 15 mins with FPP followed by [14C] IPP addition and further incubated for 20 mins by scintillation counting method
Measurement: IC50 = 43200 nM (pChEMBL 4.369999885559082)
Descriptors: MW 429.56, ALogP 4.26, HBA 7, HBD 4, PSA 111.64, QED 0.41
Compound (SMILES): NC1(C(=O)O)CCCC1CCCB(O)O
InChIKey: HBEGNHDSKKYWSU-UHFFFAOYSA-N
Target: Arginase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05089
Assay: Inhibition of human recombinant arginase 1 expressed in Escherichia coli BL21 (DE3) assessed as reduction in urea production using L-arginine as substrate in presence of MnSO4 incubated for 60 mins by o-phthaldialdehyde/N-(1-naphthyl)ethylene-diamine dihydrochloride reagent based colorimetric assay
Measurement: IC50 = 48000 nM (pChEMBL 4.320000171661377)
Descriptors: MW 215.06
Compound (SMILES): COC(=O)N[C@H](NC(=O)N1CCOC[C@H]1c1nc2ccc(-c3ccc4cc(-c5cnc([C@@H]6COCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]5)ccc4c3)cc2[nH]1)C(C)C
InChIKey: XSLTUSLFYQABCH-ZYADHFCISA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 1a replicons NS5A infected in human Huh7 cells by luciferase reporter gene assay
Measurement: EC50 = 2.85 nM (pChEMBL 8.539999961853027)
Descriptors: MW 809.92, ALogP 5.47, HBA 10, HBD 5, PSA 205.13, QED 0.11
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)C(CSC(C)=O)CSC(C)=O
InChIKey: ISBDGKGTFDHHAX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Kinase assay: KINOMEscan is based on a competition binding assay that quantitatively measures the ability of a compound to compete with an immobilized, active-site directed ligand. The assay is performed by combining three components: DNA-tagged kinase; immobilized ligand; and a test compound. The ability of the test compound to compete with the immobilized ligand is measured via quantitative PCR of the DNA tag.For most assays, kinase-tagged T7 phage strains were prepared in an E. coli host derived from the BL21 strain. E. coli were grown to log-phase and infected with T7 phage and incubated with shaking at 32° C. until lysis. The lysates were centrifuged and filtered to remove cell debris. The remaining kinases were produced in HEK-293 cells and subsequently tagged with DNA for qPCR detection. Streptavidin-coated magnetic beads were treated with biotinylated small molecule ligands for 30 minutes at room temperature to generate affinity resins for kinase assays. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce nonspecific binding. Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). All reactions were performed in polystyrene 96-well plates in a final volume of 0.135 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 M non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 575.09, ALogP 6.16, HBA 9, HBD 2, PSA 121.18, QED 0.29
Compound (SMILES): COc1ccc(C(O)c2sc3nnc(C)c(C)c3c2N)cc1
InChIKey: UTSTZNOQLUFBQE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation activity at rat M4 receptor expressed in CHO cells co-expressing Gqi5 protein assessed as potentiation of EC20 acetyl choline-induced response by calcium mobilization assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 315.4, ALogP 2.98, HBA 6, HBD 2, PSA 81.26, QED 0.78
Compound (SMILES): CS(=O)(=O)C(c1nnc(CC2SC(=O)NC2=O)o1)c1nc2ccc(-c3ccccc3)cc2s1
InChIKey: FOURCEVMOOIJLT-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition of endothelial lipase in human HT1080 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins in presence of human serum by fluorescence assay
Measurement: IC50 = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 500.58, ALogP 3.37, HBA 10, HBD 1, PSA 132.12, QED 0.42
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2cc(OCC)cc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c2)c1)[C@@H](CC)N(O)C=O
InChIKey: BBKUXAVSLNIJJY-KWXIBIRDSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 642.71, ALogP 3.04, HBA 8, HBD 6, PSA 211.67, QED 0.04
Compound (SMILES): CC(=O)Nc1ncc(CN2CCC3(CCN(c4cc(C)nc(C)c4)C3)C2)s1
InChIKey: IXQVLWJKRQGPGL-UHFFFAOYSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition of recombinant human full length OGA using FM-GlcNAc as substrate preincubated for 60 mins followed by substrate addition and measured after 6 hrs by fluorescence assay
Measurement: IC50 = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 385.54, ALogP 3.22, HBA 6, HBD 1, PSA 61.36, QED 0.88
Compound (SMILES): CN1CC2CN(c3cc(C(F)(F)F)ccc3CN3CCN(C(=O)OC(C(F)(F)F)C(F)(F)F)CC3)CC2C1
InChIKey: GLGGKOKQRXGJIL-UHFFFAOYSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 562.48, ALogP 4.45, HBA 5, HBD 0, PSA 39.26, QED 0.51
Compound (SMILES): Nc1nc(-c2ccc(CO)cc2)nc2sc(-c3ccco3)nc12
InChIKey: RVEWYNPAAMHLSW-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]NECA from human adenosine A2A receptor expressed in CHO cells after 3 hrs by scintillation counting method
