lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(c1cccc([N+](=O)[O-])c1)N1CCN(c2ccc(/C=C/c3cc(Cl)cc(Cn4ccnc4)c3)cc2)CC1
InChIKey: KWFBNXKZPFTQGK-SNAWJCMRSA-N
Target: Steroid 21-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: P08686
Assay: Inhibition of recombinant CYP21 (unknown origin) expressed in human AD293 cells using 17alpha-hydroxyprogesterone as substrate pretreated for 60 mins followed by substrate addition and measured after 45 mins by LC/MS analysis
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 528.01, ALogP 5.63, HBA 6, HBD 0, PSA 84.51, QED 0.18
Compound (SMILES): CC(C#N)Nc1nc(Nc2ccnc(C(C)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: DOYNKYWVGHFSIP-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 450.38, ALogP 4.53, HBA 8, HBD 2, PSA 112.3, QED 0.53
Compound (SMILES): O=C(O)[C@H]1[C@H](c2ccccc2)[C@H](C(=O)OCc2ccc(Br)cc2)[C@H]1c1ccccc1
InChIKey: TUIVMGPGCGTISM-MLCQCVOFSA-N
Target: Fatty acid-binding protein, brain (SINGLE PROTEIN), Homo sapiens
UniProt: O15540
Assay: Displacement of ANS from recombinant human N-terminal His-tagged FABP7 expressed in Escherichia coli BL21(DE3) after 20 mins by fluorescence assay
Measurement: Ki = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 465.34, ALogP 5.39, HBA 3, HBD 1, PSA 63.6, QED 0.5
Compound (SMILES): Nc1oc2cnccc2c1Nc1cccc(F)c1
InChIKey: RDAVYNWFTYZCHG-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 243.24, ALogP 3.29, HBA 4, HBD 2, PSA 64.08, QED 0.72
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N(C)[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: LJWQJIJAFSXBTK-GONAQTSYSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 4064.54
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1CN(S(=O)(=O)c2cccc(C#N)c2)CC12CC2
InChIKey: DHEBFJJCQBLOPI-KRWDZBQOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 using GGEEEEYFELVKKKK as substrate after 40 mins in presence of [gamma-33P-ATP] by scintillation counting method
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 408.49, ALogP 2.12, HBA 6, HBD 1, PSA 105.98, QED 0.71
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N/N=C/c2ccc(N3CCN(C(=O)c4ccco4)CC3)cc2)cc1
InChIKey: CIWLILAMCOWUAO-PCLIKHOPSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant carbonic anhydrase 7 assessed as CO2 hydration preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye-based stopped-flow assay
Measurement: Ki = 78.8 nM (pChEMBL 7.099999904632568)
Descriptors: MW 481.53, ALogP 1.65, HBA 7, HBD 2, PSA 138.31, QED 0.41
Compound (SMILES): CC(=O)N1CCN([C@H]2CC[C@H](Nc3ncnn4ccc([C@H](C)CC(N)=O)c34)CC2)CC1
InChIKey: RGHNWSCEPVZMFH-KBAYOESNSA-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 = 21.38 nM (pChEMBL 7.670000076293945)
Descriptors: MW 427.55, ALogP 1.6, HBA 7, HBD 2, PSA 108.86, QED 0.72
Compound (SMILES): NC(=O)c1cnc2c(NC3CC3)cc(Nc3ccccc3)nn12
InChIKey: QZGWYLPGPJWINC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 JH1 domain (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 308.35, ALogP 2.15, HBA 6, HBD 3, PSA 97.34, QED 0.67
Compound (SMILES): C[C@H]1COc2c1c(=O)oc(=O)c1c3c(ccc21)C(C)(C)CCC3
InChIKey: ROYYPPPACDMYJY-JTQLQIEISA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE using butyrylhiocholine as substrate
Measurement: IC50 = 2844 nM (pChEMBL 5.550000190734863)
Descriptors: MW 312.37, ALogP 3.26, HBA 4, HBD 0, PSA 56.51, QED 0.75
Compound (SMILES): Cc1cc(-c2nccc3c(Nc4ccccc4)c(N)oc23)ccn1
InChIKey: AUYRXLGPFQBYPV-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 316.36, ALogP 4.52, HBA 5, HBD 2, PSA 76.97, QED 0.58
Compound (SMILES): Cc1nn(-c2cc(C(=O)O)ccn2)c(O)c1-c1ccccc1
