lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(OCC3CC3)c3ccccc3)ccc2F)c1
InChIKey: HIMJVDQVZQMIPM-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Plasma Kallikrein Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader (Winooski, Vt., USA). Data were analyzed using SigmaPlot software (Systat Software, Inc., San Jose, Calif., USA) (Four Parameter Logistic Curve). Ki values for the inhibitors were determined using the Cheng-Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099).
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 538.55, ALogP 6.26, HBA 5, HBD 2, PSA 82.17, QED 0.25
Compound (SMILES): CC(C)(O)COc1nc(OCCC(F)(F)F)c(CO)cc1-c1ccc(S(C)(=O)=O)cc1
InChIKey: ZFNUYYFTMQCDOW-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX-2 using arachidonic acid as substrate preincubated for 60 mins followed by substrate addition for 2 secs by ADPH based fluorometric analysis
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 463.47, ALogP 3.13, HBA 7, HBD 2, PSA 105.95, QED 0.59
Compound (SMILES): COc1ncc(C2=CCOCC2)cc1S(=O)(=O)Nc1cncc(-c2ccc(CN3CCCC3)cc2)c1
InChIKey: JYXMRJMVWFEYNI-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal His6-tagged full length P110alpha/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 506.63, ALogP 4.35, HBA 7, HBD 1, PSA 93.65, QED 0.49
Compound (SMILES): CCOC(=O)C1=C(NN2CCN(CC(F)(F)F)CC2)O/C(=C\c2c[nH]c3ncccc23)C1=O
InChIKey: DNTVXDZWVOVLOD-GDNBJRDFSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin) in presence of 1 mM ATP without preincubation
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 465.43, ALogP 1.96, HBA 8, HBD 2, PSA 99.79, QED 0.38
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cc(c(F)cc1F)C(=O)NCc1cncc(c1)-c1ccnc3ccc-2cc13
InChIKey: GXDHTIMAUFICAI-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using Luciferin-H as substrate at 10 uM preincubated with enzyme and substrate for 5 mins followed by addition of NADPH regeneration system and measured after 60 mins by luminescence method
Measurement: IC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 559.55, ALogP 4.69, HBA 7, HBD 2, PSA 123.17, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc([Se]CC(O)CSc2ncccn2)cc1
InChIKey: LBIZFRBYQYAPDX-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 404.38
Compound (SMILES): CN1CCN(c2cccc(Nc3nccc(-c4cn(C)c5ncccc45)n3)c2)CC1
InChIKey: PETRMFAIRNHKGK-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) using HYSPTSPSYSPTSPSYSPTSPSKKKK-O substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 399.5, ALogP 3.53, HBA 7, HBD 1, PSA 62.11, QED 0.57
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(N)=O
InChIKey: HUJPRSPSMBVKRV-LQDUMDOSSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 882.8, ALogP 3.33, HBA 6, HBD 8, PSA 221.39, QED 0.03
Compound (SMILES): C#Cc1cccc(Nc2ncnc3cc(OC)c(OCCCCCCCN/C(=N\C#N)Nc4ccncc4)cc23)c1
InChIKey: WIIOTLRKRPDWPS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human recombinant EGFR L858R mutant (668 to 1210 residues) expressed in baculovirus expression system by Z'-LYTE kinase assay
Measurement: IC50 = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 548.65, ALogP 5.63, HBA 8, HBD 3, PSA 129.37, QED 0.06
Compound (SMILES): COC(=O)/C(=N\Nc1ccc(C)cc1)C(=O)C(F)(F)F
InChIKey: WBTOVOOOKUVTED-MFOYZWKCSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Competitive inhibition of human erythrocyte AChE by double reciprocal Lineweaver-Burk plot analysis
Measurement: Ki = 10100 nM (pChEMBL 5)
Descriptors: MW 288.23, ALogP 2.07, HBA 5, HBD 1, PSA 67.76, QED 0.4
Compound (SMILES): COCC(CC1(C)NC(=O)NC1=O)C(=O)N1CCN(c2cc(Cl)cc(Cl)c2)CC1
InChIKey: OBQNFIXICFYDBT-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: In Vitro Assay: MMP2: Protocol 2: The basis for the assay is the cleavage of the substrate 390 MMP FRET substrate I (Anaspec, Catalog n#: AS-27076) by human MMP2 (R&D SYSTEMS INC., Cat #902-MP).For the dose response (10 point), 4 μL of a dilution series of compound (2 mM highest concentration, 1/5 dilution in DMSO further diluted 1 in 10 in water, corresponding to a final highest concentration of 20 μM), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 μL buffer solution (45 mM Tris pH 7.5, 9 mM CaCl2, 135 mM NaCl, 0.045% Brij35) containing MMP2 (0.03 ng/L) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration).The reaction is initiated by adding to the assay plate 390 MMP FRET substrate I (10 μL, 2.5 μM, Anaspec) in the same buffer.Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 30 min at room temperature (Excitation 485 nm, Emission 530).
