lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(COc2ccc(S(=O)(=O)N(C)[C@@H]3CN(S(C)(=O)=O)C[C@@H]3C(=O)NO)cc2)c2ccccc2n1
InChIKey: APXFOOYBBSAICN-JTHBVZDNSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0F8
Assay: Inhibition of TACE in mouse RAW264.7 cells assessed as inhibition of LPS-stimulated TNFalpha production pretreated for 1 hr followed by LPS stimulation for 4 hrs by ELISA
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 548.64, ALogP 1.51, HBA 8, HBD 2, PSA 146.21, QED 0.32
Compound (SMILES): C=CC(=O)Nc1ccc(OC)c(Nc2cc(-c3[nH]c(SC)nc3C3CC3)ccn2)c1
InChIKey: KINJDOYURKOJNZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human N-terminal GST-fused EGFR T790M/L858R double mutant (669 to 1210 residues) expressed in baculovirus using TK-substrate-biotin preincubated for 30 mins followed by substrate addition measured after 20 mins by HTFR assay
Measurement: IC50 = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 421.53, ALogP 4.95, HBA 6, HBD 3, PSA 91.93, QED 0.35
Compound (SMILES): NP(=O)(OCCCCOc1ccc2ncnc(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2c1)N(CCCl)CCCl
InChIKey: NMKALLBHRSIRRM-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human His-tagged HER2 cytoplasmic domain (676 to 1255 residues) expressed in baculovirus expression system using Poly (Glu, Tyr) as substrate after 40 mins in presence of ATP by luminescence assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 670.94, ALogP 7.77, HBA 7, HBD 2, PSA 111.83, QED 0.07
Compound (SMILES): COc1c(Br)cc2cc(C(=O)O)c(=O)oc2c1Br
InChIKey: ZOKHPBNWSIXUEO-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at GPR35 in human HT-29 cells by DMR assay
Measurement: EC50 = 887.16 nM (pChEMBL 6.050000190734863)
Descriptors: MW 377.97, ALogP 3.02, HBA 4, HBD 1, PSA 76.74, QED 0.81
Compound (SMILES): Cc1cc(Nc2cc(N3CCN(C)CC3)nc(Nc3ccc(NC(=O)C4CC4)cc3)n2)n[nH]1
InChIKey: FXGOMJXGESCWPD-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q60855
Assay: Inhibition of RIPK1 in mouse L929sA cells transfected with human Fas assessed as inhibition in TNF-induced necroptosis pretreated for 24 hrs followed by TNF and zVAD.fmk addition measured after 3 hrs by Hoechst 33342/propidium iodide staining-based assay
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 447.55, ALogP 3.1, HBA 8, HBD 4, PSA 114.1, QED 0.44
Compound (SMILES): COc1ccccc1/C=C/C(=O)c1ccc[nH]1
InChIKey: UKBOFKJNWJETFB-CMDGGOBGSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of human CYP1B1 bound to yeast microsomal membrane using 7-ethoxyresorufin as substrate after 10 mins by fluorescence assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 227.26, ALogP 2.92, HBA 2, HBD 1, PSA 42.09, QED 0.64
Compound (SMILES): CS(=O)(=O)NC(=O)[C@H]1CCC[C@@H](c2nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c3c(N)nccn23)C1
InChIKey: UTFDTGYMNKCNRG-MSOLQXFVSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC
Measurement: IC50 = 648 nM (pChEMBL 6.190000057220459)
Descriptors: MW 601.61, ALogP 3.99, HBA 9, HBD 3, PSA 161.44, QED 0.3
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(NC(=O)/C(Cl)=C(\Cl)c2cccnc2)cc1
InChIKey: LBBCGPBNWBUZNU-VHEBQXMUSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 (1 to 482 residues) expressed in Baculovirus using Ac-Leu-Gly-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence assay
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 427.29, ALogP 4.7, HBA 4, HBD 3, PSA 97.11, QED 0.41
Compound (SMILES): O=C(CN(Cc1cccc(C(=O)O)c1)S(=O)(=O)c1cccc(C(=O)O)c1)NO
InChIKey: GIPQLXQKJNGLLA-UHFFFAOYSA-N
Target: Meprin A subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q16819
Assay: Inhibition of recombinant human meprin alpha expressed in S2 insect cells using Abz-YVADAPK(Dnp)G-OH as substrate by fluorescence assay
Measurement: IC50 = 27350 nM (pChEMBL 4.559999942779541)
Descriptors: MW 408.39, ALogP 0.78, HBA 6, HBD 4, PSA 161.31, QED 0.37
Compound (SMILES): Cc1ccccc1C(=O)c1ccc(N2CCC[C@H]2CC(=O)O)cc1
InChIKey: MSLNMZLFQLWPSI-KRWDZBQOSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Binding affinity to human GPR40 expressed in HEK293 cell membranes after 1 hr by radioligand displacement based scintillation counting method
Measurement: Ki > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 323.39, ALogP 3.67, HBA 3, HBD 1, PSA 57.61, QED 0.85
Compound (SMILES): CCCCCCCC(=O)Nc1ccc2c(c1)c1nc(SCC(=O)NC3CCCCC3)n(-c3ccccc3)c(=O)c1n2C
InChIKey: DIWCKMVPGWRSRR-UHFFFAOYSA-N
Target: Toll-like receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q9QUK6
