lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@H]4CC[C@H](N)C4)nc32)cc1
InChIKey: OSHLPUOBFBCDRP-QWRGUYRKSA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Inhibition of recombinant His6-GST fusion tagged ERK3 (1 to 471 residues) (unknown origin) expressed in Sf21 insect cells using MK5 K51A mutant as substrate by ADP-Glo assay
Measurement: IC50 = 1330 nM (pChEMBL 5.880000114440918)
Descriptors: MW 325.38, ALogP 1.51, HBA 8, HBD 2, PSA 103.77, QED 0.75
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2n[nH]c3ncc(-c4ccc(C(=O)NCC(O)CO)cc4)cc23)c1F
InChIKey: DFLAUZQTMHLJTJ-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P45985
Assay: Inhibition of MEKK2 (unknown origin) using casein as substrate in presence of [gamma-33P]-ATP by scintillation counter assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 573.58, ALogP 2.37, HBA 8, HBD 5, PSA 174.37, QED 0.17
Compound (SMILES): c1cncc(-c2cnc3[nH]nc(-c4nc5c(-c6cccs6)cccc5[nH]4)c3c2)c1
InChIKey: NXZXAVYRNORZOB-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 394.46, ALogP 5.29, HBA 5, HBD 2, PSA 83.14, QED 0.43
Compound (SMILES): O=S(=O)(N[C@@H]1CCN(CCCc2noc3ccccc23)C1)c1csc2ccccc12
InChIKey: VJVSHSVLEVBQER-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from recombinant human 5HT7 receptor expressed in CHOK1 cell membranes measured after 120 mins by microbeta counting method
Measurement: Ki = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 441.58, ALogP 4.03, HBA 6, HBD 1, PSA 75.44, QED 0.47
Compound (SMILES): CN(C)CCNc1cc(F)cc(-c2cccc3[nH]c(-c4n[nH]c5cnc(-c6cncc(NC(=O)C(C)(C)C)c6)cc45)cc23)c1
InChIKey: ZQSZZKZNYSJZPR-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 590.71, ALogP 6.93, HBA 6, HBD 4, PSA 114.62, QED 0.15
Compound (SMILES): Cc1ccc2occ(C(=O)NC3CCN(Cc4ccccc4)CC3)c(=O)c2c1
InChIKey: NOZXTWSXCFNMEK-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using p-tyramine as substrate preincubated with enzyme for 15 mins followed incubation with substrate for 20 mins by Amplex red reagent based fluorescence based analysis
Measurement: IC50 = 19460 nM (pChEMBL 4.710000038146973)
Descriptors: MW 376.46, ALogP 3.5, HBA 4, HBD 1, PSA 62.55, QED 0.76
Compound (SMILES): COc1cc(C(=O)NC2CC3CCC(C2)N3Cc2ccccc2)nc2ccccc12
InChIKey: GAAFXVBYENZECG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserin from rat cerebral cortex 5HT2A receptor measured after 20 mins by liquid scintillation counter method
Measurement: Ki = 495 nM (pChEMBL 6.300000190734863)
Descriptors: MW 401.51, ALogP 4.17, HBA 4, HBD 1, PSA 54.46, QED 0.7
Compound (SMILES): O=C(O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c[nH]c12
InChIKey: FOKTYDOFGDMPCB-JTQLQIEISA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 371.83, ALogP 3.14, HBA 5, HBD 4, PSA 102.93, QED 0.56
Compound (SMILES): CN(C)C/C=C/C(=O)N1CCOc2cc(C(=O)N3CC[C@@H](Nc4ncc5ccccc5n4)C3)ccc21
InChIKey: JMVIDMZVTXZHKA-WKOQKXSESA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 486.58, ALogP 2.8, HBA 7, HBD 1, PSA 90.9, QED 0.54
Compound (SMILES): Br.N=C(N)[Se]Cc1ccc(CN2C(=O)C(=O)c3cc(F)ccc32)cc1
InChIKey: CHHFXKLWJHNWMA-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, dimeric NADP-preferring (SINGLE PROTEIN), Homo sapiens
UniProt: P30838
Assay: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate
Measurement: IC50 = 2364 nM (pChEMBL 5.630000114440918)
Descriptors: MW 390.28
Compound (SMILES): COc1ccc(-c2ccc3c(NC(=O)CCCCCCC(=O)NO)n[nH]c3c2)cc1OC
InChIKey: GEBDTLNMVKZFRC-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length C-terminal His-tagged HDAC8 expressed in sf9 insect cells using Boc-Lys(TFA)-AM as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 440.5, ALogP 4.03, HBA 6, HBD 4, PSA 125.57, QED 0.2
Compound (SMILES): CN1CCN(c2nccc3[nH]c(-c4n[nH]c5ccc(-c6cncc(CN7CCCC7)c6)cc45)cc23)CC1
InChIKey: CKPQSSPVMWMOKG-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 885 nM (pChEMBL 6.050000190734863)
Descriptors: MW 492.63, ALogP 4.52, HBA 6, HBD 2, PSA 79.97, QED 0.38
