lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)n1nnnc1C(c1ccccc1)N1CCN(c2cccc(Cl)c2)CC1
InChIKey: NVGAXFXPUAFVHB-UHFFFAOYSA-N
Target: Mucolipin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IZK6
Assay: Agonist activity at human TRPML1 expressed in HEK293 cells incubated for 1 hr by FLIPR assay
Measurement: EC50 = 36900 nM (pChEMBL 4.429999828338623)
Descriptors: MW 396.93, ALogP 3.82, HBA 6, HBD 0, PSA 50.08, QED 0.66
Compound (SMILES): Cc1[nH]c(C(=O)Nc2ccc(C(N)=O)cc2N2CCOC(C)C2)c(Cl)c1Cl
InChIKey: YNLBRYHGQNTVQG-UHFFFAOYSA-N
Target: DNA topoisomerase 2-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P11388
Assay: Inhibition of human DNA topoisomerase 2 alpha assessed as relaxation of supercoiled plasmid pNO1 DNA incubated for 30 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 411.29, ALogP 3.21, HBA 4, HBD 3, PSA 100.45, QED 0.72
Compound (SMILES): CSc1ccc(C(=O)/C=C/c2cc(O)cc(O)c2)cc1
InChIKey: RJZCHVBMWLZCCN-FARCUNLSSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R4B8
Assay: Inhibition of NLRP3 inflammasome activation in mouse J774.A1 cells assessed as reduction in LPS-stimulated IL-1beta level pretreated for 1 hr followed by nigericin treatment for 1 hr by ELISA
Measurement: IC50 = 1570 nM (pChEMBL 5.800000190734863)
Descriptors: MW 286.35, ALogP 3.72, HBA 4, HBD 2, PSA 57.53, QED 0.51
Compound (SMILES): O=C1COc2ccc(N3CC(CCNCCC4Cc5cccc(Cl)c5C4)OC3=O)nc2N1
InChIKey: XFTTVFZHMRAGMV-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase ATPase activity incubated for 80 mins
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 456.93, ALogP 3.18, HBA 6, HBD 2, PSA 92.79, QED 0.62
Compound (SMILES): CN(Cc1ccncc1)c1ncnc2[nH]c(-c3ccc(CO)cc3)cc12
InChIKey: KOTRVAMMDDKVHE-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (530 to 910 residues) (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 345.41, ALogP 3.15, HBA 5, HBD 2, PSA 77.93, QED 0.58
Compound (SMILES): CNc1nc2ccccc2n1-c1nc(N2CCOC[C@H]2C)c2scc([S+](C)[O-])c2n1
InChIKey: ANDBABGYQBFAHL-KTDAUSLXSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR (unknown origin)
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 442.57, ALogP 3.03, HBA 9, HBD 1, PSA 91.16, QED 0.49
Compound (SMILES): Cc1ccc(S(=O)(=O)n2c(C)c(-c3cnc(NCc4ccco4)n4cnnc34)c3ccccc32)cc1
InChIKey: AUPDOUQWHYGBCZ-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: Binding affinity to recombinant human N-terminal GST tagged EED (1 to 441 residues) expressed in Escherichia coli BL21 (DE3) assessed as inhibition of EED interaction to H3K27me3 peptide incubated for 2 hrs in presence of biotinylated H3K27me3 peptide (19 to 33 residues) by HTRF assay
Measurement: IC50 = 195.75 nM (pChEMBL 6.710000038146973)
Descriptors: MW 498.57, ALogP 4.8, HBA 9, HBD 1, PSA 107.32, QED 0.35
Compound (SMILES): COc1nnc(NC(=O)c2cnc(C)cc2-c2ccc3c(c2)C(=O)NC3)s1
InChIKey: QJCBBUJAOWSXEE-UHFFFAOYSA-N
Target: DNA polymerase theta (SINGLE PROTEIN), Homo sapiens
UniProt: O75417
Assay: Inhibition of human DNA polymerase theta (1 to 899 residues) ATPase activity using dT50 single strand DNA as substrate by NADH oxidation-coupled enzymatic assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 381.42, ALogP 2.41, HBA 7, HBD 2, PSA 106.1, QED 0.72
Compound (SMILES): COc1c(COc2ccc(CNCCNC(C)=O)c(OCc3cccc(F)c3)c2)cccc1-c1ccccc1
InChIKey: YTLSMCCLGQYYLS-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/PD-L1 interaction (unknown origin) incubated for 1 hr by HTRF assay
Measurement: IC50 = 11300 nM (pChEMBL 4.949999809265137)
Descriptors: MW 528.62, ALogP 5.89, HBA 5, HBD 2, PSA 68.82, QED 0.21
Compound (SMILES): Cc1cc(Nc2nc(NCc3ccc(Cl)c(C(=O)Nc4ccc(F)cc4)c3)nc3c2cnn3C2CCOCC2)n[nH]1
InChIKey: JWODVWOSUKHGSK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00444
Assay: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay
Measurement: IC50 = 23.4 nM (pChEMBL 7.630000114440918)
Descriptors: MW 576.04, ALogP 5.61, HBA 9, HBD 4, PSA 134.67, QED 0.19
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2cc(Cl)c(-c3cccc(C#N)c3)c(Cl)c2)cc1
InChIKey: CTGZCTCAWVZFIP-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at biotinylated APC-labeled RORgammat LBD (unknown origin) assessed as inhibition of europium-labeled SRC1 coactivator peptide recruitment incubated for 1 hr by dual FRET assay
Measurement: XC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 473.38, ALogP 5.51, HBA 4, HBD 1, PSA 87.03, QED 0.51
Compound (SMILES): COc1cc(C#N)ccc1COc1cccc(N2C=NN(Cc3nc4c(F)cc(C(=O)O)cc4n3C[C@@H]3CCO3)CC2)n1
InChIKey: IWSFXPJTZZPMBZ-QFIPXVFZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 585.6, ALogP 3.78, HBA 11, HBD 1, PSA 138.33, QED 0.29
Compound (SMILES): CN(C)c1ccc2nc[nH]c(=O)c2c1
InChIKey: QEZGFZRXRIPXJC-UHFFFAOYSA-N