Assay: Agonist activity at mouse TLR4 expressed in HEK293 blue cells assessed as induction of NF-kappaB activation-mediated SEAP production after 20 to 24 hrs by colorimetric assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 587.79, ALogP 6.72, HBA 7, HBD 2, PSA 98.02, QED 0.11
Compound (SMILES): Cc1[nH]c2ncnc(N[C@H]3CC[C@H](N(C)C)CC3)c2c1C
InChIKey: KZQFVVXWGJWYKK-JOCQHMNTSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full length His-tagged human IRAK4 expressed in baculovirus expression system using 5-FAM-IPTSPITTTYFFFKKK-COOH as substrate after 240 mins in presence of ATP by mobility shift assay
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 287.41, ALogP 2.86, HBA 4, HBD 2, PSA 56.84, QED 0.91
Compound (SMILES): COc1ccc2c(c1)[C@@H]1C[C@]1(C(=O)N1[C@@H]3CC[C@H]1CN(C)C3)Cn1c-2c(C2CCCCC2)c2ccc(C(=O)NS(=O)(=O)N(C)C)cc21
InChIKey: ZTTKEBYSXUCBSE-QDFUAKMASA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV Con1 genotype 1b NS5B RNA dependent RNA polymerase P495L mutant-mediated incorporation of radiolabeled nucleotides by scintillation proximity assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 659.85, ALogP 4.69, HBA 7, HBD 1, PSA 104.19, QED 0.41
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)N1CCc2ccccc2C1=O)B(O)O
InChIKey: QFRRATPZZZKVAM-SFTDATJTSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of trypsin-like activity of 20S proteasome in human HL60 cells using Z-LRRaminoluciferin as substrate after 2 hrs by fluorescence analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 451.33
Compound (SMILES): c1ccc2c(c1)CN[C@@H](CN(CCCCN(Cc1ccncc1)Cc1ccncc1)[C@H]1CCCc3cccnc31)C2
InChIKey: ZEEABZKRGAFENX-NOCHOARKSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6 expressed in microsomes of insect cells using AMMC as substrate preincubated for 30 mins followed by NADP addition after 45 mins by fluorescence analysis
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 546.76, ALogP 5.75, HBA 6, HBD 1, PSA 57.18, QED 0.23
Compound (SMILES): O=C(N[C@@H](c1ccccc1)C(F)(F)F)c1c(CN2CCC(N3CCCCC3)CC2)c(-c2cccc(C(F)(F)F)c2)nc2ccccc12
InChIKey: OTPMKDLEGDWPCS-XIFFEERXSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Antagonist activity at human TRPV4 expressed in HEK293 cells assessed as inhibition of GSK634775A-induced calcium influx preincubated for 10 mins followed by GSK634775A addition by Fura-4 dye based FLIPR assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 654.7, ALogP 8.4, HBA 4, HBD 1, PSA 48.47, QED 0.2
Compound (SMILES): O=C(NCc1cccs1)c1cnc2c(SSc3cccc4cc(C(=O)NCc5cccs5)cnc34)cccc2c1
InChIKey: AEWRJZQAZXRVBK-UHFFFAOYSA-N
Target: COP9 signalosome complex subunit 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92905
Assay: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 598.8, ALogP 7.57, HBA 8, HBD 2, PSA 83.98, QED 0.17
Compound (SMILES): Cc1ccc(C(=O)NCC2NCCc3ccccc32)cc1C
InChIKey: VWJLMWIMGWFRII-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]naloxone from recombinant human MOR expressed in HEK cell membranes incubated for 60 mins
Measurement: Ki = 36.4 nM (pChEMBL 7.440000057220459)
Descriptors: MW 294.4, ALogP 2.92, HBA 2, HBD 2, PSA 41.13, QED 0.91
Compound (SMILES): Cc1c(C#N)c(=O)oc2cc(OCc3ccc(Br)cc3)ccc12
InChIKey: BIGMVPGNLCXHRW-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B assessed as reduction in 4-hydroxyquinolone production using kynuramine as substrate after 20 mins by fluorescence assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 370.2, ALogP 4.31, HBA 4, HBD 0, PSA 63.23, QED 0.64
Compound (SMILES): Cc1cc(OCCCn2ccc3cc(OCc4ccccc4C(=O)O)ccc32)cc(C)c1Cl
InChIKey: XNENLWGUIGBLAZ-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of 6-carboxyfluorescein succinimidyl ester fluorescence tagged-Bid BH3 peptide (79 to 99 residues) binding to Bcl-2 (unknown origin) after 30 mins by fluorescence polarization assay
Measurement: Ki = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 463.96, ALogP 6.66, HBA 4, HBD 1, PSA 60.69, QED 0.28
Compound (SMILES): Cc1ccc([C@@H]2CN(C(=O)CC3CCNCC3)C[C@H]2c2ccc(C#N)cc2)cc1
InChIKey: UNSAISCBUIYRDT-ZEQRLZLVSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant human N-terminal truncated LSD1 (151 to 852 residues) expressed in Escherichia coli using histone H3(1-21)K4(Me1) biotin peptide as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 387.53, ALogP 3.97, HBA 3, HBD 1, PSA 56.13, QED 0.86
Compound (SMILES): COCCN(CC1CCCN(Cc2ccccc2)C1)S(=O)(=O)c1ccc2ccccc2c1
InChIKey: NIHBOOKOQZGYSF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: P21836
Assay: Inhibition of mouse AChE using acetylthiocholine iodide as substrate preincubated for 300 secs followed by substrate addition measured for 1 min by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 452.62, ALogP 4.39, HBA 4, HBD 0, PSA 49.85, QED 0.48