Compound (SMILES): CCN1CCC(c2ncc(-c3cnc(N)c(OCc4ccncc4)c3)s2)CC1
InChIKey: TXTGAMLGBOIHAX-UHFFFAOYSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Inhibition of human GCK using MBP as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 10.2 nM (pChEMBL 7.989999771118164)
Descriptors: MW 395.53, ALogP 3.96, HBA 7, HBD 1, PSA 77.16, QED 0.68
Compound (SMILES): CCN1CCC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4cc(C#N)ccc34)n2)C1
InChIKey: FZKQPRZULNOSBW-AWEZNQCLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 414.44, ALogP 4.41, HBA 5, HBD 2, PSA 80.63, QED 0.66
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN3CCO)nc1-c1cnn(C(C)C)c1
InChIKey: PHHFHRWXQDFKOB-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 2060 nM (pChEMBL 5.690000057220459)
Descriptors: MW 378.48, ALogP 3.33, HBA 7, HBD 2, PSA 79.1, QED 0.68
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4ccc(Cl)cc4n3)C2)cc1
InChIKey: YOZIGRVBNKWGQI-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 437.93, ALogP 4.35, HBA 5, HBD 2, PSA 87.22, QED 0.62
Compound (SMILES): CCN(CC)c1ccc2sc(C(=O)NCc3cccc(NC(=O)c4cccs4)c3)c(OCc3ccccc3)c2c1
InChIKey: JKAIIHVUZRLPKN-UHFFFAOYSA-N
Target: Sentrin-specific protease 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96HI0
Assay: Inhibition of recombinant human SNEP5 (567 to 755 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis
Measurement: IC50 = 30600 nM (pChEMBL 4.510000228881836)
Descriptors: MW 569.75, ALogP 7.57, HBA 6, HBD 2, PSA 70.67, QED 0.17
Compound (SMILES): c1ccc2[nH]c(-c3n[nH]c4ncc(-c5cncc(CN6CCCC6)c5)cc34)cc2c1
InChIKey: AAPDUJLOYISXLW-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 362 nM (pChEMBL 6.440000057220459)
Descriptors: MW 394.48, ALogP 4.76, HBA 4, HBD 2, PSA 73.49, QED 0.46
Compound (SMILES): O=C(c1cc(O)c(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c(O)c1)c1cccs1
InChIKey: ZVLXZKPJQVEUKM-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human recombinant cannabinoid CB2 receptor expressed in HEK cells transfected with CNG assessed as increase in cAMP level measured up to 1 hr by ACTOne membrane potential dye based assay
Measurement: EC50 = 676.08 nM (pChEMBL 6.170000076293945)
Descriptors: MW 432.34, ALogP 6.09, HBA 4, HBD 2, PSA 57.53, QED 0.39
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cnc(NC(=O)C2CC2)cc1Nc1cc(F)cc(-c2ncccn2)c1OC
InChIKey: KSSADOYRTUNEDM-FIBGUPNXSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in human whole blood assessed as decrease in IFNalpha-induced STAT5 phosphorylation
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
Compound (SMILES): Cc1ccc(COc2c(C(=O)NCc3cccc(NC(=O)c4ccccc4)c3)sc3ccccc23)cc1
InChIKey: NUMUAWYVVQMXBG-UHFFFAOYSA-N
Target: Sentrin-specific protease 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96HI0
Assay: Inhibition of recombinant human SNEP5 (567 to 755 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis
Measurement: IC50 = 10200 nM (pChEMBL 4.989999771118164)
Descriptors: MW 506.63, ALogP 6.97, HBA 4, HBD 2, PSA 67.43, QED 0.24
Compound (SMILES): O=C(c1ccc2c(c1)OCCO2)N1CCC[C@H](c2ccnc3ncnn23)C1
InChIKey: KDUYCGXHIZWGQY-AWEZNQCLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Inhibition of 6xHis-tagged rat recombinant PDE10A2 expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 1148 nM (pChEMBL 5.940000057220459)
Descriptors: MW 365.39, ALogP 1.92, HBA 7, HBD 0, PSA 81.85, QED 0.69
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2nn(C)c3c2C[C@H](C(F)(F)F)CC3)COc2ccccc21