Measurement: IC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 443.33, ALogP 1.89, HBA 5, HBD 2, PSA 90.98, QED 0.66
Compound (SMILES): CNc1cc(Oc2c(C)cc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2C)ncn1
InChIKey: FECAKHQZOGVGGX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf (unknown origin)
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 431.42, ALogP 5.59, HBA 5, HBD 3, PSA 88.17, QED 0.49
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)NC(=O)NCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: GQQOUWMFSIQFNW-JPRYDEJLSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human neuropeptide Y Y4 receptor expressed in CHO-mtAEQ cells co-expressing Gqi5 by calcium aequorin assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1125.3
Compound (SMILES): Cn1cc(-c2cc3ncnc(Nc4ccc(CC(=O)Nc5cc(C(C)(C)C)nn5C)cc4)c3s2)cn1
InChIKey: CFAOOHPDKFUMTF-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora B (unknown origin)
Measurement: IC50 = 1990 nM (pChEMBL 5.699999809265137)
Descriptors: MW 500.63, ALogP 5.05, HBA 9, HBD 2, PSA 102.55, QED 0.34
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)c4cscn4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: MQKBHIPASUSQRC-IHPCNDPISA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Activity Assay: Activity Against Mer Tyrosine Kinase.
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 496.68, ALogP 4.98, HBA 8, HBD 2, PSA 96.17, QED 0.48
Compound (SMILES): CN(CCC=C1c2ccccc2-c2ccccc21)C(CCO)C(=O)NCc1ccccc1
InChIKey: QTUSIFYNKFDOPP-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 978 nM (pChEMBL 6.010000228881836)
Descriptors: MW 426.56, ALogP 4.49, HBA 3, HBD 2, PSA 52.57, QED 0.41
Compound (SMILES): CCC(=O)CCCCC[C@@H]1NC(=O)[C@H]2CC23CCN(CCCOCCCn2ccc4cc(ccc4c2=O)-c2cnc1[nH]2)CC3
InChIKey: PLWBVDLCWWJINE-IHLOFXLRSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 808 nM (pChEMBL 6.090000152587891)
Descriptors: MW 601.79, ALogP 5.39, HBA 7, HBD 2, PSA 109.32, QED 0.35
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CN(C)C1)c1ncc(-c2ccccc2)[nH]1
InChIKey: BTPNRALWSPISIP-FQEVSTJZSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 249 nM (pChEMBL 6.599999904632568)
Descriptors: MW 396.54, ALogP 3.73, HBA 4, HBD 2, PSA 78.09, QED 0.57
Compound (SMILES): Cc1c(NC(=O)CCN2CCCC2)c[nH]c1/C=C1\C(=O)Nc2ccc(F)cc21
InChIKey: WSCLCZKFOUHIBA-WJDWOHSUSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of c-KIT (unknown origin) incubated for 30 mins in presence of ATP by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 382.44, ALogP 3.38, HBA 3, HBD 3, PSA 77.23, QED 0.69
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2[C@@H]3C[C@@H](O)C[C@@H]32)cc2c1OC[C@@]2(C)c1ccccc1
InChIKey: FNHHVPPSBFQMEL-HURDOVMISA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of recombinant human BRD4 BD1 (44 to 168 residues) expressed in bacterial expression system by bromoscan assay
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 406.48, ALogP 2.24, HBA 4, HBD 3, PSA 87.66, QED 0.73
Compound (SMILES): COCC(=O)N1Cc2cc(S(C)(=O)=O)ccc2C1C(=O)Nc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: RKYGMCSLWMPQPS-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: FRET Assay: The assay was run in black 384 well plates (Greiner cat no: 784900). Various concentrations of test ligands in 0.1 microlitres DMSO were dispensed to assay plates using an Echo acoustic dispenser. Two pre-mixes were prepared and incubated for 1 h at room temp in the dark. Pre-mix 1 comprised 100 nM Protein (Biotinylated HN-Avi-MBP-TCS-hRORÎ³ (258-518)) and 60 nM Streptavidin APC in assay buffer, 50 mM MOPS pH7.4, 50 mM KF, 0.003% (w/v) CHAPS, 10 mM DTT and 0.01% (w/v) BSA and pre-mix 2 comprised 160 nM biotinylated SRC-1 peptide (NCOA1-677-700) and 20 nM Europium-W8044 labelled Streptavidin in assay buffer. Five microlitres of pre-mix 2 was dispensed to assay plates containing 0.1 microlitres of test compound and was incubated for 15 minutes prior to adding five microlitres of pre-mix 1. Plates were incubated at room temperature for 1 hour in the dark, prior to reading in a Pherastar multi-mode plate reader using HTRF filter set (ex 320, em 612 and 665). The FRET signal at 665 nm was divided by the signal at 612 nm and multiplied by 10,000 to generate a signal ratio value for each well. The raw data was transformed to % effect using the equation:Compound % effect=100*[(Xâmin)/(maxâmin)],where X represents the normalized value for the compound based on the Min (vehicle) and Max (reference compound) inhibition control.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 554.47, ALogP 3.07, HBA 6, HBD 2, PSA 113.01, QED 0.53