Measurement: Ki = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 324.37, ALogP 3.09, HBA 7, HBD 2, PSA 98.06, QED 0.6
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CCCSC[C@@H](C(=O)NCC(=O)N[C@@H](CSCC(=O)NCCOCCOCCOCCNC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: FPBNLTNKIOCIEZ-XHVWRCNQSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Agonist activity at recombinant human Gi/Go-coupled OTR expressed in CHOK1 cells assessed as induction of beta-arrestin recruitment measured after 90 mins in absence of 10% FBS by pathhunter assay
Measurement: EC50 = 3.41 nM (pChEMBL 8.470000267028809)
Descriptors: MW 1452.8
Compound (SMILES): Cc1ccc2nc(CSc3nnc(NC(=O)Nc4ccccc4C(F)(F)F)s3)cc(=O)n2c1
InChIKey: VZJJEUDTFJIVFB-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of His-tagged recombinant human ATP-activated TRKA kinase domain (441 to 796 residues) expressed in baculovirus expression system preincubated with enzyme/ATP mixture for 20 mins followed by TK substrate-biotin addition followed by further incubation for 15 mins in presence of ATP by HTRF assay
Measurement: IC50 = 67.6 nM (pChEMBL 7.170000076293945)
Descriptors: MW 492.51, ALogP 4.81, HBA 8, HBD 2, PSA 101.28, QED 0.31
Compound (SMILES): CCn1cnc(NC(=O)c2ccc3nc(C(O)(c4ccccc4)c4ccccc4)n(CC)c3c2)c1
InChIKey: SMVWNGLTQBHKAF-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of ACSS2 in human HCT116 cells pre-incubated for 2 hrs before [1,2-14C] sodium acetate addition and measured after 3 hrs by [14C]-Acetate uptake assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 465.56, ALogP 4.81, HBA 6, HBD 2, PSA 84.97, QED 0.36
Compound (SMILES): CCn1ncc(-c2nc3c(NC4CC(=O)N(CC(C)C)C4)ncnc3n2C)c1C
InChIKey: CBJZJWGYMFLHTH-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged recombinant full length human p110delta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 396.5, ALogP 2.22, HBA 8, HBD 1, PSA 93.76, QED 0.69
Compound (SMILES): Cc1c(N2CCN(C)CC2)ccc2c3c(c(=O)oc12)CN(C(=O)c1ccc(NS(C)(=O)=O)c(Cl)c1)CC3
InChIKey: DHJUEJALVPLBJH-UHFFFAOYSA-N
Target: C-1-tetrahydrofolate synthase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: P11586
Assay: Inhibition of recombinant MTHFD1 (unknown origin) using THF as substrate incubated for 30 mins in presence of NAD
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 545.06, ALogP 3.08, HBA 7, HBD 1, PSA 103.17, QED 0.5
Compound (SMILES): CCOc1nc2ccc(C#C[C@](C)(O)c3ncc(C)o3)cc2n1-c1ccnc(N)n1
InChIKey: HZWIAHGTTPPVAC-NRFANRHFSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin) using ATP as substrate by transcreener ADP assay based fluorescence correlation spectroscopic analysis
Measurement: Ki = 634 nM (pChEMBL 6.199999809265137)
Descriptors: MW 404.43, ALogP 2.35, HBA 9, HBD 2, PSA 125.11, QED 0.5
Compound (SMILES): Cc1c(C(=O)N2CCN(S(C)(=O)=O)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: GZTICBXICRNKCR-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 405.44, ALogP -0.77, HBA 8, HBD 1, PSA 125.67, QED 0.61
Compound (SMILES): O=S(=O)(NCc1ccccc1)c1ccccc1-c1nnc(S)n1/N=C/c1ccccc1
InChIKey: YAQBNVNYLHGFKP-HZHRSRAPSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX2 assessed as reduction in oxidized TMPD using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by colorimetric assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 449.56, ALogP 3.59, HBA 7, HBD 2, PSA 89.24, QED 0.33
Compound (SMILES): Brc1ccc(OCc2cc(OC[C@@H]3CCCN3)no2)cc1.Cl
InChIKey: TYHKXUCENBAAAI-YDALLXLXSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from rat brain sigma2 receptor by PDSP assay
Measurement: Ki = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 353.22, ALogP 3.15, HBA 5, HBD 1, PSA 56.52, QED 0.86
Compound (SMILES): CC(C)C[C@@H]1NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: GYEPIDGLKZAHSN-CVIYXSBDSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Inhibition of human vitronectin binding to human integrin alphavbeta5 receptor after 1 hr by solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 805.93, ALogP -3.02, HBA 10, HBD 10, PSA 314.42, QED 0.06
Compound (SMILES): Cc1c(Cn2cc(C(=O)c3cncnc3N[C@@H]3C[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]3O)c3cc(F)ccc32)cccc1C(F)(F)F
InChIKey: ZCKFJAREHQZZOB-KTIWIZFTSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13564
Assay: Inhibition of NAE (unknown origin) using GST-tagged Ubc12 and Flag-tagged Nedd8 measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 637.61, ALogP 2.92, HBA 10, HBD 4, PSA 169.66, QED 0.16
Compound (SMILES): O=C(NCc1cccnc1)C1CCN(Cc2ccccc2)CC1
InChIKey: LCCWWQQATKKNKK-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylthiocholine iodide as substrate by Ellman's method
