lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1CCCCN1C(=O)CCN1CCCc2ccccc21
InChIKey: OYQSJQCVYUUOTR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 286.42, ALogP 3.23, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): Cn1cc(Nc2nccc(N3CC4CCC(C3)N4C(=O)[C@@H]3CC3(F)F)n2)cn1
InChIKey: BUWBRTXGQRBBHG-RUXDESIVSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human Tyk2 expressed in sf21 baculovirus expression system assessed as phosphorylation level in presence of 1 mM ATP
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 389.41, ALogP 1.79, HBA 7, HBD 1, PSA 79.18, QED 0.86
Compound (SMILES): Nc1nn2cc(-c3ccc(Br)cc3)[nH]c2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: XQQUUIQYQFCYDD-GHVJWSGMSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 52.8 nM (pChEMBL 7.28000020980835)
Descriptors: MW 460.32, ALogP 3.74, HBA 7, HBD 3, PSA 143.99, QED 0.4
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CC2)cc1)c1ccccc1
InChIKey: KOVNLGSITVPOLE-JTHROIFXSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to GST-tagged ERalpha LBD (unknown origin) using fluorescein PGC1alpha as coactivator incubated for 1 hr by LanthaScreen TR-FRET co-regulator assay
Measurement: IC50 = 296 nM (pChEMBL 6.53000020980835)
Descriptors: MW 415.53, ALogP 4.82, HBA 4, HBD 2, PSA 52.7, QED 0.37
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)NCCCN1C(=O)CC(SC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2ccccc2)NC(=O)CNC(=O)CNC(=O)[C@@H](N)Cc2ccc(O)cc2)C(N)=O)C1=O
InChIKey: PQNMDRSESKVMOM-MSDKKNTMSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at DOP (unknown origin) expressed in SH-SY5Y cell membranes co-expressing beta-arrestin2-RGFP protein assessed as induction of beta-arrestin2 activation incubated for 15 mins by BRET assay
Measurement: EC50 = 131.83 nM (pChEMBL 6.880000114440918)
Descriptors: MW 1050.38
Compound (SMILES): O=[N+]([O-])c1ccc(N/C(Cc2ccc(F)cc2)=N\O)c2nonc12
InChIKey: KCXXQNDUBKRRLN-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 assessed as N-formylkynurenine formation using L-tryptophan as substrate measured after 1.5 hrs by HPLC analysis
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 331.26, ALogP 2.71, HBA 7, HBD 2, PSA 126.68, QED 0.25
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1c(=O)n(CC1=NC3C=CC=CC3C(C)=N1)c(=O)n2C
InChIKey: KQPQOENOYPKDIN-LMDPOFIKSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of DPP2 (unknown origin) using AMC substrate by fluorometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 474.57, ALogP 0.83, HBA 10, HBD 1, PSA 115.8, QED 0.66
Compound (SMILES): CN[C@H](CNc1cc(F)c(S(=O)(=O)Nc2ncc(F)s2)cc1Cl)CC(C)(C)C.Cl
InChIKey: LUPTXVASMFPNNE-PPHPATTJSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 452.98, ALogP 4.31, HBA 6, HBD 3, PSA 83.12, QED 0.56
Compound (SMILES): CCN(C)C(=O)Oc1ccc(/C=C/C(=O)N2CCCCC2)cc1OC
InChIKey: KIQCSORRMFIOHM-PKNBQFBNSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 346.43, ALogP 3.17, HBA 4, HBD 0, PSA 59.08, QED 0.77
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(-c4ccccc4)c3)nn(-c3nc(C(=O)O)cs3)c2C2(C(F)(F)F)CC2)cc1
InChIKey: NAIVYQUEYSWGAU-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 624.67, ALogP 6.19, HBA 7, HBD 2, PSA 128.17, QED 0.21
Compound (SMILES): Cc1ccc(-c2nc3c(/N=N/c4ccc(S(N)(=O)=O)cc4)c(N)nn3c(N)c2C#N)cc1
InChIKey: XIEZNUNKXXLJEK-CYYJNZCTSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 48.8 nM (pChEMBL 7.309999942779541)
Descriptors: MW 447.48, ALogP 2.8, HBA 10, HBD 3, PSA 190.9, QED 0.4
Compound (SMILES): Cc1ccc(C#Cc2cc(-c3nn(-c4nc(C(=O)O)cs4)c(CCC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)ccc2F)s1
InChIKey: TUBDVUGKZZYCEK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 664.78, ALogP 6.32, HBA 8, HBD 2, PSA 128.17, QED 0.18
Compound (SMILES): O=C(Nc1cnccn1)c1n[nH]c2ccc(-c3cncc(CN4CCCCCC4)c3)cc12