Target: Inositol hexakisphosphate kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92551
Assay: Inhibition of IP6K1 (unknown origin) incubated for 30 min in presence of ATP by ADPGlo reagent based assay
Measurement: IC50 = 75400 nM (pChEMBL 4.119999885559082)
Descriptors: MW 189.22, ALogP 0.99, HBA 3, HBD 1, PSA 48.99, QED 0.73
Compound (SMILES): CCOP(=O)(OCC)C(Nc1nncs1)c1ccc(OCc2nc3ccccc3c(=O)n2-c2ccc(F)cc2)c(OC)c1
InChIKey: ZVCIGFZJQSFSGN-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by DTNB based Ellman's method
Measurement: IC50 = 361 nM (pChEMBL 6.440000057220459)
Descriptors: MW 625.62, ALogP 6.34, HBA 12, HBD 1, PSA 126.69, QED 0.15
Compound (SMILES): CC(C)(Oc1cccc(C2CCCN(C(=O)OCC3CCCCC3)C2)c1)C(=O)O
InChIKey: DPYJZJDKDKILKG-UHFFFAOYSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of N-terminal His6-tagged full-length recombinant beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 DE3/N-terminal FAM tagged BCL9 HD2(350 to 375 residues) (unknown origin) protein-protein interaction assessed as inhibition constant incubated for 3 hrs by competitive fluorescence polarization assay
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 403.52, ALogP 4.82, HBA 4, HBD 1, PSA 76.07, QED 0.74
Compound (SMILES): Nc1nncc2cc(C3CCN(c4ccccc4)CC3)ccc12
InChIKey: UQTNTBSIGQMKDY-UHFFFAOYSA-N
Target: Complement C1s subcomponent (SINGLE PROTEIN), Homo sapiens
UniProt: P09871
Assay: Inhibition of human recombinant N-terminal IgG tagged and C-terminal His tagged C1S (358 to 688 aa residues) expressed in HEK293 cells using Z-Lys-SBzl peptide as substrate pretreated with compound followed by substrate addition incubated for 60 mins
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 304.4, ALogP 3.6, HBA 4, HBD 1, PSA 55.04, QED 0.79
Compound (SMILES): Cc1cc(N)nc(-c2c(Cl)cc3c(N4CCNC[C@@H]4C)nc(OC[C@@H]4CCCN4C)nc3c2F)c1C(F)(F)F
InChIKey: XPOSONRWHCKUDU-GJZGRUSLSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of GDP-bound biotinylated-KRAS G12D mutant (1 to 169 residues) (unknown origin) assessed as suppression of SOS1-mediated nucleotide exchange by measuring reduction in KRAS G12D mutant-RAF RBD complex formation preincubated for 60 mins followed by SOS1 addition and further incubated for 60 mins and subsequent addition of KRAS G12D mutant-RAF RBD mixture measured after 30 to 60 mins by FRET assay
Measurement: IC50 = 76.9 nM (pChEMBL 7.110000133514404)
Descriptors: MW 568.02, ALogP 4.66, HBA 8, HBD 2, PSA 92.43, QED 0.43
Compound (SMILES): C#CCCC1(CCOc2ccc(CNc3nc(NCC4(N)CC4)nc4c3cnn4C)cc2Cl)N=N1
InChIKey: CMQXENABWJZPPM-UHFFFAOYSA-N
Target: RNA 5'-monophosphate methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z5W3
Assay: Inhibition of BCDIN3D (unknown origin) using mini-helix and SAM as substrate incubated for 1 hr by RapidFire High Throughput mass spectrometry
Measurement: IC50 = 179 nM (pChEMBL 6.75)
Descriptors: MW 494, ALogP 3.88, HBA 10, HBD 3, PSA 127.63, QED 0.33
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3c(OCc4ccncc4)cc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: JQPGWBRHOSJHIJ-UHFFFAOYSA-N
Target: DNA gyrase subunit B (SINGLE PROTEIN), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli full length wildtype GyrB24 (residue 1 to 220) supercoiling in presence of pNO1 plasmid incubated for 30 mins by microplate reader assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 477.33, ALogP 5.16, HBA 6, HBD 3, PSA 117.2, QED 0.35
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)ncc1F)N1[C@H]2CC[C@@H]1c1ccnc(F)c1C2
InChIKey: ANKKWFQGAFZQSN-ISVAXAHUSA-N
Target: G-protein coupled receptor 65 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IYL9
Assay: Antagonist activity at recombinant human GPR65 expressed in human 1321N1 cells assessed as reduction in cAMP level incubated for 30 mins by HTRF assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 384.31, ALogP 4.07, HBA 3, HBD 1, PSA 58.12, QED 0.6
Compound (SMILES): Cc1ccc(OCCNCCCF)c(F)c1[C@@H]1c2[nH]c3ccccc3c2C[C@@H](C)N1CC(F)(F)F
InChIKey: VDHHNYKYQYVKKQ-CRICUBBOSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by LanthaScreen TR-FRET competitive binding assay
Measurement: IC50 = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 495.54, ALogP 5.84, HBA 3, HBD 2, PSA 40.29, QED 0.29
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC[C@@H](NC(=O)Nc3ccccc3F)C2)nc1
InChIKey: JCECPTHRURCVHN-LLVKDONJSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 379.42, ALogP 1.27, HBA 5, HBD 3, PSA 117.42, QED 0.74
Compound (SMILES): COc1cccc(-c2cccc(Nc3nc(NCCN)nc4c3cnn4C)c2)c1
InChIKey: KYTLYDWYJOSGIH-UHFFFAOYSA-N
Target: RNA 5'-monophosphate methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z5W3
Assay: Inhibition of BCDIN3D (unknown origin) using mini-helix and SAM as substrate incubated for 1 hr by RapidFire High Throughput mass spectrometry
