lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)Nc1cc(Oc2ccc(NC(=O)Cc3ccccc3C(F)(F)F)cc2)ncn1
InChIKey: PFGNOYJAWUKCEW-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (unknown origin) preincubated for 60 mins followed by ATP addition and measured after 1 hr by ADP-Glo assay
Measurement: IC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 430.39, ALogP 4.43, HBA 5, HBD 2, PSA 93.21, QED 0.6
Compound (SMILES): O=c1[nH]n2c(=O)c3ccccc3nc2/c1=C/c1ccc(Br)cc1
InChIKey: QXOHUUUSFJPFTN-LCYFTJDESA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human COX-1 using acetylcholinesterase as substrate preincubated for 10 mins followed by substrate addition and measured after 30 sec by Ellman's method
Measurement: IC50 = 667.6 nM (pChEMBL 6.170000076293945)
Descriptors: MW 368.19, ALogP 1.85, HBA 4, HBD 1, PSA 67.23, QED 0.56
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCCCCCCN3CCC(OC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: QJBDLOQOXGQJTD-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M4 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 0.86 nM (pChEMBL 9.069999694824219)
Descriptors: MW 959.69, ALogP 13.82, HBA 5, HBD 2, PSA 76.92, QED 0.05
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 380.5 nM (pChEMBL 6.420000076293945)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NC[C@H](C)O
InChIKey: JZVPITOQWJPGIA-AWEZNQCLSA-N
Target: Bone morphogenetic protein receptor type-1A (SINGLE PROTEIN), Homo sapiens
UniProt: P36894
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using 7- ethoxyresorufin as substrate by LC-MS analysis
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C)cc4n3[C@H](C)c3ccc(C)cc3)cc2)cc1
InChIKey: IGPRUALXJOEVNF-XMMPIXPASA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at human GAL4-fused RORbeta LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 551.71, ALogP 6.9, HBA 5, HBD 1, PSA 81.06, QED 0.23
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged CECR2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): O=c1cc(CNC[C@@H](CO)Cc2ccsc2)[nH]c2ccc(F)cc12
InChIKey: IPKYJQPHFTVWOU-ZDUSSCGKSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at DRD4 expressed in human HEK293T cells assessed as cAMP accumulation incubated for 15 mins by split-luciferase-based biosensor analysis
Measurement: EC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 346.43, ALogP 2.67, HBA 4, HBD 3, PSA 65.12, QED 0.62
Compound (SMILES): Fc1ccc(CN2CCCC3(CCN(Cc4cc5ccc(Cl)cc5[nH]4)C3)C2)cc1F
InChIKey: JGUJMJSODMVSHV-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from D2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 429.94, ALogP 5.59, HBA 2, HBD 1, PSA 22.27, QED 0.58
Compound (SMILES): CS(=O)(=O)n1cc(COc2ccc3[nH]ccc3c2)c2cc(C(=O)OCc3cc(C#N)[nH]c(=O)c3)ccc21
InChIKey: ILUBXGLQULCOCH-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of human recombinant His6 tagged SENP1 catalytic domain expressed in Escherichia coli BL21 (DE3) using SUMO3-AMC as substrate incubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 516.54, ALogP 3.43, HBA 8, HBD 2, PSA 147.04, QED 0.32
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human CYP17A1 lyase activity
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CN1CC2CCC(C1=O)C2c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: NRBSFHSUWBAYCI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of recombinant human FGFR2 (400 to 821 residues) using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by HTRF assay
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 337.39, ALogP 1.34, HBA 6, HBD 1, PSA 92.59, QED 0.76
