lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CNc1nc(Nc2ccc(-n3cnc(C)n3)c(OC)c2)nc2c1CC[C@@H]2c1ccc(F)cc1
InChIKey: NDVMOVOEROCRIO-GOSISDBHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Time-dependent inhibition of CYP3A4 in human liver microsomes assessed as inhibition constant by Kitz-Wilson plot analysis
Measurement: Ki = 82500 nM (pChEMBL 4.079999923706055)
Descriptors: MW 445.5, ALogP 4.38, HBA 8, HBD 2, PSA 89.78, QED 0.46
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 IFN-alpha stimulated human Kit225 T cells by luciferase reporter gene assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 436.45, ALogP 3.14, HBA 7, HBD 3, PSA 118.13, QED 0.52
Compound (SMILES): CO[C@H]1C(=O)C[C@H]2O[C@]1(C)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: CQEYKSOPHNOEBZ-KAZGAHJFSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of N-terminal His10-StrepII tagged human ROCK2 catalytic domain (1 to 553 residues) expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 451.48, ALogP 4.34, HBA 6, HBD 1, PSA 74.49, QED 0.41
Compound (SMILES): Cc1ccc(COc2c(C(=O)NCc3cccc(NC(=O)c4ccccc4)c3)sc3ccccc23)cc1
InChIKey: NUMUAWYVVQMXBG-UHFFFAOYSA-N
Target: Sentrin-specific protease 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC62
Assay: Inhibition of recombinant human SNEP2 (365 to 589 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 = 15800 nM (pChEMBL 4.800000190734863)
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: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of 6xHis-tagged human recombinant PDE3A expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 398 nM (pChEMBL 6.400000095367432)
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 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 422.41, ALogP 2.24, HBA 5, HBD 1, PSA 76.46, QED 0.81
Compound (SMILES): COc1ccccc1-c1cc2c(SCC(=O)O)ncnc2s1
InChIKey: ODQJHYVVOZLCDH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17B (SINGLE PROTEIN), Homo sapiens
UniProt: O94768
Assay: Binding affinity to C-terminal nano-luciferase tagged STK17B (unknown origin) expressed in HEK293 cells incubated for 2 hrs by nano-BRET assay based cellular target engagement assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 332.41, ALogP 3.54, HBA 6, HBD 1, PSA 72.31, QED 0.57
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 A673 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 547 nM (pChEMBL 6.260000228881836)
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), Rattus norvegicus
UniProt: Q6R6I6
Assay: Agonist activity at rat RXFP1 expressed in human HEK296 cells assessed as increase in IBMX-induced cAMP accumulation pretreated with IBMX for 40 mins followed by compound addition and measured after 30 mins by HTRF assay
Measurement: EC50 = 0.9 nM (pChEMBL 9.050000190734863)
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 CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
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 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of JNK2 (unknown origin) using ATF2 as substrate after 22 mins in presence of ATP by HTRF assay
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 401.88, ALogP 4.12, HBA 5, HBD 3, PSA 88.05, QED 0.6
Compound (SMILES): CCOC(=O)c1c(NC(=S)Nc2ccc(F)cc2)sc2c1C(C)CCC2
InChIKey: ZWMOVJILIPZWSQ-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Antagonist activity at CXCR4 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
Measurement: IC50 = 11700 nM (pChEMBL 4.929999828338623)
Descriptors: MW 392.52, ALogP 5.31, HBA 4, HBD 2, PSA 50.36, QED 0.55
Compound (SMILES): Cc1ccc2c(c1)C(C1=C[C@H](C)N(C)CC1)=Nc1ccccc1N2
InChIKey: AFKGLNWCCRQRMJ-HNNXBMFYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Binding affinity to human dopamine D1 receptor