Compound (SMILES): Cc1ccc(C(C)NC(=O)/N=C(\N)NCCCc2sc(N)nc2C)cc1
InChIKey: LIBHXUIZGKHXII-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P47747
Assay: Agonist activity at guinea pig right atrium histamine H2 receptor assessed as increase in heart rate incubated for 30 mins in presence of cimetidine
Measurement: EC50 = 22.39 nM (pChEMBL 7.650000095367432)
Descriptors: MW 374.51, ALogP 2.65, HBA 4, HBD 4, PSA 118.42, QED 0.35
Compound (SMILES): O=C1c2ccccc2S(=O)(=O)N1CCCCCN1CCN(c2cccc(Cl)c2Cl)CC1
InChIKey: RWQZSXGTDPICOA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2AR expressed in CHO cells
Measurement: Ki = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 482.43, ALogP 4.13, HBA 5, HBD 0, PSA 60.93, QED 0.56
Compound (SMILES): Cc1nc(Nc2ncc(C(=O)Nc3c(C)cncc3Cl)s2)cc(N2CCN(CCO)CC2)n1
InChIKey: TZEWBPGVTYPITP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase SIK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K2
Assay: Inhibition of SIK3 (unknown origin) using RBER-CHKtide as substrate in presence of [32P]gammaATP by microplate scintillation counter analysis
Measurement: IC50 = 677 nM (pChEMBL 6.170000076293945)
Descriptors: MW 489.01, ALogP 2.71, HBA 10, HBD 3, PSA 119.4, QED 0.46
Compound (SMILES): C=CCn1c(SCc2ccc(C(=O)NO)cc2)nnc1-c1ccncc1
InChIKey: ZLWNIOZDEQOURO-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human full-length recombinant C-terminal His-tagged HDAC8 expressed in baculovirus infected Sf9 insect cells preincubated for 5 mins followed by HDAC substrate addition and further incubated for 45 mins by fluorescence microplate reader assay
Measurement: IC50 = 28370 nM (pChEMBL 4.550000190734863)
Descriptors: MW 367.43, ALogP 2.94, HBA 7, HBD 2, PSA 92.93, QED 0.29
Compound (SMILES): CNc1cc(Oc2c(Cl)cc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2Cl)ncn1
InChIKey: QOQADIYOLOHRAW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 472.25, ALogP 6.28, HBA 5, HBD 3, PSA 88.17, QED 0.41
Compound (SMILES): O=C(O)CCNC(=S)NCCCNc1nc(CCc2c[nH]c3ccccc23)ncc1C(=O)O
InChIKey: XZKJHCUXRYHRMJ-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate incubated for 1 hr in presence of 100 uM NAD+ by fluorescence based analysis
Measurement: IC50 = 11900 nM (pChEMBL 4.920000076293945)
Descriptors: MW 470.56, ALogP 2.18, HBA 6, HBD 6, PSA 152.26, QED 0.17
Compound (SMILES): COc1ncc(C2=CCOCC2)cc1S(=O)(=O)Nc1cncc(-c2ccc(CN3CCN(C)CC3)cc2)c1
InChIKey: ZDAXIXBZLNLYRI-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as reduction in cytostim-stimulated IFNgamma production preincubated for 1 hr followed by cytostim stimulation and measured after 20 hrs by electrochemiluminescence assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 535.67, ALogP 3.5, HBA 8, HBD 1, PSA 96.89, QED 0.47
Compound (SMILES): [2H]C([2H])(NC(=O)c1cc(C(=O)NCc2ccc(F)c(C)c2)ncn1)c1ccc(C(=O)O)cc1
InChIKey: LXZKIXQSLYEDMA-KBMKNGFXSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 using QXL520-gamma-Abu-Pro-Cha-Abu-Smc-His-Ala-Dab(5-FAM)-Ala-Lys-NH2 as substrate measured every 5 mins for 2 hrs by FRET assay
Measurement: IC50 = 74000 nM (pChEMBL 4.130000114440918)
Descriptors: MW 422.42, ALogP 2.48, HBA 5, HBD 3, PSA 121.28, QED 0.54
Compound (SMILES): CC(=O)N1CCN(c2ccc(Nc3nccc(-c4cn(S(=O)(=O)c5ccc(C)cc5)c5ccccc45)n3)cc2)CC1
InChIKey: XWAXWDPAAMQUQH-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) using HYSPTSPSYSPTSPSYSPTSPSKKKK-O substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 566.69, ALogP 5.06, HBA 8, HBD 1, PSA 100.43, QED 0.31
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NC[C@@H](C)c1ccccc1
InChIKey: IQHAIFKWYGPTRN-GFCCVEGCSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P47747
Assay: Agonist activity at guinea pig right atrium histamine H2 receptor assessed as increase in heart rate incubated for 30 mins in presence of cimetidine
Measurement: EC50 = 12.88 nM (pChEMBL 7.889999866485596)
Descriptors: MW 374.51, ALogP 2.38, HBA 4, HBD 4, PSA 118.42, QED 0.34
Compound (SMILES): COc1ccc(OC)c(C2CC(c3cc(F)ccc3F)=NN2c2ccc(S(N)(=O)=O)cc2)c1