Compound (SMILES): CC1(C(=O)NS(=O)(=O)c2ccc(Cl)s2)CCN(c2nc3c(cc2C#N)C(=O)OC3)CC1
InChIKey: OTWUQESYHAXXJO-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 480.96, ALogP 2.45, HBA 9, HBD 1, PSA 129.46, QED 0.66
Compound (SMILES): CC(C)(C)c1ccc(-n2cnc3c(NC(=O)Cc4ccc(C(=O)O)cc4)cccc32)cc1
InChIKey: VEHCUCLQBZOABJ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Partial agonist activity at PPARgamma (unknown origin) by luciferase reporter gene assay
Measurement: EC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 427.5, ALogP 5.2, HBA 4, HBD 2, PSA 84.22, QED 0.46
Compound (SMILES): Cn1nc(-c2ccnc(N)n2)c2cc(C#CC(C)(C)O)ccc21
InChIKey: QOLYGQOTGMKVNP-UHFFFAOYSA-N
Target: Tau-tubulin kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TCY1
Assay: Inhibition of TTBK1 in human HEK293T cells incubated for 1 hrs by HTRF assay
Measurement: IC50 = 3603 nM (pChEMBL 5.440000057220459)
Descriptors: MW 307.36, ALogP 1.73, HBA 6, HBD 2, PSA 89.85, QED 0.67
Compound (SMILES): COc1cccc(/C=C/C(=O)NC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)c1
InChIKey: YQXARSVRDPJIEQ-NCSHYYEOSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 518.56, ALogP 4.43, HBA 4, HBD 2, PSA 84.5, QED 0.39
Compound (SMILES): CN(C)CCCNc1nc(NC2CCN(Cc3ccccc3)CC2)c2ccccc2n1
InChIKey: OVNOBEWSTIRPLG-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of human G9a expressed in HEK293 cells
Measurement: IC50 = 41300 nM (pChEMBL 4.380000114440918)
Descriptors: MW 418.59, ALogP 4.07, HBA 6, HBD 2, PSA 56.32, QED 0.51
Compound (SMILES): COc1cccc(F)c1-c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: CGNKHHSWDZOKRN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μl of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech). Ki values were determined.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 324.32, ALogP 2.57, HBA 6, HBD 1, PSA 81.51, QED 0.63
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(CCc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: MDHIFDZZMWLNKL-WZOWOQAZSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from kappa opioid receptor (unknown origin) assessed as inhibition constant incubated for 180 mins by competitive radioligand binding assay
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 456.59, ALogP 3.93, HBA 5, HBD 0, PSA 42.01, QED 0.52
Compound (SMILES): Cc1noc(-c2ccccc2)c1C#CCCCCCNC(=O)C(C)(C)S
InChIKey: AUWLDIJACPXDCN-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 370.52, ALogP 4.39, HBA 4, HBD 2, PSA 55.13, QED 0.43
Compound (SMILES): C[N+]1=C(/C=C/C=C/C=C2\N(CCCCCC(=O)NCCCCCCn3cc(CCCCN4CCC5(CC4)OCc4ccccc45)c4ccccc43)c3ccccc3C2(C)C)C(C)(C)c2ccccc21.[I-]
InChIKey: PYGSKQVDDNNOJX-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of (+)-pentazocine from sigma 1 receptor in human MCF7 cells assessed as dissociation constant in presence of 2-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl)-5-methoxy-3,4-dihydroisoquinolin-1(2H)-one incubated for 120 mins by saturation binding assay
Measurement: Kd = 19.32 nM (pChEMBL 7.710000038146973)
Descriptors: MW 925.34, ALogP 13.22, HBA 5, HBD 1, PSA 52.75, QED 0.05
Compound (SMILES): CCOC(=O)c1ncc2[nH]c3ccc(O)cc3c2c1COC
InChIKey: VJVAWKPXJCDEQG-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Binding affinity to human recombinant GABAA alpha5 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 300.31, ALogP 2.74, HBA 5, HBD 2, PSA 84.44, QED 0.72
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: OHTCHFUKVDURAI-MMDZAOKXSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Inhibition of human somatostatin receptor type 4