Measurement: IC50 = 58890 nM (pChEMBL 4.230000019073486)
Descriptors: MW 309.41, ALogP 2.61, HBA 3, HBD 1, PSA 45.23, QED 0.92
Compound (SMILES): Cl.Cn1c(SCCCNCC2CC2c2cc(F)ccc2OCCF)nnc1-c1ccccc1
InChIKey: JFPQLMHSAZGNCS-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]-SCH23390 from recombinant human D1 receptor transiently expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 368.7 nM (pChEMBL 6.429999828338623)
Descriptors: MW 458.58, ALogP 4.85, HBA 6, HBD 1, PSA 51.97, QED 0.31
Compound (SMILES): O=C(CF)CNC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(F)c2ccccc12
InChIKey: COZDKQNJDUPHIX-NRFANRHFSA-N
Target: Cysteine protease ATG4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4P1
Assay: Inhibition of ATG4B (unknown origin) expressed in HEK293T cells coexpressing HTRA4 and Actin-LC3B-dNGLuc after 24 hrs by luciferase release assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 410.42, ALogP 2.97, HBA 3, HBD 2, PSA 75.27, QED 0.6
Compound (SMILES): Cl.O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2cccc(Cl)c2Cl)CC1
InChIKey: RGPRJSBINXTKTD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1AR expressed in HEK293 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 482.46, ALogP 6.49, HBA 3, HBD 0, PSA 26.79, QED 0.34
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cccc(C(=O)NC4(c5ccccn5)CC4)c3)cc12
InChIKey: JZKYEGPUISOCLD-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1a NS5B RNA dependent RNA polymerase infected in human HuH7 replicon cells after 3 days by luciferase reporter gene assay
Measurement: EC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 505.55, ALogP 6.08, HBA 4, HBD 2, PSA 84.23, QED 0.29
Compound (SMILES): O=C(CCc1csc(Cc2ccccc2)n1)NO
InChIKey: KSQTWVRHOOJJHN-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using fluorogenic HDAC substrate 3 pre-incubated for 30 mins followed by HDAC developer addition and measured after 15 mins by fluorogenic assay
Measurement: IC50 = 19101 nM (pChEMBL 4.71999979019165)
Descriptors: MW 262.33, ALogP 2.17, HBA 4, HBD 2, PSA 62.22, QED 0.64
Compound (SMILES): COCCNC(=O)c1cc(C(=O)N[C@@H](Cc2ccccc2)[C@H](O)CNC(C)(C)c2cccc(OC)c2)cc(N2CCCCC2)c1
InChIKey: LENHFBMFSSMDGV-JHOUSYSJSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human cathepsin D using DABCYL-Glu-Arg-Nle-Phe-Leu-Ser-Phe-Pro-EDANS as substrate preincubated for 30 mins followed by substrate addition and measured every min for 8 to 15 mins by FRET assay
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 616.8, ALogP 4.29, HBA 7, HBD 4, PSA 112.16, QED 0.19
Compound (SMILES): CCCCCCC(Sc1nc2ccc(NCc3cc(Cl)cc(Cl)c3)cc2s1)C(=O)O
InChIKey: NULRHNFUZMPYBN-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Partial agonist activity at Gal4-fused PPARgamma LBD (unknown origin) expressed in HEK293T cells after 14 to 16 hrs by dual-Glo luciferase assay
Measurement: EC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 483.49, ALogP 7.73, HBA 5, HBD 2, PSA 62.22, QED 0.22
Compound (SMILES): CNCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)O)[C@@H](C)OC)C(C)C
InChIKey: GQCJLKQQKSHGDL-GMIULXCTSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human AT1R expressed in HEK293 cells incubated for 30 mins by IP1 accumulation assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 928.06, ALogP -2.92, HBA 13, HBD 13, PSA 364.28, QED 0.03
Compound (SMILES): C[C@@H]1c2nnc(-c3ccc4ccccc4n3)n2CCN1C(=O)c1ccc(F)cc1
InChIKey: YKPRLSIENHBXFV-CQSZACIVSA-N
Target: Neuromedin-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P29371
Assay: 3H-SB222200 Binding Competition Assay with Human NK-3 Receptor: The ability of the compounds of the invention to inhibit the binding of the NK-3 receptor selective antagonist SB222200 was assessed by an in vitro radioligand binding assay. Membranes were prepared from Chinese hamster ovary recombinant cells which express the human NK3 receptor. The membranes were incubated with 5 nM 3H-SB222200_(ARC) in a HEPES 25 mM/NaCl 0.1M/CaCl2 1 mM/MgCl2 5 Mm/BSA 0.5%/Saponin 10 μg/ml buffer at pH 7.4 and various concentrations of the compounds of the invention. The amount of tritiated SB222200 bound to the receptor was determined after filtration by the quantification of membrane associated radioactivity using the TopCount-NXT reader (Packard). Competition curves were obtained for compounds of the invention and the concentrations of compounds which displaced 50% of bound radioligand (IC50) were determined and then apparent inhibition constant Ki values were calculated by the following equation: Ki=IC50/(1+[L]/KD) where [L] is the concentration of free radioligand and KD is its dissociation constant at the receptor, derived from saturation binding experiments (Cheng and Prusoff, 1973).