InChIKey: KMUJDVMSVNQUBP-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: Wnt activity assay: Reporter cell lines were generated by stably transducing cells of cancer cell lines (e.g., colon cancer) with a lentiviral construct that include a Wnt-responsive promoter driving expression of the firefly luciferase gene.Lentiviral constructs were made in which the SP5 promoter, a promoter having eight TCF/LEF binding sites derived from the SP5 promoter, was linked upstream of the firefly luciferase gene. The lentiviral constructs included a hygromycin resistance gene as a selectable marker. The SP5 promoter construct was used to transduce SW480 cells, a colon cancer cell line having a mutated APC gene that generates a truncated APC protein, leading to de-regulated accumulation of β-catenin. A control cell line was generated using another lentiviral construct containing the luciferase gene under the control of the SV40 promoter which does not require β-catenin for activation.Cultured SW480 cells bearing a reporter construct were distributed at approximately 10,000 cells per well into 384 well multiwell plates. Compounds were then added to the wells in half-log dilutions using a three micromolar top concentration. A series of control wells for each cell type received only buffer and compound solvent. Twenty-four hours after the addition of compound, reporter activity for luciferases was assayed, for example, by addition of the BrightGlo luminescence reagent (Promega) and the Victor3 plate reader (Perkin Elmer). Readings were normalized to DMSO only treated cells, and normalized activities were then used for the IC50 calculations.
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 427.51, ALogP 4.04, HBA 6, HBD 2, PSA 99.69, QED 0.5
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1N[C@@H]1CCN(Cc2cccc(OC)c2)C[C@@H]1F
InChIKey: QYCQCEJRCQDCKL-RBUKOAKNSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 411.48, ALogP 2.96, HBA 5, HBD 3, PSA 82.28, QED 0.58
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccc(/C=C/C(=O)NO)cc3C2)c(O)cc1O
InChIKey: PFHGIFRDCPUONW-GQCTYLIASA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using RHK-K(Ac)-AMC as substrate by fluorescence based assay
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 382.42, ALogP 2.9, HBA 5, HBD 4, PSA 110.1, QED 0.37
Compound (SMILES): CC(=O)NC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: UEULRQISGVDABJ-WOUKDFQISA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 308.3, ALogP -1.84, HBA 9, HBD 4, PSA 148.41, QED 0.52
Compound (SMILES): CCOC(=O)CC[C@H]1[C@@H]2CCC[C@@]1(c1cccc(O)c1)CCN2CCc1ccccc1
InChIKey: XHAHHMALYFEUTK-KLJDGLGGSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Activity at human MOR expressed in CHOK1 cells co-expressing beta-arrestin2 EFC assessed as beta-arrestin2 EFC recruitment measured after 90 mins by PathHunter assay
Measurement: EC50 = 11.57 nM (pChEMBL 7.940000057220459)
Descriptors: MW 421.58, ALogP 5.09, HBA 4, HBD 1, PSA 49.77, QED 0.6
Compound (SMILES): C[C@@H]1NC(=O)CN(CCN)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: CPQMVJLVQNQWOE-JHGMFKEXSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 963.15, ALogP -0.8, HBA 10, HBD 9, PSA 294.35, QED 0.06
Compound (SMILES): CCCCc1nc(COc2cccc([C@@H](CC(=O)O)C3CC3)c2)cnc1-c1cc(OC)ccc1F
InChIKey: CAASMGSVVAKSNP-QHCPKHFHSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Calcium Flux Assay: Compounds were tested in a calcium flux assay using transfected HEK293 cells stably expressing either human GPR40 or rat GPR40. Human GPR40 expressing cells were cultured in DMEM-High Glucose media supplemented with 10% fetal bovine serum, 1×L-Glutamine, 1× Penicillin/Streptomycin and 500 μg/mL G418. Rat GPR40 expressing cells were cultured in DMEM-High Glucose media supplemented with 10% fetal bovine serum and 1 μg/mL puromycin. Cells were plated into poly-D-lysine coated 384-well plates and cultured overnight in a 37° C. humidified tissue culture incubator under 5% CO2/90% O2 atmosphere. On the day of the experiment, the culture media was replaced with assay buffer (HBSS, 20 mM HEPES, 0.1% BSA) and the cells incubated at 37° C. for 1 h. Calcium-sensitive fluorescent dye (Fluo 8 No-Wash Calcium Dye, ABD Bioquest) was then added and the cells incubated for another 30 min at 37° C. followed by 15 min at room temperature while protected from the light. The cell plate and a plate of diluted compounds of Formula (I) were loaded into a fluorescent plate reader that added compounds onto the cells while measuring the fluorescence intensity of each well. The plate reader recorded fluorescence intensity at 1 second intervals for 8 min and provided the data for analysis in an Excel format.