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 621.74, ALogP -0.09, HBA 7, HBD 8, PSA 221.53, QED 0.1
Compound (SMILES): CCOC(=O)c1sc2[nH]cn/c(=N\[C@H]3CCN(CC)C3)c2c1C
InChIKey: PLEPSJGJESSGQG-NSHDSACASA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at D4R (unknown origin) by camp reporter assay
Measurement: EC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 334.45, ALogP 2.1, HBA 6, HBD 1, PSA 70.58, QED 0.87
Compound (SMILES): CCc1c(C(=O)OC)nc(C)c2[nH]c3cc(OC)c(OC)cc3c12
InChIKey: NHJRHDMRNNOSLV-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Binding affinity to human recombinant GABAA alpha5 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 328.37, ALogP 3.39, HBA 5, HBD 1, PSA 73.44, QED 0.74
Compound (SMILES): Cc1c(Oc2ccc(CN)cc2F)ccc2c1B(O)OC2
InChIKey: ZCITXZXBLWIHHP-UHFFFAOYSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25098
Assay: Competition Binding Assay: Phosphorylation of activity of ROCK1 and ROCK2 and those of other kinases, AKT1, GRK2, PKA, PKCa and RSK1 were performed by Reaction Biology (Malvern, Pa.) (Ma et al., 2008) The ROCK1 enzyme tested was GST[1-535] ROCK1 (Genbank, NP 005397), ROCK2 was GST[5-554] (Genbank, 3327051). For the kinase assay buffers contained 20 mM Hepes, 10 mM MgCl2, 2 mM DTT, 0.02 mg/mL BSA, 0.1% DMSO, 1 mM EGTA, 0.02% Brij-35, 10 uM ATP, [γP33]-ATP and for ROCK enzymes, 20 uM long S6-peptide (32 amino acids length). Appropriate substrates and activation was applied for the other kinases tested. Each enzyme was preincubated with test compound for 15 min., and the reaction started by addition of ATP. Samples were incubated at room temperature for 120 min, and applied to P81 ion exchange paper and washed extensively; the radioactive content of the filters were determined.
Measurement: IC50 > 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 287.1
Compound (SMILES): C=CC(=O)N1CCC(n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)CC1
InChIKey: LNJMXIZSFNEQQF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) using Poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA analysis
Measurement: IC50 = 45.5 nM (pChEMBL 7.340000152587891)
Descriptors: MW 432.48, ALogP 3.08, HBA 7, HBD 2, PSA 123.04, QED 0.48
Compound (SMILES): Cc1ccccc1/N=N/c1cc(S(=O)(=O)O)c2ccccc2c1N
InChIKey: PIWJSAOBFMHEAW-FMQUCBEESA-N
Target: Sentrin-specific protease 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BQF6
Assay: Binding Assay: The binding of SPI-01 to the enzyme-substrate complex was investigated. CSP analysis was carried out on the 40 kDa complex of 15N-labeled full length precursor SUMO-1-GGHSTV (SUMO-1-FL) with unlabeled SENP1-C603S. An equimolar amount of SPI-01 was added to the 1:1 enzyme-substrate complex. The only observed CSP on the 15N-labeled precursor SUMO-1-FL was on the C-terminal residues S99 and V101 (FIGS. 7 and 8) (Song et al., PNAS 101:14373-8 (2004)). This result indicates that SPI-01 binds the enzyme-substrate complex at the interface between SENP and the C-terminal tails of precursor SUMO-FL. X-ray crystal structures showed that the C-terminal tail of precursor SUMO sits in and projects out of the catalytic tunnel of SENPs (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006)). In the case of SENP1, the region that interacts with the projected C-terminus is predominantly acidic and favors the C-terminus of SUMO-1, which is polar and positively charged, over that of SUMO-2, whose C-terminus is mainly hydrophobic (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006); and Shen et al., The Biochemical Journal 397:279-88 (2006)).
