lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(CCCc1ccccc1)CNC(=O)/N=C(\N)NCCCc1nnc(N)s1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RMUCLANWKRJBIV-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H] mepyramine from human histamine H1 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RGS4 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 403.56, ALogP 2.33, HBA 5, HBD 4, PSA 131.31, QED 0.27
Compound (SMILES): Cc1nc(SCC2CCN(S(=O)(=O)c3ccc4c(c3)CCO4)CC2)n(C)c1C
InChIKey: MJLNGNOEHXUILR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Antagonist activity at human muscarinic M5 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by Fluo-4AM staining based fluorescence assay
Measurement: IC50 = 741.31 nM (pChEMBL 6.130000114440918)
Descriptors: MW 421.59, ALogP 3.16, HBA 6, HBD 0, PSA 64.43, QED 0.69
Compound (SMILES): N#Cc1ccc2c(c1)OCC[C@H]2Nc1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: VWXCQCAVLRAQIE-LJQANCHMSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of full length LRRK2 G2019S mutant (unknown origin) by LRRKtide Adapta assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 367.41, ALogP 4.43, HBA 5, HBD 2, PSA 86.62, QED 0.56
Compound (SMILES): Cc1cc(N2Nc3c(c(=O)oc4cc(O)ccc34)-c3ccc(O)cc32)ccc1OCCN1CCC=C(C(=O)O)C1
InChIKey: QYQAEJHFGLDXRT-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at ERbeta (unknown origin)
Measurement: IC50 = 45.43 nM (pChEMBL 7.340000152587891)
Descriptors: MW 541.56, ALogP 4.75, HBA 9, HBD 4, PSA 135.71, QED 0.25
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)nc2)ccn1
InChIKey: QWEXPXGCXPEXGZ-IBGZPJMESA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q3UHJ0
Assay: Displacement of 3H-LP-927443 from AAK1 in C57BL6 mouse brain homogenate assessed as inhibition constant incubated for 1 hr by liquid scintillation counter analysis
Measurement: Ki = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 358.44, ALogP 3.46, HBA 6, HBD 2, PSA 99.36, QED 0.79
Compound (SMILES): CCCn1c(=O)c2[nH]c(-c3cccc(S(=O)(=O)F)c3)nc2n(CCC)c1=O
InChIKey: JBZRNNQMLIEBDY-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine A2B receptor expressed in CHO cell membrane preincubated for 4 hrs followed by [3H]PSB-603 addition and measured after 0.5 hrs by radioligand displacement assay
Measurement: Ki = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 394.43, ALogP 2.03, HBA 7, HBD 1, PSA 106.82, QED 0.64
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1c(F)cccc1F)B(O)O
InChIKey: QTRFWSIBLJYXFJ-ROUUACIJSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 418.25
Compound (SMILES): Cc1c(C#Cc2cnc3ccc(N4CCC[C@H](N)C4)nn23)cccc1C(=O)Nc1cc(Cl)cc(C(F)(F)F)c1
InChIKey: AADXSEVDTNPICQ-NRFANRHFSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TRKC (unknown origin) using Ser/Thr 06 peptide as substrate incubated for 1 hr in presence of 50 uM ATP by FRET based Z'-Lyte assay
Measurement: IC50 = 21.3 nM (pChEMBL 7.670000076293945)
Descriptors: MW 552.99, ALogP 5.29, HBA 6, HBD 2, PSA 88.55, QED 0.34
Compound (SMILES): Cc1cccc2sc(NC(=O)CCN3CCN(C4CCN(C)CC4)CC3)nc12
InChIKey: AQTMZCRUEMQFRJ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human recombinant BuChe using butyrylthiocholine iodide as substrate incubated for 10 mins by DTNB reagent based Ellman's method
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 401.58, ALogP 2.65, HBA 6, HBD 1, PSA 51.71, QED 0.83
Compound (SMILES): CC(C)NC(=O)c1ccc(-c2onc3ccc(C(=O)O)cc23)cc1
InChIKey: WIEHNEUJMGUSIY-UHFFFAOYSA-N
Target: Inositol hexakisphosphate kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHH9
Assay: Inhibition of N-terminal 6His-tagged/TEV cleavage site fused recombinant human IP6K2 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 324.34, ALogP 3.33, HBA 4, HBD 2, PSA 92.43, QED 0.77
Compound (SMILES): Nc1nc(N)c2nc(C(=O)NCc3ccccc3)cnc2n1
InChIKey: WLYXRTNAMJDXRJ-UHFFFAOYSA-N
Target: Pteridine reductase 1 (SINGLE PROTEIN), Leishmania major
UniProt: Q01782
Assay: Inhibition of recombinant Leishmania major PTR1 expressed in Escherichia coli BL21 (DE3) cells using H2B as substrate in presence of cytochrome c and NADPH by envision multilabel reader
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 295.31, ALogP 0.51, HBA 7, HBD 3, PSA 132.7, QED 0.64
Compound (SMILES): C=C(C(N)=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](C)N(C)C(=O)[C@@H](N)Cc1c(C)cc(O)cc1C)c1ccccc1
InChIKey: IPPUMPUWHRNDMW-UJLGHMMASA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]DAMGO from MOP (unknown origin) stably expressed in HEK293 cells by liquid scintillation counter analysis
Measurement: Ki = 0.0511 nM (pChEMBL 10.289999961853027)
Descriptors: MW 599.73, ALogP 2.35, HBA 6, HBD 5, PSA 167.85, QED 0.19
Compound (SMILES): Cc1ccc(-c2cnc(NCc3c(F)ccc4c3CCO4)n3cnnc23)c(C)n1