Measurement: IC50 = 762.2 nM (pChEMBL 6.119999885559082)
Descriptors: MW 389.46, ALogP 3.15, HBA 8, HBD 3, PSA 102.91, QED 0.45
Compound (SMILES): CCOc1ncccc1-c1ccc(N2CCN(C(=O)c3ccc(Cl)cc3C(F)(F)F)C[C@H]2CC)c(C(=O)NCCNC)c1
InChIKey: LSQCQZGUVZRQPB-JOCHJYFZSA-N
Target: Adrenocorticotropic hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01718
Assay: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 618.1, ALogP 5.51, HBA 6, HBD 2, PSA 86.8, QED 0.29
Compound (SMILES): Cc1ccc(C(C)(C)C)cc1Nc1nc(C(=O)NS(=O)(=O)N(C)C)co1
InChIKey: LJBQOGPXGDQSHL-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 in LPS/nigericin-induced human THP-1 cells assessed as inhibition of IL-1beta production pretreated with LPS for 3 hrs followed by incubation with compound for 15 mins and later stimulated with nigericin for 90 mins by AlphaLISA assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 380.47, ALogP 2.56, HBA 6, HBD 2, PSA 104.54, QED 0.83
Compound (SMILES): Cc1ccc(OCCNCCCF)cc1[C@@H]1c2[nH]c3ccccc3c2C[C@@H](C)N1CC(F)(F)F
InChIKey: GDFODPGZJWMOLV-IQGLISFBSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by LanthaScreen TR-FRET competitive binding assay
Measurement: IC50 = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 477.55, ALogP 5.7, HBA 3, HBD 2, PSA 40.29, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)CCCC[C@@H]2SC[C@@H]3NC(=O)N[C@@H]32)cc1
InChIKey: PYUKJNGCYVMNAJ-ZOBUZTSGSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant preincubated for 15 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 426.56, ALogP 0.72, HBA 5, HBD 4, PSA 130.39, QED 0.34
Compound (SMILES): NCC(O)c1cccc(OCC2CCCCC2)c1
InChIKey: SLBRDVHUUWJYQS-UHFFFAOYSA-N
Target: Retinoid isomerohydrolase (SINGLE PROTEIN), Bos taurus
UniProt: Q28175
Assay: Inhibition of RPE65 in bovine microsomes assessed as reduction on 11-cis-retinol production incubated for 1 hr by HPLC analysis
Measurement: IC50 = 3190 nM (pChEMBL 5.5)
Descriptors: MW 249.35, ALogP 2.64, HBA 3, HBD 2, PSA 55.48, QED 0.84
Compound (SMILES): COc1ccc(-c2nc(Nc3ccc(CC(N)=O)cc3)nc(Oc3c(Cl)cccc3Cl)n2)cc1
InChIKey: JWGPHGQFEKHZLA-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GST-tagged RORgammat ligand binding domain (unknown origin) assessed as inhibition of biotinylated SRC1/SA-APC recruitment incubated for 1 hr by dual FRET assay
Measurement: IC50 = 18.1 nM (pChEMBL 7.739999771118164)
Descriptors: MW 496.35, ALogP 5.42, HBA 7, HBD 2, PSA 112.25, QED 0.34
Compound (SMILES): CC(C)CC1(CCOc2cc(Cl)cc(CC(=O)O)c2)CCN(c2nc3ccc(Cl)cc3s2)CC1
InChIKey: WTRKBMOSZADWDF-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human PPARdelta (138 to 441 residues) expressed in CHO-K1 cells co-transfected with GAL4 and pGluc reporter gene plasmid assessed as receptor transactivation incubated for 24 to 28 hrs by luciferase reporter gene assay
Measurement: EC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 521.51, ALogP 7.33, HBA 5, HBD 1, PSA 62.66, QED 0.32
Compound (SMILES): C/C=C/C(=O)NCc1cc(NC2CCN(C)CC2)c2cc(OC)c(OCCCN3CCCC3)cc2n1
InChIKey: KVCAIHGGEZGHSN-XBXARRHUSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a (unknown origin) by AlphaLISA assay
Measurement: IC50 = 0.52 nM (pChEMBL 9.279999732971191)
Descriptors: MW 495.67, ALogP 3.81, HBA 7, HBD 2, PSA 78.96, QED 0.36
Compound (SMILES): CC(C)(C)CNCc1ccc2nc(Cn3cc(-c4cc(Cl)cc5[nH]ncc45)nn3)cn2c1
InChIKey: GLBCKELBHNMCSM-UHFFFAOYSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of full length His-tagged METTL3 (unknown origin) co-expressed with full length FLAG-tagged METTL14 in baculovirus expression system preincubated using 5'P-uacacucgaucuggacuaaagcugcuc-3' as substrate and SAM as cosubstrate pre-incubated for 10 mins followed by addition of substrates and measured after 60 mins by RapidFire mass spectrometry (RF/MS) analysis
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 448.96, ALogP 4.31, HBA 7, HBD 2, PSA 88.72, QED 0.4
Compound (SMILES): CC#CC(=O)N1CCC2(CC1)CN(C1=C(Cl)C(=O)c3cccnc3C1=O)C2
InChIKey: YDIINXBBPNTGSJ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD2 (SINGLE PROTEIN), Homo sapiens
UniProt: O96028
Assay: Inhibition of recombinant human NSD2 (941 to 1240 residues) using SAM as substrate incubated for 3 hrs by AlphaLISA assay
Measurement: IC50 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 383.84, ALogP 1.86, HBA 5, HBD 0, PSA 70.58, QED 0.69
Compound (SMILES): O=C(O)c1ccccc1OCCc1cn(-c2ccc(-c3ccccc3)cc2)c2ccc(-c3ccc(F)cc3)cc12
InChIKey: CVCHHVMZVRQNST-UHFFFAOYSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9HCE5
Assay: Inhibition of METTL3/METTL14 (unknown origin)
Measurement: IC50 = 2950 nM (pChEMBL 5.53000020980835)
Descriptors: MW 527.6, ALogP 8.42, HBA 3, HBD 1, PSA 51.46, QED 0.22