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 341.39, ALogP 4.39, HBA 5, HBD 2, PSA 105.11, QED 0.42
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)O[C@@H](C)C(C)(C)C)nc2C2(CCC(F)(F)CC2)C1(C)C
InChIKey: BQJACMMFLPJGCR-ZDUSSCGKSA-N
Target: Thyrotropin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P16473
Assay: Antagonist activity at human TSHR in HEK293 cells assessed as inhibition of bTSH-induced cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 438.52, ALogP 5.05, HBA 5, HBD 1, PSA 84.42, QED 0.7
Compound (SMILES): COC(=O)c1cc2c(cn1)[nH]c1ccc(NCc3ccccc3)cc12
InChIKey: JTYYMOMTGZSRFM-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Binding affinity to human recombinant GABAA alpha5 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 331.38, ALogP 4.11, HBA 4, HBD 2, PSA 67.01, QED 0.55
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC2(CCCN2Cc2ccc(F)c(F)c2)CC1
InChIKey: GYHRANYJOBNLHW-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH23390 from D1 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 447.96, ALogP 5, HBA 3, HBD 1, PSA 35.58, QED 0.7
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NCC(N)=O
InChIKey: YJKNBYBEJYUUHW-UHFFFAOYSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 11.7 nM (pChEMBL 7.929999828338623)
Descriptors: MW 441.89, ALogP 4.02, HBA 5, HBD 3, PSA 110, QED 0.51
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C(F)F)c2)n1
InChIKey: FRYSBKWOXOBQNB-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.45, ALogP 5.94, HBA 5, HBD 2, PSA 71.42, QED 0.34
Compound (SMILES): CC(C)Oc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: PPBVLCXRMSVIEI-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 3295.5 nM (pChEMBL 5.480000019073486)
Descriptors: MW 475.52, ALogP 3.03, HBA 8, HBD 1, PSA 142.07, QED 0.51
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: ATFCNLVUGGJYEX-DHRBKSIMSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant
Measurement: Ki = 25700 nM (pChEMBL 4.590000152587891)
Descriptors: MW 701.8, ALogP -0.95, HBA 10, HBD 6, PSA 252.68, QED 0.09
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4cccc(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: WAYSVGLDKMEZLH-KRWDZBQOSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin)
Measurement: IC50 = 1.42 nM (pChEMBL 8.850000381469727)
Descriptors: MW 512.97, ALogP 4.89, HBA 7, HBD 1, PSA 85.81, QED 0.45
Compound (SMILES): Cc1ncc(-c2nc3c(OC4(C)CC4)nc(Nc4cnn(C5CCN(C)CC5)c4)nc3cc2F)cn1
InChIKey: SZURKEABSBIIMJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) in presence of 600 uM ATP
Measurement: IC50 > 9000 nM (pChEMBL 5.046000003814697)
Descriptors: MW 489.56, ALogP 4.07, HBA 10, HBD 1, PSA 106.77, QED 0.43
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)[C@H](C)C2)c1
InChIKey: HVXGLCUTIOCPRK-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): CC(C)=CCN1CC[C@@]2(C)c3cc(O)ccc3C[C@H]1[C@H]2C
InChIKey: VOKSWYLNZZRQPF-MDASCCDHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [ 3H]-naloxone from rat brain membrane mu opioid receptor assessed as inhibition constant by radioligand binding assay
Measurement: Ki = 2370 nM (pChEMBL 5.619999885559082)
Descriptors: MW 285.43, ALogP 3.88, HBA 2, HBD 1, PSA 23.47, QED 0.83
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCNCCCCCCN3CCC(COC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: POIIDLJXIAHDFT-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 18 nM (pChEMBL 7.75)
Descriptors: MW 1002.76
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)[C@@H](C)n2nnnc2N1C
InChIKey: BVMAEXVWFIGNKQ-SECBINFHSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 2180 nM (pChEMBL 5.659999847412109)
Descriptors: MW 324.35, ALogP 1.47, HBA 7, HBD 2, PSA 104.62, QED 0.74
Compound (SMILES): COc1ccc(S(=O)(=O)N2CC(C)(C)C(CCSCc3ccccc3)C2C(=O)NO)cc1
InChIKey: APCLVQAXJIHPKK-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of human MMP13 using Dnp-Pro-Cha-Gly-Cys(Me)-His-Ala-Lys(Nma)-NH2 substrate by fluorimetric analysis
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 478.64, ALogP 3.54, HBA 6, HBD 2, PSA 95.94, QED 0.33