InChIKey: LGHMDXIUHIJXQC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2
Measurement: IC50 = 4.45 nM (pChEMBL 8.350000381469727)
Descriptors: MW 473.5, ALogP 3.99, HBA 6, HBD 1, PSA 94.22, QED 0.58
Compound (SMILES): CCCC(Oc1cccc(Cl)c1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: QZFWMMJJIHHXCY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L receptor expressed in HEK293 cells measured after 1 hr by microbeta counting method
Measurement: Ki = 495 nM (pChEMBL 6.300000190734863)
Descriptors: MW 411.34, ALogP 3.43, HBA 7, HBD 1, PSA 80.4, QED 0.78
Compound (SMILES): COc1ccc(C2CC(c3ccccc3C)=NN2c2ccc(C(=O)N3CCN(C)CC3)cc2)cc1F
InChIKey: YKESFJBBYRLROW-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of recombinant full length GST-tagged PDE2A (unknown origin) expressed in baculovirus infected Sf9 insect cells using TAMRA-cGMP as substrate incubated for 1.5 hrs by IMAP-FP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 486.59, ALogP 4.89, HBA 5, HBD 0, PSA 48.38, QED 0.52
Compound (SMILES): COc1ncc(C2=CCOCC2)cc1S(=O)(=O)Nc1cncc(-c2ccc(CN3CCNCC3)cc2)c1
InChIKey: NGBQRIOODLGVTA-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human whole blood assessed as reduction in cytostim-stimulated IFNgamma production preincubated for 1 hr followed by cytostim stimulation and measured after 20 hrs by electrochemiluminescence assay
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 521.64, ALogP 3.16, HBA 8, HBD 2, PSA 105.68, QED 0.47
Compound (SMILES): N#CCCn1cc(-n2c(-c3cccs3)cc3cnc4[nH]ccc4c32)cn1
InChIKey: CYCLMLGHCBIXRH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 signaling pathway in human TF-1 cells assessed as reduction in GM-CSF induced STAT5 phosphorylation preincubated for 2 hrs followed by GM-CSF addition and measured after 10 mins by HTRF method
Measurement: IC50 = 306 nM (pChEMBL 6.510000228881836)
Descriptors: MW 358.43, ALogP 4.35, HBA 6, HBD 1, PSA 75.22, QED 0.52
Compound (SMILES): O=C(Nc1cc(F)c(F)cc1C(=O)O)c1ccc(-n2ccnc2)nn1
InChIKey: WEBVQIJGIZVRGA-UHFFFAOYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at human 6His-tagged recombinant wild type STING CTD (139 to 37 residues) expressed in Escherichia coli BL21 (DE3) incubated for 10 mins by FRET assay
Measurement: IC50 = 9810 nM (pChEMBL 5.010000228881836)
Descriptors: MW 345.26, ALogP 1.89, HBA 6, HBD 2, PSA 110, QED 0.75
Compound (SMILES): O=C(O)c1cccc(COc2ccc(Cl)c(Cl)c2Cl)c1
InChIKey: BWVVXJGGTAVJTR-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 50 uM of obeticholic acid by HTRF assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 331.58, ALogP 4.92, HBA 2, HBD 1, PSA 46.53, QED 0.81
Compound (SMILES): N#Cc1ccc2[nH]cc(CCCCN3CCN(c4ccc(-n5ccc6ncccc6c5=O)cc4)CC3)c2c1
InChIKey: FGYLPIJGSRWQAL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Rat Synaptosome Binding Assay: The synaptosomes (150 μg) prepared from a rat brain were incubated at 37° C. for 15 minutes with 0.1 μCi [3H]5-HT in the absence or presence of the test compound or the reference compound in a buffer solution containing 106.2 mM NaCl, 4.5 mM KCl, 2.25 mM MgSO4, 1.08 mM NaH2PO4, 22.5 mM NaHCO3, 9.9 mM glucose, 9 μM EGTA and 45 μM ascorbic acid (pH 7.4).The basal control activity was determined by incubating the same mixture at 4° C. for 15 minutes in the presence of 10 μM imipramine to block the uptake of 5-HT, which was taken as the standard reference compound and tested in each experiment at several concentrations to obtain an inhibition curve.Following the incubation, the samples were filtered rapidly under vacuum through glass fiber filters (GF/B, Packard) and rinsed twice with an ice-cold incubation buffer using a 96-sample cell harvester (Unifilter, Packard) to eliminate free [3H]5-HT. The filters were dried and the retained radioactivity was measured in a scintillation counter (Topcount, Packard) using a scintillation cocktail (Microscint 0, Packard). The experimental results were expressed as a percent inhibition of the control uptake of [3H]5-HT.Data AnalysisInhibition of serotonin transporter in rat synaptosome was measured by the concentrations of [3H]5-HT. The test compounds were required to be tested at least twice in the case of the concentration thereof being greater than 6 log, and the obtained data were subjected to a nonlinear regression analysis via a curve of Hill equation, to obtain IC50 value.