Compound (SMILES): CN(C)S(=O)(=O)Nc1ccc(NCC2CCCO2)nc1Nc1ccc2[nH]nnc2c1
InChIKey: WMHVUKOICBIIMZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of N-terminal GST-tagged/C-terminal 6His-tagged BRD4 BD1 (47 to 170 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using SGRGK(Ac)GGK(Ac)GLGK(Ac) GGAK(Ac)RHRK-biotinylated peptide as substrate incubated for 60 mins by alpha screen assay
Measurement: IC50 = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 432.51, ALogP 1.91, HBA 8, HBD 4, PSA 137.16, QED 0.42
Compound (SMILES): CC1=NN(c2nc(-c3ccc(F)cc3)cs2)C(=O)/C1=C/c1ccc(C(=O)O)cc1
InChIKey: FIVOQEQVFUNHEA-LICLKQGHSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human SIRT5 by fluorescence based analysis
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 407.43, ALogP 4.45, HBA 5, HBD 1, PSA 82.86, QED 0.65
Compound (SMILES): COc1ccc(-c2ccc3[nH]c(C(=O)N4CCc5cc(OC)c(OC)cc5C4)cc3c2)c(OC)c1
InChIKey: WXVDSVAMBGPONC-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp-mediated multidrug resistance in doxorubicin-resistant human MCF7/ADR cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 incubated for 48 hrs by CCK-8 assay
Measurement: IC50 = 437 nM (pChEMBL 6.360000133514404)
Descriptors: MW 472.54, ALogP 5.07, HBA 5, HBD 1, PSA 73.02, QED 0.42
Compound (SMILES): CC1(COc2ccc(Nc3ncc(C(F)(F)F)c(N[C@H]4CC[C@@H](O)CC4)n3)cc2)COC1
InChIKey: RRANDNHQYJZJJN-FZNQNYSPSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild type FLT3 (unknown origin)
Measurement: IC50 = 9.46 nM (pChEMBL 8.020000457763672)
Descriptors: MW 452.48, ALogP 4.37, HBA 7, HBD 3, PSA 88.53, QED 0.57
Compound (SMILES): O=C(c1ccccc1)N1CCN(c2nnc(Cc3ccccc3)c3ccccc23)CC1
InChIKey: VVVOXIMEZCMSSA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 (unknown origin) by FRET assay
Measurement: IC50 = 62.46 nM (pChEMBL 7.199999809265137)
Descriptors: MW 408.5, ALogP 4.18, HBA 4, HBD 0, PSA 49.33, QED 0.51
Compound (SMILES): CCOP(=O)(OCC)C(Nc1ccccc1C(F)(F)F)c1ccc(OCc2nc3ccccc3c(=O)n2-c2ccc(F)cc2)c(OC)c1
InChIKey: KXDQPAPDYNGFQI-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by DTNB based Ellman's method
Measurement: IC50 = 341 nM (pChEMBL 6.46999979019165)
Descriptors: MW 685.61, ALogP 8.51, HBA 9, HBD 1, PSA 100.91, QED 0.1
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3ccc(C(=O)NO)cc3)s2)n1
InChIKey: UAEQCSXHYDCDJO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length N-terminal GST-tagged human recombinant HDAC6 (1 to 1215 residues) expressed in Sf9 cells using ZMAL as fluorogenic substrate incubated for 90 mins by microplate reader analysis
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 429.53, ALogP 2.99, HBA 8, HBD 3, PSA 117.1, QED 0.23
Compound (SMILES): Cc1cc(-c2cc(Cl)ncc2OC(F)F)c(C(=O)Nc2nnc(O[C@H]3CC[C@@](C)(O)CC3)s2)cn1
InChIKey: BXXFGSUEVFQGFZ-LMRGUYSOSA-N
Target: DNA polymerase theta (SINGLE PROTEIN), Homo sapiens
UniProt: O75417
Assay: Inhibition of human DNA polymerase theta (1 to 899 residues) ATPase activity using dT50 single strand DNA as substrate by NADH oxidation-coupled enzymatic assay
Measurement: IC50 <= 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 525.97, ALogP 4.88, HBA 9, HBD 2, PSA 119.35, QED 0.42
Compound (SMILES): CC(=O)N1CCC(Nc2cc3c(cn2)C2(CC2)CN(C[C@H](O)CN2CCc4ccccc4C2)C3=O)CC1
InChIKey: GIIXXTIREUPXSF-XMMPIXPASA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG potassium channel in human HEK293 cells by manual patch clamp assay
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 503.65, ALogP 2.41, HBA 6, HBD 2, PSA 89.01, QED 0.63
Compound (SMILES): O=C(N[C@@H]1CN(C(=O)c2ccccc2)CC[C@H]1c1ccc(F)c(F)c1)c1cc2c(s1)OCCn1ncc(Br)c1-2
InChIKey: CBNVPJOTRQVATB-FDDCHVKYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT1 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 613.48, ALogP 5.47, HBA 6, HBD 1, PSA 76.46, QED 0.33
Compound (SMILES): Cc1ccc2c(c1)[C@@H](N)C1(CCN(c3cnc4nc(Sc5ccnc(N)c5Cl)ccc4n3)CC1)C2
InChIKey: ZJCWKDUZVMTXRX-HSZRJFAPSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant full length 6His-tagged SHP2 (2 to 527 residues) (unknown origin) expressed in Escherichia coli using DiFMUP as substrate incubated for 15 mins by microplate reader analysis
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 504.06, ALogP 4.96, HBA 8, HBD 2, PSA 106.84, QED 0.4
Compound (SMILES): CCN1CCC[C@@H](Nc2cc(C)c(-c3ccc(C#N)cc3O)nn2)C1.O=CO
InChIKey: AEVGCUPGIBWAQT-XFULWGLBSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated with compound for 3 hrs followed by nigericin stimulation and measured after 1 hrs by resazurin dye based plate reader analysis
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 337.43, ALogP 2.93, HBA 6, HBD 2, PSA 85.07, QED 0.89
Compound (SMILES): CCN(CC)CCCNc1cc2nc(/C=C/c3ccc(C(C)C)cc3)n(Cc3cccc(Br)c3)c(=O)c2cc1F