Measurement: EC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 478.56, ALogP 6.18, HBA 5, HBD 1, PSA 81.54, QED 0.33
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cn2c1-c1ccc(F)cc1
InChIKey: XDAABESJGOZBJI-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in antiIgM/CD40L-induced human B cells assessed as reduction in cell viability preincubated for 30 mins followed by antiIgM/CD40L addition and measured after 72 hrs by [3H]-thymidine incorporation assay
Measurement: IC50 = 90.5 nM (pChEMBL 7.039999961853027)
Descriptors: MW 391.39, ALogP 3.7, HBA 7, HBD 2, PSA 104.92, QED 0.55
Compound (SMILES): CN1CCN(c2ccnc3[nH]c(-c4n[nH]c5ncc(-c6cn[nH]c6)cc45)cc23)CC1
InChIKey: BVDIFGPTNZXGTI-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 678 nM (pChEMBL 6.170000076293945)
Descriptors: MW 399.46, ALogP 2.64, HBA 6, HBD 3, PSA 105.41, QED 0.43
Compound (SMILES): C[Si](C)(CN1CCCC1)c1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(O)cc2)cc1.Cl
InChIKey: BCHMTKSQGNLVMN-DHKWPOFJSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to GST-tagged ERalpha LBD (unknown origin) using fluorescein PGC1alpha as coactivator incubated for 1 hr by LanthaScreen TR-FRET co-regulator assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 471.72
Compound (SMILES): COc1cc(/C=N/Nc2ncnc3c2c(-c2ccc(Cl)cc2)cn3-c2ccc(S(N)(=O)=O)cc2)ccc1O
InChIKey: FIIAWOKNGQJSAR-IURWMYGYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 304.3 nM (pChEMBL 6.519999980926514)
Descriptors: MW 549.01, ALogP 4.55, HBA 9, HBD 3, PSA 144.72, QED 0.2
Compound (SMILES): CCCc1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(C(=O)O)=C[C@@H]21
InChIKey: BTTRWQMCLAXICU-ZIAGYGMSSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes after 90 mins
Measurement: Ki = 589.7 nM (pChEMBL 6.230000019073486)
Descriptors: MW 316.4, ALogP 4.02, HBA 3, HBD 2, PSA 66.76, QED 0.88
Compound (SMILES): COc1ccc2c3c([nH]c2c1)[C@@H]1N(CC3)C(=O)c2c(OC)cccc2N1C
InChIKey: WNMIZGXEPWFQCU-FQEVSTJZSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of human PDE4D2 catalytic domain (86 to 413 residues) using [3H]cAMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 363.42, ALogP 3.33, HBA 4, HBD 1, PSA 57.8, QED 0.76
Compound (SMILES): COC1CN(C(=O)CCN2CCCc3ccccc32)C1
InChIKey: CGOUBIILQTVZLS-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 20417.38 nM (pChEMBL 4.690000057220459)
Descriptors: MW 274.36, ALogP 1.69, HBA 3, HBD 0, PSA 32.78, QED 0.84
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2cccc(O)c2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: FCLJOJCWQWXZBU-YEJMJCSASA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 1394.69
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc3oc(C(=O)c4cc5cc(O)ccc5[nH]4)cc3c2)no1
InChIKey: RADJMCVKNQBZOY-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 incubated for 30 mins by Kinobead based assay
Measurement: EC50 = 1768 nM (pChEMBL 5.75)
Descriptors: MW 458.47, ALogP 5.78, HBA 6, HBD 4, PSA 133.39, QED 0.25
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccn3ncnc3c2)[nH]1
InChIKey: MBOHSZYVCDRFBU-YADHBBJMSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 249 nM (pChEMBL 6.599999904632568)
Descriptors: MW 491.64, ALogP 3.94, HBA 7, HBD 2, PSA 108.28, QED 0.39
Compound (SMILES): CCn1nc2c(c1Nc1nc(-c3ccc(-n4cnc(C)c4)c(OC)n3)cs1)CCCCC2
InChIKey: RJBHTARGFMGGBA-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 85000 nM (pChEMBL 4.070000171661377)
Descriptors: MW 449.58, ALogP 4.94, HBA 9, HBD 1, PSA 82.68, QED 0.42
Compound (SMILES): Cc1cc(NC(=O)c2occc2C)c(F)cc1N1C(=O)c2ccccc2C1=O
InChIKey: WMBNMWWQJFWLEY-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00222
Assay: Positive allosteric modulation of mGluR8 (unknown origin) by calcium mobilization assay
Measurement: EC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 378.36, ALogP 4.09, HBA 4, HBD 1, PSA 79.62, QED 0.7