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCCCCCCN3CCC(COC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: JGOIBENTSQHWDQ-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 973.71, ALogP 14.06, HBA 5, HBD 2, PSA 76.92, QED 0.05
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(C(F)(F)F)c1
InChIKey: WECCALUSSAUMLJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate by LC-MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 404.37, ALogP 3.9, HBA 5, HBD 2, PSA 71.42, QED 0.51
Compound (SMILES): CC(=O)Nc1cc(Oc2ccc(NC(=O)Cc3ccccc3C(F)(F)F)cc2)ncn1
InChIKey: PFGNOYJAWUKCEW-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of PDGFRalpha (unknown origin) preincubated for 60 mins followed by ATP addition and measured after 1 hr by ADP-Glo assay
Measurement: IC50 = 83.8 nM (pChEMBL 7.079999923706055)
Descriptors: MW 430.39, ALogP 4.43, HBA 5, HBD 2, PSA 93.21, QED 0.6
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCCCCCCN3CCC(OC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: QJBDLOQOXGQJTD-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 959.69, ALogP 13.82, HBA 5, HBD 2, PSA 76.92, QED 0.05
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 2118 nM (pChEMBL 5.670000076293945)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NC[C@H](C)O
InChIKey: JZVPITOQWJPGIA-AWEZNQCLSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 32.5 nM (pChEMBL 7.489999771118164)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate by LC-MS analysis
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C)cc4n3[C@H](C)c3ccc(C)cc3)cc2)cc1
InChIKey: IGPRUALXJOEVNF-XMMPIXPASA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Inverse agonist activity at human GAL4-fused RORalpha LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 551.71, ALogP 6.9, HBA 5, HBD 1, PSA 81.06, QED 0.23
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged TAF1 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): Fc1ccc(CN2CCCC3(CCN(Cc4cc5ccc(Cl)cc5[nH]4)C3)C2)cc1F
InChIKey: JGUJMJSODMVSHV-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from D3 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 345 nM (pChEMBL 6.460000038146973)
Descriptors: MW 429.94, ALogP 5.59, HBA 2, HBD 1, PSA 22.27, QED 0.58
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human CYP17A1 hydroxylase activity
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CN1CC2CCC(C1=O)C2c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: NRBSFHSUWBAYCI-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of recombinant human ALK2 (147 to end residues) expressed in Sf9 infected baculovirus expression system using TRF0130 as substrate incubated for 3 hrs in presence of APT
Measurement: IC50 = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 337.39, ALogP 1.34, HBA 6, HBD 1, PSA 92.59, QED 0.76
Compound (SMILES): CC1(C(=O)NS(=O)(=O)c2ccc(Cl)s2)CCN(c2nc3c(cc2C#N)C(=O)OC3)CC1
InChIKey: OTWUQESYHAXXJO-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using Midazolam as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 480.96, ALogP 2.45, HBA 9, HBD 1, PSA 129.46, QED 0.66
Compound (SMILES): CC(C)(C)c1ccc(-n2cnc3c(NC(=O)Cc4ccc(C(=O)O)cc4)cccc32)cc1
InChIKey: VEHCUCLQBZOABJ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Partial agonist activity at PPARgamma (unknown origin) in presence of GW1929
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 427.5, ALogP 5.2, HBA 4, HBD 2, PSA 84.22, QED 0.46
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(CCc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: MDHIFDZZMWLNKL-WZOWOQAZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at HA-tagged mouse mu opioid receptor expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by Glo Sensor assay
Measurement: EC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 456.59, ALogP 3.93, HBA 5, HBD 0, PSA 42.01, QED 0.52
Compound (SMILES): C[N+]1=C(/C=C/C=C/C=C2\N(CCCCCC(=O)NCCCCCCn3cc(CCCCN4CCC5(CC4)OCc4ccccc45)c4ccccc43)c3ccccc3C2(C)C)C(C)(C)c2ccccc21.[I-]
InChIKey: PYGSKQVDDNNOJX-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Binding affinity to sigma 2 receptor in human MCF7 cells assessed as displacement of compound by measuring inhibition constant of DTG incubated for 120 mins by saturation binding assay