Measurement: Ki = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 317.44, ALogP 4.82, HBA 3, HBD 1, PSA 27.63, QED 0.82
Compound (SMILES): COc1ccc([C@@H]2CNC(=O)[C@@H]2NC(=O)Nc2ccc(Cl)cc2)cc1
InChIKey: KHWQLQMKSMNUBQ-JKSUJKDBSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Agonist activity at human FPR1 expressed in HEK 293 cells co-expressing Galpha15 measured every 1.5 sec for 80 sec by Fluo-4 NW staining based scanning fluorometric method
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 359.81, ALogP 2.75, HBA 3, HBD 3, PSA 79.46, QED 0.78
Compound (SMILES): Cc1cc(-c2cnc3[nH]cc(C(=O)O)c3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: KYAAFPYKBXXNET-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins measured after 120 mins by by alphalisa assay
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 375.43, ALogP 3.99, HBA 3, HBD 2, PSA 86.29, QED 0.72
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: P68400
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 = 1510 nM (pChEMBL 5.820000171661377)
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 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Antagonist activity at human MC3R 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 = 586 nM (pChEMBL 6.230000019073486)
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: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant N-terminal His-tagged full-length human PI3K p120gamma 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 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 389.46, ALogP 3.42, HBA 5, HBD 1, PSA 79.6, QED 0.74
Compound (SMILES): O=c1c2cc(-c3ccn[nH]3)ccc2ncn1Cc1ccccc1
InChIKey: LBPQORPUUBGMMC-UHFFFAOYSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P34947
Assay: Binding affinity to GRK5 (unknown origin) by Thermofluor thermal shift assay
Measurement: Kd > 83300 nM (pChEMBL 4.078999996185303)
Descriptors: MW 302.34, ALogP 2.83, HBA 4, HBD 1, PSA 63.57, QED 0.63
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 = 28.18 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 Y181C 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 = 78.3 nM (pChEMBL 7.110000133514404)
Descriptors: MW 421.44, ALogP 4.85, HBA 6, HBD 2, PSA 105.62, QED 0.48
Compound (SMILES): CC(C)(O)c1cc(Nc2cc(Oc3cn(C4CC4)nc3C3CC(F)(F)C3)ccn2)ccn1
InChIKey: MVQOWTPMVHJPMY-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Mus musculus
UniProt: Q64729
Assay: Inhibition of TGF-beta type 1 receptor in mouse NIH3T3 cells expressing Luc-Smad 2/3 measured after 24 hrs incubation by cell based Bright-Glo Luciferase assay
Measurement: IC50 = 42.5 nM (pChEMBL 7.369999885559082)
Descriptors: MW 441.48, ALogP 5.28, HBA 7, HBD 2, PSA 85.09, QED 0.52
Compound (SMILES): CC1CCCN(C(=O)CCN2CCCc3ccccc32)C1
InChIKey: CCQBBHNLKQFRRR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 407.38 nM (pChEMBL 6.389999866485596)
Descriptors: MW 286.42, ALogP 3.09, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): O=C(C1CCCCC1)N1CCCC(c2ccnc3ncnn23)C1
InChIKey: CQVXJONSDPSGPL-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of 6xHis-tagged human recombinant PDE3B expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 617 nM (pChEMBL 6.210000038146973)
Descriptors: MW 313.41, ALogP 2.41, HBA 5, HBD 0, PSA 63.39, QED 0.85
Compound (SMILES): C/C(=N\NC(=S)NCCCCCC(=O)NO)c1cccc(Br)c1
InChIKey: PKGSNZSUSOFAJI-WOJGMQOQSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorimetric assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 401.33, ALogP 2.7, HBA 4, HBD 4, PSA 85.75, QED 0.18
Compound (SMILES): COc1ccc(C(=O)Nc2ccc(-c3cn4c(=O)n(-c5ccccc5)nc4c(N)n3)cc2)cc1OC
InChIKey: VYUZNYKJEXWEDG-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]-HEMADO from human A3 receptor stably expressed in CHO cell membranes by radioligand competitive binding assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