Measurement: IC50 = 0.23 nM (pChEMBL 9.640000343322754)
Descriptors: MW 502.62, ALogP 4.88, HBA 6, HBD 1, PSA 80.95, QED 0.32
Compound (SMILES): FC(F)c1cncc(-c2ccc3ncc4nnc(C5CCOCC5)n4c3c2)c1
InChIKey: KMVHNMPETPMFRJ-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK in human HT-144 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay
Measurement: IC50 = 1130 nM (pChEMBL 5.949999809265137)
Descriptors: MW 381.39, ALogP 4.17, HBA 6, HBD 0, PSA 65.2, QED 0.53
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)c4ccncc4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: DWFDADABQIDXBP-VJBMBRPKSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 490.65, ALogP 4.92, HBA 7, HBD 2, PSA 96.17, QED 0.49
Compound (SMILES): COc1ccccc1-c1n[nH]cc1N1CCCNCC1
InChIKey: JNRZTHXAPWDTFP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: Binding affinity to 5HT1B receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 272.35, ALogP 1.89, HBA 4, HBD 2, PSA 53.18, QED 0.9
Compound (SMILES): O=S(=O)(c1cccc(F)c1)n1ccc2c(N3CCNCC3)nc3ccccc3c21
InChIKey: QNKGTIWNFNPEJL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5HT7 receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 2997 nM (pChEMBL 5.519999980926514)
Descriptors: MW 410.47, ALogP 2.98, HBA 6, HBD 1, PSA 67.23, QED 0.56
Compound (SMILES): O=C(CCCO/N=C1C(=C2/C(=O)Nc3ccccc32)/Nc2ccccc2/1)NO
InChIKey: PFMKIDRZHBZULH-FTCCNZMVSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombiant human HDAC6 using fluorogenic HDAC substrate 3 measured after 30 mins by fluorescence microplate reader assay
Measurement: IC50 = 128.6 nM (pChEMBL 6.889999866485596)
Descriptors: MW 378.39, ALogP 2.48, HBA 6, HBD 4, PSA 112.05, QED 0.28
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](C)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)[C@H](CCC(=O)O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N2
InChIKey: GZGKKKXTMZQENA-HGXMALQZSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta2/beta3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12391
Assay: Inhibition of rat alpha6/alpha3beta2beta3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response by two-electrode voltage-clamp method
Measurement: IC50 = 269 nM (pChEMBL 6.570000171661377)
Descriptors: MW 1602.82
Compound (SMILES): C[C@H](Oc1ccc(C(=O)NC2CC2)cc1-c1cn(C)nn1)c1ccccn1
InChIKey: NTLLKKOHPKDCSW-ZDUSSCGKSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Inhibition of 6His-Thr-BRD3 (1 to 435 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 12589.25 nM (pChEMBL 4.900000095367432)
Descriptors: MW 363.42, ALogP 2.91, HBA 6, HBD 1, PSA 81.93, QED 0.73
Compound (SMILES): COc1ccc(Cl)cc1[C@@H]1C[C@H]1CNCCCOc1ccc2ccc(=O)[nH]c2c1
InChIKey: SREQHVVABVWCKT-QFBILLFUSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 194.98 nM (pChEMBL 6.710000038146973)
Descriptors: MW 412.92, ALogP 4.35, HBA 4, HBD 2, PSA 63.35, QED 0.51
Compound (SMILES): Cc1nc(Nc2ncc(C(=O)Nc3c(C)csc3Cl)s2)cc(N2CCN(CCO)CC2)n1
InChIKey: JKDJAOQUTMBBQB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of ABL1 (unknown origin) G250E mutant using poly(Ala, Glu, Lys, Tyr) as substrate in presence of [32P]gammaATP by microplate scintillation counter analysis
Measurement: IC50 = 9160 nM (pChEMBL 5.039999961853027)
Descriptors: MW 494.05, ALogP 3.38, HBA 10, HBD 3, PSA 106.51, QED 0.46
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)N[C@@H](C)c1ccccc1
InChIKey: QTIAXUAWMLBIGP-NSHDSACASA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2L receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 360.49, ALogP 2.34, HBA 4, HBD 4, PSA 118.42, QED 0.36
Compound (SMILES): Fc1ccc2c(C3CCN(CCCOc4ccc(CCN5CCOCC5)cc4)CC3)noc2c1
InChIKey: BTEMXIHCAGOPHX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Binding affinity to 5-HT6 receptor (unknown origin)
Measurement: Ki = 141 nM (pChEMBL 6.849999904632568)
Descriptors: MW 467.59, ALogP 4.49, HBA 6, HBD 0, PSA 50.97, QED 0.43
Compound (SMILES): c1ccc(-c2n[nH]cc2N2CCCNCC2)cc1
InChIKey: PASQZXJWBXINCO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: Binding affinity to 5HT1B receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 242.33, ALogP 1.88, HBA 3, HBD 2, PSA 43.95, QED 0.84
Compound (SMILES): C=CCn1c(SCCCCCC(=O)Nc2ccccc2N)nnc1-c1ccncc1
InChIKey: CNCARDFKOBXULC-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin) by FRET-based Z'-Lyte assay
Measurement: IC50 = 14300 nM (pChEMBL 4.840000152587891)
Descriptors: MW 422.56, ALogP 4.4, HBA 7, HBD 2, PSA 98.72, QED 0.21
Compound (SMILES): NC(=O)c1cccc2cc(C(=O)N3CCN(Cc4cc5nc(-c6cnc(N)nc6)nc(N6CCOCC6)c5o4)CC3)oc12
InChIKey: UPTYBPOYVNYQMT-UHFFFAOYSA-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 2 hrs by ADP-glo plus luminescence assay
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 583.61, ALogP 1.9, HBA 12, HBD 2, PSA 182.97, QED 0.3