InChIKey: SNHQVYACCUJHMV-DTQAZKPQSA-N
Target: RecQ-like DNA helicase BLM (SINGLE PROTEIN), Homo sapiens
UniProt: P54132
Assay: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5'-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 605.6, ALogP 7.78, HBA 5, HBD 1, PSA 50.16, QED 0.17
Compound (SMILES): CC(C)C(=O)N(CC(C)N1CCC(c2ccccc2)CC1)c1ccccn1
InChIKey: YVSNWYWRNYSZHQ-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at mu-opioid receptor (unknown origin) expressed in CHO cells assessed as inhibition of intracellular cAMP production measured after 45 mins by HTRF-based assay
Measurement: EC50 = 200.6 nM (pChEMBL 6.699999809265137)
Descriptors: MW 365.52, ALogP 4.34, HBA 3, HBD 0, PSA 36.44, QED 0.76
Compound (SMILES): CN1CCC=C(c2n[nH]c3c(Cl)cc(F)cc23)C1
InChIKey: LBFGAEZHJXZHFC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at 5-HT2A (unknown origin) expressed in HEK293T cells co-transfected with RLuc-fused Galphaq/GFP2/Gy9/Gbeta3 assessed as Gaq hetero trimeric G protein activation incubated for 30 mins using coelenterazine 400a as a substrate by BRET assay
Measurement: EC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 265.72, ALogP 3.07, HBA 2, HBD 1, PSA 31.92, QED 0.86
Compound (SMILES): Cc1c(OCCN2CC(CF)C2)ccc(F)c1[C@@H]1c2[nH]c3ccccc3c2C[C@@H](C)N1C[C@H](C)C(=O)O
InChIKey: JFQOQCQVFRGWOZ-QLPUUCHCSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by LanthaScreen TR-FRET competitive binding assay
Measurement: IC50 = 2.512 nM (pChEMBL 8.600000381469727)
Descriptors: MW 511.61, ALogP 4.95, HBA 4, HBD 2, PSA 68.8, QED 0.43
Compound (SMILES): CCN(CC)C(=O)c1ccc2c(c1)nc(Cc1ccc(OC(=O)N(C)C)cc1)n2CCC(C)C
InChIKey: SKPVSXMCZMZIKN-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Pseudo-irreversible inhibition of human BChE using butyrylthiocholine iodide as substrate incubated for 20 mins followed by substrate addition by Ellman's method based UV analysis
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 464.61, ALogP 5.22, HBA 5, HBD 0, PSA 67.67, QED 0.44
Compound (SMILES): Cc1cn(CC(=O)N[C@@H](CCCCn2cc(-c3ccncc3F)nn2)C(N)=O)c(=O)[nH]c1=O
InChIKey: SYXMAANOUXWFDG-HNNXBMFYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Binding affinity to TNKS1 (unknown origin) assessed as dissociation constant
Measurement: Kd = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 458.45, ALogP -0.52, HBA 9, HBD 3, PSA 170.65, QED 0.34
Compound (SMILES): Cc1n[nH]c2ccc(-c3cnc4ccc(N5CCOC(C)(C)C5)nn34)cc12
InChIKey: LTURCSDXMCABMJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of human TAK1 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 362.44, ALogP 3.2, HBA 6, HBD 1, PSA 71.34, QED 0.59
Compound (SMILES): O=C(O)C1CCc2ccc(-c3cccc(Cl)c3OC3CCC3)cc21
InChIKey: ILFWIPWRPDLECC-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Displacement of 1,8-ANS from FABP4 (unknown origin) assessed as inhibition constant by fluorescence based analysis
Measurement: Ki = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 342.82, ALogP 5.05, HBA 2, HBD 1, PSA 46.53, QED 0.84
Compound (SMILES): COc1ccc(-c2ocnc2C(=O)NCCCCNC(=O)c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc1Cl
InChIKey: ZTSKCBNHQFCIHV-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEE as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by Kinase-Glo luminescent kinase assay
Measurement: IC50 = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 556.1, ALogP 6.24, HBA 6, HBD 3, PSA 113.69, QED 0.27
Compound (SMILES): Cc1n[nH]c2ccc(-c3cnc4ccc(N5C[C@@H]6C[C@H]5CO6)nn34)cc12
InChIKey: SNQYZBOKCGMIJQ-KBPBESRZSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of human TAK1 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot kinase assay
Measurement: IC50 = 208 nM (pChEMBL 6.679999828338623)
Descriptors: MW 346.39, ALogP 2.56, HBA 6, HBD 1, PSA 71.34, QED 0.6
Compound (SMILES): O=[N+]([O-])c1ccc(-n2cc(COc3ccnc4cc(Cl)ccc34)nn2)cc1
InChIKey: ARTQBCIGFSSHOE-UHFFFAOYSA-N
Target: Falcipain 2 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q9N6S8
Assay: Inhibition of recombinant Plasmodium falciparum FP2 using ZFR-AMC as substrate incubated for 10 mins by fluorescence based assay
Measurement: IC50 = 16160 nM (pChEMBL 4.789999961853027)
Descriptors: MW 381.78, ALogP 3.96, HBA 7, HBD 0, PSA 95.97, QED 0.38
Compound (SMILES): COc1ccc(-c2ccc3c(c2)-n2c(nnc2-c2ccc(N4CCNCC4)c(C(F)(F)F)c2)CC(=O)N3)cn1
InChIKey: PTKYEQBTNBDEQV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase RIO2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BVS4
Assay: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant by KINOMEscan assay
Measurement: Kd > 1000 nM (pChEMBL 6)
Descriptors: MW 535.53, ALogP 3.93, HBA 8, HBD 2, PSA 97.2, QED 0.41