InChIKey: VMLMHVMQZCMCBR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 295.3, ALogP 2.65, HBA 5, HBD 2, PSA 88.24, QED 0.78
Compound (SMILES): Cc1cc(C)c(Nc2ccnc(Nc3ccc(Cl)cc3)n2)c(C)c1
InChIKey: UKMJJMHWYKEQMZ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant HIV1 reverse transcriptase K103N mutant
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 338.84, ALogP 5.54, HBA 4, HBD 2, PSA 49.84, QED 0.66
Compound (SMILES): CC[N+](CC)(CC)CCCCCCOc1ccc(/C=C/c2ccccc2)cc1.[I-]
InChIKey: FXBKAVKFPWOCQQ-CMBBICFISA-M
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Antagonist activity at human alpha7 nACHR expressed in xenopous laevis oocyte assessed as inhibition of ACh-induced channel current after 5 mins at -70 mV holding potential by two electrode voltage clamp method
Measurement: IC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 380.6, ALogP 6.67, HBA 1, HBD 0, PSA 9.23, QED 0.21
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-n2ccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: ZFCNVKABVPLJJM-NXEZZACHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 381.41, ALogP 3.5, HBA 7, HBD 2, PSA 80.55, QED 0.76
Compound (SMILES): O=C(CCCCN1CCC(c2noc3cc(F)ccc23)CC1)c1cc2c3c(c1)CCC(=O)N3CCC2
InChIKey: BVYIKBKMXWQFAK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserine from serotonin 5-HT2A receptor in rat brain cortex homogenates incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 489.59, ALogP 5.42, HBA 5, HBD 0, PSA 66.65, QED 0.33
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(C(N)=O)cc3)CC2)nc2ccn(S(=O)(=O)c3ccccc3)c12
InChIKey: YZXUXBNFEONHAY-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 reverse transcriptase infected in human MT4 cells assessed as reduction in biotin-dUTP incorporation
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 635.75, ALogP 5.12, HBA 10, HBD 2, PSA 156.23, QED 0.22
Compound (SMILES): CC(F)(F)c1cccc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: YRSZQQILDIHZRT-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 432.37, ALogP 4.46, HBA 6, HBD 2, PSA 75.62, QED 0.66
Compound (SMILES): CS(=O)(=O)Nc1nnc2cc(COc3ccc(Cl)c(Cl)c3)c(C3CC3)cn12
InChIKey: XLCJRUIKGPCZSQ-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay (EP) (In Vitro Assay): The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured using the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaC12, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaC12, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. In some studies, the external sodium was reduced by equimolar replacement with choline. Osmolarity in the CsF internal and NaCl external solutions was adjusted to 300 mOsm/kg and 310 mOsm/kg with glucose, respectively. All recordings were performed at ambient temperature in a bath chamber with a volume of 150 μL. Control sodium currents were measured in 0.5% DMSO. Controls and representative compounds of the invention were applied to the recording chamber through a 4-pinch or 8-pinch valve bath perfusion system manufactured by ALA Scientific Instruments.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 427.31, ALogP 3.86, HBA 6, HBD 1, PSA 85.59, QED 0.65
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1n[nH]nc1O
InChIKey: CTPZCVRODHKARO-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of human IKKepsilon using ERLLDDRHDSGLDSMKDEE as substrate after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 340.18, ALogP 2.8, HBA 4, HBD 3, PSA 90.9, QED 0.73
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(-c3ccccc3)[se]2)cc1