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2C[C@@]3(F)CN(c4nc5ccccc5o4)C[C@@]3(F)C2)c1
InChIKey: NINDNNCRDYFQQU-ZRZAMGCNSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human orexin 2 receptor expressed in HEK293 cells assessed as inhibition of orexin-induced calcium mobilization after 60 mins by FLIPR assay
Measurement: IC50 = 575 nM (pChEMBL 6.239999771118164)
Descriptors: MW 450.45, ALogP 3.11, HBA 7, HBD 0, PSA 80.29, QED 0.48
Compound (SMILES): O=C(NO)c1cccc(-c2csc(CSc3ccccc3)n2)c1
InChIKey: KWDXMPXINALNFB-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 342.45, ALogP 4.22, HBA 5, HBD 2, PSA 62.22, QED 0.41
Compound (SMILES): C=CC(=O)Nc1cc(Cl)cc(-n2c(=O)cc(C)c3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)c1
InChIKey: KFZFISVIQSCUCO-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal 6His/TEV protease cleavage site-tagged human EGFR L858R/T790M double mutant (696 to 1022 residues) using poly (Glu,Tyr) 4:1 as substrate after 1 hr by ELISA
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 560.06, ALogP 4.37, HBA 9, HBD 2, PSA 104.62, QED 0.32
Compound (SMILES): COc1cc(CNC(=O)C#Cc2cn(Cc3ccc(C(=O)NCCO)cc3)c(=O)[nH]c2=O)ccc1F
InChIKey: AZHGXAJGYOMYKJ-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of C-terminal tagged human recombinant MMP13 catalytic domain expressed in Escherichia coli using (5-FAM/QX) FRET peptide as substrate by fluorescence assay
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 494.48, ALogP 0.12, HBA 7, HBD 4, PSA 142.52, QED 0.33
Compound (SMILES): c1cc(-c2cn(CCC3CC3)c3cnccc23)ccn1
InChIKey: BQHLLYYLOWNJKJ-UHFFFAOYSA-N
Target: Nuclear factor of activated T-cells, cytoplasmic 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95644
Assay: Induction of nuclear translocation of human GFP-tagged NFATc1 expressed in virus infected primary human skeletal muscle myoblasts after 3 hrs by DAPI staining based assay
Measurement: EC50 = 1590 nM (pChEMBL 5.800000190734863)
Descriptors: MW 263.34, ALogP 3.9, HBA 3, HBD 0, PSA 30.71, QED 0.71
Compound (SMILES): C[C@@]1(O)CC[C@H]2[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](C(=O)Cn4cc(C#N)cn4)CC[C@@H]32)C1
InChIKey: HARRKNSQXBRBGZ-GVKWWOCJSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 409.57, ALogP 4.34, HBA 5, HBD 1, PSA 78.91, QED 0.81
Compound (SMILES): Cc1cc(COc2ccc(S(=O)(=O)N[C@@H]3COC[C@@H]3C(=O)NO)cc2)c2ccccc2n1
InChIKey: STQWVQNLHJHEFT-PZJWPPBQSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0F8
Assay: Inhibition of TACE in mouse RAW264.7 cells assessed as inhibition of LPS-stimulated TNFalpha production pretreated for 1 hr followed by LPS stimulation for 4 hrs by ELISA
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 457.51, ALogP 1.92, HBA 7, HBD 3, PSA 126.85, QED 0.37
Compound (SMILES): C[C@H]1CN(c2cc(-c3cc(Cl)c4c(N)ncnn34)ccc2C#N)C(=O)C(C)(C)O1
InChIKey: SHKYAELFWYZOMT-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in ACD-treated human whole blood assessed as reduction in IFNgammaX production measured after 1 hr
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 410.87, ALogP 3.03, HBA 7, HBD 1, PSA 109.54, QED 0.69
Compound (SMILES): Cc1ccccc1Nc1nc2ccccc2n2nnnc12
InChIKey: KGWMQKYMDTVWSU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of TNKS1 (unknown origin) expressed in HEK293 cells co-expressing TCF/LEF luciferase plasmid assessed as reduction in wnt3a ligand-induced Wnt-dependent increase in beta-catenin preincubated for 1 hr followed by wnt3a ligand stimulation for 24 hrs by luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 276.3, ALogP 2.72, HBA 6, HBD 1, PSA 68, QED 0.61
Compound (SMILES): CCOC(=O)[C@@H]1C[C@@H]1Cc1c(Br)c(Br)c(OC)c(OC)c1Br
InChIKey: HBSUSNOAQHGZPQ-HTQZYQBOSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 using para-nitrophenylacetate as substrate measured over 3 mins by UV-vis spectrophotometric method
Measurement: Ki = 7.22 nM (pChEMBL 8.140000343322754)
Descriptors: MW 501.01, ALogP 4.73, HBA 4, HBD 0, PSA 44.76, QED 0.42
Compound (SMILES): Cc1n[nH]cc1-c1cc2nc(CN3CCC(c4ccccc4)C3)[nH]c(=O)c2s1
InChIKey: WVDSPMABZYFEEH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of full length human CDC2 (1 to 298 residues)/human N-terminal GST-tagged CyclinE1 (1 to 410 residues) expressed in baculovirus expression system using histone H1 as substrate measured after 90 mins by Kinase-Glo luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 391.5, ALogP 3.67, HBA 5, HBD 2, PSA 77.67, QED 0.56
Compound (SMILES): CCS/C(N)=N\C(=N/S(=O)(=O)c1ccc(Cl)cc1)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1