InChIKey: GPOYFENWQYULOI-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: EED-H3K27Me3 Peptide Competition Binding Assay by AlphaScreen: To assess the compounds potency in the EED-H3K27Me3 competition binding assay, compounds were serially diluted 3-fold in DMSO to obtain a total of twelve concentrations. Then compounds at each concentration (75 nL of each) were transferred by Mosquito into a 384-well Perkin Elmer ProxiPlate 384 plus plates. 8 uL of solutions containing 30 nM EED (1-441)-His protein and 15 nM biotin-H3K27Me3 (19-33) peptide in the buffer (25 mM HEPES, pH 8, 0.02% Tween-20, 0.5% BSA) were added to the wells and then incubated with compound for 20 min. AlphaScreen detection beads mix was prepared immediately before use by mixing nickel chelate acceptor beads and streptavidin donor beads in a 1:1 ratio (Perkin Elmer, Product No. 6760619C/M/R) into the buffer described above. Then 4 μL of detection beads mix was added to the plate and incubate in the dark at the rt for 1 h. The final concentration of donor and acceptor beads was 10 μg/mL for each. Plates were read on EnVision (PerkinElmer) using the AlphaScreen setting adapted for optimal signal detection with a 615 nm filter, after sample excitation at 680 nm. The emission signal at 615 nm was used to quantify compounds inhibition. AlphaScreen signals were normalized based on the reading coming from the positive (maximum signal control) and negative controls (minimum signal control) to give percentage of activities left. The data were then fit to a dose response equation using the program Helios (Novartis) to get the IC50 values. Helios is a Novartis in-house assay data analysis software using the methods described by Normolle, D. P., Statistics in Medicine, 12:2025-2042 (1993); Formenko, I. et al, Computer Methods and Programs in Biomedicine, 82, 31-37 (2006); Sebaugh, J. L., Pharmaceutical Statistics, 10:128-134 (2011); Kelly, C. et al., Biometrics, 46(4):1071-1085 (1990); and Kahm, M. et al., Journal of Statistical Software, 33(7): (2010) (grofit: Fitting Biological Growth Curves with R, pages 1-21, available at http://www.jstatsoft.org/).Each compound was counterscreened to determine if it interfered with the AlphaScreen beads. Compounds were diluted as described in the preceding section, and the assay was performed by adding 12 μL of 10 nM biotin-miniPEG-His6 peptide in the above buffer and incubating for 20 min at rt prior to addition of the beads to 10 μg/mL each. The plates were then incubated for 1 h at rt in dark before being read on EnVison.
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 390.42, ALogP 3.49, HBA 7, HBD 1, PSA 77.23, QED 0.57
Compound (SMILES): C=CC(=O)Nc1cccc(Cl)c1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: KIBMUWUZKRLPOM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown orgin) using Tyr 04 peptide as substrate incubated for 1 hr in presence of 25 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 529.81, ALogP 7.14, HBA 6, HBD 2, PSA 85.37, QED 0.25
Compound (SMILES): CC(C)COc1ccc(CNC(=O)N(Cc2ccc(F)cc2)C2CCN(CC(=O)N(C)C)CC2)cc1
InChIKey: VMMZTSPODIBJBF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Inverse agonist activity at 5-HT2A receptor (unknown origin) expressed in mouse NIH3T3 cells using o-nitrophenyl-D-galacto pyranoside incubated for 120 hrs
Measurement: IC50 = 86.4 nM (pChEMBL 7.059999942779541)
Descriptors: MW 498.64, ALogP 4.12, HBA 4, HBD 1, PSA 65.12, QED 0.54
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C)c2)ccn1
InChIKey: TXMDTZHAXIIOSY-NRFANRHFSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q3UHJ0
Assay: Displacement of 3H-LP-927443 from AAK1 in C57BL6 mouse brain homogenate assessed as inhibition constant incubated for 1 hr by liquid scintillation counter analysis
Measurement: Ki = 0.08 nM (pChEMBL 10.100000381469727)
Descriptors: MW 371.48, ALogP 4.38, HBA 5, HBD 2, PSA 86.47, QED 0.75
Compound (SMILES): Cc1cc(-c2c(-c3ccncc3)n[nH]c2C)ccc1-c1cccc(S(N)(=O)=O)c1
InChIKey: KFWXZDCRTGGFFN-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of full-length LRRK2 G2019S mutant (unknown origin) using LRRKtide as substrate incubated for 1 hr in presence of ATP by TR-FRET based ADAPTA assay
Measurement: IC50 = 6.15 nM (pChEMBL 8.210000038146973)
Descriptors: MW 404.5, ALogP 4.07, HBA 4, HBD 2, PSA 101.73, QED 0.54
Compound (SMILES): Cc1nc2cnc3ccc(-c4ccc(O)c(C(F)(F)F)c4)cc3c2n1C1CCN(C)CC1
InChIKey: VUNDBTGQUNIPSI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Kinase/Tyr 6 peptide as substrate incubated for 1 hrs in presence of ATP by fluorescence microplate reader analysis
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 440.47, ALogP 5.55, HBA 5, HBD 1, PSA 54.18, QED 0.44
Compound (SMILES): c1cc(N2CCN(c3cccc4cn[nH]c34)CC2)c2ncncc2c1
InChIKey: PGUXDJSNMWQQLR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in CHO-K1 cells membrane by scintillation counter analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 330.39, ALogP 2.83, HBA 5, HBD 1, PSA 60.94, QED 0.61
Compound (SMILES): O=C(NC12CC3CC(CC(C3)C1)C2)c1cc2cccnc2n(CCCCF)c1=O
InChIKey: LYLVHFQOOVHCMT-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-WIN55212-2 from human CB2 receptor transfected in CHO cells membrane incubated for 90 mins