InChIKey: FMNYHPPTHRSLST-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 652.3 nM (pChEMBL 6.190000057220459)
Descriptors: MW 363.3
Compound (SMILES): Cc1cnc2[nH]cnc2c1Oc1ccc(NC(=O)c2cccn(-c3ccc(F)cc3)c2=O)cc1F
InChIKey: YRBKYXALWNAECE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of recombinant GST-tagged human Mer (578 to 872 residues) cytoplasmic domain expressed in Baculovirus system using poly (Glu-Ala-Tyr) peptide as substrate after 5 mins in presence of ADP by fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 473.44, ALogP 4.74, HBA 6, HBD 2, PSA 101.9, QED 0.38
Compound (SMILES): COc1ccc(OC)c(Nc2cc(Nc3ccc(N4CCN(C)CC4)cc3)ncn2)c1
InChIKey: NOCZBAPODZWEKE-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P21860
Assay: Inhibition of recombinant human GST-tagged EGFR L858R mutant cytoplasmic domain expressed in baculovirus expression system using FAM-labeled peptide as substrate after 10 mins by mobility shift assay
Measurement: IC50 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 420.52, ALogP 3.73, HBA 8, HBD 2, PSA 74.78, QED 0.6
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(S(C)(=O)=O)cc3)CC2)nc2cc[nH]c12
InChIKey: HHCHXGKUZNYZPD-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 reverse transcriptase infected in human MT4 cells assessed as reduction in biotin-dUTP incorporation
Measurement: IC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 530.65, ALogP 4.72, HBA 8, HBD 2, PSA 124, QED 0.35
Compound (SMILES): Fc1cccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)c1
InChIKey: BBWOOOREENNAAQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.36, ALogP 4.13, HBA 5, HBD 1, PSA 72.28, QED 0.51
Compound (SMILES): Nc1nc2cc(-c3ccccc3)ccc2c2[nH]c(CN3CCCC3=O)nc12
InChIKey: SUBWHJLGYZCPRD-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 (unknown origin) expressed in HEK-Blue cells
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 357.42, ALogP 3.48, HBA 4, HBD 2, PSA 87.9, QED 0.59
Compound (SMILES): CC(C)(C)S(=O)(=O)c1ccc2nccc(Nc3cc[nH]n3)c2c1
InChIKey: MXYFRVNXUQVOQV-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells by Qpatch clamp assay
Measurement: IC50 = 8305 nM (pChEMBL 5.079999923706055)
Descriptors: MW 330.41, ALogP 3.27, HBA 5, HBD 2, PSA 87.74, QED 0.77
Compound (SMILES): CCCCN1C(=O)C(=NNC(=O)c2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: QSUZYQZAQILTBO-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 27.4 nM (pChEMBL 7.559999942779541)
Descriptors: MW 400.46, ALogP 1.61, HBA 5, HBD 2, PSA 121.93, QED 0.72
Compound (SMILES): Ic1[nH]nnc1-c1ccnc(-c2cn(CCc3cccc4ccccc34)cn2)c1
InChIKey: GBYIAZVBQUPCIC-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PHF8 expressed in baculovirus infected Sf9 cells using H3K9mel-biotin labelled peptide as substrate measured after 15 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 492.32, ALogP 4.73, HBA 5, HBD 1, PSA 72.28, QED 0.36
Compound (SMILES): Nc1oc2c(-c3ccccc3Cl)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: FBDPZQVATXMGMR-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 388.23, ALogP 6.27, HBA 4, HBD 2, PSA 64.08, QED 0.43
Compound (SMILES): O=C1[C@@H]2[C@H](C(=O)N1CCCCN1CCN(c3cccc4c3OC(F)(F)O4)CC1)[C@H]1C=C[C@@H]2C1
InChIKey: HWQRTZYDLYMZFE-OBMJPTGESA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 2840 nM (pChEMBL 5.550000190734863)
Descriptors: MW 459.49, ALogP 2.72, HBA 6, HBD 0, PSA 62.32, QED 0.37
Compound (SMILES): Cc1cc(Cn2c(=O)n(Cc3cnn(C)c3)c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc32)n(C)n1