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cc2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: AJNPQBGORGGVKZ-OAQYLSRUSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: In Vitro Assay: Nuclear extract preparations and DNA-binding activity/electrophoretic mobility shift assay (EMSA) were carried out as previously described (Zhang X, et al., (2010) Biochem Pharmacol 79:1398-409; Zhang X, et al., (2012) Proc Natl Acad Sci USA 109:9623-8). The 32P-labeled oligonucleotide probes used were hSIE (high affinity sis-inducible element from the c-fos gene, m67 variant, 5′-AGCTTCATTTCCCGTAAATCCCTA) (SEQ ID NO: 1) that binds Stat1 and Stat3 and MGFe (mammary gland factor element from the bovine β-casein gene promoter, 5′-AGATTTCTAGGAATTCAA) (SEQ ID NO: 2) for Stat1 and Stat5 binding. Except where indicated, nuclear extracts were pre-incubated with compound for 30 min at room temperature prior to incubation with the radiolabeled probe for 30 min at 30° C. before subjecting to EMSA analysis. Where appropriate, bands corresponding to Stat3:DNA complexes were scanned and quantified for each concentration of compound using ImageJ and plotted as percent of control (DMSO) against concentration of compound, from which the IC50 values were derived.
Measurement: IC50 = 583 nM (pChEMBL 6.230000019073486)
Descriptors: MW 638.61, ALogP 5.83, HBA 5, HBD 2, PSA 115.22, QED 0.18
Compound (SMILES): CO[C@@H](C)c1c(NC(=O)Nc2ccnc(C(F)(F)F)c2)cnc2cc(Cl)nn12
InChIKey: ZMPUACZRXUZAJD-QMMMGPOBSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 414.78, ALogP 4.15, HBA 6, HBD 2, PSA 93.44, QED 0.67
Compound (SMILES): Cc1cc(-c2ccc3c(c2)-c2nnc(Oc4cccc(Cl)c4F)n2CCO3)ccn1
InChIKey: IBBPPJIKHAEYMX-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 422.85, ALogP 5.29, HBA 6, HBD 0, PSA 62.06, QED 0.45
Compound (SMILES): CC(=O)Nc1nc2cc(-c3cc(C)c4c(c3)CN([C@@H](C)C3CC3)C4=O)ccc2[nH]1
InChIKey: FGRYSELYJLRQCW-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 388.47, ALogP 4.25, HBA 3, HBD 2, PSA 78.09, QED 0.7
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1C2CCC1C(Oc1ccc(C(F)(F)F)cn1)C2
InChIKey: AXBDWANXRUPESE-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Binding affinity to human OX2R
Measurement: Ki = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 429.4, ALogP 3.51, HBA 6, HBD 0, PSA 73.14, QED 0.63
Compound (SMILES): Cc1cc(C(=O)O)nc(N2CCC(COc3ccccc3C(F)(F)F)C2)n1
InChIKey: YNIAPSNMAZHUHD-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at PPARgamma (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 381.35, ALogP 3.41, HBA 5, HBD 1, PSA 75.55, QED 0.86
Compound (SMILES): CC1(N)CCN(c2cnc(Sc3ccccc3Cl)c(N)n2)CC1
InChIKey: HPRNFWNEHIBURH-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Allosteric Inhibition Assay: SHP2 is allosterically activated through binding of bis-tyrosyl-phorphorylated peptides to its Src Homology 2 (SH2) domains. The latter activation step leads to the release of the auto-inhibitory interface of SHP2, which in turn renders the SHP2 protein tyrosine phosphatase (PTP) active and available for substrate recognition and reaction catalysis. The catalytic activity of SHP2 was monitored using the surrogate substrate DiFMUP in a prompt fluorescence assay format.More specifically, the phosphatase reactions were performed at room temperature in 384-well black polystyrene plate, flat bottom, low flange, non-binding surface (Corning, Cat#3575) using a final reaction volume of 25 μL and the following assay buffer conditions: 60 mM HEPES, pH 7.2, 75 mM NaCl, 75 mM KCl, 1 mM EDTA, 0.05% P-20, 5 mM DTT.The inhibition of SHP2 by compounds of the invention (concentrations varying from 0.003-100 μM) was monitored using an assay in which 0.5 nM of SHP2 was incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222 (sequence: H2N-LN(pY)IDLDLV(dPEG8)LST(pY)ASINFQK-amide) (SEQ ID NO:1). After 30-60 minutes incubation at 25° C., the surrogate substrate DiFMUP (Invitrogen, cat#D6567) was added to the reaction and incubated at 25° C. for 30 minutes. The reaction was then quenched by the addition of 5 μl of a 160 μM solution of bpV(Phen) (Enzo Life Sciences cat#ALX-270-204). The fluorescence signal was monitored using a microplate reader (Envision, Perki-Elmer) using excitation and emission wavelengths of 340 nm and 450 nm, respectively. The inhibitor dose response curves were analyzed using normalized IC50 regression curve fitting with control based normalization.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 349.89, ALogP 3.18, HBA 6, HBD 2, PSA 81.06, QED 0.89