Compound (SMILES): CCCCCCCCCCCC(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)O
InChIKey: AGOMRKDKPHWGMJ-VABKMULXSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of human MMP12 catalytic subunit by fluorometric analysis
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 644.88, ALogP 0.88, HBA 8, HBD 10, PSA 241.62, QED 0.03
Compound (SMILES): COc1cc(N2Cc3cnc4[nH]ccc4c3N(C)C2=O)c(Cl)c(OC)c1Cl
InChIKey: RWCAQQLPZYSTLH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 407.26, ALogP 4.46, HBA 4, HBD 1, PSA 70.69, QED 0.7
Compound (SMILES): CC(C)(O)COc1nc(OCCC(F)(F)F)c(CO)cc1-c1ccc(S(C)(=O)=O)cc1
InChIKey: ZFNUYYFTMQCDOW-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX2 in human whole blood assessed as reduction in LPS stimulated PGE2 production incubated for 1 hr by ELISA
Measurement: IC50 = 877 nM (pChEMBL 6.059999942779541)
Descriptors: MW 463.47, ALogP 3.13, HBA 7, HBD 2, PSA 105.95, QED 0.59
Compound (SMILES): CCOC(=O)C1=C(NN2CCN(CC(F)(F)F)CC2)O/C(=C\c2c[nH]c3ncccc23)C1=O
InChIKey: DNTVXDZWVOVLOD-GDNBJRDFSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin) in presence of 1 mM ATP with preincubation
Measurement: IC50 = 227 nM (pChEMBL 6.639999866485596)
Descriptors: MW 465.43, ALogP 1.96, HBA 8, HBD 2, PSA 99.79, QED 0.38
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cc(c(F)cc1F)C(=O)NCc1cncc(c1)-c1ccnc3ccc-2cc13
InChIKey: GXDHTIMAUFICAI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using LuciferinH-EG as substrate at 10 uM preincubated with enzyme and substrate for 5 mins followed by addition of NADPH regeneration system and measured after 60 mins by luminescence method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 559.55, ALogP 4.69, HBA 7, HBD 2, PSA 123.17, QED 0.31
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(N)=O
InChIKey: HUJPRSPSMBVKRV-LQDUMDOSSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Agonist activity at mouse MC4R expressed in HEK293 cells assessed as induction of cAMP level incubated for 2 hr by alphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 882.8, ALogP 3.33, HBA 6, HBD 8, PSA 221.39, QED 0.03
Compound (SMILES): COC(=O)/C(=N\Nc1ccc(C)cc1)C(=O)C(F)(F)F
InChIKey: WBTOVOOOKUVTED-MFOYZWKCSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Competitive inhibition of equine serum BuChE by double reciprocal Lineweaver-Burk plot analysis
Measurement: Ki = 29200 nM (pChEMBL 4.539999961853027)
Descriptors: MW 288.23, ALogP 2.07, HBA 5, HBD 1, PSA 67.76, QED 0.4
Compound (SMILES): COCC(CC1(C)NC(=O)NC1=O)C(=O)N1CCN(c2cc(Cl)cc(Cl)c2)CC1
InChIKey: OBQNFIXICFYDBT-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: In Vitro Assay: MMP-13:The basis for the assay is the cleavage of the substrate 390 MMP FRET Substrate I (Anaspec Cat # AS-27076) by human MMP13 (Chemicon, Cat #CC068).For the dose response (10 point), 4 μL of a dilution series of compound (20 μM highest concentration, 1/5 dilution in water), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 μL buffer solution (50 mM Tris pH7.5, 150 mM NaCl, 10 mM CaCl2, 0.05% CHAPS, 5 μM ZnCl2) containing MMP13 (0.01 ng/IL) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration). Human MMP13 is preactivated by incubated the enzyme in the same buffer complemented with 1 mM freshly prepared p-Aminophenylmercuric acetate (AMPA) for 1 hour at 37° C.The reaction is initiated by adding to the assay plate 390 MMP FRET Substrate I (10 μL, 2.5 μM) in the same buffer.Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 45 min at room temperature (Excitation 485 nm, Emission 530).
Measurement: IC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 443.33, ALogP 1.89, HBA 5, HBD 2, PSA 90.98, QED 0.66
Compound (SMILES): Cn1cc(-c2cc3ncnc(Nc4ccc(CC(=O)Nc5cc(C(C)(C)C)nn5C)cc4)c3s2)cn1
InChIKey: CFAOOHPDKFUMTF-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (unknown origin)
Measurement: IC50 = 13600 nM (pChEMBL 4.869999885559082)
Descriptors: MW 500.63, ALogP 5.05, HBA 9, HBD 2, PSA 102.55, QED 0.34
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)c4cscn4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: MQKBHIPASUSQRC-IHPCNDPISA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 496.68, ALogP 4.98, HBA 8, HBD 2, PSA 96.17, QED 0.48
Compound (SMILES): CN(CCC=C1c2ccccc2-c2ccccc21)C(CCO)C(=O)NCc1ccccc1
InChIKey: QTUSIFYNKFDOPP-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human recombinant BACE1 using Rh-EVNLDAEFK-quencher as substrate incubated for 60 mins by FRET assay
Measurement: IC50 = 19500 nM (pChEMBL 4.710000038146973)
Descriptors: MW 426.56, ALogP 4.49, HBA 3, HBD 2, PSA 52.57, QED 0.41
Compound (SMILES): Cc1c(NC(=O)CCN2CCCC2)c[nH]c1/C=C1\C(=O)Nc2ccc(F)cc21