InChIKey: OVZCFDSZHNYEBG-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of PARG in human HeLa cells assessed as induction of MMS-induced PAR chains preincubated for 1 hr followed by MMS addition and measured after 1 hr by Alexofluor 488-conjugated secondary antibody and Hoechst 33342 staining based assay
Measurement: EC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 497.58, ALogP 0.87, HBA 10, HBD 1, PSA 125.81, QED 0.4
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NCC3CC3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: MVIKPHSCGJFANI-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 429.38, ALogP 4.53, HBA 7, HBD 2, PSA 99.41, QED 0.56
Compound (SMILES): Cc1cc(-c2nccc3c(Nc4cccc(C(F)(F)F)c4)c(N)oc23)ccn1
InChIKey: HGDJPWIVWFLKKP-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 384.36, ALogP 5.54, HBA 5, HBD 2, PSA 76.97, QED 0.48
Compound (SMILES): NC(=O)c1ccc(OCc2cccc(Br)c2)cc1
InChIKey: WNYIDDKTEYNPSM-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP15 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N3
Assay: Inhibition of PARP15 (482 to 678 residues) (unknown origin) expressed in Escherichia coli using NAD+ as substrate incubated for 3 hrs by fluorescence based assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 306.16, ALogP 3.13, HBA 2, HBD 1, PSA 52.32, QED 0.94
Compound (SMILES): CC1(NC#N)CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: PTCVBQDKOCSZKC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 JH1 domain using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 289.34, ALogP 2.86, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)c(Cl)c1)c1cccc(Br)c1
InChIKey: JXAKOAQJURHBQY-UHFFFAOYSA-N
Target: Thiosulfate sulfurtransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16762
Assay: Inhibition of refolded rhodanese (unknown origin) preincubated with Escherichia coli GroEL/GroES for 60 mins in absence of compound followed by compound addition by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 475.82, ALogP 7.12, HBA 4, HBD 1, PSA 41.99, QED 0.34
Compound (SMILES): NCCCCCCNC(=O)COc1ccc(CCCn2ncc3c2nc(N)n2nc(-c4ccco4)nc32)cc1
InChIKey: IIWORMMMUYFWCH-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from recombinant human adenosine receptor A1 expressed in HEK293 cell membranes after 1 hr by FACS analysis
Measurement: Ki = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 531.62, ALogP 2.96, HBA 11, HBD 3, PSA 164.41, QED 0.18
Compound (SMILES): COc1cc2[nH]c(C(=O)NCCC3CCN(Cc4ccccc4)CC3)cc(=O)c2cc1OC
InChIKey: FYEQJLDNQJUZMM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE expressed in HEK293 cells using varying levels of acetylthiocholine iodide as substrate by Lineweaver-burk plot analysis
Measurement: Ki = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 449.55, ALogP 3.58, HBA 5, HBD 2, PSA 83.66, QED 0.55
Compound (SMILES): COCCOc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: ZSYSQOMASXIARJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 403.82, ALogP 3.22, HBA 7, HBD 1, PSA 95.7, QED 0.55
Compound (SMILES): OCC1CCCC(c2ccc(O)cc2)CC1
InChIKey: TYZPZHWTUNATHL-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at full length ERalpha (unknown origin) after 24 hrs by ERE-driven luciferase reporter gene assay
Measurement: EC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 220.31, ALogP 3.05, HBA 2, HBD 2, PSA 40.46, QED 0.75
Compound (SMILES): c1ccc(N2CCN(CCCOc3ccc4ccccc4c3)CC2)cc1
InChIKey: YNOWHDNGRNBDQJ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Binding affinity to human D3 receptor expressed in CHO cells assessed as inhibition constant by scintillation counting method
Measurement: Ki = 0.34 nM (pChEMBL 9.470000267028809)
Descriptors: MW 346.47, ALogP 4.43, HBA 3, HBD 0, PSA 15.71, QED 0.61