Compound (SMILES): CCC(NC(=O)c1ccc(-c2cncc(OC(C)C)n2)cc1)c1ccnc(NS(=O)(=O)C2CC2)n1
InChIKey: TVMPQKOUKVAQRZ-UHFFFAOYSA-N
Target: CTP synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17812
Assay: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 496.59, ALogP 3.51, HBA 8, HBD 2, PSA 136.06, QED 0.44
Compound (SMILES): CC(C)CN(C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)Cc1cccc(O)c1)S(=O)(=O)c1ccc(N)cc1
InChIKey: KQIZNFRJIDGOSS-RRPNLBNLSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of HIV-1 protease by fluorescence resonance energy transfer analysis
Measurement: IC50 = 5.55 nM (pChEMBL 8.260000228881836)
Descriptors: MW 525.67, ALogP 2.95, HBA 6, HBD 4, PSA 132.96, QED 0.27
Compound (SMILES): CN(CC1CCN(Cc2ccccc2)CC1)c1ncnc2[nH]c(-c3ccc(CO)cc3)nc12
InChIKey: BRILIZSIILQKKP-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (unknown origin) using FRET-peptide as substrate incubated in presence of ATP by FRET based Z-LYTE assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 442.57, ALogP 3.86, HBA 6, HBD 2, PSA 81.17, QED 0.45
Compound (SMILES): Nc1nnc(-c2ccccc2O)cc1N1CCCCC1
InChIKey: RJVQZTLPHCJXNB-UHFFFAOYSA-N
Target: Protein polybromo-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U86
Assay: Binding affinity to PBRM1 bromodomain 5 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay
Measurement: Kd = 10 nM (pChEMBL 8)
Descriptors: MW 270.34, ALogP 2.42, HBA 5, HBD 2, PSA 75.27, QED 0.88
Compound (SMILES): Cc1c(OCc2nnc(SCc3cccc(CN4CCCCC4C(=O)O)c3)o2)cccc1-c1ccccc1
InChIKey: JLPPDOMCBOXTJL-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/PD-L1 (unknown origin) protein-protein interaction by HTRF assay
Measurement: IC50 = 82.5 nM (pChEMBL 7.079999923706055)
Descriptors: MW 529.66, ALogP 6.36, HBA 7, HBD 1, PSA 88.69, QED 0.24
Compound (SMILES): CCOC(=O)CNc1ncnc2sc3c(c12)CCCC3
InChIKey: KUZKNHMNMHRTPV-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of sheep COX-1
Measurement: IC50 = 15150 nM (pChEMBL 4.820000171661377)
Descriptors: MW 291.38, ALogP 2.55, HBA 6, HBD 1, PSA 64.11, QED 0.88
Compound (SMILES): Cc1ncsc1C(CNC(=O)c1c(F)cccc1Cl)N1CCC(OCc2cc(F)cc(F)c2)CC1
InChIKey: PRXRNXLRIFVBAQ-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: human P2X7 channel assay by automated patch-clamp: In order to directly monitor the block of P2X7 channel, an electrophysiological assay was developed and implemented on the QPatch16X automated electrophysiology instrument.HEK-293 cells expressing the P2X7 channels were cultured in modified EMEM.72 hours before experiment, 5 million cells were seeded onto T225 flasks. Just before the experiment cells were washed twice, detached from the flask with trypsin-EDTA, re-suspended in the suspension solution and placed on the QPatch 16x.The compounds (20 mM in a 100% DMSO) stored at −20° C. were prepared the day of the experiment (a first dilution 1:20 in 100% DMSO to prepare a 1 mM stock solution, then a 1 microM solution in external solution+a serial dilution 1:10).The standard whole-cell voltage clamp experiments were performed at room temperature. For these experiments the multihole technology was used and the data were sampled at 2 KHz.The intracellular solution contained (mM) 135 CsF, 10 NaCl, 1 EGTA, 10 HEPES, (pH 7.2 with CsOH) whereas the extracellular contained (mM) 145 NaCl, 4 KCl, 0.5 MgCl2, 1 CaCl2, 10 HEPES, 10 Glc (pH 7.4 with NaOH).After establishment of the seal and the passage in the whole cell configuration, the cells were held at −80 mV. The P2XR7 current was evoked by applying 100 microM of BzATP alone (4 times) and then in the presence increasing concentrations of the compound under investigation (1, 10, 100 and 1000 nM).The pre-incubation periods 5 to 8 contain increasing concentrations of the compound of interest (1, 10, 100 and 1000 nM), as illustrated in FIGURE.The maximal inward current evoked by BzATP in absence or presence of increasing concentrations of the compounds under investigation was measured and normalized. The potential modulatory effect was measured as % of control and as IC50 determined fitting the dose-response curves data with the following equation:Y=100/(1+10^((Log IC50-X)*HillSlope))where:X: log of concentrationY: normalized response, 100% down to 0%, decreasing as X increases.LogIC50: same log units as XHillSlope: slope factor or HS, unitless.
Measurement: IC50 = 35.1 nM (pChEMBL 7.460000038146973)
Descriptors: MW 524.01, ALogP 5.67, HBA 5, HBD 1, PSA 54.46, QED 0.41
Compound (SMILES): CCn1c(=O)[nH]c(=O)c2c1nc(Cc1cn3c(n1)CCCC3)n2Cc1ccccc1
InChIKey: XFMJUABYLXDYGS-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17752
Assay: In Vitro Enzyme Activity Assay: The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, Mass., USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).