InChIKey: WSCLCZKFOUHIBA-WJDWOHSUSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (unknown origin) incubated for 30 mins in presence of ATP by mobility shift assay
Measurement: IC50 = 715.6 nM (pChEMBL 6.139999866485596)
Descriptors: MW 382.44, ALogP 3.38, HBA 3, HBD 3, PSA 77.23, QED 0.69
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2[C@@H]3C[C@@H](O)C[C@@H]32)cc2c1OC[C@@]2(C)c1ccccc1
InChIKey: FNHHVPPSBFQMEL-HURDOVMISA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Inhibition of recombinant human BRD3 BD2 (306 to 416 residues) expressed in bacterial expression system by bromoscan assay
Measurement: IC50 = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 406.48, ALogP 2.24, HBA 4, HBD 3, PSA 87.66, QED 0.73
Compound (SMILES): Cc1nc(Nc2ncc(C(=O)Nc3c(C)cncc3Cl)s2)cc(N2CCN(CCO)CC2)n1
InChIKey: TZEWBPGVTYPITP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of ABL1 (unknown origin) G250E mutant using poly(Ala, Glu, Lys, Tyr) as substrate in presence of [32P]gammaATP by microplate scintillation counter analysis
Measurement: IC50 = 45600 nM (pChEMBL 4.340000152587891)
Descriptors: MW 489.01, ALogP 2.71, HBA 10, HBD 3, PSA 119.4, QED 0.46
Compound (SMILES): C=CCn1c(SCc2ccc(C(=O)NO)cc2)nnc1-c1ccncc1
InChIKey: ZLWNIOZDEQOURO-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin) by FRET-based Z'-Lyte assay
Measurement: IC50 = 46120 nM (pChEMBL 4.340000152587891)
Descriptors: MW 367.43, ALogP 2.94, HBA 7, HBD 2, PSA 92.93, QED 0.29
Compound (SMILES): CNc1cc(Oc2c(Cl)cc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2Cl)ncn1
InChIKey: QOQADIYOLOHRAW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TNNI3K (SINGLE PROTEIN), Homo sapiens
UniProt: Q59H18
Assay: Binding affinity to full length human His-MBP-TNNI3K assessed as off-rate constant in presence of rhodamine green labeled GW805818X by fluorescence competitive binding assay
Measurement: Ki = 0.54 nM (pChEMBL 9.270000457763672)
Descriptors: MW 472.25, ALogP 6.28, HBA 5, HBD 3, PSA 88.17, QED 0.41
Compound (SMILES): O=C(O)CCNC(=S)NCCCNc1nc(CCc2c[nH]c3ccccc23)ncc1C(=O)O
InChIKey: XZKJHCUXRYHRMJ-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate incubated for 1 hr in presence of 50 uM NAD+ by fluorescence based analysis
Measurement: IC50 = 7620 nM (pChEMBL 5.119999885559082)
Descriptors: MW 470.56, ALogP 2.18, HBA 6, HBD 6, PSA 152.26, QED 0.17
Compound (SMILES): [2H]C([2H])(NC(=O)c1cc(C(=O)NCc2ccc(F)c(C)c2)ncn1)c1ccc(C(=O)O)cc1
InChIKey: LXZKIXQSLYEDMA-KBMKNGFXSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 using QXL520-gamma-Abu-Pro-Cha-Abu-Smc-His-Ala-Dab(5-FAM)-Ala-Lys-NH2 as substrate measured every 5 mins for 2 hrs by FRET assay
Measurement: IC50 = 98000 nM (pChEMBL 4.010000228881836)
Descriptors: MW 422.42, ALogP 2.48, HBA 5, HBD 3, PSA 121.28, QED 0.54
Compound (SMILES): COc1ccc(OC)c(C2CC(c3cc(F)ccc3F)=NN2c2ccc(S(N)(=O)=O)cc2)c1
InChIKey: LGHMDXIUHIJXQC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2
Measurement: Ki = 4.29 nM (pChEMBL 8.369999885559082)
Descriptors: MW 473.5, ALogP 3.99, HBA 6, HBD 1, PSA 94.22, QED 0.58
Compound (SMILES): COc1ccc(C2CC(c3ccccc3C)=NN2c2ccc(C(=O)N3CCN(C)CC3)cc2)cc1F
InChIKey: YKESFJBBYRLROW-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of recombinant GST-tagged PDE3A (669 to end residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using FAM-cAMP as substrate incubated for 1.5 hrs by IMAP-FP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 486.59, ALogP 4.89, HBA 5, HBD 0, PSA 48.38, QED 0.52
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: SNXCJPFZRZMRKK-ZFSRTOEPSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method
Measurement: IC50 = 10.7 nM (pChEMBL 7.96999979019165)
Descriptors: MW 1608.88
Compound (SMILES): NCC1CCc2c(c(-c3c[nH]nc3C(F)(F)F)nc3c(F)cc4[nH]ncc4c23)C1
InChIKey: RWZLXWPAWBIAIB-UHFFFAOYSA-N
Target: CDK2/Cyclin A1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/Cyclin A1 (unknown origin) at 1 uM using histone H1 as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding method
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 404.37, ALogP 3.72, HBA 4, HBD 3, PSA 96.27, QED 0.44
Compound (SMILES): CC(=O)NCCNCc1cc(Cl)c(OCc2cccc(-c3cccc4c3CCN4CCCN3CCCC3)c2C)cc1OCc1cccc(C#N)c1
InChIKey: SHXKETUCQSSEHA-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD1 (unknown origin)/PDL1 (unknown origin) protein-protein interaction by HTRF assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 706.33, ALogP 7.42, HBA 7, HBD 2, PSA 89.86, QED 0.12
Compound (SMILES): COc1cc(-c2cccc(-c3cccc(-c4ccc(CNC(O)CC(=O)O)c(OC)c4)c3C)c2C)ccc1CNC(O)CC(=O)O
InChIKey: BQWJSGMLPKQJRG-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of Tag2-PD1/Tag1-PD-L1 (unknown origin) protein-protein interaction preincubated for 15 mins followed by addition of anti-Tag1-Eu3+ and anti-Tag2-XL665 measured after 2 hrs in dark by HTRF assay