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), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full-length Prolink-tagged GPR40 fused with EA-tagged beta-arrestin expressed in human HEK293 cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 11 nM (pChEMBL 7.960000038146973)
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: 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): CN1CCCn2cc(nn2)-c2nccc3[nH]c(nc23)-c2n[nH]c3ccc(cc23)-c2cncc(c2)C1
InChIKey: FKDIRJDOTOCJHL-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 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 462.52, ALogP 3.66, HBA 8, HBD 2, PSA 117.09, QED 0.35
Compound (SMILES): O=C(Nc1c[nH]nc1-c1cc(Cl)ccc1OC(F)F)c1cnc2[nH]ccc2n1
InChIKey: VLGTVRUUTFWJMF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
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 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 404.76, ALogP 3.86, HBA 5, HBD 3, PSA 108.58, QED 0.47
Compound (SMILES): C=CC(=O)N1CCC=C(c2ccc(CC(=O)Nc3cc(C4CC4)[nH]n3)cn2)C1
InChIKey: XRMFYNTXRQPSMN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Biochemical Assay for CDK7: The inhibitory activity of the test compounds was assessed by the LANCE TR-FRET assay, which detects the ATP-dependent phosphorylation of an ULight-myelin basic protein (MBP) substrate peptide (100 nM) by CDK7 (10 nM). Briefly, the enzyme reaction was run in reaction buffer (20 mM HEPES (pH 7.5), 10 mM MgCl2, 0.01% Triton x, 100 μM Sodium Orthovanadate, 1 mM DTT). The assay was performed in 384-well plate. The end concentration of the ATP substrate was 1 mM/100 μM, and that of the ULight-MBP substrate peptide was 100 nM, and of CDK7 was 10 nM. Pre-incubation of the compound and enzyme was performed for 60 min at room temperature. After 60 min incubation at room temperature, the reaction was terminated by the addition of 40 mM EDTA and 1 nM Eu-labeled anti-phospho-MBP-binding protein antibody in the buffer. Time-resolved fluorescence (excitation, 320 nm; emission donor, 615 nm; emission acceptor, 665 nm) was monitored by using 2030 multilabel reader Victor5 (PerkinElmer). The readout was calculated as (acceptor counts/donor counts)×1000. The IC50 values were derived by fitting a sigmoidal dose-response curve to a plot of assay readout over inhibitor concentration. All fits were computed with the program Prism 5.03 (Graph Pad Software, San Diego, Calif.).
Measurement: IC50 = 1730 nM (pChEMBL 5.760000228881836)
Descriptors: MW 377.45, ALogP 2.67, HBA 4, HBD 2, PSA 90.98, QED 0.76
Compound (SMILES): O=C(NCCCCN1CCO[C@@H]2c3cc(O)ccc3OC[C@@H]21)c1cc2ccccc2[nH]1
InChIKey: XUAGVHSWKPRGFP-JTHBVZDNSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]-SCH23390 from human D1 receptor expressed in HEK293 cells after 60 mins by microbeta counting based assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 421.5, ALogP 3.22, HBA 5, HBD 3, PSA 86.82, QED 0.53
Compound (SMILES): COCc1ccc(-c2ccc(N(C[C@@H](N)[C@@H](C)OC)C(=O)[C@@H]3C[C@H]3c3ccccn3)cc2)cc1.Cl
InChIKey: SRMSUPBGLUBVJZ-KLXOBSBYSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Displacement of [35S]GTPgammaS from PPLS-HA tagged human GPR88 overexpressed in CHO cells membrane incubated for 60 mins radioligand binding assay
Measurement: EC50 = 64.7 nM (pChEMBL 7.190000057220459)
Descriptors: MW 459.59, ALogP 4.39, HBA 5, HBD 1, PSA 77.68, QED 0.49
Compound (SMILES): COc1cccc(C(=O)CSc2nnc(-c3ccc(S(N)(=O)=O)cc3)o2)c1
InChIKey: FOZDSNVHRHBPTP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 1328 nM (pChEMBL 5.880000114440918)
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: 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 468.48, ALogP 4.17, HBA 6, HBD 3, PSA 87.63, QED 0.42
Compound (SMILES): NC(=O)c1c(NC(=S)NC(=O)c2ccc(Cl)cc2)sc2c1CCC2
InChIKey: OZBIYLGREOSUQC-UHFFFAOYSA-N