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 397.49, ALogP 3.84, HBA 4, HBD 1, PSA 63.99, QED 0.75
Compound (SMILES): CCNNC(=O)c1ccc(CN2c3ccccc3CC(=O)c3ccccc32)cc1
InChIKey: XOVRMAYXPVDKOS-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant HDAC2 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 385.47, ALogP 4.02, HBA 4, HBD 2, PSA 61.44, QED 0.65
Compound (SMILES): COc1cc(Oc2c(-c3cc(F)c(F)cc3C(C)(F)F)sc3c2ccc2[nH]ncc23)ccc1NC1CN(CCCF)C1
InChIKey: FUONBUGRIAXKMC-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha expressed in HEK293/Gal4 cells incubated for 24 hrs in presence of estradiol by luciferase reporter gene assay
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 602.63, ALogP 8.09, HBA 6, HBD 2, PSA 62.41, QED 0.16
Compound (SMILES): CCN(CC)Cc1ccccc1CNC(=O)c1cccc(NC(=O)c2ccc(Cl)cc2)c1
InChIKey: GBGKTJHGBHPXNO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 0.76 nM (pChEMBL 9.119999885559082)
Descriptors: MW 449.98, ALogP 5.36, HBA 3, HBD 2, PSA 61.44, QED 0.46
Compound (SMILES): CNC1CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: XBUGKPLRNYLQPI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant human SHP2 PTP domain (237 to 535 residues) using DiFMUP as substrate preincubated for 30 mins and followed by substrate addition and measured by microplate reader method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.27, ALogP 3.22, HBA 5, HBD 2, PSA 67.07, QED 0.89
Compound (SMILES): NC(=O)CNC(=O)[C@@H]1CCC(=O)NCCCC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1
InChIKey: YTJSRWAACLOYAQ-JFQCQQJMSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from human DOP expressed in CHO-K1 cell membrane incubated for 60 mins by Microscint-counting analysis
Measurement: Ki = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 809.92, ALogP -0.15, HBA 9, HBD 10, PSA 279.73, QED 0.1
Compound (SMILES): Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(NCCCN3CCCCC3)c3cc(Cl)ccc32)c(C)c1
InChIKey: LGRRCPOBUDWYDA-UHFFFAOYSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Antagonist activity at human V2 receptor expressed in CHO cells assessed as reduction in vasopressin induced cAMP production preincubated for 30 mins followed by vasopressin stimulation and measured after 30 mins
Measurement: IC50 = 169.82 nM (pChEMBL 6.769999980926514)
Descriptors: MW 573.18, ALogP 7.16, HBA 4, HBD 2, PSA 64.68, QED 0.28
Compound (SMILES): CN1CCC(N(Cc2ccc(F)cn2)C(=O)NCc2ccc(OCCC(F)F)cc2)CC1
InChIKey: QSDLAVURJSELLX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Inverse agonist activity at 5-HT2A receptor (unknown origin) expressed in mouse NIH3T3 cells using o-nitrophenyl-D-galacto pyranoside incubated for 120 hrs
Measurement: IC50 = 6.54 nM (pChEMBL 8.180000305175781)
Descriptors: MW 450.51, ALogP 4.06, HBA 4, HBD 1, PSA 57.7, QED 0.63
Compound (SMILES): C=CC(=O)N1CCC(Oc2nc(Nc3ccc(N(C)CCN(C)C)cc3OC)nc3[nH]ccc23)CC1
InChIKey: MLSAXWOQWBHGSP-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human recombinant wild type EGFR (695 to end residues) expressed in baculovirus-infected Sf9 cells using poly (4:1 Glu,Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 59.3 nM (pChEMBL 7.230000019073486)
Descriptors: MW 493.61, ALogP 3.26, HBA 8, HBD 2, PSA 98.85, QED 0.42
Compound (SMILES): O=C(NC1CCCC1)[C@@H]1CCCCOc2cccc(c2)CC2(COC2)C(=O)N[C@@H](CCN2CCOCC2)C(=O)N1
InChIKey: ZLMGXUADQANIFT-UIOOFZCWSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S immunoproteasome beta-5i subunit using Ac-ANW-AMC as substrate measured after 1.2 hrs in presence of SDS
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 556.7, ALogP 1.56, HBA 7, HBD 3, PSA 118.23, QED 0.5
Compound (SMILES): CCCC1CNCc2c1[nH]c(=O)c(C#N)c2N1CCC2(CC1)CC2.Cl
InChIKey: RVOZYMPVGIVNJX-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition of full length human PDE9A expressed in Sf9 insect cells using [3H]-cGMP as substrate incubated for 60 mins by microbeta scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 326.44, ALogP 2.61, HBA 4, HBD 2, PSA 71.92, QED 0.9
Compound (SMILES): COc1ccc(Cn2cnc3ccc(-c4nnc(N)s4)cc32)cc1OC
InChIKey: ZVUKRZZLKCUEMQ-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of recombinant human QC using H-Gln-AMC hydrobromide as fluorogenic substrate incubated for 6 hrs by fluorometric microplate reader analysis
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 367.43, ALogP 3.2, HBA 8, HBD 1, PSA 88.08, QED 0.58
Compound (SMILES): O=C(O)c1cn(Cc2ccc(F)cc2)c2ccc(OCc3ccc(Cl)c(Cl)c3)cc2c1=O
InChIKey: LIWJAEQQTJOFLY-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase associated RNA-dependent DNA polymerase activity using poly(A)-oligo(dT) as template/primer incubated for 30 mins by multilabel counter plate reader analysis
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 472.3, ALogP 5.77, HBA 4, HBD 1, PSA 68.53, QED 0.39
Compound (SMILES): COC(C)(C)c1ccc2[nH]c3c(c2c1)-c1nc(N)ncc1CCC3
InChIKey: WEOKTZLKOGDIBJ-UHFFFAOYSA-N
Target: 1-phosphatidylinositol 3-phosphate 5-kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2I7