Measurement: IC50 = 412 nM (pChEMBL 6.380000114440918)
Descriptors: MW 404.47, ALogP 2.08, HBA 7, HBD 1, PSA 90.5, QED 0.55
Compound (SMILES): CSc1ccc(CNC(=O)[C@H]2CCCN(c3ncnc4nn(-c5ccc(CO)cc5)cc34)C2)cc1
InChIKey: DIOSHJCPGOFTBT-FQEVSTJZSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Positive allosteric modulation of C-terminal His6-tagged wild type human NAMPT using NAM and PRPP as substrates measured for 1 hr by NMNAT1-coupled enzyme assay
Measurement: EC50 = 313 nM (pChEMBL 6.5)
Descriptors: MW 488.62, ALogP 3.56, HBA 8, HBD 2, PSA 96.17, QED 0.38
Compound (SMILES): C[C@@H](CC(=O)O)c1ccc(OCc2ccc3c(-c4cc(Cl)c(CO)c(Cl)c4)nn(C4CCCC4)c3c2)cc1
InChIKey: SUAYMYLVEKORAN-SFHVURJKSA-N
Target: Chemerin-like receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99788
Assay: Antagonist activity at human CMKLR1 expressed in CHO-K1 cells co-expressing Galpha-16 assessed as change in intracellular calcium concentration incubated for 30 mins in presence of chemerin-9 by FLIPR calcium 5 assay
Measurement: IC50 = 38.9 nM (pChEMBL 7.409999847412109)
Descriptors: MW 553.49, ALogP 7.77, HBA 5, HBD 2, PSA 84.58, QED 0.22
Compound (SMILES): O=C(CCCCCCNC(=O)c1ncc(-c2ccc(C(F)(F)F)cc2)o1)NO
InChIKey: KTLIMLRKGNTACF-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human HDAC1 using Boc-Lys (acetyl)-AMC as substrate pretreated with compound for 1 hrs followed by substrate addition measured after 1 hrs by microplate reader analysis
Measurement: IC50 = 42.82 nM (pChEMBL 7.369999885559082)
Descriptors: MW 399.37, ALogP 3.55, HBA 5, HBD 3, PSA 104.46, QED 0.34
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(Nc2ccc(C#N)cc2)nc2c1CN(C(=O)c1ccc([N+](=O)[O-])cc1)CC2
InChIKey: HAZDLVVWMDFKQZ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase assessed as assessed as reduction of biotin-dUTP incorporation into protein incubated for 1 hrs by ELISA analysis
Measurement: IC50 = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 545.56, ALogP 5.48, HBA 9, HBD 1, PSA 158.07, QED 0.24
Compound (SMILES): Cc1ccc(C2=C(n3ccnn3)C(=O)N[C@@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)C2)cc1
InChIKey: PPMZNAUMLDUKGH-QHCPKHFHSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: Inhibition of human MGAT2 using 2-oleoylglycerol and oleoyl-coenzyme A as substrate by LC-MS analysis
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 524.47, ALogP 5.65, HBA 5, HBD 1, PSA 69.04, QED 0.32
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)N[C@H]4CCC(=O)NC4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: UWHASCJACBEQFV-QJPLHOCPSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin) using UCUGGACUAAA-biotin and 3H-SAM as substrates incubated for 30 mins and measured by TopCount scintillation counter method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 456.46, ALogP -1.57, HBA 11, HBD 5, PSA 182.44, QED 0.31
Compound (SMILES): COC/C=C/C(=O)N1CC[C@H](n2ncc3c(O[C@@H](C)[C@@H]4CCCN4C)nc4c(F)c(-c5nccc6cccc(C#N)c56)c(Cl)cc4c32)C[C@H]1CC#N
InChIKey: HYPQQUNFPQOUSP-VDAYNZGYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant (unknown origin) by measuring exchange of bodipy-GDP for GppNHp incubated for 2 hrs
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 721.24, ALogP 6.97, HBA 10, HBD 0, PSA 133.19, QED 0.15
Compound (SMILES): C[C@H]1CCN1c1nc(N2CCC(C)(CC(=O)O)C2)cc(C(F)(F)F)c1C#N
InChIKey: VSMIGCJYQSVJIX-PIJUOJQZSA-N
Target: Ketohexokinase (SINGLE PROTEIN), Homo sapiens
UniProt: P50053
Assay: Inhibition of N-terminal his tagged human recombinant KHK-C expressed in Escherichia coli incubated for 60 mins in presence of ATP by ADP Glo assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 382.39, ALogP 3.26, HBA 5, HBD 1, PSA 80.46, QED 0.86
Compound (SMILES): O=c1[nH]c(-c2ccc(OCCCCCC(F)(F)F)cc2)cc(-c2ccc(C3CC3)s2)c1-c1nnn[nH]1
InChIKey: MIIWSEIHLORHLV-UHFFFAOYSA-N
Target: 2-acylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q80W94
Assay: Inhibition of mouse MGAT2 by LC-MS analysis
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 515.56, ALogP 6.33, HBA 6, HBD 2, PSA 96.55, QED 0.24
Compound (SMILES): OC(CNCc1cccc(Cl)c1)Cn1c2ccccc2c2ccccc21
InChIKey: RBGYMEZQFLKKGL-UHFFFAOYSA-N
Target: Dynamin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05193
Assay: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 364.88, ALogP 4.6, HBA 3, HBD 2, PSA 37.19, QED 0.52
Compound (SMILES): N/C(=N\c1cncnc1)N1CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: UOTATAAQOIWXBF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric Inhibition of H2N-LN(pY)IDLDLV(dPEG8)LST(pY)ASINFQKASINFQK-amide-activated SHP2 (unknown origin) using DiFMUP as substrate pretreated with enzyme for 1 hr followed by substrate addition and measured after 20 mins by fluorescence based analysis
Measurement: IC50 = 210.4 nM (pChEMBL 6.679999828338623)
Descriptors: MW 444.33, ALogP 2.59, HBA 7, HBD 2, PSA 122.44, QED 0.47
Compound (SMILES): COc1ccc(-c2ccc(S(=O)(=O)N3CCC[C@H]3C(=O)NN(CC(N)=O)C(=O)CF)cc2)cc1
InChIKey: VLYMOAAMGREIHP-IBGZPJMESA-N
Target: Legumain (SINGLE PROTEIN), Homo sapiens
UniProt: Q99538
Assay: Inhibition of human 8His-tagged AEP (V18 to Y433 residues) using Z-Ala-Ala-Asn-Rhl 10-(D-Pro) as substrate incubated for 30 mins followed by substrate addition by fluorescence based microplate reader analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 492.53, ALogP 0.83, HBA 6, HBD 2, PSA 139.11, QED 0.52