InChIKey: XYJCKGKOLPUUIN-YPMHNXCESA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Biochemical Assay: The ability of the receptor interacting protein kinase (RIPK1) to catalyze the hydrolysis of adenosine-5′-triphosphate (ATP) is monitored using the Transcreener ADP (adenosine-5′-diphosphate) assay (BellBrook Labs). Purified human RIP1 kinase domain (2-375) (50 nM) derived from a baculovirus-infected insect cell expression system is incubated with test compounds for 2 hours in 50 mM Hepes buffer (pH 7.5) containing 30 mM MgCl2, 1 mM dithiothreitol, 50 uM ATP, 0.002% Brij-35, and 0.5% dimethyl sulfoxide (DMSO). Reactions are quenched by the addition of 1× Bell Brooks Stop buffer B (20 mM Hepes (ph7.5), 40 mM ethylenediaminetetraacetic acid and 0.02% Brij-35) containing an additional 12 mM EDTA and 55 ug/mL ADP2 antibody and 4 nM ADP-AlexaFluor® 633 tracer. The tracer bound to the antibody is displaced by the ADP generated during the RIP1K reaction, which causes a decrease in fluorescence polarization that is measured by laser excitation at 633 nm with a FP microplate reader M1000.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 422.41, ALogP 2.24, HBA 5, HBD 1, PSA 76.46, QED 0.81
Compound (SMILES): Cc1ccc(C#Cc2cccc(-c3nn(-c4nc(C(=O)O)cs4)c(CCC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)c2)o1
InChIKey: RZBQIRQNPQLIFT-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 417 nM (pChEMBL 6.380000114440918)
Descriptors: MW 630.72, ALogP 5.72, HBA 8, HBD 2, PSA 141.31, QED 0.2
Compound (SMILES): CCCCCCCCCCCCCCCCC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](C)CNC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](C)CNC(=O)[C@@H](C)CNC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(C)=O)C(C)C)[C@@H](C)CC)[C@@H](C)O
InChIKey: JTXFKSDPJRGPGY-STBXYDCBSA-N
Target: Relaxin receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBX9
Assay: Agonist activity at RXFP1 endogenously expressed in human OVCAR-5 cells assessed as increase in IBMX-induced cAMP accumulation pretreated with IBMX for 40 mins followed by compound addition and measured after 30 mins in presence of 2 % HSA by HTRF assay
Measurement: EC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 4066.82
Compound (SMILES): O=C(Nc1cccnc1)c1n[nH]c2cnc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: YIGQRJCMNZBKAK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 601 nM (pChEMBL 6.21999979019165)
Descriptors: MW 413.49, ALogP 3.65, HBA 6, HBD 2, PSA 99.69, QED 0.52
Compound (SMILES): O=C(Nc1cnn(-c2csc(C(=O)NC3CC3)c2)c1)Nc1ccccc1Cl
InChIKey: MJPWAJUXPIZNIX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin) using ATF2 as substrate after 22 mins in presence of ATP by HTRF assay
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 401.88, ALogP 4.12, HBA 5, HBD 3, PSA 88.05, QED 0.6
Compound (SMILES): CC(C)(C)OC(=O)N(CCOCCO)c1ccn2ncc(-c3ccc(C(=O)O)c(O)c3)c2n1
InChIKey: DBCKRCZJYUIKNW-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Displacement of fluorescent tracer from full-length human C-terminal NanoLuc-tagged CK2alpha' expressed in HEK293T cells measured after 2 hrs by NanoBRET assay
Measurement: IC50 = 7640 nM (pChEMBL 5.119999885559082)
Descriptors: MW 458.47, ALogP 2.55, HBA 9, HBD 3, PSA 146.72, QED 0.43
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1Cc2cnnn2CCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: DYRPZKYWKBUEOV-MREPYCEBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as reduction in alpha-MSH-induced cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: IC50 = 33.11 nM (pChEMBL 7.480000019073486)
Descriptors: MW 1098.28
Compound (SMILES): CC(=O)Nc1nc2ccc(-c3cc(C)c4c(c3)CN([C@@H](C)C3CC3)C4=O)cn2n1
InChIKey: WLZFGIFJFBBTJD-ZDUSSCGKSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 389.46, ALogP 3.42, HBA 5, HBD 1, PSA 79.6, QED 0.74
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(-c3ccccc3)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: YIYFGSBFHVAQLI-MREPYCEBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Agonist activity at human MC4R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as effect on cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 1100.3
Compound (SMILES): N#Cc1ccc(Nc2nccc([C@@H](O)c3ccc(-c4ccc(C#N)cc4)cc3F)n2)cc1
InChIKey: RSDODWDGOTXMEA-DEOSSOPVSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase Y188L mutant in HIV-1 3B infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 >= 2301.6 nM (pChEMBL 5.638000011444092)