Assay: Inhibition of PIKFYVE in HEK293 cells by NanoBRET assay
Measurement: IC50 = 314 nM (pChEMBL 6.5)
Descriptors: MW 322.41, ALogP 3.58, HBA 4, HBD 2, PSA 76.82, QED 0.76
Compound (SMILES): Cc1c([C@@H](C)Nc2nnc(C)c3cnc(N4CCOCC4)cc23)cccc1S(C)(=O)=O
InChIKey: PIEKGDZPZNXAAB-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibiting SOS1-Mediated GTP Nucleotide Exchange by Blocking Mant-GDP Exchange: Table 24: This Example illustrates that exemplary compounds of the present invention prevent KRas-mediated GTP nucleotide exchange mediated by SOS1 to inhibit KRas activity thereby inhibiting the generation of the downstream effector pERK. MKN1 cells (15,000/w) or H358 (30,000/w) were seeded in a black clear flat bottom 96-well cell culture plate (Corning, #3904) and incubated at 37° C. overnight. Assay day 1, cells were dosed with compounds of Formula (I) with a 10 μm starting concentration and serially diluted 3× for a total of 9 concentrations. The cells were incubated for approximately 0.5-1 hour with the compounds solubilized in DMSO at 37° C. Cells were immediately fixed by adding 50 μL of 4% formaldehyde to all wells in a fume hood and the plates were incubated for 20 minutes at room temperature. The formaldehyde was discarded from the plates and 150 μL of ice-cold methanol was added to permeabilize the cells for 10 minutes at −20° C. The methanol was discarded from each of the plates and any liquid remaining in the plate by tapping the plate against paper towels. Cells were then blocked with 150 μL of Odyssey blocking buffer (LI-COR Biosciences #927-50010) using 0.05% Tween for 1 hour at room temperature on a shaker. The blocking buffer was discarded and 50 μL of primary antibodies pERK (cell signaling Technology #9101L; Rabbit, 1:500) and GapDH (Millipore #MAB34; Mouse, 1:5000) diluted in Odyssey blocking buffer was added. The plates were incubated overnight at 4° C. on a shaker. On Assay Day 2, the primary antibody solution was removed. Each plate was washed 3× times with 150 μL of 1×PBST (PBS+0.1% Tween 20) and incubated with 50 μL of secondary antibodies: Anti-Rabbit (LI-COR Biosciences #926-32211) and Anti-Mouse (LI-COR Biosciences #68070) at 1:800 dilution in Odyssey blocking buffer with Tween at room temperature on a shaker for 2 hours (protected from light). The secondary antibody solution as removed and each plate was washed with PBST 3× times. Any liquid remaining was discarded and the plate was imaged using the Licor Odyssey machine according to the manufacturer's instruction, using a set focus length at 3 mm and both 800 nm and 700 nm filters. The GAPDH normalized scan values for each well were divided by the average of vehicle wells to get the % of pERK inhibition. The IC50 values were then calculated with the Graph pad Prism software.
Measurement: IC50 = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 441.56, ALogP 3.05, HBA 8, HBD 1, PSA 97.31, QED 0.65
Compound (SMILES): CNC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)CCC(C)C)C(C)C)C(=O)N[C@@H](CC1CCCC1)C(=O)N[C@@H](C)c1nc2cccc(-c3ccccc3)c2[nH]1
InChIKey: IUJXGKCRDZTFSX-BJPBVECGSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Binding affinity to MBP-tagged human recombinant ENL (489 to 559 residues) incubated for 40 mins by measuring fluorescence polarization by microplate reader method
Measurement: Ki = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 771.02, ALogP 4.74, HBA 7, HBD 6, PSA 177.42, QED 0.11
Compound (SMILES): COc1ccc(Cc2nnc(CCc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)cc1
InChIKey: YTQVUYDROYEQLB-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 267.2 nM (pChEMBL 6.570000171661377)
Descriptors: MW 440.55, ALogP 4.5, HBA 5, HBD 2, PSA 84.41, QED 0.33
Compound (SMILES): O=C(Nc1cnn(CC2CCNCC2)c1)c1cc(C(=O)c2c(Cl)ccc(Cl)c2F)c[nH]1
InChIKey: RMXRWGZHGVSUOH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13164
Assay: Inhibition of ERK5 phosphorylation in human HeLa cells incubated for 1 hr by Western blot densitometry analysis
Measurement: IC50 = 671 nM (pChEMBL 6.170000076293945)
Descriptors: MW 464.33, ALogP 4.14, HBA 5, HBD 3, PSA 91.81, QED 0.38
Compound (SMILES): N#CCNC(=O)c1ccc(-c2ccnc(Nc3ccc(N4CCC(c5ccco5)CC4)cc3)n2)cc1
InChIKey: HPVHLFGAJGALJV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 kinase domain
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 478.56, ALogP 5.12, HBA 7, HBD 2, PSA 107.08, QED 0.36
Compound (SMILES): CCC(=O)N(Cc1ccccc1)C1CCN(Cc2ccccc2)CC1
InChIKey: UBXNIOQMIRVNIT-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHO-K1 cell membranes incubated for 90 mins measured by MicroBeta scintillation counter method
Measurement: Ki = 837.1 nM (pChEMBL 6.079999923706055)
Descriptors: MW 336.48, ALogP 4.09, HBA 2, HBD 0, PSA 23.55, QED 0.79
Compound (SMILES): C[C@@H](Nc1ccn2ncc(-c3cnn(C4CCOC4)c3)c2n1)c1cc(F)ccc1F