Measurement: Ki < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 387.42, ALogP 3.85, HBA 5, HBD 0, PSA 63.91, QED 0.52
Compound (SMILES): Cn1cc(Cl)c2c(Oc3c(F)cc(Nc4cc(Cl)nc(N)n4)cc3F)ccnc21
InChIKey: LQNZFNWBROGUOM-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: GPCRScan assay: inhibition of KOR
Measurement: Ki = 390.57 nM (pChEMBL 6.409999847412109)
Descriptors: MW 437.24, ALogP 5.07, HBA 7, HBD 2, PSA 90.88, QED 0.43
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2ccc(Cl)c(F)c2)n(C)c1=O
InChIKey: UQRBIGXUXYIMBJ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX2 from recombinant human adenosine A2a receptor expressed in HEK293 cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 377.81, ALogP 1.64, HBA 7, HBD 0, PSA 65.06, QED 0.68
Compound (SMILES): FC(F)(F)c1cc(Oc2nccn3ccnc23)ccc1-c1cccc2nccn12
InChIKey: NHJDTTMQXSWJTJ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at recombinant human D1 receptor expressed in HEK29T cells assessed as induction of stimulatory G-protein-mediated cAMP accumulation measured after 15 mins by Glosensor-based FLIPR assay
Measurement: EC50 = 181.97 nM (pChEMBL 6.739999771118164)
Descriptors: MW 395.34, ALogP 4.86, HBA 6, HBD 0, PSA 56.72, QED 0.44
Compound (SMILES): COc1cc(NC(=O)NC2CCC(=O)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NC(C)=O)n1
InChIKey: SNYQSPGQFDKITH-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human N-terminal GST-tagged ALK (1058 to 1620 residues) cytoplasmic domain L1196M mutant expressed in baculovirus expression system using srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 538.01, ALogP 5.22, HBA 8, HBD 5, PSA 146.37, QED 0.26
Compound (SMILES): CCOC(=O)Cc1ccc(-c2cnc(N)c(-c3ccc4c(c3)CCNC4=O)n2)cc1
InChIKey: PSQPYQSESWLEAM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of MST1 (unknown origin) pre-incubated for 10 mins before addition of 50 uM ATP and Z'-Lyte S/T Pep7 and further incubated for 1 hr
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 402.45, ALogP 2.78, HBA 6, HBD 2, PSA 107.2, QED 0.64
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)/C(Cc2ccccc2)=N/O)cc1
InChIKey: DPFBQWMZIHXZPO-XDJHFCHBSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 expressed in Escherichia coli GOLD BL21 (DE3) by stopped-flow CO2 hydration assay
Measurement: Ki = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 347.4, ALogP 1.02, HBA 5, HBD 3, PSA 121.85, QED 0.41
Compound (SMILES): Cc1c(CC(=O)O)c(=O)oc2c(C)c(OCc3cccc(Br)c3)ccc12
InChIKey: STHJGDCGBDTTHP-UHFFFAOYSA-N
Target: Chloride anion exchanger (SINGLE PROTEIN), Homo sapiens
UniProt: P40879
Assay: Inhibition of DRA (unknown origin) expressed in FRT cells coexpressing iodide-sensitive YFP assessed as reduction in iodine flux measured after 10 mins by fluorescence based assay
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 417.26, ALogP 4.38, HBA 4, HBD 1, PSA 76.74, QED 0.62
Compound (SMILES): CCn1cncc1-c1c[nH]c2ccc(C(=O)OC)cc12
InChIKey: JBKOPAJOLXKSND-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from recombinant human 5HT6 receptor expressed in HEK293 cells measured after 1 hr by microbeta counting method
Measurement: Ki = 6062 nM (pChEMBL 5.21999979019165)
Descriptors: MW 269.3, ALogP 2.84, HBA 4, HBD 1, PSA 59.91, QED 0.74
Compound (SMILES): NC(=O)c1cccc([C@H]2C[C@H]3CC[C@@H](C2)N3CCN(CC2CCCCC2)C(=O)C(F)(F)F)c1
InChIKey: DTZRKUZWZUCVAL-KOUNCHBCSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DPN from recombinant human mu opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay
Measurement: Ki = 0.7943 nM (pChEMBL 9.100000381469727)
Descriptors: MW 465.56, ALogP 4.47, HBA 3, HBD 1, PSA 66.64, QED 0.65
Compound (SMILES): O=C1COc2ccc(-c3cnc(Cl)c(NS(=O)(=O)c4ccc(F)cc4)c3)cc2N1c1ccc(F)cc1
InChIKey: HDSMUPUIAQXKLB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human N-terminal FLAG-tagged mTOR (1362 to end residues) using Ulight-4E-BP1 as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 17.9 nM (pChEMBL 7.75)
Descriptors: MW 527.94, ALogP 5.54, HBA 5, HBD 1, PSA 88.6, QED 0.34
Compound (SMILES): CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCCN)C(=O)NCCCCC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: IKZQUGCXKOIVLF-CZZKCPPWSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from human muscarinic M3 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 739.92, ALogP 3.98, HBA 8, HBD 6, PSA 186.2, QED 0.11