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccccc2F)nc1C#N
InChIKey: KVQDFPCKXYVWSX-GGAORHGYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 493.63, ALogP 4.91, HBA 5, HBD 2, PSA 101.88, QED 0.43
Compound (SMILES): C=CC(=O)Nc1ccc(-c2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)cc1
InChIKey: UXJWKEBWYYWGQW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 cytoplasmic domain (866 to 1154 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 401.47, ALogP 3.85, HBA 6, HBD 2, PSA 79.38, QED 0.61
Compound (SMILES): Nc1nc(-n2cc(C(=O)O)c(=O)c3cc(F)c(N4CC(N)C4)c(Cl)c32)c(F)cc1F
InChIKey: ZHLAKLNFEZYKHL-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 13600 nM (pChEMBL 4.869999885559082)
Descriptors: MW 439.78, ALogP 1.88, HBA 7, HBD 3, PSA 127.47, QED 0.57
Compound (SMILES): C[C@](O)(Cn1cc(Br)c(F)n1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
InChIKey: RJKNGSHMZNYUDQ-AWEZNQCLSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Human Androgen Receptor (hAR) Ligand Binding Domain (LBD) Affinity Assay: Methods: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone.Increasing concentrations of SARDs or DHT (range: 10−12 to 10−4 M) were incubated with [3H]mibolerone and AR-LBD using the conditions described above. Following incubation, the ligand bound AR-LBD complex was isolated using BiogelHT hydroxyapatite, washed and counted in a scintillation counter after adding scintillation cocktail.
Measurement: Ki = 606 nM (pChEMBL 6.21999979019165)
Descriptors: MW 435.18, ALogP 3.06, HBA 5, HBD 2, PSA 90.94, QED 0.72
Compound (SMILES): CCN1CCc2ccc(OCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2C1=O
InChIKey: NGSZJZCWVNVBQV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 451.54, ALogP 4.63, HBA 5, HBD 0, PSA 58.81, QED 0.49
Compound (SMILES): C[C@@H](OCc1ccccc1)[C@@H](C#N)NC(=O)[C@H](Cc1cccc(Cl)c1)NC(=O)c1cccc(-c2cccnc2)c1
InChIKey: PHUPMBKAOHPRFE-ZDERHKTGSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B at pH 6 using Z-Phe-Arg-AMC fluorogenic peptide as substrate preincubated for 2 mins followed by substrate addition and measured for 5 mins by fluorescence assay
Measurement: IC50 = 9.01 nM (pChEMBL 8.039999961853027)
Descriptors: MW 553.06, ALogP 5.36, HBA 5, HBD 2, PSA 104.11, QED 0.26
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccc2Cl)CC1
InChIKey: FYASYGQIQFXRDM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 549.54 nM (pChEMBL 6.260000228881836)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): FC(F)(F)c1cnc(Nc2ccc3ncccc3c2)nc1NC1CC1
InChIKey: GWRHBTXTQFLVSP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: ULK1 inhibition assay: Gamma-32P assays to measure ULK1 kinase activity were performed as previously described. Briefly, Flag ULK1 was transfected into HEK293T cells and 20 hours later treated as indicated. The immmunoprecipitate was washed in IP buffer 3 times, and washed in kinase buffer (25 mM MOPS, pH 7.5, 1 mM EGTA, 0.1 mM Na3VO4, 15 mM MgCl2,). Hot and cold ATP were added at a 100 μM final concentration. As substrates, GST or the recombinant protein GST-Atg101 purified from E. coli were used at 1 μg for each reaction. Reactions were boiled, run out on SDS page gel. The gel was dried, and imaged using PhosphoImager software. For cold assays to asses ULK1, Flag ULK1 which was transiently overexpressed and immunoprecipited from HEK293T cells. Reactions were then run out on SDS page gel, transferred to PVDF membrane and blotted for total levelsFluorescence MicroscopyVps34flox/flox MEFs were reconstituted with Flag-VPS34 and either p40FX or GFP-DFCP1. 