InChIKey: UTKGVSMIITVYNO-JBZHPUCOSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA G595R mutant (unknown origin) using TK-sub-biotin peptide as substrate incubated for 30 mins followed by treated with ATP and substrate for 40 mins by FRET-based-Z'-lyte kinase assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 410.43, ALogP 4.01, HBA 7, HBD 1, PSA 69.27, QED 0.54
Compound (SMILES): NC(=O)c1ccc(OCC2CCCCC2)cc1F
InChIKey: LSOUNQHPJFJTGF-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of human PARP-10 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 = 954.99 nM (pChEMBL 6.019999980926514)
Descriptors: MW 251.3, ALogP 2.88, HBA 2, HBD 1, PSA 52.32, QED 0.89
Compound (SMILES): COCC1CN(c2ncc(C(C)C)c3cc(Nc4ccnc(N5CC[C@@H](O)[C@@](C)(F)C5)n4)ncc23)C1
InChIKey: GBJAYAQWPSVFJF-RLWLMLJZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST tagged recombinant wild type human EGFR expressed in baculovirus infected Sf9 insect cells expression system using 5-FAM-EEPLYINSFPAKKK-CONH peptide as substrate preincubated for 10 mins followed by peptide substrate addition in presence of ATP
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 495.6, ALogP 3.67, HBA 9, HBD 2, PSA 99.53, QED 0.51
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H]([C@H](C)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: WQPPCADSQXXOLW-FVPVMZIUSA-N
Target: Melanoma-associated antigen 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P43358
Assay: Binding affinity to recombinant N-terminal His-tagged MAGEA4-MH domain (unknown origin) expressed in Escherichia coli BL21-(DE3) by isothermal titration calorimetry
Measurement: Kd = 47.4 nM (pChEMBL 7.320000171661377)
Descriptors: MW 1656.94
Compound (SMILES): CC1(C)c2cc(NS(C)(=O)=O)ccc2C(=O)c2c1oc1cc(C#Cc3cc(OCC4CC4)ccn3)ccc21
InChIKey: CNWIKXJNZAJWKF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of KDR (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 526.61, ALogP 5.26, HBA 6, HBD 1, PSA 98.5, QED 0.36
Compound (SMILES): NS(=O)(=O)Oc1ccc(-c2cn(-c3cc(F)cc(F)c3)nn2)cc1
InChIKey: PIUMPOYUIZUFMN-UHFFFAOYSA-N
Target: Steryl-sulfatase (SINGLE PROTEIN), Homo sapiens
UniProt: P08842
Assay: Inhibition of human placental STS using [3H]E1S as substrate incubated for 3 hrs by radioisotope enzymatic assay
Measurement: IC50 = 36.78 nM (pChEMBL 7.429999828338623)
Descriptors: MW 352.32, ALogP 1.79, HBA 6, HBD 1, PSA 100.1, QED 0.77
Compound (SMILES): Cc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC(C)C)cc1C1CCN(C(=S)SCC(=O)N(C)C)CC1
InChIKey: DITFLYXLIQETNM-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type N-terminal GST tagged ALK G1202R mutant cytoplasmic domain (1058 to 1620 end residues) (unknown origin) expressed in Sf21 cells incubated for 1 hr in presence of ATP
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 719.4, ALogP 7.18, HBA 10, HBD 2, PSA 116.76, QED 0.2
Compound (SMILES): O=C(CCCCCCC(=O)Nc1nc2c(s1)C[C@@H](NC(=O)c1cccc3ccccc13)CC2)NO
InChIKey: WODPQZOZWZAOTM-SFHVURJKSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 494.62, ALogP 4.37, HBA 6, HBD 4, PSA 120.42, QED 0.19
Compound (SMILES): N#Cc1ccc(NC(=O)CCc2cccc(-c3cnc4[nH]ccc4c3)c2)cc1C(F)(F)F
InChIKey: UPPDETQJTDKFRY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 in human HCT-116 cells transfected with TOPFlash luciferase reporter plasmid assessed as reduction in TCF/LEF transcriptional activity
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 434.42, ALogP 5.69, HBA 3, HBD 2, PSA 81.57, QED 0.42
Compound (SMILES): CCOc1ccc(C(=O)Cn2c(=O)n(CC(=O)Nc3ccccc3OC)c(=O)c3ccccc32)cc1Cl
InChIKey: BVJNVFFXFHFQRV-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Displacement of [32P]S1P from human recombinant S1PR1 incubated for 60 mins by competitive binding assay based scintillation counter
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 521.96, ALogP 3.75, HBA 8, HBD 1, PSA 108.63, QED 0.34
Compound (SMILES): Cc1ccc(C2CC(c3ccc(F)cc3F)=NN2C(=O)COc2ccc(/C=C3/SC(=O)NC3=O)cc2)cc1
InChIKey: SVJZOFSLJQBMFT-BRJLIKDPSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human N-terminal His6-SUMO-tagged C-terminal SII-tagged HDAC8 expressed in Escherichia coli (BL21) DE3 pLysS cells using BocLys(trifluoroacetyl)-AMC as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 533.56, ALogP 5.35, HBA 6, HBD 1, PSA 88.07, QED 0.43
Compound (SMILES): Nc1ncc2c(n1)-c1c([nH]c3ccc(C4CC4)cc13)CCCC2
InChIKey: XIVFOAKTTGQHLJ-UHFFFAOYSA-N
Target: 1-phosphatidylinositol 3-phosphate 5-kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2I7
Assay: Inhibition of PIKFYVE in HEK293 cells by NanoBRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 304.4, ALogP 3.96, HBA 3, HBD 2, PSA 67.59, QED 0.71
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccc(N2CCOCC2)cc1
InChIKey: HGBGJBHLOOHMDO-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 69.3 nM (pChEMBL 7.159999847412109)
Descriptors: MW 460.54, ALogP 5.26, HBA 6, HBD 1, PSA 71.86, QED 0.39
Compound (SMILES): CCCCCCCCCCn1cc[n+](Cc2c(OC)cc(OC)cc2OC)c1C.[Cl-]
InChIKey: YCCUOMQAEKRODN-UHFFFAOYSA-M
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis
Measurement: Ki = 27.87 nM (pChEMBL 7.550000190734863)
Descriptors: MW 403.59, ALogP 5.3, HBA 4, HBD 0, PSA 36.5, QED 0.32
Compound (SMILES): Cc1coc2c1C(=O)C(=O)c1c-2ccc2c1CCC(=O)C2(C)C
InChIKey: FKFLVAPDJGFZBA-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO assessed as reduction in N-formylkynurenine formation using L-tryptophan as substrate and measured after 15 mins
Measurement: IC50 = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 308.33, ALogP 3.43, HBA 4, HBD 0, PSA 64.35, QED 0.7
Compound (SMILES): CCSc1nc2ccccc2c(=O)n1CCc1ccc(S(N)(=O)=O)cc1
InChIKey: FONDQFJKIULAHB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 57.8 nM (pChEMBL 7.239999771118164)
Descriptors: MW 389.5, ALogP 2.4, HBA 6, HBD 1, PSA 95.05, QED 0.52
Compound (SMILES): CC(C)COc1ccc(CNC(=O)N(Cc2ccc(F)nn2)C2CCN(C)CC2)cc1
InChIKey: ONXQZYXVGHSNHX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Inverse agonist activity at 5-HT2A receptor (unknown origin) expressed in mouse NIH3T3 cells using o-nitrophenyl-D-galacto pyranoside incubated for 120 hrs
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 429.54, ALogP 3.46, HBA 5, HBD 1, PSA 70.59, QED 0.7
Compound (SMILES): CCC(CC)c1cc(N[C@H]2CC[C@H](N)C2)n2nccc2n1
InChIKey: VYKCLMALANGCDF-STQMWFEESA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 287.41, ALogP 2.92, HBA 5, HBD 2, PSA 68.24, QED 0.89
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1nc(N)c(C(=O)c2c(Cl)cccc2Cl)s1
InChIKey: UISRWLSAXIOCND-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQ88
Assay: Inhibition of N-terminus or C-terminus NLuc fused CDK11A (unknown origin) transfected in HEK293 cells by NanoBRET assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 492.43, ALogP 4.77, HBA 8, HBD 2, PSA 83.72, QED 0.48
Compound (SMILES): Cc1cc(C(=O)O)ccc1CN1CCC[C@H](O[C@H](CS(C)(=O)=O)c2cc(Cl)cc(Cl)c2)[C@@H]1c1ccccc1
InChIKey: XBACYIOZLSYPCB-IARZGTGTSA-N
Target: cGMP-dependent protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13976
Assay: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay
Measurement: EC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 576.54, ALogP 6.51, HBA 5, HBD 1, PSA 83.91, QED 0.31
Compound (SMILES): Cc1cc2c(C(N)=O)c(N)n(-c3c(C)ccc(O)c3C)c2nc1C
InChIKey: ARBRHWRTXPWZGN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 324.38, ALogP 2.65, HBA 5, HBD 3, PSA 107.16, QED 0.67
Compound (SMILES): CC(C)C[C@H](NC(=O)CN(C)C(=O)c1cc(Cl)ccc1Cl)B(O)O
InChIKey: UCEKFUNOSMHCBH-ZDUSSCGKSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis
Measurement: IC50 > 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 375.06
Compound (SMILES): CC[C@H](Nc1nc(N)nc(N)c1C#N)c1nn(-c2cccnc2)c2cc(Cl)ccc12
InChIKey: VTCNQSUIAAFERP-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by ADP-Glo assay
Measurement: IC50 = 576 nM (pChEMBL 6.239999771118164)
Descriptors: MW 419.88, ALogP 3.46, HBA 9, HBD 3, PSA 144.35, QED 0.45
Compound (SMILES): CCC(=O)N1CC[C@H](Nc2ncnc3sc(-c4cnc(OC)nc4)cc23)C1
InChIKey: MDDVLVLXLZPCOV-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate measured after 1 hr in presence of ATP by ADP-glo luminescence assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 384.47, ALogP 2.58, HBA 8, HBD 1, PSA 93.13, QED 0.72
Compound (SMILES): CNS(=O)(=O)[C@@H]1CC[C@@H](Nc2ncc3c(Br)nn(-c4ccc5ncccc5c4)c3n2)C1
InChIKey: OWDNMCJGFKIMJP-UKRRQHHQSA-N
Target: eIF-2-alpha kinase GCN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2K8
Assay: Inhibition of GCN2 in human SK-OV-3 cells assessed as reduction in phosphorylation of eIF2alpha by cellular assay
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 502.4, ALogP 3.01, HBA 8, HBD 2, PSA 114.69, QED 0.43
Compound (SMILES): C[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCC[C@@H]2CO
InChIKey: HINZNLWGIFHPEI-BEFAXECRSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P06536
Assay: Agonist activity at glucocorticoid receptor in rat INS-1 832/13 cells transfected with 3XGRE-promoter luciferase plasmid construct assessed as induction of receptor transactivation by luciferase reporter gene assay
Measurement: EC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 312.39, ALogP 3.75, HBA 3, HBD 1, PSA 38.05, QED 0.92
Compound (SMILES): CCCC[C@@H](NC(=O)[C@@H](Cc1ccccc1)NC(=O)[C@H](N)Cc1cccc(F)c1)C(=O)N[C@H](CCCNC(=N)N)C(N)=O
InChIKey: FTKQNSREVFDFLI-ZGFBMJKBSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Agonist activity at KOR in guinea pig brain membranes assessed as stimulation of [35S]GTPgammaS binding measured after 1 hr by liquid scintillation counting analysis
Measurement: EC50 = 22.39 nM (pChEMBL 7.650000095367432)
Descriptors: MW 598.72, ALogP 0.33, HBA 6, HBD 8, PSA 218.31, QED 0.07
Compound (SMILES): CC1(C)c2cc(OCCN3CCNC(=O)C3)ccc2C(=O)c2c1oc1cc(C#Cc3cc(OCC4CC4)ccn3)ccc21
InChIKey: QTJHBCKEZSYXTG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of KDR (unknown origin)
Measurement: IC50 = 413 nM (pChEMBL 6.380000114440918)
Descriptors: MW 575.67, ALogP 4.7, HBA 7, HBD 1, PSA 93.9, QED 0.32