Descriptors: MW 421.44, ALogP 4.85, HBA 6, HBD 2, PSA 105.62, QED 0.48
Compound (SMILES): CC1CCCN(C(=O)CCN2CCCc3ccccc32)C1
InChIKey: CCQBBHNLKQFRRR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 602.56 nM (pChEMBL 6.21999979019165)
Descriptors: MW 286.42, ALogP 3.09, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): COc1ccc(C(=O)Nc2ccc(-c3cn4c(=O)n(-c5ccccc5)nc4c(N)n3)cc2)cc1OC
InChIKey: VYUZNYKJEXWEDG-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 482.5, ALogP 3.4, HBA 9, HBD 2, PSA 125.77, QED 0.38
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CCc5ccccc54)CC3)cc2)cc1
InChIKey: WKVVLTUTCPYXBP-LJAQVGFWSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q76JU9
Assay: Agonist activity at Prolink-tagged mouse GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 0.88 nM (pChEMBL 9.0600004196167)
Descriptors: MW 493.65, ALogP 6.33, HBA 3, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4cc(Cl)ccc4n3)C2)cc1
InChIKey: MLHCNCBAGXONLE-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 437.93, ALogP 4.35, HBA 5, HBD 2, PSA 87.22, QED 0.62
Compound (SMILES): O=C(Nc1c[nH]nc1-c1cc(Cl)ccc1OC(F)F)c1cnc2[nH]ccc2n1
InChIKey: VLGTVRUUTFWJMF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: JAK Enzyme Assay: The activity of the isolated recombinant JAK1 and JAK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr, fluorescently labeled on the N-terminus with 5-carboxyfluorescein) using the Caliper LabChip® technology (Caliper Life Sciences, Hopkinton, Mass.). To determine inhibition constants (Ki), compounds were diluted serially in DMSO and added to 50 μL kinase reactions containing purified enzyme (1.5 nM JAK1, or 0.2 nM JAK2), 100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 1.5 μM peptide substrate, ATP (25 μM), 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 μL of an EDTA containing solution (100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM. After termination of the kinase reaction, the proportion of phosphorylated product was determined as a fraction of total peptide substrate using the Caliper LabChip® 3000 according to the manufacturer's specifications. Ki values were then determined using the Morrison tight binding model.
Measurement: Ki = 0.34 nM (pChEMBL 9.470000267028809)
Descriptors: MW 404.76, ALogP 3.86, HBA 5, HBD 3, PSA 108.58, QED 0.47
Compound (SMILES): O=C(NCCCCN1CCO[C@@H]2c3cc(O)ccc3OC[C@@H]21)c1cc2ccccc2[nH]1
InChIKey: XUAGVHSWKPRGFP-JTHBVZDNSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in HEK293 cells after 60 mins by microbeta counting based assay
Measurement: Ki = 12300 nM (pChEMBL 4.909999847412109)
Descriptors: MW 421.5, ALogP 3.22, HBA 5, HBD 3, PSA 86.82, QED 0.53
Compound (SMILES): COc1cccc(C(=O)CSc2nnc(-c3ccc(S(N)(=O)=O)cc3)o2)c1
InChIKey: FOZDSNVHRHBPTP-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 491.5 nM (pChEMBL 6.309999942779541)
Descriptors: MW 405.46, ALogP 2.37, HBA 8, HBD 1, PSA 125.38, QED 0.47
Compound (SMILES): Cn1cc(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)ccc1=O
InChIKey: KJJMNWWMDYYZSU-INIZCTEOSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 468.48, ALogP 4.17, HBA 6, HBD 3, PSA 87.63, QED 0.42
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#Cc4cccs4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: WGFNHVCWSDXXPH-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 636.73, ALogP 5.62, HBA 8, HBD 2, PSA 128.17, QED 0.21
Compound (SMILES): COCCNc1ncc2c(n1)N(C)CCN(c1cccc(-c3nnc(C)o3)c1)C2=O
InChIKey: UITIZVOWNYPKSR-UHFFFAOYSA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Binding Assay: α2δ-1: Binding Assay to Human α2δ-1 Subunit of Cav2.2 Calcium Channel.Human α2δ-1 enriched membranes (2.5 μg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10 mM, pH 7.4.NSB (non specific binding) was measured by adding 10 μM pregabalin. After 60 min incubation at 27° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 409.45, ALogP 1.99, HBA 9, HBD 1, PSA 109.51, QED 0.61