Compound (SMILES): Cc1cc(O)ccc1-c1ccc(-c2ccc(OCCN3CCCCC3)cc2C)[se]1
InChIKey: ZCDMMPPECKZMSK-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at ERbeta (unknown origin) expressed in HEK293T cells assessed as inhibition of 17beta-estradiol stimulated transcriptional activity after 24 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 1235 nM (pChEMBL 5.909999847412109)
Descriptors: MW 454.47
Compound (SMILES): c1ccc2c(c1)OCCC2Cn1cnc(-c2cc(-c3c[nH]nn3)ccn2)c1
InChIKey: XLKANUGVGKJAFP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 358.41, ALogP 3.3, HBA 6, HBD 1, PSA 81.51, QED 0.61
Compound (SMILES): O=C(CCN1CCN(c2ccc(Cl)cc2)CC1)c1cc2c3c(c1)CCC(=O)N3CCC2
InChIKey: JGMBAFJTUVFCTA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserine from serotonin 5-HT2A receptor in rat brain cortex homogenates incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 720.4 nM (pChEMBL 6.139999866485596)
Descriptors: MW 437.97, ALogP 3.96, HBA 4, HBD 0, PSA 43.86, QED 0.66
Compound (SMILES): CC(C)(C)c1cc(-c2nccc3c(Nc4ccc(F)c(Cl)c4)c(N)oc23)ccn1
InChIKey: ODPNRWJAAAYBBF-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 410.88, ALogP 6.31, HBA 5, HBD 2, PSA 76.97, QED 0.41
Compound (SMILES): CC(=O)Nc1ccc(C(=O)Nc2ccc(F)cc2N)cc1
InChIKey: RRJDFENBXIEAPD-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human full length C-terminal His/FALG-tagged HDAC1 expressed in Sf9 insect cells using FAM-labeled acetylated peptide A as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 1080 nM (pChEMBL 5.96999979019165)
Descriptors: MW 287.29, ALogP 2.62, HBA 3, HBD 3, PSA 84.22, QED 0.76
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-n2cc(I)cn2)n1)C1CC1
InChIKey: XKHRDUPMIXLGTD-NXEZZACHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 439.31, ALogP 3.08, HBA 7, HBD 2, PSA 80.55, QED 0.65
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)c(Cl)c1)c1cccc(Br)c1O
InChIKey: FHLUNTRPMOXZED-UHFFFAOYSA-N
Target: Thiosulfate sulfurtransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16762
Assay: Inhibition of refolded rhodanese (unknown origin) preincubated with Escherichia coli GroEL/GroES for 60 mins in absence of compound followed by compound addition by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 491.82, ALogP 6.82, HBA 5, HBD 2, PSA 62.22, QED 0.33
Compound (SMILES): CC[C@H](C)[C@@H]1C(=O)O[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)OCc1ccccc1)C(C)C)C(C)C
InChIKey: YREKTTIVMIRGOJ-RKFFNLMFSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human Jurkat cell lysate using Suc-LLVY-AMC as substrate pretreated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 460.57, ALogP 2.6, HBA 6, HBD 2, PSA 110.8, QED 0.49
Compound (SMILES): COc1ccc(C(=O)NCCCCN2CCc3cc(OC)c(O)cc3C2)cc1
InChIKey: JFKCCUAHUNXNFQ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human dopamine D3 receptor assessed as inhibition of beta-arrestin recruitment by Tango assay
Measurement: EC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 384.48, ALogP 2.98, HBA 5, HBD 2, PSA 71.03, QED 0.68
Compound (SMILES): CNc1cc(Nc2cc(C)cc(C)c2)nn2c(C(=O)NC3CC3)cnc12
InChIKey: UNAWOCNJDJPOHK-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IFNalpha-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 350.43, ALogP 3.02, HBA 6, HBD 3, PSA 83.35, QED 0.66
Compound (SMILES): Cc1ccc(C2=Nc3c(n[nH]c3C)Nc3nc(NC(C)C)ncc32)cc1
InChIKey: DVDNHJJINLEZSO-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using STK S2 as substrate after 40 mins by HTRF assay
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 347.43, ALogP 3.86, HBA 6, HBD 3, PSA 90.88, QED 0.52