Compound (SMILES): CCC1(CC)CC(=O)N([C@@H]2CCOc3ccc(C(=O)N[C@@H]4c5ccccc5OC4(C)C)cc32)C(=N)N1
InChIKey: MDTDXKZXNMWATA-HYBUGGRVSA-N
Target: Plasmepsin IX (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q8ILG2
Assay: Inhibition of Plasmodium falciparum 3D7 HA-glms-tagged PMIX using DABCYL-HSFIQEGKEE-EDANS as substrate measured after 2 hrs by FRET assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 490.6, ALogP 4.47, HBA 5, HBD 3, PSA 103.75, QED 0.57
Compound (SMILES): Cc1ccc(-c2onc3ccc(/C=C/C(=O)O)cc23)cc1
InChIKey: YPDPEHKRYOMXIP-WEVVVXLNSA-N
Target: Inositol hexakisphosphate kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHH9
Assay: Inhibition of N-terminal 6His-tagged/TEV cleavage site fused recombinant human IP6K2 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay
Measurement: IC50 = 6510 nM (pChEMBL 5.190000057220459)
Descriptors: MW 279.3, ALogP 3.9, HBA 3, HBD 1, PSA 63.33, QED 0.74
Compound (SMILES): CCCCCCCCCCCCCCNC(=O)/C=C\C(=O)OCC#N
InChIKey: ZHLZCERGMUGXQL-PFONDFGASA-N
Target: Palmitoyltransferase ZDHHC2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIJ5
Assay: Inhibition of human myc-His6-tagged zDHHC2 expressed in HEK293T cells using 5-FAM-GTQGCMGLPCVVM-COOH as substrate preincubated for 30 mins followed by substrate addition and measured at 1 min interval for 2 hrs in presence of palmitoyl-CoA by fluorescence polarization assay
Measurement: IC50 = 2660 nM (pChEMBL 5.579999923706055)
Descriptors: MW 350.5, ALogP 4.43, HBA 4, HBD 1, PSA 79.19, QED 0.25
Compound (SMILES): Cc1[nH]nc(-c2ccncc2)c1-c1ccc(-c2cccc(S(N)(=O)=O)c2C)cc1
InChIKey: DZIYQCFTIACOFU-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of full-length LRRK2 G2019S mutant (unknown origin) using LRRKtide as substrate incubated for 1 hr in presence of ATP by TR-FRET based ADAPTA assay
Measurement: IC50 = 61.4 nM (pChEMBL 7.210000038146973)
Descriptors: MW 404.5, ALogP 4.07, HBA 4, HBD 2, PSA 101.73, QED 0.54
Compound (SMILES): COc1cc2ncnc3c2cc1OCCOCCOc1cc(ccc1Cl)N3
InChIKey: CDSJYIPKIVLHEK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) Del19 mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 = 492.9 nM (pChEMBL 6.309999942779541)
Descriptors: MW 387.82, ALogP 3.82, HBA 7, HBD 1, PSA 74.73, QED 0.68
Compound (SMILES): CSc1nc(-c2cccc(NC(=O)c3c(F)ccc(O)c3CN3Cc4ccccc4C3=O)c2)c(-c2ccnc(NC(C)=O)c2)[nH]1
InChIKey: KSPSPBKQQQAFJU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR L858R/T790M/C797S mutant expressed in Sf9 insect cells in presence of ATP measured by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 622.68, ALogP 6.07, HBA 7, HBD 4, PSA 140.31, QED 0.15
Compound (SMILES): C[C@H]1COC(=O)c2c(c3cc(Nc4ccnc(Cl)c4C#N)ccc3n(C)c2=O)N1
InChIKey: HECAYGOIQMGZQS-JTQLQIEISA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Inhibition of human N-terminal thioredoxin 6-His tagged BCL6 BTB domain (5 to 129 residues) expressed in Escherichia coli BL21-AI using BCOR-AF633 peptide as substrate incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 409.83, ALogP 3.17, HBA 8, HBD 2, PSA 109.04, QED 0.49
Compound (SMILES): CCCCc1sc(C2CCN(CCCCc3cn(CCC)c4ccc(C#N)cc34)CC2)nc1-c1ccc(Oc2ccc(Cl)cc2)cc1
InChIKey: GAPUGWGLQCHKNL-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) expressed in human HEK293 cells
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 665.35, ALogP 11.04, HBA 6, HBD 0, PSA 54.08, QED 0.11
Compound (SMILES): O=C(CNC1CC1)Nc1ccc(-c2nc(-c3ccnc(Nc4ccc(OC(F)(F)F)cc4)c3)no2)cc1
InChIKey: BQLYBTLOWYZEAG-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured after 5 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 24270 nM (pChEMBL 4.619999885559082)
Descriptors: MW 510.48, ALogP 5.13, HBA 8, HBD 3, PSA 114.2, QED 0.28
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OC(=O)c1ccc(F)nc1)CCc1cc2c(cc1-3)OCO2.[Cl-]
InChIKey: VFTDRGLUOYWWQB-UHFFFAOYSA-M
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Binding affinity to human Cht expressed in Pichia pastoris GS115 using MU-(GlcNAc)2 as substrate assessed as inhibition constant incubated for 25 mins by dixon plot analysis
Measurement: Ki = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 445.43, ALogP 3.84, HBA 6, HBD 0, PSA 70.76, QED 0.21
Compound (SMILES): COC(=O)/C=C/c1ccc(OCCCCCN2CCN(CC(=O)Nc3c4c(nc5ccccc35)CCCC4)CC2)c(OC)c1
InChIKey: CZQSTWRTKNOMPM-BMRADRMJSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BuchE (unknown origin) using butylthicoline iodide as substrate preincubated for 10 mins followed by substrate addition and measured after 10 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 106.9 nM (pChEMBL 6.96999979019165)
Descriptors: MW 600.76, ALogP 5.11, HBA 8, HBD 1, PSA 93.23, QED 0.16
Compound (SMILES): CCc1ccc(-c2nc3ccc(NC(=O)c4cc([N+](=O)[O-])ccc4Cl)cc3n2C)cc1
InChIKey: MHEJOGKKTNUSDE-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Inverse agonist activity at PPARgamma in human RT112/84-FABP4 cells assessed as reduction in PPARgamma transactivation measured by Nanoluciferase reporter gene assay