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C3CCc4c(B(O)O)cccc43)S(C)(=O)=O)c(C3CC3)cc12
InChIKey: AJDOHLSGOKTGAK-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1b NS5B RNA dependent RNA polymerase C316N mutant infected in human HuH7 Lunet replicon cells assessed as reduction in viral replication after 48 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 562.43
Compound (SMILES): C[C@@H](Nc1nc2c(cnn2C2CCCC2)c(=O)[nH]1)C(=O)N1CCOCC1
InChIKey: GESQMVSOZXARLD-LLVKDONJSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition of recombinant human PDE9A2 catalytic domain (181 to 506 residues) expressed in Escherichia coli BL21 using 3H-cGMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 360.42, ALogP 0.89, HBA 7, HBD 2, PSA 105.14, QED 0.84
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](C)NC(=O)CN2CCOCC2)C(=O)N[C@@H](C[C@@H]2CCCC3CCCCC32)C(=O)[C@@]2(C)CO2)cc1
InChIKey: IJXUVRJYZJRYCL-JBHDBRJSSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S constitutive proteasome beta 5 chymotrypsin-like activity in human Raji cell lysates after 1 hr by competitive ABPP assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 640.82, ALogP 2.4, HBA 8, HBD 3, PSA 138.6, QED 0.26
Compound (SMILES): Cc1cc(-c2nc(C)c3c(C)nc4scnc4n23)ccn1
InChIKey: LXBIRDIHQJGZAB-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of recombinant human N-terminal His-tagged PDE10A2 expressed in HEK293 cells using cAMP as substrate measured after 60 mins
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 295.37, ALogP 3.33, HBA 6, HBD 0, PSA 55.97, QED 0.54
Compound (SMILES): CNCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)c(Cl)c1)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)O)[C@@H](C)OC)C(C)C
InChIKey: DCYNUSJJYCIKCX-ZLNBOQQZSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 962.51, ALogP -2.27, HBA 13, HBD 13, PSA 364.28, QED 0.03
Compound (SMILES): NC(=O)c1cccc2c1O/C(=C\c1cccc(C(=O)NCCc3nc4ccccc4[nH]3)c1)C2=O
InChIKey: YUGPMHBCTWCTLL-STZFKDTASA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 452.47, ALogP 3.25, HBA 5, HBD 3, PSA 127.17, QED 0.39
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2cccc(NS(C)(=O)=O)c2)c1
InChIKey: OMBBXCDTSGWLCU-OAQYLSRUSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 504.61, ALogP 2.57, HBA 6, HBD 4, PSA 144.91, QED 0.1
Compound (SMILES): O=C1Nc2cccc(n2)-c2nncn2CCCCOc2ccc(N3CC4(COC4)C3)cc21
InChIKey: PRUJNFMDYCFTPX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: TR-FRET Assay: Table 1: Briefly, 20 μL aliquots of a 1.5× stock of ASK1, STK Substrate 3 and Assay Buffer were distributed in the wells of a white 384 well Optiplate, prior to addition of 0.3 μL of a 100× compound stock in DMSO, or DMSO alone in Blank and 100% Activity Controls. After a 10 minute pre-incubation, ASK1 protein kinase activity was initiated by addition of 10 μL of 300 μM ATP. After 5 hours, the kinase activity was quenched by addition of 30 μL of CisBio Kit 62ST3PEJ components: 0.5 μM of Streptavidin XL665; and 100×STK Antibody-Eu Cryptate; in Detection Buffer containing sufficient EDTA to chelate Mg2+ in the assay buffer. The plates were read after 65 minutes in an Envision Plate reader, with the following components and settings: Top Mirror, Lance Delfia Dual (662); UV Ex Filter, 320 nm (111); Emission Filter for donor, 615 nm (203); Emission Filter for Acceptor; 665 nM (205); and 100 usec delay, with 665/615 ratio output.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 432.48, ALogP 2.6, HBA 8, HBD 1, PSA 94.4, QED 0.63
Compound (SMILES): O=C(N[C@@H](Cc1ccccc1)C(=O)N[C@H](/C=C/c1ccccn1)Cc1ccccc1)OCc1ccccc1
InChIKey: JSIMZLXUNMBVPN-OSEFVOAZSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human Cathepsin L assessed as rate constant for enzyme-inhibitor-substrate complex using Cbz-Phe-Arg-AMC as substrate measured up to 40 mins by fluorescence assay
Measurement: Ki = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 505.62, ALogP 5.36, HBA 4, HBD 2, PSA 80.32, QED 0.29
Compound (SMILES): COC[C@H](Nc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl)c1ccccc1