Compound (SMILES): CN1CCCCC1CCN1c2ccc(Br)cc2Sc2cc(Br)ccc21.Cl
InChIKey: XZKCKZLJVQITEO-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 cells
Measurement: Ki = 2149 nM (pChEMBL 5.670000076293945)
Descriptors: MW 482.29, ALogP 6.69, HBA 3, HBD 0, PSA 6.48, QED 0.48
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Cc2ccc(Nc3ncnc4[nH]c(-c5ccc(S(C)(=O)=O)cc5)cc34)cc2)no1
InChIKey: ZBZATSVLKXDTMV-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin)
Measurement: IC50 = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 544.64, ALogP 5.24, HBA 8, HBD 3, PSA 142.87, QED 0.25
Compound (SMILES): CN1CCC[C@H]1COc1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(O)cc2)cc1.Cl
InChIKey: OCAIWVBOBFRZBY-CJGRHYNCSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to GST-tagged ERalpha LBD (unknown origin) using fluorescein PGC1alpha as coactivator incubated for 1 hr by LanthaScreen TR-FRET co-regulator assay
Measurement: IC50 = 1063 nM (pChEMBL 5.96999979019165)
Descriptors: MW 443.59, ALogP 5.6, HBA 4, HBD 2, PSA 52.93, QED 0.42
Compound (SMILES): Cl.O=C1Nc2ccc(F)cc2/C1=C1/Nc2ccccc2/C1=N\OCCN1CCNCC1
InChIKey: YRBWCJJMWLQUOQ-WCFRLSLOSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human c-SRC in presence of ATP
Measurement: IC50 = 9.52 nM (pChEMBL 8.020000457763672)
Descriptors: MW 407.45, ALogP 2.24, HBA 6, HBD 3, PSA 77.99, QED 0.41
Compound (SMILES): CCN(C(=O)c1ccc(C(C)(C)C)cc1)c1ccc(C(=O)NO)cc1
InChIKey: XEXFBFZWKSNYMQ-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 340.42, ALogP 3.77, HBA 3, HBD 2, PSA 69.64, QED 0.66
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@H](C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)O)C(C)C)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: QLMICPWFXLJOEI-HKENPCLDSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 579.69, ALogP 2.33, HBA 8, HBD 5, PSA 140.59, QED 0.3
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCC(Cc3ccccc3)CC2)ccc1OC(=O)N(C)C
InChIKey: DGIUFKOTVNGVKP-ZRDIBKRKSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 16600 nM (pChEMBL 4.78000020980835)
Descriptors: MW 422.53, ALogP 4.25, HBA 4, HBD 0, PSA 59.08, QED 0.65
Compound (SMILES): CC#C[C@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1
InChIKey: FHRWHNJJQGSCQC-GDLZYMKVSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q76JU9
Assay: Agonist activity at Prolink-tagged mouse GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 491.63, ALogP 6.41, HBA 3, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): CO[C@H]1C[C@@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)N(C)C1=O
InChIKey: WQGALPRYPWUIGZ-VRIJDZSUSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as IL-17 production by ELISA
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 654.58, ALogP 4.58, HBA 5, HBD 0, PSA 83.99, QED 0.35
Compound (SMILES): CC(C)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: FRZSASJCYQFEKM-AWEZNQCLSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 335.46, ALogP 3.91, HBA 4, HBD 3, PSA 65.63, QED 0.68
Compound (SMILES): Cc1cc(-c2ccc(OCC34CCC(N)(CC3)CC4)c(F)c2)c2cnc(N)nn12
InChIKey: NOMVDZUKCKOVTL-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at TLR8 in human THP-1 cells assessed as inhibition of resiquimod-induced TNFalpha production
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 395.48, ALogP 3.86, HBA 6, HBD 2, PSA 91.46, QED 0.7
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)o2)cc1
InChIKey: NCQOCNBTDFNURU-VWLOTQADSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q76JU9
Assay: Agonist activity at Prolink-tagged mouse GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 481.59, ALogP 6, HBA 4, HBD 1, PSA 62.91, QED 0.4
Compound (SMILES): N#CC1(NC(=O)[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(-c3ccccc3)cc2)CC1