Measurement: Ki = 3.14 nM (pChEMBL 8.5)
Descriptors: MW 925.34, ALogP 13.22, HBA 5, HBD 1, PSA 52.75, QED 0.05
Compound (SMILES): CCOC(=O)c1ncc2[nH]c3ccc(O)cc3c2c1COC
InChIKey: VJVAWKPXJCDEQG-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16445
Assay: Binding affinity to human recombinant GABAA alpha6 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 300.31, ALogP 2.74, HBA 5, HBD 2, PSA 84.44, QED 0.72
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: OHTCHFUKVDURAI-MMDZAOKXSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Inhibition of human somatostatin receptor type 5
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 621.74, ALogP -0.09, HBA 7, HBD 8, PSA 221.53, QED 0.1
Compound (SMILES): CCc1c(C(=O)OC)nc(C)c2[nH]c3cc(OC)c(OC)cc3c12
InChIKey: NHJRHDMRNNOSLV-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16445
Assay: Binding affinity to human recombinant GABAA alpha6 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 328.37, ALogP 3.39, HBA 5, HBD 1, PSA 73.44, QED 0.74
Compound (SMILES): Cc1c(Oc2ccc(CN)cc2F)ccc2c1B(O)OC2
InChIKey: ZCITXZXBLWIHHP-UHFFFAOYSA-N
Target: Protein kinase C alpha type (SINGLE PROTEIN), Homo sapiens
UniProt: P17252
Assay: Competition Binding Assay: Phosphorylation of activity of ROCK1 and ROCK2 and those of other kinases, AKT1, GRK2, PKA, PKCa and RSK1 were performed by Reaction Biology (Malvern, Pa.) (Ma et al., 2008) The ROCK1 enzyme tested was GST[1-535] ROCK1 (Genbank, NP 005397), ROCK2 was GST[5-554] (Genbank, 3327051). For the kinase assay buffers contained 20 mM Hepes, 10 mM MgCl2, 2 mM DTT, 0.02 mg/mL BSA, 0.1% DMSO, 1 mM EGTA, 0.02% Brij-35, 10 uM ATP, [γP33]-ATP and for ROCK enzymes, 20 uM long S6-peptide (32 amino acids length). Appropriate substrates and activation was applied for the other kinases tested. Each enzyme was preincubated with test compound for 15 min., and the reaction started by addition of ATP. Samples were incubated at room temperature for 120 min, and applied to P81 ion exchange paper and washed extensively; the radioactive content of the filters were determined.
Measurement: IC50 > 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 287.1
Compound (SMILES): C=CC(=O)N1CCC(n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)CC1
InChIKey: LNJMXIZSFNEQQF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells at -80 mV holding potential by automated patch clamp method
Measurement: IC50 = 1130 nM (pChEMBL 5.949999809265137)
Descriptors: MW 432.48, ALogP 3.08, HBA 7, HBD 2, PSA 123.04, QED 0.48
Compound (SMILES): Cc1ccccc1/N=N/c1cc(S(=O)(=O)O)c2ccccc2c1N
InChIKey: PIWJSAOBFMHEAW-FMQUCBEESA-N
Target: Sentrin-specific protease 1/Small ubiquitin-related modifier 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P63165
Assay: Enzyme Kinetic Assay: The inhibitors confer the non-competitive inhibitory mechanism, as shown by nuclear magnetic resonance (NMR) and quantitative enzyme kinetic analysis.
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 341.39, ALogP 4.39, HBA 5, HBD 2, PSA 105.11, QED 0.42
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)O[C@@H](C)C(C)(C)C)nc2C2(CCC(F)(F)CC2)C1(C)C
InChIKey: BQJACMMFLPJGCR-ZDUSSCGKSA-N
Target: Thyrotropin receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P21463
Assay: Antagonist activity at TSHR in rat FRTL-5 cells assessed as inhibition of M22-induced cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 438.52, ALogP 5.05, HBA 5, HBD 1, PSA 84.42, QED 0.7
Compound (SMILES): COC(=O)c1cc2c(cn1)[nH]c1ccc(NCc3ccccc3)cc12
InChIKey: JTYYMOMTGZSRFM-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16445
Assay: Binding affinity to human recombinant GABAA alpha6 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 331.38, ALogP 4.11, HBA 4, HBD 2, PSA 67.01, QED 0.55
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NCC(N)=O
InChIKey: YJKNBYBEJYUUHW-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 441.89, ALogP 4.02, HBA 5, HBD 3, PSA 110, QED 0.51
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C(F)F)c2)n1