Compound (SMILES): Cn1nc(C(F)(F)F)c2cc(C(=O)Nc3cccc(-c4nncn4C4CCCC4)c3)c(=O)[nH]c21
InChIKey: UJQDYXDMQWMPBJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of human recombinant ASK1 using MBP as substrate preincubated for 1 hr followed by reagent addition incubated for 40 mins by ATP-Glo kinase assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 471.44, ALogP 3.91, HBA 7, HBD 2, PSA 110.49, QED 0.47
Compound (SMILES): Nc1nc(NC2=NC(c3ccccc3)=CC(c3ccccc3Cl)O2)nc(N2CCOCC2)n1
InChIKey: KAMHSKDHTIWRAS-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human recombinant DPP-4 using H-GlyPro-AMC as substrate incubated for 10 mins by fluorescence based assay
Measurement: IC50 = 52.1 nM (pChEMBL 7.28000020980835)
Descriptors: MW 463.93, ALogP 3.52, HBA 9, HBD 2, PSA 110.78, QED 0.6
Compound (SMILES): COc1ccc(CNCc2cn([C@@H]3OC[C@@H](O)[C@@H](O)[C@H]3O)nn2)cc1OCc1cccc(-c2ccccc2)c1C
InChIKey: IRWGAFXQIBUNOW-LOIHPRHOSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/PD-L1 (unknown origin) interaction incubated for 15 mins by HTRF assay
Measurement: IC50 = 2259 nM (pChEMBL 5.650000095367432)
Descriptors: MW 546.62, ALogP 2.74, HBA 10, HBD 4, PSA 131.12, QED 0.24
Compound (SMILES): COc1ccc2sc(C(=O)NNc3cc(Cl)cc(Cl)c3)cc2c1
InChIKey: ZDJFIKFQLKJRBA-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of human CLK1 using GRSRSRSRSRSRSRS as substrate incubated for 15 mins in presence of ATP by gamma32P-ATP based analysis
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 367.26, ALogP 4.97, HBA 4, HBD 2, PSA 50.36, QED 0.64
Compound (SMILES): CCCn1c(=O)[nH]c(=O)c2c1nc(Cc1cn3ccccc3n1)n2Cc1ccccc1
InChIKey: GOHNCSPZIXYWEG-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17752
Assay: In Vitro Enzyme Activity Assay: The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, Mass., USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).
Measurement: IC50 = 758 nM (pChEMBL 6.119999885559082)
Descriptors: MW 414.47, ALogP 2.58, HBA 7, HBD 1, PSA 89.98, QED 0.46
Compound (SMILES): O=C(NC1(c2ccc(Cl)cc2)COC1)c1ccc(-c2cc[nH]n2)s1
InChIKey: SEUCOARRLOTMHQ-UHFFFAOYSA-N
Target: WD repeat-containing protein 91 (SINGLE PROTEIN), Homo sapiens
UniProt: A4D1P6
Assay: Binding affinity to C-terminal His6-tagged truncated WDR91 (unknown origin) (P392 to A747 residues) expressed in baculovirus-infected Sf9 cells assessed as dissociation constant incubated for 72 to 96 hrs by SPR analysis
Measurement: Kd = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 359.84, ALogP 3.45, HBA 4, HBD 2, PSA 67.01, QED 0.75
Compound (SMILES): CC(CN(C(=O)c1ccco1)c1ccccn1)N1CCN(c2ccccc2)CC1
InChIKey: DNYKNZHZOIGPHI-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at mu-opioid receptor (unknown origin) expressed in CHO cells assessed as inhibition of intracellular cAMP production measured after 45 mins by HTRF-based assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 390.49, ALogP 3.53, HBA 5, HBD 0, PSA 52.82, QED 0.64
Compound (SMILES): COCCN1C(=O)CC(c2ccc(Cl)cc2)C(C(=O)OCc2ccc(C(=O)OC)cc2)=C1C
InChIKey: BSJHDFBQMITXAS-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at human TGR5 receptor expressed in HEK293 cells cotransfected with pCMV tag4b-TGR5 assessed as activation of intracellular cAMP production incubated overnight by luciferase reporter gene assay
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 471.94, ALogP 4.11, HBA 6, HBD 0, PSA 82.14, QED 0.54
Compound (SMILES): Nc1nc2c(c(=O)[nH]1)[n+](Cc1cc3cc(Cl)ccc3[nH]1)cn2C/C=C\CP(=O)(O)O
InChIKey: JSTMWLOUXSFOCX-UPHRSURJSA-O
Target: Eukaryotic translation initiation factor 4E (SINGLE PROTEIN), Homo sapiens
UniProt: P06730
Assay: Inhibition of EDA-m7GTP-5-FAM binding to 10-His tagged human eIF4E expressed in Escherichia coli BL21 (DE3) cells incubated for 40 mins under shaking condition by competition fluorescence polarization assay
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 449.82, ALogP 1.51, HBA 5, HBD 5, PSA 153.9, QED 0.17
Compound (SMILES): Oc1ccc2cc(-c3cc(O)c(O)c(O)c3)oc2c1
InChIKey: WTQKBROURKZUNY-UHFFFAOYSA-N
Target: Calcitonin gene-related peptide type 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16602
Assay: Inhibition of human CGRP1
Measurement: IC50 = 2772 nM (pChEMBL 5.559999942779541)
Descriptors: MW 258.23, ALogP 2.92, HBA 5, HBD 4, PSA 94.06, QED 0.5
Compound (SMILES): NC(=O)c1cnc2[nH]ccc2c1NC1[C@@H]2CC3C[C@H]1CC(O)(C3)C2
InChIKey: DREIJXJRTLTGJC-JQCLMNFQSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of N-terminal GST tagged catalytic domain human JAK1 (850 to 1154 end residues) expressed in Sf21 insect cells using Biotin-Lyn-Substrate-2 as substrate incubated for 1 hr followed by substrate addition in presence of ATP by ELISA method
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 326.4, ALogP 2.01, HBA 4, HBD 4, PSA 104.03, QED 0.69
Compound (SMILES): Cc1noc(NC(=O)[C@H]2O[C@@H](n3cc(-c4ccn(C)n4)c4c(N)ncnc43)[C@H](O)[C@@H]2O)c1C
InChIKey: SUOAUXYCHOXOBQ-LDNFRZNASA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin) using UCUGGACUAAA-biotin and 3H-SAM as substrates incubated for 30 mins and measured by TopCount scintillation counter method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 454.45, ALogP 0.28, HBA 12, HBD 4, PSA 179.37, QED 0.33