InChIKey: IGIOAPDPCSXDKR-QHCPKHFHSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of recombinant human cathepsin S expressed in insect cells using Z-Phe-Arg-AMC as substrate measured after 60 mins by fluorimetric assay
Measurement: Ki = 75.4 nM (pChEMBL 7.119999885559082)
Descriptors: MW 445.54, ALogP 3.42, HBA 4, HBD 2, PSA 99.06, QED 0.55
Compound (SMILES): O=C(CS(=O)(=O)c1ccccc1)c1cc2cc(Br)ccc2oc1=O
InChIKey: IVJVIPNZHIFFSU-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 6 hrs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 45.7 nM (pChEMBL 7.340000152587891)
Descriptors: MW 407.24, ALogP 3.21, HBA 5, HBD 0, PSA 81.42, QED 0.49
Compound (SMILES): COCCn1c(C(N)=O)cc2c1-c1ccncc1OC21CCOCC1
InChIKey: IQJKHKMDUAVVBY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Haspin Kinase Assay: The kinase assay relies on ADP-GloKM biochemical kinase assay (Promega). This is a luminescent kinase assay that measures ADP formed from a kinase reaction. Then ADP is converted into ATP, which is transformed into a light signal by Ultra-Glo Luciferase. The luminescent signal positively correlates with kinase activity. The assay measures the intrinsic ATPase activity (in the absence of peptidic substrate as phosphate acceptor).The enzyme was purchase from Invitrogen (PV5708) as the kinase domain of GST tagged recombinant human proteins.Assay conditions were as indicated by the kit manufacturers with the following adaptations:Assay buffer: 15 mM HEPES pH 7.4, 20 mM NaCl, 1 mM EGTA, 0.02% Tween 20, 10 mM MgCl2, 0.1 mg/ml BGGAssay volume: 20 μlIncubation time and temperature: 60 min at 30° C.Haspin concentration: 20 nMATP concentration: 150 μMTested compound: Serial 1:3 dilutionsFinal DMSO concentration in the assay: 1%Assays were performed in 384-well plates. The final read out was generated using an EnVision plate reader (Perkin-Elmer). Luminescent relative units are normalized against the control activity included for each compound (i.e., 100% Haspin activity, without compound) and the percentage of inhibition is calculated.
Measurement: IC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 343.38, ALogP 1.69, HBA 6, HBD 1, PSA 88.6, QED 0.91
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccc(-c3cn[nH]c3)cc12
InChIKey: JASLFJDPMFIVTK-AWEZNQCLSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 427.43, ALogP 4.2, HBA 5, HBD 4, PSA 94.31, QED 0.39
Compound (SMILES): CN(C)c1ccc(CN(CCc2ccc(S(N)(=O)=O)cc2)C(=O)Cn2cc(F)c(=O)[nH]c2=O)cc1
InChIKey: IPTOMBOQPSLELC-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human CA1 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 581.9 nM (pChEMBL 6.239999771118164)
Descriptors: MW 503.56, ALogP 0.66, HBA 7, HBD 2, PSA 138.57, QED 0.44
Compound (SMILES): CC(C)c1ccc(NC(=O)OCC2CCCN(Cc3ccccc3)C2)cc1
InChIKey: LNSFUBYHUNTELH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 366.51, ALogP 5.27, HBA 3, HBD 1, PSA 41.57, QED 0.76
Compound (SMILES): O=c1cc(-c2ccc(OCCCCN3CCc4ccccc4C3)cc2)oc2cc(OCCCCN3CCc4ccccc4C3)cc(O)c12
InChIKey: YNXCNTICEBIQKR-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE by Ellman's method
Measurement: IC50 = 15800 nM (pChEMBL 4.800000190734863)
Descriptors: MW 644.81, ALogP 7.6, HBA 7, HBD 1, PSA 75.38, QED 0.13
Compound (SMILES): CCNCc1cncc(-c2cc3c(-c4cc5c(-c6ccccc6F)ccnc5[nH]4)n[nH]c3cn2)c1
InChIKey: YCRFDIRUPFSENE-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with medium containing 1% fetal bovine serum and incubated overnight at 37° C. and 5% CO2. Following incubation, 20 μl of BrightGlo luminescence reagent (Promega) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. response-variable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 463.52, ALogP 5.48, HBA 5, HBD 3, PSA 95.17, QED 0.3
Compound (SMILES): O=C(Nc1ccc([N+](=O)[O-])cc1)C(c1ccccc1)N(C(=O)c1ccccc1I)c1ccccc1
InChIKey: MIENZPZOHXCZQM-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of MMP-13 (unknown origin) by colorimetric assay
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 577.38, ALogP 6.23, HBA 4, HBD 1, PSA 92.55, QED 0.16