InChIKey: FRYSBKWOXOBQNB-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.45, ALogP 5.94, HBA 5, HBD 2, PSA 71.42, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4cccc(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: WAYSVGLDKMEZLH-KRWDZBQOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR A763-Y764 ins FQEA mutant (unknown origin)
Measurement: IC50 = 0.116 nM (pChEMBL 9.9399995803833)
Descriptors: MW 512.97, ALogP 4.89, HBA 7, HBD 1, PSA 85.81, QED 0.45
Compound (SMILES): Cc1ncc(-c2nc3c(OC4(C)CC4)nc(Nc4cnn(C5CCN(C)CC5)c4)nc3cc2F)cn1
InChIKey: SZURKEABSBIIMJ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) in presence of 75 uM ATP
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 489.56, ALogP 4.07, HBA 10, HBD 1, PSA 106.77, QED 0.43
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)[C@H](C)C2)c1
InChIKey: HVXGLCUTIOCPRK-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Agonist activity at Gal4-fused mouse PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): CC(C)=CCN1CC[C@@]2(C)c3cc(O)ccc3C[C@H]1[C@H]2C
InChIKey: VOKSWYLNZZRQPF-MDASCCDHSA-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 brain membrane assessed as inhibition constant measured for 150 mins
Measurement: Ki = 35.1 nM (pChEMBL 7.460000038146973)
Descriptors: MW 285.43, ALogP 3.88, HBA 2, HBD 1, PSA 23.47, QED 0.83
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)[C@@H](C)n2nnnc2N1C
InChIKey: BVMAEXVWFIGNKQ-SECBINFHSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 324.35, ALogP 1.47, HBA 7, HBD 2, PSA 104.62, QED 0.74
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(C(F)(F)F)c1
InChIKey: WECCALUSSAUMLJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Binding affinity to recombinant human HPK1 (1 to 346 residues) expressed sf9 cells incubated for 1 hr by LanthaScreen assay
Measurement: Ki = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 404.37, ALogP 3.9, HBA 5, HBD 2, PSA 71.42, QED 0.51
Compound (SMILES): CC(=O)Nc1cc(Oc2ccc(NC(=O)Cc3ccccc3C(F)(F)F)cc2)ncn1
InChIKey: PFGNOYJAWUKCEW-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) preincubated for 60 mins followed by ATP addition and measured after 1 hr by ADP-Glo assay
Measurement: IC50 = 90.8 nM (pChEMBL 7.039999961853027)
Descriptors: MW 430.39, ALogP 4.43, HBA 5, HBD 2, PSA 93.21, QED 0.6
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 23.8 nM (pChEMBL 7.619999885559082)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NC[C@H](C)O
InChIKey: JZVPITOQWJPGIA-AWEZNQCLSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 20.4 nM (pChEMBL 7.690000057220459)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS analysis
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to ZsGreen fused-BRD9 (M1 to T597 residues) (unknown origin) expressed in human U2OS-C433 cells assessed as induction of protein bromodomain localization from chromatin by measuring formation of large nuclear puncta by fluorescence based assay
Measurement: EC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): Fc1ccc(CN2CCCC3(CCN(Cc4cc5ccc(Cl)cc5[nH]4)C3)C2)cc1F
InChIKey: JGUJMJSODMVSHV-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from D5 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 429.94, ALogP 5.59, HBA 2, HBD 1, PSA 22.27, QED 0.58
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG mediated tail current in HEK293 cells at 10 uM and measured after 5 to 6 mins at -80 mV holding potential by whole cell patch clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Macaca fascicularis
UniProt: Q2XVA1
Assay: Inhibition of cynomolgus monkey CYP17A1 lyase activity
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CN1CC2CCC(C1=O)C2c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: NRBSFHSUWBAYCI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant N-terminal His-tagged human FGFR3 V555L mutant using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by HTRF assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 337.39, ALogP 1.34, HBA 6, HBD 1, PSA 92.59, QED 0.76
Compound (SMILES): CC1(C(=O)NS(=O)(=O)c2ccc(Cl)s2)CCN(c2nc3c(cc2C#N)C(=O)OC3)CC1
InChIKey: OTWUQESYHAXXJO-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 480.96, ALogP 2.45, HBA 9, HBD 1, PSA 129.46, QED 0.66