48 hours post infection with adenovirus expressing Cre recombinase (MOI of 100), cells were plated on glass coverslips at a density of 3×105 cells per well in 6-well tissue culture plates. 18 h later, cells were fixed in 4% PFA in PBS for 10 minutes and permeabilized in 0.2% Triton in PBS for 10 minutes. The following primary antibodies were used: mouse anti-Myc epitope and LC3B XP antibody (2276 and 3868 respectively, Cell Signaling Technologies). Secondary antibodies were anti-rabbit Alexa488 and anti-mouse Alexa594 (Molecular Probes, 1:1000. Cells were then fixed and counter stained with DAPI. Coverslips were mounted in FluoromountG (SouthernBiothech). Images were acquired on a Zeiss Axioplan2 epifluorescence microscope coupled to the Openlab software. Confocal images of mitotracker were taken on Zeiss LSM 710 laser scanning confocal microscope. 10 random fields per condition were acquired using the 100× objective and representative images shown. Glass coverslips were mounted directly on plate with FluoromountG and images taken on Zeiss Axioplan2 epifluorescence microscope.
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 345.33, ALogP 4.36, HBA 5, HBD 2, PSA 62.73, QED 0.74
Compound (SMILES): CN1CCC(n2cc(C(=O)Nc3cc4cc(-c5cncc6[nH]ccc56)ccc4cn3)cn2)CC1
InChIKey: LFPGRXUUHQLPMT-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay : The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated ("0% Control") and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.
Measurement: EC50 = 9071 nM (pChEMBL 5.039999961853027)
Descriptors: MW 451.53, ALogP 4.49, HBA 6, HBD 2, PSA 91.73, QED 0.42
Compound (SMILES): CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](Nc2ncnc3ccc(OC(F)(F)F)cc23)C1=O
InChIKey: QRKQGOWSACQLGK-QAJUQPOASA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 522.57, ALogP 3.36, HBA 7, HBD 3, PSA 108.48, QED 0.53
Compound (SMILES): C[C@H]1CC(=O)Nc2cc(C(=O)NCCC3CC3)ccc2N1C(=O)N1CC2CC2C1
InChIKey: CKFRXCBNKKOFGO-IGEOTXOUSA-N
Target: Histone-lysine N-methyltransferase SMYD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H7B4
Assay: Selectivity interaction (SPR measurement) EUB0000221b SMYD3
Measurement: Kd = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 396.49, ALogP 2.83, HBA 3, HBD 2, PSA 81.75, QED 0.82
Compound (SMILES): CC(C)(Oc1ccc(-c2cnc(N)c(-c3ccc(Cl)cc3)c2)cc1)C(=O)O
InChIKey: BYWYWLKBKIJAAJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 382.85, ALogP 4.89, HBA 4, HBD 2, PSA 85.44, QED 0.66
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccc(F)cc3F)c3ccc(O)cc3)cc2)CC1.Cl
InChIKey: RFLKZWHLEAHIRJ-QDDHFQMKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 20200 nM (pChEMBL 4.699999809265137)
Descriptors: MW 491.62, ALogP 6.99, HBA 3, HBD 2, PSA 43.7, QED 0.33
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(Nc4ccc(CNC(=S)Nc5ccc(N=C=S)cc5)cc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: QHBDGFBJMKRHNZ-UMCMBGNQSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Irreversible agonist activity at human adenosine A3 receptor expressed in Flp-In-CHO cells assessed as effect on forskolin-induced cAMP accumulation incubated for 30 mins by LANCE cAMP detection assay
Measurement: EC50 = 44.67 nM (pChEMBL 7.349999904632568)
Descriptors: MW 564.65, ALogP 2.4, HBA 12, HBD 6, PSA 161.97, QED 0.14
Compound (SMILES): Cc1cc(-c2ccc3nc(N)nn3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: DNBUJELVNKASMK-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 347.42, ALogP 3.04, HBA 5, HBD 1, PSA 76.52, QED 0.79
Compound (SMILES): CN(C)C(=O)c1ccccc1Nc1nc(Nc2ccc3nc(CN4CCCC4)[nH]c3c2)ncc1Cl
InChIKey: WTEVQSAOHYKUTI-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST-tagged human FLT3 cytoplasmic domain (564 to 993 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 = 103.1 nM (pChEMBL 6.989999771118164)
Descriptors: MW 491, ALogP 4.79, HBA 7, HBD 3, PSA 102.07, QED 0.34
Compound (SMILES): Fc1ccc(CCCCN2C3CCC2CN(c2ccc(Cl)cn2)C3)cc1