InChIKey: HAHBYABDAIXZLF-INIZCTEOSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 25662 nM (pChEMBL 4.590000152587891)
Descriptors: MW 441.94, ALogP 4.54, HBA 6, HBD 2, PSA 80.32, QED 0.54
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: JQENMIHVVBTWDQ-ZRFHBHASSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Agonist activity at human amylin receptor expressed in BHK570 cells co-expressing RAMP3 assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.092 nM (pChEMBL 10.039999961853027)
Descriptors: MW 3838.29
Compound (SMILES): CN1CCN(Cc2ccc3nc4n(c(=O)c3c2)-c2ccccc2C4=O)CC1
InChIKey: SWZUEZDIXYKAGY-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO expressed in Escherichia coli BL21 (DE3) assessed as reduction in conversion of L-tryptophan to N-formyl kynurenine using L-tryptophan as substrate after 30 mins by methylene blue assay
Measurement: IC50 = 2410 nM (pChEMBL 5.619999885559082)
Descriptors: MW 360.42, ALogP 1.68, HBA 6, HBD 0, PSA 58.44, QED 0.54
Compound (SMILES): O=c1cc(-c2cc(Cl)cc(Cl)c2)oc2c1ccc1ccccc12
InChIKey: MUXNCWKFJVXJGD-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human recombinant CYP1A2 using 7-ethoxyresorufin as substrate in presence of glucose-6-phosphate, glucose-6-phosphate dehydrogenase and NADPH-generating system incubated for 50 mins by fluorometry
Measurement: IC50 = 156.9 nM (pChEMBL 6.800000190734863)
Descriptors: MW 341.19, ALogP 5.92, HBA 2, HBD 0, PSA 30.21, QED 0.4
Compound (SMILES): COc1ccc(CCN(C(=O)OC2C[C@H]3CC[C@H](C2)N3C)c2ccccc2)cc1
InChIKey: WMGWWIZDKKAUOR-NHCUHLMSSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 394.52, ALogP 4.51, HBA 4, HBD 0, PSA 42.01, QED 0.72
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4cc5c(cc4OC)C(=O)N(C)C5)c3)cnnc21
InChIKey: XPSAGIQSESMIJK-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18507
Assay: Displacement of [3H]-flumazenil from human GABAA alpha5beta2gamma2 receptor expressed in HEK293 cell membranes measured after 2 hrs by liquid scintillation counting method
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 417.44, ALogP 3.91, HBA 6, HBD 0, PSA 73.14, QED 0.5
Compound (SMILES): CCc1ccc(NC(=O)Nc2nnc(SCc3cc(=O)n4cc(C)ccc4n3)s2)cc1
InChIKey: QRUDZSUVRFKFHU-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of His-tagged recombinant human ATP-activated TRKA kinase domain (441 to 796 residues) expressed in baculovirus expression system preincubated with enzyme/ATP mixture for 20 mins followed by TK substrate-biotin addition followed by further incubation for 15 mins in presence of ATP by HTRF assay
Measurement: IC50 = 18.8 nM (pChEMBL 7.730000019073486)
Descriptors: MW 452.57, ALogP 4.35, HBA 8, HBD 2, PSA 101.28, QED 0.33
Compound (SMILES): COC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)c1cnc(C)s1)C(=O)N[C@H](/C=C/S(C)(=O)=O)Cc1ccc(CN)cc1
InChIKey: LMXBCHXXOUDFDR-KVISLYRKSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of 20S constitutive proteasome beta 2 trypsin-like activity in human Raji cell lysates after 1 hr by competitive ABPP assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 593.77, ALogP 1.47, HBA 9, HBD 4, PSA 169.58, QED 0.24
Compound (SMILES): C=CCc1ccccc1OCC(O)CNCCOCCOCCOCCOCCNC(=O)CS(=O)(=O)O
InChIKey: QKBNVHOVHIVAOY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Antagonist activity at human 5HT1A expressed in BAF3 cells by fluorimetry analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 548.66, ALogP -0.19, HBA 10, HBD 4, PSA 161.88, QED 0.08
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(-c3cn(C)c4cccnc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: SLWGAMHEUFJZOW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR (696-end residues) expressed in baculovirus expression system using Srctide as substrate by fluorescence assay
Measurement: IC50 = 63000 nM (pChEMBL 4.199999809265137)
Descriptors: MW 500.61, ALogP 3.9, HBA 9, HBD 2, PSA 100.44, QED 0.32
Compound (SMILES): CC(C)(C)OC(=O)Nc1cccc(-c2csc(NC(=O)CCCCCC(=O)Nc3ccccc3N)n2)c1
InChIKey: DIFQOQWBAQGDGD-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using (FAM)-labeled acetylated peptide as substrate measured after 17 hrs by fluorescence assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 523.66, ALogP 6.27, HBA 7, HBD 4, PSA 135.44, QED 0.18