InChIKey: AUKQWTDOTAXTQT-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: P47746
Assay: Inverse agonist at mouse brain CB1R expressed in CHOK1 cell membranes assessed as inhibition of CP55940-stimulated [35S]GTP-gammaS binding measured after 60 mins by scintillation spectrometry
Measurement: IC50 = 534 nM (pChEMBL 6.269999980926514)
Descriptors: MW 560.53, ALogP 5.61, HBA 4, HBD 1, PSA 100.48, QED 0.32
Compound (SMILES): CNS(=O)(=O)c1cccc(Nc2cc(Nc3cccc(S(=O)(=O)NC)c3)ncn2)c1
InChIKey: QWZZLPLERLAQAL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 448.53, ALogP 1.78, HBA 8, HBD 4, PSA 142.18, QED 0.41
Compound (SMILES): CCOP(=O)(OCC)C(CO)CCc1ccccc1
InChIKey: WDEDQBGGFKXLQY-UHFFFAOYSA-N
Target: Beta-lactamase VIM-2 (SINGLE PROTEIN), Pseudomonas aeruginosa
UniProt: Q9K2N0
Assay: Inhibition of Pseudomonas aeruginosa 301-5473 6His-tagged VIM-2 (V27 to E268 residues) expressed in Escherichia coli BL21 Star(DE3) pLysS using nitrocefin as substrate preincubated for 5 mins followed by substrate addition by spectrophotometric analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 286.31, ALogP 3.25, HBA 4, HBD 1, PSA 55.76, QED 0.71
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CNC(=O)[C@H](CC1CCCCC1)NC(=O)[C@H](C)N)[C@@H](C)CC)C(=O)NCC(N)=O
InChIKey: OZUJXEXKIYCYOP-QPZZXYADSA-N
Target: Atrial natriuretic peptide receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17342
Assay: Displacement of [125I]-human ANP from His-tagged and Fc fragment containing human NPR-3 extracellular domain expressed in FreeStyle 293 cells incubated for 2 hrs by top count method
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 1066.28
Compound (SMILES): Cc1nncn1C1CCN(Cc2cc3nc(-c4cccc5[nH]ccc45)nc(N4CCOCC4)c3s2)CC1
InChIKey: DALQHZZOEYFELJ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins in presence of ATP by HTRF method
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 514.66, ALogP 4.41, HBA 9, HBD 1, PSA 87.99, QED 0.37
Compound (SMILES): C[C@@](Cc1c[nH]c2ccccc12)(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)Cc1cccs1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: FGWYTKNQZADWFN-NKEBBNOXSA-N
Target: Neuromedin-U receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HB89
Assay: Agonist activity at human NMUR1 expressed in CHO cells assessed as induction of Ca2+ flux after 18 hrs by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 938.13, ALogP 1.67, HBA 9, HBD 13, PSA 329.39, QED 0.03
Compound (SMILES): O=C(NCC[C@H](O)CN1CCN(c2cccc(Cl)c2Cl)CC1)c1cnc2ccccc2c1
InChIKey: DCPPWKFRGIUQDU-IBGZPJMESA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor expressed in HEK293 cells after 1 hr by MicroBeta microplate counting method
Measurement: Ki = 23.4 nM (pChEMBL 7.630000114440918)
Descriptors: MW 473.4, ALogP 3.84, HBA 5, HBD 2, PSA 68.7, QED 0.55
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](CC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)CC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)CC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)CC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)CC(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](CC(N)=O)Cc1ccccc1)C(C)C)C(C)C)Cc1c[nH]c2ccccc12
InChIKey: PUCHPMOWLLDGCJ-OBASUGJZSA-N
Target: Parathyroid hormone/parathyroid hormone-related peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q03431
Assay: Agonist activity at PTH1 receptor (unknown origin) assessed as induction of cAMP
Measurement: EC50 = 0.13 nM (pChEMBL 9.890000343322754)
Descriptors: MW 4250.04
Compound (SMILES): CCCCCCCCCCCC(=O)OCC(COP(=O)(O)OCCNC(=O)c1ccc(Cn2c(=O)[nH]c3c(N)nc(OCCOC)nc32)cc1)OC(=O)CCCCCCCCCCC
InChIKey: DFFGHPOFYMBXJP-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Fluorescent High Throughput P450 Assays: The interaction of SC12 with cytochrome P450 enzymes was tested using Fluorescent High Throughput P450 assays (Gentest); The IC50s of the compounds was calculated on isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2C8, CYP2B6, CYP2D6, CYP2E1, CYP3A4 and CYP3A5).Materials and Methods: Inhibition of the P450 isoforms was measured in specific assays using specific substrates that become fluorescent upon CYP metabolism. Compounds, dissolved in ACN (acetonitrile) (CYP2E1, CYP2C8, CYP2B6, CYP3A5) or DMSO (all remaining isoforms), were tested in duplicate (n=2) in concentration-response curves (eight concentrations) in a 96-well plate containing incubation/NADPH regenerating buffer. Specific isoenzymes and substrates were added and incubated at 37° C. Reactions were terminated at different times, depending on the assays, and plates read on a Fluoroskan Ascent at the appropriate emission/excitation wavelengths.