Compound (SMILES): Cc1ccc2oc(-c3ccc(OCCCCc4cn(CCOCCOCCOc5ccc6c(=O)cc(-c7ccccc7)oc6c5)nn4)cc3)cc(=O)c2c1
InChIKey: STLVHIWKDXQFLB-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 133.8 nM (pChEMBL 6.869999885559082)
Descriptors: MW 727.81, ALogP 7.65, HBA 11, HBD 0, PSA 128.05, QED 0.08
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1cccc(CO)c1
InChIKey: YWMPCCYNGABIMS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 309.33, ALogP 2.34, HBA 5, HBD 2, PSA 88.24, QED 0.77
Compound (SMILES): O=C(c1cnccn1)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(C4CC4)cn23)CC1
InChIKey: LXLKXWCGENJJBA-UHFFFAOYSA-N
Target: Potassium channel subfamily K member 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPC2
Assay: Inhibition In Vito Assay: The investigations on the inhibition of the recombinant TASK-1 and TASK-3 channels were carried out using stably transfected CHO cells. Here, the compounds according to the invention were tested with administration of 40 mM of potassium chloride in the presence of a voltage-sensitive dye for high-throughput screening of potassium channel from Molecular Devices FLIPR Application Note: Measuring membrane potential using the FLIPR membrane potential assay kit on Fluorometric Imaging Plate Reader (FLIPR) systems. The activity of the test substances was determined as their ability to inhibit a depolarization induced in the recombinant cells by 40 mM potassium chloride.
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 472.98, ALogP 4.28, HBA 6, HBD 0, PSA 66.63, QED 0.43
Compound (SMILES): O=C(O)[C@H]1[C@H](c2ccccc2)[C@H](C(=O)Oc2cc(Cl)c(Cl)cc2Cl)[C@H]1c1ccccc1
InChIKey: YFFCYEHSEKHTGI-CMOCDZPBSA-N
Target: Fatty acid-binding protein, brain (SINGLE PROTEIN), Homo sapiens
UniProt: O15540
Assay: Displacement of ANS from recombinant human N-terminal His-tagged FABP7 expressed in Escherichia coli BL21(DE3) after 20 mins by fluorescence assay
Measurement: Ki = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 475.75, ALogP 6.45, HBA 3, HBD 1, PSA 63.6, QED 0.26
Compound (SMILES): C[C@@H](Nc1nc(N[C@H]2CCCC[C@@H]2O)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: DNYYBCNJEMMGNA-ZLDLUXBVSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 422.46, ALogP 3.88, HBA 7, HBD 3, PSA 95.85, QED 0.65
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(CSc3ccccc3)[se]2)cc1
InChIKey: AEADENKIWYZXNX-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 6860 nM (pChEMBL 5.159999847412109)
Descriptors: MW 409.39
Compound (SMILES): CN(CCOc1ccc(/C=C2\COc3ccccc3C2=O)cc1)Cc1ccccc1
InChIKey: SUGWAZSXKZVAHS-OQKWZONESA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B assessed as reduction in H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex red reagent based fluorescence assay
Measurement: IC50 = 2280 nM (pChEMBL 5.639999866485596)
Descriptors: MW 399.49, ALogP 4.86, HBA 4, HBD 0, PSA 38.77, QED 0.53
Compound (SMILES): N#C/C=C/c1ccc(Nc2cc(NCCCN3CCOCC3)nc(Nc3ccc(C#N)cc3)n2)cc1
InChIKey: SIAJTAVXVUUNHN-HNQUOIGGSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase K103N/Y181C double mutant infected in human MT4 cells harboring GFP by scanning microscopic analysis
Measurement: EC50 = 97.72 nM (pChEMBL 7.010000228881836)
Descriptors: MW 480.58, ALogP 4.51, HBA 9, HBD 3, PSA 121.92, QED 0.28
Compound (SMILES): CO/C=C/C(=O)c1cc2c3c(c(N)cc(NC(=O)C(C)C)c3n1)N=C2
InChIKey: OKZVXALNOKYCRL-SNAWJCMRSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to human PI3Kdelta after 1 hr by KINOMEscan assay
Measurement: Kd = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 338.37, ALogP 2.82, HBA 6, HBD 2, PSA 106.67, QED 0.32