Compound (SMILES): Cc1nc(OCc2ccc(F)cc2)c(C(=O)NC2CCCCCC2)cc1-c1ccc(F)cc1
InChIKey: CWCNFLHREXQUPX-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL in human U937 cells using [glycerol-1,2,3-3H]2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 450.53, ALogP 6.37, HBA 3, HBD 1, PSA 51.22, QED 0.44
Compound (SMILES): NC(=O)c1n[nH]c2ccc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: DTCMONXKIUJLND-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: DYRK1A activity assay: SH-SY5Y cells are cultured in DMEM/F-12 medium supplemented with 15% FBS, Non-essential Amino Acid and Penicillin/Streptamycin. Two days before treatment, cells are seeded onto 96 well plates at 20e5 cells/well.DMSO-resuspended compounds are dispensed to 8 wells as a serial titration from 10 μM to 4.6 nM final and cells are exposed overnight (16-18 h) before harvest. Wells are visualized checked for cell death or change in morphology and supernatants are tested for cytotoxicity by measurement of lactate dehydrogenase release (LDH, CytoToxOne kit, Progema) if necessary. As controls, commercially available DYRK1A inhibitors, Harmine and Indy were shown to have good DYRK1A inhibition in the kinase assay with no CDK1 activity (EC50 18 and 53n M respectively, 6 μM for CDK1) but weak EC50 in the Tau assay: about 10 μM for Harmine and 30 μM for Indy.Cells are lyzed with RIPA buffer complemented with phosphatase and protease inhibitors (Thermo Scientific) then lysates are sonicated and spun down at 12,000 g for 10 min to remove any cellular debris. Lysates are then either directly tested for pSer396 by ELISA (Life Technology, Kit KHB7031) or loaded on NuPage Bis-Tris gels for western blot analysis. Colorimetric detection of ELISA signal is performed by Cytation3 plate reader (Biotek) and the chemoluminecence signal for HRP-linked antibodies used in western blotting is detected using a Carestream Image Station. The same pSer396 antibody is used for detection of pTau in both assays.Blot densitometry for pSer396 and beta-actin are analyzed using ImageJ (NIH) and pSer396/Total Tau ELISA signal was used to plot, draw the curve fitting, and determine each compounds EC50 in Prism (GraphPad).
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 335.41, ALogP 2.71, HBA 4, HBD 2, PSA 87.9, QED 0.77
Compound (SMILES): C#CCN1CCC(COC(=O)Nc2ccc(C(C)C)cc2)CC1
InChIKey: UWGQVPIXFJKBAU-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 314.43, ALogP 3.7, HBA 3, HBD 1, PSA 41.57, QED 0.84
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O
InChIKey: NEXJVRPYTRBUSR-IHZBLBIESA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
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: Kd = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 725.85, ALogP 0.34, HBA 7, HBD 8, PSA 255.69, QED 0.05
Compound (SMILES): C=CC(=O)N1CC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2F)CC1
InChIKey: NHAPVTICMSFRIR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Binding affinity to CDK13 (unknown origin) by TR-FRET assay
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 408.48, ALogP 3.97, HBA 3, HBD 2, PSA 78.09, QED 0.71
Compound (SMILES): Nc1nc(N)c2nc3c(ccc4ccccc43)nc2n1
InChIKey: DHGUFUVSUAYZAH-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of PRMT5/MEP50 (unknown origin) using biotin-labeled histone H4-20 peptide as substrate incubated for 8 mins in presence of [3H]-SAM cofactor by scintillation proximity assay
Measurement: IC50 = 62100 nM (pChEMBL 4.210000038146973)
Descriptors: MW 262.28, ALogP 1.89, HBA 6, HBD 2, PSA 103.6, QED 0.37
Compound (SMILES): CN(C)S(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: JYGHIHQUUSIMSX-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 468.51, ALogP 3.06, HBA 6, HBD 3, PSA 103.01, QED 0.53
Compound (SMILES): C#CCN1CCC(O)CC1
InChIKey: CEUZTHSDJADUSJ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 139.2, ALogP 0.08, HBA 2, HBD 1, PSA 23.47, QED 0.52