Measurement: IC50 = 33400 nM (pChEMBL 4.480000019073486)
Descriptors: MW 921.08, ALogP 7.94, HBA 15, HBD 4, PSA 245.51, QED 0.02
Compound (SMILES): Cc1coc(-c2nnc3n2CCN(C(=O)c2ccc(-c4cccs4)cc2)[C@@H]3C)n1
InChIKey: WDEZNVHYSZEMLM-CQSZACIVSA-N
Target: Neuromedin-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P29371
Assay: Competitive Binding Assay: NK3: The ability of compounds of the invention to inhibit the binding of the NK-3 receptor selective antagonist 3H-SB222200 was assessed by an in vitro radioligand binding assay. Membranes were prepared from Chinese hamster ovary recombinant cells stably expressing the human NK3 receptor. The membranes were incubated with 5 nM 3H-SB222200(ARC) in a HEPES 25 mM/NaCl 0.1M/CaCl2 1 mM/MgCl2 5 Mm/BSA 0.5%/Saponin 10 μg/ml buffer at pH 7.4 and various concentrations of compounds of the invention. The amount of 3H-SB222200 bound to the receptor was determined after filtration by the quantification of membrane associated radioactivity using the TopCount-NXT reader (Packard)
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 405.48, ALogP 4.19, HBA 7, HBD 0, PSA 77.05, QED 0.51
Compound (SMILES): CC(C)C[C@@H](NC(=O)[C@@H](Cc1ccccc1)NC(=O)[C@H](N)Cc1ccccc1)C(=O)N[C@H](CNC(=N)N)C(=O)N1CCCNCC1
InChIKey: GHQNIOZRNSDSPI-BIYDSLDMSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET)-Based cAMP Immunoassay: Mouse R1.G1 cells (ATCC, Manassas, Va.) were grown in suspension in high glucose-DMEM (Dulbecco's Modified Eagle's Medium, Cellgro, Herndon, Va.) containing 10% horse serum and 2% glutaMax (Invitrogen, Carlsbad. Calif.) without added antibiotics. On the day of the experiment, cells were spun at 1,000 rpm for 5 minutes at room temperature and then washed once with HBSS (HEPES Buffered Saline Solution, Invitrogen, Carlsbad, Calif.). Cells were then spun again and resuspended in stimulation buffer (HBSS with 0.05% FAF-BSA (Fatty acid-free bovine serum albumin, Roche Applied Science, Indianapolis, Ind.), 5 mM HEPES) to 2 million cells per ml. Antibody supplied with the LANCE™ cAMP immunoassay kit was then added to the cells according to the manufacturer's instructions, and 12,000 cells per well were then added to the wells containing forskolin to a predetermined fixed final concentration (typically about 2.5 μM) and the previously determined amount of the synthetic peptide amide to be tested. The synthetic peptide amides were tested in a range of concentrations to determine potency. Cells were incubated with the synthetic peptide amide plus forskolin for about 20 minutes at room temperature. After incubation, cells are lysed by adding 12 μl of detection mix as supplied with the LANCE™ kit, followed by incubation for one hour at room temperature. Time resolved fluorescence was read using a 330-380 nm excitation filter, a 665 nm emission filter, dichroic mirror 380, and Z=1 mm.
Measurement: EC50 = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 635.81, ALogP -0.4, HBA 7, HBD 8, PSA 207.56, QED 0.1
Compound (SMILES): O=C(Nc1ccc(S(=O)(=O)C(F)(F)F)cc1)c1cnc(N2CC[C@@H](O)C2)c(-c2cncnc2)c1
InChIKey: SVNHJEFMPSZFOG-MRXNPFEDSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Caliper ABL : The assay plates were prepared by addition of 50 nL per well of compound solution in 90% DMSO. The kinase reactions were started by stepwise addition of 4.5 uL per well of peptide/ATP-solution (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 uM sodium orthovanadate, 20 mM MgCl2, 2 mM MnCl2, 4 uM ATP, 4 uM peptide (FITC-Ahx-EAIYAAPFAKKK-NH2)) and 4.5 uL per well of enzyme solution (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 uM sodium orthovanadate, 20 mM MgCl2, 2 mM MnCl2, 3.5 nM ABL (ABL(64-515), produced in-house from E. coli)). Kinase reactions were incubated at 30° C. for 60 minutes and subsequently terminated by addition of 16 uL per well of stop solution (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35). Plates with terminated kinase reactions were transferred to the Caliper LC3000 workstations for reading. Phosphorylated and unphosphorylated peptides were separated using the Caliper microfluidic mobility shift technology.
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 493.47, ALogP 2.66, HBA 8, HBD 2, PSA 125.38, QED 0.56
Compound (SMILES): O=C(Nc1ccc([C@H]2CNCCO2)cc1)c1ccc(Cl)cc1
InChIKey: KGPOKGIHPOHHOL-MRXNPFEDSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Radioligand Binding Assay: HEK-293 cells stably expressing rat TAAR1 were maintained at 37° C. and 5% CO2 in DMEM high glucose medium, containing fetal calf serum (10%, heat inactivated for 30 min at 56° C.), penicillin/streptomycin (1%), and 375 ug/ml geneticin (Gibco). Cells were released from culture flasks using trypsin/EDTA, harvested, washed twice with ice-cold PBS (without Ca2+ and Mg2+), pelleted at 1,000 rpm for 5 min at 4° C., frozen and stored at -80° C. Frozen pellets were suspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 10 mM EDTA and homogenized with a Polytron (PT 6000, Kinematica) at 14,000 rpm for 20 s. The homogenate was centrifuged at 48,000Ã¿g for 30 min at 4° C. Subsequently, the supernatant was removed and discarded, and the pellet resuspended in 20 ml HEPES-NaOH (20 mM, pH 7.4) containing 0.1 mM EDTA using the Polytron (20 s at 14,000 rpm). This procedure was repeated and the final pellet resuspended in HEPES-NaOH containing 0.1 mM EDTA and homogenized using the Polytron. Typically, aliquots of 2 ml membrane portions were stored at -80° C. With each new membrane batch the dissociation constant (Kd) was determined via a saturation curve. The TAAR1 radioligand 3[H]â¿¿(S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine (described in WO 2008/098857) was used at a concentration equal to the calculated Kd value, that was usually around 2.3 nM, resulting in the binding of approximately 0.2% of the radioligand and a specific binding representing approximately 85% of the total binding. Nonspecific binding was defined as the amount of 3[H]â¿¿(S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine bound in the presence of 10 uM unlabeled ligand. All compounds were tested at a broad range of concentrations (10 pM to 10 uM) in duplicates. The test compounds (20 ul/well) were transferred into a 96 deep well plate (TreffLab), and 180 ul of HEPES-NaOH (20 mM, pH 7.4) containing MgCl2 (10 mM) and CaCl2 (2 mM) (binding buffer), 300 ul of the radioligand 3[H]â¿¿(S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine at a concentration of 3.3xKd in nM and 500 ul of the membranes (resuspended at 50 ug protein per ml) added. The 96 deep well plates were incubated for 1 hr at 4° C. Incubations were terminated by rapid filtration through Unifilter-96 plates (Packard Instrument Company) and glass filters GF/C (Perkin Elmer) presoaked for 1 hr in polyethylenimine (0.3%) and washed 3 times with 1 ml of cold binding buffer. After addition of 45 ul of Microscint 40 (PerkinElmer) the Unifilter-96 plate was sealed and after 1 hr the ratioactivity counted using a TopCount Microplate Scintillation Counter (Packard Instrument Company).