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1cccc(F)c1
InChIKey: IEUSSUSUNMFYEH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 297.29, ALogP 2.99, HBA 4, HBD 1, PSA 68.01, QED 0.81
Compound (SMILES): CNS(=O)(=O)Nc1nnc2cc(OCC34CC5CC(CC(C5)C3)C4)c(C3CC3)cn12
InChIKey: ROVSAJMSDNDAPG-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay (EP) (In Vitro Assay): The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured using the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaC12, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaC12, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. In some studies, the external sodium was reduced by equimolar replacement with choline. Osmolarity in the CsF internal and NaCl external solutions was adjusted to 300 mOsm/kg and 310 mOsm/kg with glucose, respectively. All recordings were performed at ambient temperature in a bath chamber with a volume of 150 μL. Control sodium currents were measured in 0.5% DMSO. Controls and representative compounds of the invention were applied to the recording chamber through a 4-pinch or 8-pinch valve bath perfusion system manufactured by ALA Scientific Instruments.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 431.56, ALogP 3.08, HBA 6, HBD 2, PSA 97.62, QED 0.7
Compound (SMILES): Nc1oc2c(-c3ccccc3)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: IMLCAFRPRFAYPQ-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 353.78, ALogP 5.61, HBA 4, HBD 2, PSA 64.08, QED 0.5
Compound (SMILES): O=C(CCCCN1CCC(c2noc3cc(F)ccc23)CC1)c1cc2c3c(c1)CCN3C(=O)CC2
InChIKey: ACOZPXLCYUQMHS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to 5HT1A receptor (unknown origin)
Measurement: Ki = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 475.56, ALogP 5.03, HBA 5, HBD 0, PSA 66.65, QED 0.35
Compound (SMILES): COc1cc2c(=O)n([C@@H](C(=O)NCC(F)(F)F)C(C)C)c3c4cc[nH]c4ncc3c2cc1OC
InChIKey: JUIHFZZNBSJCSO-GOSISDBHSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter-binding method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 476.46, ALogP 3.92, HBA 6, HBD 2, PSA 98.24, QED 0.41
Compound (SMILES): Nc1sc2ccccc2c1Nc1ccc(Cl)c(C(F)(F)F)c1
InChIKey: DSTUXLXRYDDCRN-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 342.77, ALogP 5.9, HBA 3, HBD 2, PSA 38.05, QED 0.61
Compound (SMILES): CC(C)c1ccn2ncnc(N[C@H]3CC[C@H](N4CCOCC4)CC3)c12
InChIKey: AEPGROUWXONGID-WKILWMFISA-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 = 15.49 nM (pChEMBL 7.809999942779541)
Descriptors: MW 343.48, ALogP 2.91, HBA 6, HBD 1, PSA 54.69, QED 0.92
Compound (SMILES): Nc1oc2c(-c3cc(F)nc(F)c3)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: DAYGTXIWUJVABE-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 390.75, ALogP 5.29, HBA 5, HBD 2, PSA 76.97, QED 0.46
Compound (SMILES): C#CCn1c(=O)n(Cc2cc(C)no2)c(=O)c2cc(S(=O)(=O)NC3(C)CC3)ccc21
InChIKey: ZPIJSBOPEGBKLB-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 428.47, ALogP 0.97, HBA 8, HBD 1, PSA 116.2, QED 0.59
Compound (SMILES): c1ccc(COc2ccccc2CCn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)cc1
InChIKey: IKZSNMQGJATBAZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 422.49, ALogP 4.55, HBA 6, HBD 1, PSA 81.51, QED 0.4
Compound (SMILES): FC(F)(F)Oc1ccccc1Cn1cnc(-c2cc(-c3nn[nH]n3)ccn2)c1
InChIKey: DSHWUABDXNNPOI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 387.33, ALogP 3.07, HBA 7, HBD 1, PSA 94.4, QED 0.57
Compound (SMILES): CCC(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: GECGVADGXPWZOI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 398.39, ALogP 4.75, HBA 5, HBD 1, PSA 72.28, QED 0.53