InChIKey: ZMDOIQGPLNKPIO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5HT7 receptor by liquid scintillation counting
Measurement: Ki = 339.4 nM (pChEMBL 6.46999979019165)
Descriptors: MW 373.9, ALogP 4.55, HBA 3, HBD 0, PSA 19.37, QED 0.69
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)C(=O)N1CCC(c2ccnc3ccc(F)cc23)CC1
InChIKey: BBNKZBRNGRLKCM-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human SKOV3 cells
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 411.86, ALogP 4.37, HBA 3, HBD 1, PSA 62.3, QED 0.64
Compound (SMILES): COc1cc(OCc2ccnc(N)c2Cl)cc2sc(N[C@@H]3CCCC[C@H]3O)nc12
InChIKey: DICVVUCQTSNJLU-ZIAGYGMSSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-TetR cells incubated for 1 hr followed by PDGF-DD stimulation and measured after 5 mins by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 434.95, ALogP 4.23, HBA 8, HBD 3, PSA 102.52, QED 0.53
Compound (SMILES): Cc1cnc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)nc1
InChIKey: BLJZKXJVIGQCID-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as stimulation of beta-arrestin recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 2754.23 nM (pChEMBL 5.559999942779541)
Descriptors: MW 424.88, ALogP 3.19, HBA 5, HBD 1, PSA 67.35, QED 0.69
Compound (SMILES): C[C@@H]1CN(c2ccc(C(C)(C)O)nc2)CCN1c1cccc(C(=O)NC2C3CC4CC2CC(O)(C4)C3)n1
InChIKey: UNRPWLPNKUXWDT-JMBJFCBPSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in pooled human liver microsomes using dextromethorphan as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 505.66, ALogP 3.09, HBA 7, HBD 3, PSA 101.82, QED 0.57
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc(-c3cccnc3)cc2)nc1C#N
InChIKey: BWTPSSSOMLHHKD-IZLXSDGUSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 552.72, ALogP 5.83, HBA 6, HBD 2, PSA 114.77, QED 0.27
Compound (SMILES): CN(C)CCN1C(=O)c2ccccc2/C=C\c2ccccc21
InChIKey: YFINOLWYBYMFPQ-QXMHVHEDSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding affinity to SERT (unknown origin)
Measurement: Ki = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 292.38, ALogP 3.38, HBA 2, HBD 0, PSA 23.55, QED 0.87
Compound (SMILES): Cc1cc(Cl)cc(N2C=Nc3cc(C)c(-c4cccc(F)c4O)cc3C2C(=O)N(C)C[C@@H]2CCCN2)c1
InChIKey: FGVUWBKWBAZBPK-SVQMELKDSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Agonist activity at SST3 (unknown origin)
Measurement: EC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 521.04, ALogP 5.9, HBA 5, HBD 2, PSA 68.17, QED 0.44
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)C2CN(C(=O)C3CCCCC3)Cc3cc(Cl)ccc32)CC1
InChIKey: RBIRVXJGAJBPAV-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human V1a receptor expressed in human 1321N1 cells assessed as decrease in Arg8-vasopressin-stimulated calcium flux by fluorometric calcium assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 480.05, ALogP 5, HBA 3, HBD 0, PSA 43.86, QED 0.62
Compound (SMILES): Nc1nnc(-c2ccccc2O)cc1N1CCNCC1
InChIKey: SZKHGLTYXIDOFH-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Inhibition of SMARCA4 BD (unknown origin)
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 271.32, ALogP 0.84, HBA 6, HBD 3, PSA 87.3, QED 0.75
Compound (SMILES): Cc1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: YDAOBULQBPBUCA-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 17.4 nM (pChEMBL 7.760000228881836)
Descriptors: MW 412.49, ALogP 1.21, HBA 5, HBD 4, PSA 147.46, QED 0.54
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: HTRPGUCLEKHUTO-TZPCGENMSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 218 nM (pChEMBL 6.659999847412109)
Descriptors: MW 1119.34
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(-c3nc4ccccc4c(=O)n3-c3ccc(OC)cc3)s2)cc1
InChIKey: UFKAMNUQGBWBJM-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 560.64, ALogP 6.45, HBA 8, HBD 1, PSA 95.34, QED 0.24
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(CN3CCN(S(N)(=O)=O)CC3)cc2)nc2sccc12