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 316.79, ALogP 3.25, HBA 3, HBD 2, PSA 50.36, QED 0.91
Compound (SMILES): O=C(Nc1cn([C@@H]2CCNC[C@H]2O)nc1-c1cc(Cl)ccc1OC(F)F)c1cnn2cccnc12
InChIKey: FKUHTTUBEZQRLI-IAGOWNOFSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: JAK Enzyme Assay: The activity of the isolated recombinant JAK1 and JAK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr, fluorescently labeled on the N-terminus with 5-carboxyfluorescein) using the Caliper LabChip® technology (Caliper Life Sciences, Hopkinton, Mass.). To determine inhibition constants (Ki), compounds were diluted serially in DMSO and added to 50 μL kinase reactions containing purified enzyme (1.5 nM JAK1, or 0.2 nM JAK2), 100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 1.5 μM peptide substrate, ATP (25 μM), 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 μL of an EDTA containing solution (100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM. After termination of the kinase reaction, the proportion of phosphorylated product was determined as a fraction of total peptide substrate using the Caliper LabChip® 3000 according to the manufacturer's specifications.
Measurement: Ki = 0.66 nM (pChEMBL 9.180000305175781)
Descriptors: MW 503.9, ALogP 3, HBA 9, HBD 3, PSA 118.6, QED 0.37
Compound (SMILES): COC[C@H]1CCCN1C(=O)c1ccc(N2CC(F)(F)C2)c(OCC2CC2)n1
InChIKey: CXSSYNNZICYZNA-CQSZACIVSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: cAMP Assay: CHO cells expressing human CB1 or CB2 receptors are seeded 17-24 hours prior to the experiment 50.000 cells per well in a black 96 well plate with flat clear bottom (Corning Costar #3904) in DMEM (Invitrogen No. 31331), 1×HT supplement, with 10% fetal calf serum and incubated at 5% CO2 and 37 °C. in a humidified incubator. The growth medium was exchanged with Krebs Ringer Bicarbonate buffer with 1 mM IBMX and incubated at 30 °C. for 30 min. Compounds were added to a final assay volume of 100 μl and incubated for 30 min at 30 °C. Using the cAMP-Nano-TRF detection kit the assay (Roche Diagnostics) was stopped by the addition of 50 μl lysis reagent (Tris, NaCl, 1.5% Triton X100, 2.5% NP40, 10% NaN3) and 50 μl detection solutions (20 μM mAb Alexa700-cAMP 1:1, and 48 μM Ruthenium-2-AHA-cAMP) and shaken for 2 h at room temperature. The time-resolved energy transfer is measured by a TRF reader (Evotec Technologies GmbH), equipped with a ND:YAG laser as excitation source. The plate is measured twice with the excitation at 355 nm and at the emission with a delay of 100 ns and a gate of 100 ns, total exposure time 10 s at 730 (bandwidth 30 nm) or 645 nm (bandwidth 75 nm), respectively. The FRET signal is calculated as follows: FRET=T730-Alexa730-P(T645-B645) with P=Ru730-B730/Ru645-B645, where T730 is the test well measured at 730 nM, T645 is the test well measured at 645 nm, B730 and B645 are the buffer controls at 730 nm and 645 nm, respectively. cAMP content is determined from the function of a standard curve spanning from 10 μM to 0.13 nM cAMP.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 381.42, ALogP 2.58, HBA 5, HBD 0, PSA 54.9, QED 0.73
Compound (SMILES): O=C1NOC[C@H]1NC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: FJUXWOXQAQGZDM-NQBHXWOUSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 355.4, ALogP 0.9, HBA 7, HBD 3, PSA 109.23, QED 0.64
Compound (SMILES): Cc1cc(N=S2(=O)CCCC2)cc2ncnc(Nc3ccc(F)cc3O[C@H](C)C(F)(F)F)c12
InChIKey: YCJJNSYFXNUIAV-CQSZACIVSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: In vitro Kinase Assay: The Z-LYTE biochemical assay employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores one at each end that make up a FRET pair.In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognizes and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 482.5, ALogP 6.04, HBA 6, HBD 1, PSA 76.47, QED 0.45
Compound (SMILES): COC(=O)c1ccc2c(c1)-c1cccc(c1)[C@@H](N1CCC(c3c(F)ccc(Cl)c3F)=CC1=O)CCC[C@@H](C)C(=O)N2
InChIKey: PQMIPRJGMKRLRT-CLYVBNDRSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: In Vitro Assay: Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4 containing 145 mM NaCl, 5 mM KCl, and 0.1% PEG 8000 (polyethylene glycol; JT Baker or Fisher Scientific). Determinations were made using purified human Factor XIa at a final concentration of 25-200 pM (Haematologic Technologies) and the synthetic substrate S-2366 (pyroGlu-Pro-Arg-pNA; CHROMOGENIX® or AnaSpec) at a concentration of 0.0002-0.001 M.