Measurement: IC50 = 4.01 nM (pChEMBL 8.399999618530273)
Descriptors: MW 628.72, ALogP 5.09, HBA 8, HBD 6, PSA 157.58, QED 0.1
Compound (SMILES): COc1ncc(C2=CCOCC2)cc1S(=O)(=O)Nc1cncc(-c2ccc(CN3CCNCC3)cc2)c1
InChIKey: NGBQRIOODLGVTA-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 521.64, ALogP 3.16, HBA 8, HBD 2, PSA 105.68, QED 0.47
Compound (SMILES): Cc1ccc(NC(=O)Cn2ncc(Cl)c(Cl)c2=O)cc1S(=O)(=O)NCCc1cccnc1
InChIKey: VRMTXLZCMYQLPQ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Displacement of fluorophore-labeled RIOK1 from human PRMT5/WDR77 hetero octameric complex expressed in Sf9 cells by competition fluorescence polarization (FP) assay
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 496.38, ALogP 2.41, HBA 7, HBD 2, PSA 123.05, QED 0.49
Compound (SMILES): O=C(O)[C@H](CO)NCc1ccc2c(Nc3cccc(-c4cccc(O)c4)c3Cl)nsc2c1
InChIKey: OAODPRVHCJIOQB-IBGZPJMESA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of Tag2-PD-1/Tag1-PDL-1 (unknown origin) interaction incubated for 15 mins by TR-FRET assay
Measurement: IC50 = 143.4 nM (pChEMBL 6.840000152587891)
Descriptors: MW 469.95, ALogP 4.6, HBA 7, HBD 5, PSA 114.71, QED 0.26
Compound (SMILES): COc1ccc2ncc(F)c(C[C@H](O)[C@H]3OC[C@H](NCc4ccc5c(n4)NC(=O)CO5)CO3)c2c1
InChIKey: LHPGCGRDVFMGGQ-QRUVEDRTSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P20831
Assay: Inhibition of Staphylococcus aureus Gyrase supercoiling activity assessed as reduction in supercoiling pBR322 DNA by measuring relaxation by bromophenol blue staining based TAE gel method
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 484.48, ALogP 1.54, HBA 9, HBD 3, PSA 124.06, QED 0.46
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)C(C)(C)NC(=O)CNC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)C(C)C)C(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)NC(C)(C)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@H](O)CN(Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(N)=O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)C(C)C
InChIKey: MXZJQZZWSAFQQT-NXCANPPYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Inhibition of gamma secretase (unknown origin) expressed in HEK293 cells assessed as reduction of A-beta40 levels using C100-FLAG as substrate incubated for 2 hrs by sandwich ELISA
Measurement: IC50 = 80.8 nM (pChEMBL 7.090000152587891)
Descriptors: MW 1963.53
Compound (SMILES): Nc1ncc(-c2cc3ccccc3s2)c(N2CCC3(CCNC3=O)CC2)c1Cl
InChIKey: BUVVQUOSYFAZRC-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8/Cyclin C (unknown origin) using RBER-CHKtide as substrate in presence of [32P]gammaATP incubated for 60 mins by microplate scintillation counter analysis
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 412.95, ALogP 4.31, HBA 5, HBD 2, PSA 71.25, QED 0.66
Compound (SMILES): Cc1n[nH]c2ccc(-c3cncc(NC(CO)c4cccc(OC(F)(F)F)c4)n3)cc12
InChIKey: BJWIBDRERMFLNX-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) incubated for 2 hrs in presence of ATP by FRET based LANCE assay
Measurement: IC50 = 633.35 nM (pChEMBL 6.199999809265137)
Descriptors: MW 429.4, ALogP 4.37, HBA 6, HBD 3, PSA 95.95, QED 0.42
Compound (SMILES): Cc1cc(C)c(S(=O)(=O)NCCc2ccccn2)cc1NC(=O)Cn1ncc(Cl)c(Cl)c1=O
InChIKey: MXHCLTBJGVXVEK-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Displacement of fluorophore-labeled RIOK1 from human PRMT5/WDR77 hetero octameric complex expressed in Sf9 cells by competition fluorescence polarization (FP) assay
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 510.4, ALogP 2.72, HBA 7, HBD 2, PSA 123.05, QED 0.48
Compound (SMILES): FC(F)(F)c1ccc(-c2cc(-c3c[nH]nc3C(F)(F)F)nc3ccc4[nH]ncc4c23)cc1
InChIKey: HEXCJTCNHZSFQB-UHFFFAOYSA-N
Target: CDK2/Cyclin A1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/Cyclin A1 (unknown origin) at 1 uM using histone H1 as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding method
Measurement: IC50 = 8240 nM (pChEMBL 5.079999923706055)
Descriptors: MW 447.34, ALogP 6.21, HBA 3, HBD 2, PSA 70.25, QED 0.32
Compound (SMILES): COc1ccc(-c2cccc(Nc3nsc4cc(CN[C@@H](CO)C(=O)O)ccc34)c2Cl)cc1OC
InChIKey: BDRCKDIOSRUXFG-IBGZPJMESA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of Tag2-PD-1/Tag1-PDL-1 (unknown origin) interaction incubated for 15 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 514, ALogP 4.91, HBA 8, HBD 4, PSA 112.94, QED 0.24
Compound (SMILES): Cc1ccc(NC(=O)Cn2ncc(Cl)c(Cl)c2=O)cc1S(=O)(=O)N1CCCCCC1
InChIKey: PDBOMFKGPSNJPR-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Displacement of fluorophore-labeled RIOK1 from human PRMT5/WDR77 hetero octameric complex expressed in Sf9 cells by competition fluorescence polarization (FP) assay
Measurement: IC50 = 12400 nM (pChEMBL 4.909999847412109)
Descriptors: MW 473.38, ALogP 3.06, HBA 6, HBD 1, PSA 101.37, QED 0.72