Compound (SMILES): CCOc1cc2c(N[C@H](C)c3ccccc3)nc(C)nc2cn1
InChIKey: QNSLJMIHABCZLJ-GFCCVEGCSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR phosphorylation at Y 1173 residues in human HeLa cells preincubated for 30 mins followed by EGF-stimulation and measured after 2 mins by ELISA
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 308.39, ALogP 3.91, HBA 5, HBD 1, PSA 59.93, QED 0.77
Compound (SMILES): C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C[C@H]1CC[C@@H](C2CCCCC2)CC1)NC(=O)[C@H](Cc1ccccc1)N=[N+]=[N-])C(=O)[C@@]1(C)CO1
InChIKey: PLWFGVRFZQSLKE-QVMCWBLBSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of catalytic activity of constitutive proteasome 20s subunit beta2 in human Raji cells incubated for 1 hr by BODIPY(FL)-LU-112 probe based competitive activity based protein profiling assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 684.88, ALogP 5.76, HBA 6, HBD 3, PSA 165.66, QED 0.09
Compound (SMILES): CNCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)O)C(C)C
InChIKey: USRSUENXGCNYPN-BKKYOMMVSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 969.12, ALogP -3.69, HBA 13, HBD 16, PSA 416.95, QED 0.02
Compound (SMILES): CC(=O)NC1=NN(c2ccc(Cl)c(Cl)c2)C[C@@H]1C
InChIKey: QTCFKQLUDHRFHP-ZETCQYMHSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Induction of human c-ABL phosphorylation at Y245/Y412 residues in bacmam-induced HEK-MSR2 cell lysates by in-cell Western blot analysis
Measurement: EC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 286.16, ALogP 2.9, HBA 3, HBD 1, PSA 44.7, QED 0.86
Compound (SMILES): Cc1ccc(NC(=O)Nc2nnc(SCc3cc(=O)n4cc(C)ccc4n3)s2)cc1
InChIKey: IWUIUIVWDUIYLY-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human full length TRKB expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 438.54, ALogP 4.1, HBA 8, HBD 2, PSA 101.28, QED 0.36
Compound (SMILES): COc1ccc2c(c1)N(Cc1ccc(C(=O)NO)cc1)c1ccccc1S2
InChIKey: WIQDMYVWEJAYQM-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of N-terminal GST-tagged and C-terminal His-tagged human HDAC4 (627 to 1084 residues) expressed in baculovirus infected Sf9 cells using Boc Lys(TFA)-AMC as substrate preincubated for 5 mins followed by substrate addition and further incubated for 30 mins by fluorogenic assay
Measurement: IC50 = 4760 nM (pChEMBL 5.320000171661377)
Descriptors: MW 378.45, ALogP 4.62, HBA 5, HBD 2, PSA 61.8, QED 0.51
Compound (SMILES): Cl.NCc1ccc(-n2c(-c3cccnc3N)nc3ccc(Cl)nc32)cc1
InChIKey: RWSBGTSJZNBCAC-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of full length unphosphorylated AKT3 (1 to 479 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-GRPRTSSFAEG as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins by Alphascreen assay
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 350.81, ALogP 3.18, HBA 6, HBD 2, PSA 95.64, QED 0.55
Compound (SMILES): Cc1cc(NC(=O)c2nn(C3CCN(C(=O)CC(C)(C)C#N)CC3)c3ccccc23)ccc1NC(=O)c1cnn2ccccc12
InChIKey: NQWJYXLLLYRYCZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ZAP-70 (SINGLE PROTEIN), Homo sapiens
UniProt: P43403
Assay: Effect on ZAP70 phosphorylation in human Jurkat cells pre-incubated for 30 mins followed by anti-CD3/CD28 stimulation measured after 10 mins
Measurement: EC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 602.7, ALogP 5.6, HBA 8, HBD 2, PSA 137.42, QED 0.25
Compound (SMILES): Cl.O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2ccc(C(F)(F)F)cc2)CC1
InChIKey: LRTRTHZPODDVLH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from human 5HT2AR expressed in CHO-K1 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 4354 nM (pChEMBL 5.360000133514404)
Descriptors: MW 481.56, ALogP 6.2, HBA 3, HBD 0, PSA 26.79, QED 0.36
Compound (SMILES): Cc1[nH]c2ccccc2c1CCNCc1ccc(/C=C/C(=O)NN(C)C)cc1.O=C(O)C(F)(F)F
InChIKey: ATKXLLSBCNUHPV-UEIGIMKUSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of recombinant human C-terminal GST/His-tagged HDAC3 (1 to 428 residues) co-expressed with human N-terminal GST-tagged NCOR2 (395 to 489 residues) in baculovirus infected Sf9 cells using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based micro plate reader analysis
Measurement: IC50 = 996.4 nM (pChEMBL 6)