Measurement: Ki > 624.8 nM (pChEMBL 6.203999996185303)
Descriptors: MW 579.04, ALogP 7.19, HBA 4, HBD 1, PSA 75.71, QED 0.26
Compound (SMILES): Cc1cc([C@](C)(O)C#Cc2ccc3c(c2)-n2nc(C(N)=O)cc2[C@H](O)CO3)no1
InChIKey: MMRJVLFFIHRZNO-OXQOHEQNSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition Assay: The ability of the nuclear factor-kappa B (NF-kB)-inducing kinase (NIK) to catalyze the hydrolysis of adenosine-5'-triphosphate (ATP) was monitored using the Transcreener ADP (adenosine-5'-diphosphate) assay (BellBrook Labs). Purified NIK (0.2-1 nM) derived from a baculovirus-infected insect cell expression system was incubated with test compounds for 1-3.5 hours in 50 mM 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid buffer (pH 7.2) containing 10 mM MgCl.sub.2, 2 mM dithiothreitol, 10 uM ATP, 0.01% Triton X-100, 0.1% gamma-globulins from bovine blood, 1% dimethylsulfoxide (DMSO), 12 ug/mL ADP antibody and 4 nM ADP-AlexaFluor.RTM. 633 tracer. Reactions were quenched by the addition of 20 mM 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid and 0.01% Brij 35. The tracer bound to the antibody was displaced by the ADP generated during the NIK reaction, which causes a decrease in fluorescence polarization that was measured by laser excitation.
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 394.39, ALogP 0.95, HBA 8, HBD 3, PSA 136.63, QED 0.55
Compound (SMILES): CC(=O)N1CC[C@@H](C(=O)N2CC[C@](c3ccc(C(OCc4c(F)cccc4F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)C1
InChIKey: NOMFZKMOYVWWES-DFXYEROKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human Jurkat cells by Gal4 reporter assay
Measurement: EC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 736.65, ALogP 6.41, HBA 5, HBD 0, PSA 83.99, QED 0.2
Compound (SMILES): Cc1cccnc1N(C(=O)c1ccc(-c2cnn(C)c2-c2nn[nH]n2)cc1)[C@@H]1CCCNC1
InChIKey: HJTMDLYIUBUNBH-GOSISDBHSA-N
Target: Proprotein convertase subtilisin/kexin type 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NBP7
Assay: Cell Free Assay: In order to eliminate the permeability barrier inherent to the WT7 and SCHH cell-based assays a cell-free system was also established to access compound activity. A sequence containing the full length human PCSK9 (NCBI reference identifier, NM-174936.3, where coding sequence start annotated at position 363) along with 84 additional 3â¿² nucleotides, comprising a V5 tag and polylinkinker followed by an in frame modified firefly luciferase reporter (corresponding to nucleotide positions 283-1929 of pGL3, Gen Bank reference identifier JN542721.1) was cloned into the pT7CFE1 expression vector (ThermoScientific). The construct was then in-vitro transcribed using the MEGAscript T7 Kit (Life Technologies) and RNA subsequently purified incorporating the MEGAclear Kit (Life Technologies) according to manufacturer's protocols. HeLa cell lysates were prepared following the protocols described by Mikami (reference is Cell-Free Protein Synthesis Systems with Extracts from Cultured Human Cells, S. Mikami, T. Kobayashi and H. Imataka; from Methods in Molecular Biology, vol. 607, pages 43-52, Y. Endo et al. (eds.), Humana Press, 2010) with the following modifications.
Measurement: IC50 = 3050 nM (pChEMBL 5.519999980926514)
Descriptors: MW 443.52, ALogP 2.37, HBA 8, HBD 2, PSA 117.51, QED 0.49
Compound (SMILES): O=C(Nc1nc2ccc(Cl)cc2s1)N1CC=C(c2ncc([C@H](O)CO)cc2F)CC1
InChIKey: AFCOBTYVNFMKKX-MRXNPFEDSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: pH-Based Assay: Two days prior to performing this assay, cells are seeded on poly-D-lysine-coated 96-well clear-bottom black plates (commercially available from Becton-Dickinson) at 75,000 cells/well in growth media containing 5 μM PonA (commercially available from Invitrogen) to induce expression of TRPV1. On the day of the assay, the plates are washed with 0.2 mL 1× Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 1.6 mM CaCl2 and 20 mM HEPES, pH 7.4 ("wash buffer"), and loaded using 0.1 mL of wash buffer containing Fluo-4 (3 μM final concentration, commercially available from Molecular Probes). After 1 h, the cells are washed twice with 0.2 mL wash buffer and resuspended in 0.05 mL 1× Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 3.5 mM CaCl2 and 10 mM Citrate, pH 7.4 ("assay buffer"). Plates are then transferred to a FLIPR for assay. The test compound is diluted in assay buffer, and 50 μL of the resultant solution is added to the cell plates and the solution is monitored for two minutes. The final concentration of the test compound is adjusted to range from about 50 picoM to about 3 μM. Agonist buffer (wash buffer titrated with 1N HCl to provide a solution having a pH of 5.5 when mixed 1:1 with assay buffer) (0.1 mL) is then added to each well, and the plates are incubated for 1 additional minute.