Compound (SMILES): CC1(C)Oc2cnccc2-c2[nH]c(C(N)=O)c(C3CC3)c21
InChIKey: ISQMHRGAJWVQET-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Haspin Kinase Assay: The kinase assay relies on ADP-GloKM biochemical kinase assay (Promega). This is a luminescent kinase assay that measures ADP formed from a kinase reaction. Then ADP is converted into ATP, which is transformed into a light signal by Ultra-Glo Luciferase. The luminescent signal positively correlates with kinase activity. The assay measures the intrinsic ATPase activity (in the absence of peptidic substrate as phosphate acceptor).The enzyme was purchase from Invitrogen (PV5708) as the kinase domain of GST tagged recombinant human proteins.Assay conditions were as indicated by the kit manufacturers with the following adaptations:Assay buffer: 15 mM HEPES pH 7.4, 20 mM NaCl, 1 mM EGTA, 0.02% Tween 20, 10 mM MgCl2, 0.1 mg/ml BGGAssay volume: 20 μlIncubation time and temperature: 60 min at 30° C.Haspin concentration: 20 nMATP concentration: 150 μMTested compound: Serial 1:3 dilutionsFinal DMSO concentration in the assay: 1%Assays were performed in 384-well plates. The final read out was generated using an EnVision plate reader (Perkin-Elmer). Luminescent relative units are normalized against the control activity included for each compound (i.e., 100% Haspin activity, without compound) and the percentage of inhibition is calculated.
Measurement: IC50 = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 283.33, ALogP 2.68, HBA 3, HBD 2, PSA 81, QED 0.89
Compound (SMILES): CCN(C)C(=O)OCC1CCCN(C2Cc3ccccc3C2)C1
InChIKey: JTNNREFXLZRASL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant microsomal MAO-A expressed in baculovirus-infected BTI-TN-5B1-4 cells assessed as inhibition of H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex Red reagent based fluorescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 316.45, ALogP 2.95, HBA 3, HBD 0, PSA 32.78, QED 0.86
Compound (SMILES): Cc1c(C(=O)/C=C/Nc2ccc(S(N)(=O)=O)cc2)sc2nc3ccccc3n12
InChIKey: VJMMUYLWFOHBSY-ZHACJKMWSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 412.5, ALogP 3.31, HBA 7, HBD 2, PSA 106.56, QED 0.39
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)N/N=C/c2ccco2)cc1
InChIKey: LWCWWDARQBRUKC-LGJNPRDNSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of N-terminal FLAG-tagged human recombinant mTOR (1362 to end residues) using ULight-4E-BP1 (Thr37/46) peptide as substrate incubated for 1 hr in presence of ATP by Lance Ultra assay
Measurement: IC50 = 598 nM (pChEMBL 6.21999979019165)
Descriptors: MW 488.53, ALogP 3.66, HBA 9, HBD 3, PSA 144.46, QED 0.28
Compound (SMILES): N#Cc1cnc(Nc2cc(NC[C@@H]3CNCCO3)c(C3CC3)cn2)cn1
InChIKey: RMLMGTBZCLAAPL-AWEZNQCLSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.41, ALogP 1.76, HBA 8, HBD 3, PSA 107.78, QED 0.72
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CN2CCN(c3ccc(Cl)cc3)CC2)cc1
InChIKey: KRFXHZLZCMFNEC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped-flow CO2 hydration assay
Measurement: Ki = 1195.7 nM (pChEMBL 5.920000076293945)
Descriptors: MW 422.94, ALogP 1.43, HBA 5, HBD 2, PSA 95.74, QED 0.73
Compound (SMILES): CNCCOc1ccccc1C(C)(C)Nc1nccn(-c2cc(C(=O)NC3CC3)ccc2C)c1=O
InChIKey: SAZVRXTVWZAHBI-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 475.59, ALogP 3.38, HBA 7, HBD 3, PSA 97.28, QED 0.39
Compound (SMILES): NS(=O)(=O)c1cccc(-n2cc(Cn3cc(F)c(=O)[nH]c3=O)nn2)c1
InChIKey: WTXXRWMSPYJIAY-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human CA1 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 8911.2 nM (pChEMBL 5.050000190734863)
Descriptors: MW 366.33, ALogP -1.05, HBA 8, HBD 2, PSA 145.73, QED 0.6
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCCC(O)C1
InChIKey: ZJCVMKKAPWXWHV-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 33113.11 nM (pChEMBL 4.480000019073486)
Descriptors: MW 288.39, ALogP 1.81, HBA 3, HBD 1, PSA 43.78, QED 0.92