Descriptors: MW 376.5, ALogP 3.41, HBA 3, HBD 3, PSA 60.16, QED 0.32
Compound (SMILES): Cc1noc(-c2ccc3nc(Nc4cc(CN5CCN(C(=O)OC(C)(C)C)CC5)ccn4)[nH]c3c2)n1
InChIKey: YFHGVXAURSKWLJ-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay
Measurement: IC50 = 914 nM (pChEMBL 6.039999961853027)
Descriptors: MW 490.57, ALogP 4.11, HBA 9, HBD 2, PSA 125.3, QED 0.42
Compound (SMILES): N#Cc1cccc(/C=C/C(=O)c2ccc(O)cc2)c1
InChIKey: IZCIYUNGVIXYJY-RUDMXATFSA-N
Target: Protein disulfide-isomerase (SINGLE PROTEIN), Homo sapiens
UniProt: P07237
Assay: Binding affinity to recombinant human N-terminal His-tagged PDI expressed in Escherichia coli BL21 (DE3) pLysS by isothermal titration calorimetry
Measurement: Kd = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 249.27, ALogP 3.16, HBA 3, HBD 1, PSA 61.09, QED 0.67
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NC(=O)OCc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: WAKHSGZPGZIDOP-BYQQZPSGSA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Inhibition of bovine thrombin using Tos-Gly-Pro-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 44000 nM (pChEMBL 4.360000133514404)
Descriptors: MW 801.95, ALogP 3.14, HBA 9, HBD 7, PSA 211.08, QED 0.11
Compound (SMILES): COC(=O)C1CCN(C(=O)c2ccc3nc(N)sc3c2)CC1
InChIKey: BVPOOCGZNPNMLK-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 319.39, ALogP 1.9, HBA 6, HBD 1, PSA 85.52, QED 0.85
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(OC)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC)C(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)O
InChIKey: XFVJLJRNFDPTHA-KQZSHLPZSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 940.12, ALogP -1.61, HBA 12, HBD 12, PSA 344.05, QED 0.03
Compound (SMILES): O=c1oc2ccccc2c2nn(S(=O)(=O)c3cccc([N+](=O)[O-])c3)cc12
InChIKey: ARKWDAHDRBYVBL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 9470 nM (pChEMBL 5.019999980926514)
Descriptors: MW 371.33, ALogP 2.29, HBA 8, HBD 0, PSA 125.31, QED 0.31
Compound (SMILES): Nc1nc(-c2ccccc2)nc2oc(-c3ccc(Cl)cc3)nc12
InChIKey: JPABNVCKPPKKBN-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Inhibition of rat striatal adenosine A2A receptor using [3H]MXS-2 measured after 30 mins by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 322.75, ALogP 4.19, HBA 5, HBD 1, PSA 77.83, QED 0.6
Compound (SMILES): COP(=O)(Nc1nn(-c2ccc(-c3cc4nccc(N)n4n3)cc2)cc1C(=O)O)c1ccc(C)cc1C
InChIKey: DXFOEMZXVYYLGH-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 3a (isolate NZL1) (HCV)
UniProt: Q81258
Assay: Inhibition of HCV genotype 3a NZL1 NS5B RNA dependent RNA polymerase
Measurement: IC50 = 334.6 nM (pChEMBL 6.46999979019165)
Descriptors: MW 517.49, ALogP 4.06, HBA 9, HBD 3, PSA 149.66, QED 0.27
Compound (SMILES): CCNC(=O)c1ccc(Nc2ncc3c(n2)N(C2CCCC2)[C@H](CC)C(=O)N3C)c(OCCO)c1
InChIKey: AILANCLYZDKELS-LJQANCHMSA-N
Target: Serine/threonine-protein kinase PLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4B4
Assay: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 406.9 nM (pChEMBL 6.389999866485596)
Descriptors: MW 482.59, ALogP 2.85, HBA 8, HBD 3, PSA 119.92, QED 0.5
Compound (SMILES): CCN1CC2(C1)CN(c1ccc(Nc3ncc(F)c(-c4cnn5c4[C@H](C)CCCC5)n3)nc1)C2
InChIKey: KMRYRPPWJDYHAL-QGZVFWFLSA-N
Target: CDK1/Cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of human recombinant full length GST-tagged CDK1/Cyclin A2 expressed in sf9 insect cells assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay
Measurement: Ki = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 462.58, ALogP 4.05, HBA 8, HBD 1, PSA 75, QED 0.61
Compound (SMILES): CCCCn1cc(C#N)c2c(-c3ccc(C(F)(F)F)cc3F)c3c(nc21)-c1ccccc1C3=O
InChIKey: YLCHGUGGACXUSP-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 RT V108I mutant using 17-mer DNA/Alexa Fluor 488 5'-end labeled DNA/Alexa Fluor 555-aha-dUTP as primer/template/substrate preincubated for 10 mins followed substarte addition measured after 30 mins by FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 463.43, ALogP 6.74, HBA 4, HBD 0, PSA 58.68, QED 0.28
Compound (SMILES): Cn1ccc(CNC(=O)c2csc(CCNCc3nc4ccccc4[nH]3)n2)n1
InChIKey: JRAMDZJYOVJHNL-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 395.49, ALogP 2.02, HBA 7, HBD 3, PSA 100.52, QED 0.4