Measurement: IC50 = 18.6 nM (pChEMBL 7.730000019073486)
Descriptors: MW 448.91, ALogP 3.83, HBA 6, HBD 3, PSA 98.58, QED 0.56
Compound (SMILES): CN[C@H](C)C(=O)Nc1cc(-c2ncnc3cnn(C)c23)cc(C#Cc2ccc3c(C)nccc3c2)n1
InChIKey: AFNPHJOFGDZGGL-QGZVFWFLSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: XIAP BIR3 & cIAP1 BIR3 Binding Assays (DELFIA): BIR3 domains (10 nM) were incubated with SMAC peptide (10 nM) in assay buffer (50 mM Tris, 120 mM NaCl, 0.1% BSA, 1 mM DTT, 0.05% TritonX100) for one hour at room temperature in the presence of inhibitory compounds. The assay mixture was transferred to a strepatvidin coated plate and incubated for one hour at room temperature to allow binding of the biotinylated peptide and associated BIR3 domains to the plate. After several washing steps Eu labeled anti-GST antibody (e.g. Perkin Elmer DELFIA Eu-N1-antiGST AD0250) was added to detect BIR3 domain-SMAC peptide interactions according to Perkin Elmer's instructions. Briefly, the antibody was added (dilution 1:5000 in Perkin Elmer DELFIA Assay Buffer 2013-01) and incubated for one hour. After 3 washing steps using Delfia Washing Buffer (Perkin Elmer DELFIA Wash 2013-05), Enhancement Solution (Perkin Elmer Enhancement Asolution 2013-02) was added and incubation continued for 10 minutes. Time resolved Europium fluorescence was measured in a Wallac Victor using Standard assay settings.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 476.54, ALogP 3.23, HBA 8, HBD 2, PSA 110.51, QED 0.38
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCc4ccccc4)[C@@H](C2)N(CC(N)=O)CC[C@]315
InChIKey: IFEHHNGEBPOACA-LDGIGSNBSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 μg membrane protein (recombinant κ opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μl binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 hr at a temperature of about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by five filtration washes with 2001 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hours.
Measurement: Ki = 16.03 nM (pChEMBL 7.789999961853027)
Descriptors: MW 504.63, ALogP 3.21, HBA 6, HBD 1, PSA 83.25, QED 0.59
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)[C@H](C)CCC[C@H](N1CCC(c3cccc(OC)c3)=CC1=O)c1cc-2ccn1
InChIKey: BURCJSBKPJCHNP-OLILMLBXSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: In Vitro Assay: Plasma kallikrein determinations were made in 0.1 M sodium phosphate buffer at a pH of 7.5 containing 0.1-0.2 M sodium chloride and 0.5% PEG 8000. Determinations were made using purified human plasma kallikrein (Enzyme Research Laboratories) at a final assay concentration of 200 pM and the synthetic substrate S-2302 (H-(D)-Pro-Phe-Arg-pNA; CHROMOGENIX®) at a concentration of 0.00008-0.0004 M.
Measurement: Ki = 534.5 nM (pChEMBL 6.269999980926514)
Descriptors: MW 554.65, ALogP 6.05, HBA 6, HBD 2, PSA 109.86, QED 0.41
Compound (SMILES): O=C(Nc1ccc(SC(F)(F)F)cc1)c1cnc(N2CC[C@@H](O)C2)c(-c2ccc[nH]2)c1
InChIKey: ZXBFSTSOASOSNX-OAHLLOKOSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Caliper Assay: The assay plates were prepared by addition of 50 nL per well of compound solution in 90% DMSO. The kinase reactions were started by stepwise addition of 4.5 μL per well of peptide/ATP-solution (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 μM sodium orthovanadate, 20 mM MgCl2, 2 mM MnCl2, 4 μM ATP, 4 μM peptide (FITC-Ahx-EAIYAAPFAKKK-NH2)) and 4.5 μL per well of enzyme solution (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 μM sodium orthovanadate, 20 mM MgCl2, 2 mM MnCl2, 3.5 nM ABL (ABL(64-515), produced in-house from E. coli)). Kinase reactions were incubated at 30° C. for 60 minutes and subsequently terminated by addition of 16 μL per well of stop solution (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35). Plates with terminated kinase reactions were transferred to the Caliper LC3000 workstations for reading. Phosphorylated and unphosphorylated peptides were separated using the Caliper microfluidic mobility shift technology. Briefly, samples from terminated kinase reactions were applied to the chip. Analytes are transported through the chip by constant buffer flow and the migration of the substrate peptide is monitored by the fluorescence signal of its label. Phosphorylated peptide (product) and unphosphorylated peptide (substrate) are separated in an electric field by their charge/mass ratio.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 448.47, ALogP 4.51, HBA 5, HBD 3, PSA 81.25, QED 0.5
Compound (SMILES): Cc1nn(C)c(C)c1-c1cn2ncc(C(N)=O)c(N[C@H]3CN(C(=O)C4(C#N)CC4)C[C@H]3C)c2n1
InChIKey: UJLKWCJZSJJLIC-WBMJQRKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 25 mM beta-glycerol phosphate, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK1 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assays was: ATP, 100 μM; fluoresceinated peptide, 1.5 μM; GST-JAK1, 12.5 nM; and DMSO, 1.6%.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 461.53, ALogP 1.41, HBA 9, HBD 2, PSA 147.23, QED 0.58