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 434.88, ALogP 5.62, HBA 5, HBD 1, PSA 90.06, QED 0.33
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCOCCCCOCCCCOc2cc3ncnc(Nc4ccc(F)c(Cl)c4)c3cc2NC(=O)/C=C/CN(C)C)C(C)(C)C)cc1
InChIKey: BXHBYEPLXDQKAT-JYCNGAFSSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: TR-FRET Assay for ERBB Kinases: All compounds and PROTACs were serially diluted in three-fold increments using 100% DMSO, followed by an intermediate 10-fold dilution using Buffer A (50 mM HEPES, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 1 mM DTT, and 0.1% Pluronic F-68). Two microliters of serially diluted compound or PROTAC were then transferred to black 384-well Proxiplates (PerkinElmer, #6008260) using an Integra Viaflo96. Next, 10 uL of protein kinase in Buffer A was added to each well of the assay plate and pre-incubated with compound for 10 minutes. Kinase reactions were then initiated by addition of 5 uL substrate mix containing 3 mM ATP and 30 uM fluorescein-labeled Poly-GluTyr (Thermo Fisher, #PV3610) in Buffer A and allowed to proceed for 10 minutes at room temperature. Reactions were quenched by addition of a 5 uL mixture containing 5 nM LanthaScreen® Tb-pY20 Antibody (Thermo Fisher, #PV3552) and 40 mM EDTA in Buffer A. Assay plates were then read using a Synergy2 (Biotek Instruments, Winooski, Vt.) via excitation thru a 340/20 nm bandpass filter and emission collected thru 490/10 nm (donor) and 520/25 nm (acceptor) bandpass filters. The final kinase concentrations used for each 15 uL reaction were as follows: 0.2 nM EGFR Exon20NPG (SignalChem, #E10-132GG), 0.1 nM wild type EGFR (BPS Bioscience, #40187), 0.3 nM EGFR L858R/T790M/C797S (BPS Bioscience, #40351), 0.1 nM EGFR L858R (BPS Bioscience, #40189), 0.4 nM L858R/T790M (BPS Bioscience, #40350), InM EGFR Dell9 (SignalChem, #E10-122JG), 10 nM EGFR Dell9 T790M (SignalChem, #E10-122KG), 0.3 nM Her2 (BPS Bioscience, #40230), 15 nM Her2 InsYVMA (SignalChem, #E27-13BG).
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 1086.77
Compound (SMILES): COc1cc(N(C)CCN(C)C)c(NC(=O)c2ncccn2)cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
InChIKey: WBOAFSSMPYWBDR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M mutant (unknown origin) by mobility shift assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 551.66, ALogP 4.43, HBA 10, HBD 2, PSA 113.33, QED 0.26
Compound (SMILES): CCOC(=O)C1CCN(C(=O)c2ccc(N(CC)Cc3cnc4nc(N)nc(N)c4n3)cc2)CC1
InChIKey: HEPDQIIFCBFHRJ-UHFFFAOYSA-N
Target: Pteridine reductase 1 (SINGLE PROTEIN), Leishmania major
UniProt: Q01782
Assay: Inhibition of recombinant Leishmania major PTR1 expressed in Escherichia coli BL21 (DE3) cells using H2B as substrate in presence of cytochrome c and NADPH by envision multilabel reader
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 478.56, ALogP 2.03, HBA 10, HBD 2, PSA 153.45, QED 0.48
Compound (SMILES): COc1cc2ncnc(N3CCC(CN4CCN(c5cccc(C(F)(F)F)c5)CC4)C3)c2cc1OC
InChIKey: GCFBAQLBLLIFNB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in CHO-K1 cells membrane by scintillation counter analysis
Measurement: Ki = 229.09 nM (pChEMBL 6.639999866485596)
Descriptors: MW 501.55, ALogP 4.31, HBA 7, HBD 0, PSA 53.96, QED 0.5
Compound (SMILES): CCCCN(C)[C@@H](Cc1c[nH]c2ccccc12)CN(C)CCC1CCCCCC1
InChIKey: JNHBUJVXUSKTKS-DEOSSOPVSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: P21836
Assay: Inhibition of mouse recombinant AChE assessed as reduction in cholinesterase activity using acetylthiocholine iodide as substrate preincubated for 1 to 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 23400 nM (pChEMBL 4.630000114440918)
Descriptors: MW 397.65, ALogP 6.1, HBA 2, HBD 1, PSA 22.27, QED 0.46
Compound (SMILES): O=C(C1CCOCC1)N(CC12CCC(c3nc(C4CC4)no3)(CC1)CC2)c1cccc(-c2nc(C3CC3)no2)c1
InChIKey: VOXSAHXZYHFEFQ-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin)
Measurement: EC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 543.67, ALogP 5.93, HBA 8, HBD 0, PSA 107.38, QED 0.34
Compound (SMILES): Cc1ccc2nc3c(c(NCCN4CCOCC4)c2c1)CCCC3
InChIKey: JHKMYOWNYNDGJT-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of C-terminal 6His-tagged human recombinant BuChE (29 to 602 residues) using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 3127 nM (pChEMBL 5.5)
Descriptors: MW 325.46, ALogP 3.17, HBA 4, HBD 1, PSA 37.39, QED 0.94
Compound (SMILES): COc1ccc(-c2cn(-c3ccc(S(=O)(=O)C4(C(=O)NO)CCOCC4)cc3)nn2)cc1
InChIKey: JHSGRRNCQDDQBC-UHFFFAOYSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of MMP-3 (unknown origin)
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 458.5, ALogP 1.77, HBA 9, HBD 2, PSA 132.64, QED 0.42
Compound (SMILES): Cc1ccc([C@@H]2NC(=O)[C@H](c3ccccc3)NC(=O)[C@H](NC(=O)[C@@H](N)Cc3c(C)cc(O)cc3C)CCCCNC(=O)C[C@@H](C(N)=O)NC2=O)cc1
InChIKey: VYNGGDWBEYATES-LNAXGRFASA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Inhibition of Wistar rat brain membrane DOP
Measurement: IC50 = 14.9 nM (pChEMBL 7.829999923706055)
Descriptors: MW 713.84, ALogP 1.05, HBA 8, HBD 8, PSA 234.84, QED 0.18