InChIKey: FXIKTRNSOFEJNE-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase F227L/V106A double mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 369 nM (pChEMBL 6.429999828338623)
Descriptors: MW 575.72, ALogP 4.7, HBA 9, HBD 2, PSA 137.47, QED 0.29
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccc(F)cc3)c3ccc(O)cc3)cc2)CC1.Cl
InChIKey: ZGYAUKANTNTUQP-FJISBNMDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 11900 nM (pChEMBL 4.920000076293945)
Descriptors: MW 473.63, ALogP 6.85, HBA 3, HBD 2, PSA 43.7, QED 0.35
Compound (SMILES): COc1ccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)cc1
InChIKey: RPMCBOIGGLBGEL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 1621.81 nM (pChEMBL 5.789999961853027)
Descriptors: MW 438.9, ALogP 4.1, HBA 4, HBD 1, PSA 50.8, QED 0.63
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(C#CC#Cc2ccc(-c3cnc([C@@H]4CCCN4C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]3)cc2-c2cccc(-c3ccccc3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: CUSIGCMDCJYENH-PLGVYSAESA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 2a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.449 nM (pChEMBL 9.350000381469727)
Descriptors: MW 863.03, ALogP 7.63, HBA 8, HBD 4, PSA 174.64, QED 0.1
Compound (SMILES): CC(C)Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)cc12
InChIKey: SFYLADBQGNFSOV-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin) by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 607.71, ALogP 5.31, HBA 7, HBD 5, PSA 151.47, QED 0.14
Compound (SMILES): Nc1nn2cc(-c3ccc(Cl)cc3)[nH]c2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: KBRGTQDAHIIWBV-GHVJWSGMSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 415.87, ALogP 3.63, HBA 7, HBD 3, PSA 143.99, QED 0.44
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CC(=O)O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: MNYBENXVWGLZEJ-YQSLKQGWSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 11.8 nM (pChEMBL 7.929999828338623)
Descriptors: MW 432.47, ALogP 0.72, HBA 7, HBD 4, PSA 128.56, QED 0.51
Compound (SMILES): CS(=O)(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: QBDMEXDBIHVBTA-SFHVURJKSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki < 0.28 nM (pChEMBL 9.553000450134277)
Descriptors: MW 450.53, ALogP -0.84, HBA 11, HBD 3, PSA 159.69, QED 0.5
Compound (SMILES): COc1ccc(-c2ccc3c(c2)COC3=O)n2nc(C3(C(=O)OCC(C)C)CC3)nc12
InChIKey: LUUUHUYQTLUIDG-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q08493
Assay: Inhibition of human PDE4C catalytic domain using cAMP and FAM-conjugated cAMP by IMAP FRET progressive binding assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 421.45, ALogP 3.31, HBA 8, HBD 0, PSA 92.02, QED 0.56
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4ccc(C(C)(C)C)cc4)c3n2)cn1
InChIKey: VQJUNEANVUYHDU-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human full length recombinant DYRK1A using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 331.42, ALogP 5.19, HBA 4, HBD 0, PSA 43.85, QED 0.51
Compound (SMILES): O=C1c2cc(Br)cc(Br)c2C(=O)C1(O)O
InChIKey: PIVDGZKJNCLWFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 2810 nM (pChEMBL 5.550000190734863)
Descriptors: MW 335.93, ALogP 1.27, HBA 4, HBD 2, PSA 74.6, QED 0.55
Compound (SMILES): Cc1cc(NC2CCc3cc(Br)ccc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: KUSWFJYHVKCDSX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63707
Assay: Inhibition of N-terminal His6-tagged rat DHODH expressed in Escherichia coli BL21 expressed in Escherichia coli BL21 using L-DHO as substrate and CoQ as co-substrate by DCIP dye based spectrophotometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): CCCCNNC(=O)c1ccc(OC)cc1
InChIKey: RFMNSSZOADXOBU-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 222.29, ALogP 1.73, HBA 3, HBD 2, PSA 50.36, QED 0.57
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2cccc(O)c2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: WAASVRUAWVMHCV-QRURJPQPSA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 1338.66