Target: Anoctamin-2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8CFW1
Assay: Inhibition of GFP-fused mouse ANO2 channel expressed in HEK293A cells assessed as inhibition of channel current amplitude at membrane potential of +80 mV by patch clamp electrophysiology assay
Measurement: IC50 = 7430 nM (pChEMBL 5.130000114440918)
Descriptors: MW 379.89, ALogP 3.12, HBA 4, HBD 3, PSA 84.22, QED 0.72
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 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 = 307 nM (pChEMBL 6.510000228881836)
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: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of human NET expressed in HEK293 cells assessed as reduction in ASP+ uptake incubated for 20 mins before ASP+ addition and measured after 90 mins by scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
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 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5HT6 receptor expressed in HEK293 cells
Measurement: Ki = 758 nM (pChEMBL 6.119999885559082)
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: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 56780 nM (pChEMBL 4.25)
Descriptors: MW 544.64, ALogP 5.24, HBA 8, HBD 3, PSA 142.87, QED 0.25
Compound (SMILES): Cc1ncc(-c2cnc3[nH]nc(-c4nc5c(-c6cccc(F)c6)nccc5[nH]4)c3c2)n1C
InChIKey: OAUCZZGUADADTK-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 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 424.44, ALogP 4.41, HBA 6, HBD 2, PSA 100.96, QED 0.44
Compound (SMILES): CN1CCC[C@H]1COc1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(O)cc2)cc1.Cl
InChIKey: OCAIWVBOBFRZBY-CJGRHYNCSA-N
Target: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
Assay: Binding affinity to GST-tagged ERRbeta LBD (unknown origin) using fluorescein PGC1alpha as coactivator incubated for 1 hr by LanthaScreen TR-FRET co-regulator assay
Measurement: IC50 = 3990 nM (pChEMBL 5.400000095367432)
Descriptors: MW 443.59, ALogP 5.6, HBA 4, HBD 2, PSA 52.93, QED 0.42
Compound (SMILES): CN(C)CCNc1cc(F)cc(-c2cccc3[nH]c(-c4n[nH]c5cnc(-c6cncc(O)c6)cc45)cc23)c1
InChIKey: OUHTZPRTFJVBLJ-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 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 507.57, ALogP 5.65, HBA 6, HBD 4, PSA 105.75, QED 0.22
Compound (SMILES): Cl.O=C1Nc2ccc(F)cc2/C1=C1/Nc2ccccc2/C1=N\OCCN1CCNCC1
InChIKey: YRBWCJJMWLQUOQ-WCFRLSLOSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Inhibition of human FLT4 in presence of ATP
Measurement: IC50 = 23.8 nM (pChEMBL 7.619999885559082)
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 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 281 nM (pChEMBL 6.550000190734863)
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: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U69,593 from kappa opioid receptor in guinea-pig brain membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 390 nM (pChEMBL 6.409999847412109)
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: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 422.53, ALogP 4.25, HBA 4, HBD 0, PSA 59.08, QED 0.65
Compound (SMILES): O=C(CCCCCCC(=O)Nc1n[nH]c2cc(-c3ccncc3)ccc12)NO
InChIKey: XJRZGSQLQPWVJK-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 = 24.5 nM (pChEMBL 7.610000133514404)
Descriptors: MW 381.44, ALogP 3.41, HBA 5, HBD 4, PSA 120, QED 0.26
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), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full-length Prolink-tagged GPR40 fused with EA-tagged beta-arrestin expressed in human HEK293 cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 491.63, ALogP 6.41, HBA 3, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): O=C(Nc1ccc2[nH]nc(/C=C/c3ccccn3)c2c1)c1cc(F)cc(F)c1
InChIKey: ROWJAVCITQHSST-GQCTYLIASA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TrkC (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay
Measurement: IC50 = 118.6 nM (pChEMBL 6.929999828338623)
Descriptors: MW 376.37, ALogP 4.66, HBA 3, HBD 2, PSA 70.67, QED 0.54
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 Gal4-fused RORgammat LBD (unknown origin) by reporter gene assay
Measurement: EC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 654.58, ALogP 4.58, HBA 5, HBD 0, PSA 83.99, QED 0.35
Compound (SMILES): CC(C)(C)C(=O)Nc1cncc(-c2cnc3[nH]nc(-c4nc5c(-c6ccoc6)cncc5[nH]4)c3c2)c1
InChIKey: WLUQGOKHLNORTQ-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 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 478.52, ALogP 5.2, HBA 7, HBD 3, PSA 138.27, QED 0.32
Compound (SMILES): CC(C)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: FRZSASJCYQFEKM-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 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 335.46, ALogP 3.91, HBA 4, HBD 3, PSA 65.63, QED 0.68
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2nc(-c3c(F)cccc3F)sc2N)C[C@@H](O)[C@]1(C)O
InChIKey: JWDZFLVIDHMWDQ-MJLIWNJOSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of PIM3 (unknown origin) using Bad peptide NH2-AGAGRSRHSSYPAGT-OH as substrate measured after 10 mins in presence of ATP by luciferase-luciferin based Kinase-Glo luminescence assay
Measurement: Ki < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 474.53, ALogP 3.94, HBA 7, HBD 4, PSA 121.36, QED 0.45
Compound (SMILES): Cc1cc(-c2ccc(OCC34CCC(N)(CC3)CC4)c(F)c2)c2cnc(N)nn12
InChIKey: NOMVDZUKCKOVTL-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at TLR7 in human PBMC assessed as inhibition of ssRNA40-induced IFNalpha production
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
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), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full-length Prolink-tagged GPR40 fused with EA-tagged beta-arrestin expressed in human HEK293 cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 62 nM (pChEMBL 7.210000038146973)
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: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human cathepsin L using Phe-Arg-pNA as substrate measured after 60 mins by spectrophotometric assay
Measurement: Ki = 173 nM (pChEMBL 6.760000228881836)
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 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 6 hrs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 76.6 nM (pChEMBL 7.119999885559082)
Descriptors: MW 407.24, ALogP 3.21, HBA 5, HBD 0, PSA 81.42, QED 0.49
Compound (SMILES): Cc1cc(N2C(=O)C3=C(CCCC3)C2=O)c(F)cc1NC(=O)c1occc1C
InChIKey: FDPGXFCCOLEURD-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay
Measurement: EC50 = 372 nM (pChEMBL 6.429999828338623)
Descriptors: MW 382.39, ALogP 4.03, HBA 4, HBD 1, PSA 79.62, QED 0.81
Compound (SMILES): Cc1[nH]c(C(=O)Nc2ccc3nc(NC(=O)C(=O)O)sc3c2)c(Cl)c1Cl
InChIKey: QOIXLMNVJYVPLA-UHFFFAOYSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1S7
Assay: Inhibition of Staphylococcus aureus DNA topoisomerase 4 using supercoiled pNO1 plasmid DNA as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 413.24, ALogP 3.52, HBA 5, HBD 4, PSA 124.18, QED 0.49
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccc(-c3cn[nH]c3)cc12
InChIKey: JASLFJDPMFIVTK-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 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 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 5.1 nM (pChEMBL 8.289999961853027)
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: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 366.51, ALogP 5.27, HBA 3, HBD 1, PSA 41.57, QED 0.76
Compound (SMILES): COc1cc(NS(=O)(=O)C(C)C)cc(-c2cc(-c3ccc(N4CCNCC4)cc3)cnc2C)c1
InChIKey: MCKKWYKONXTPFI-UHFFFAOYSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Inhibition of human NOD2 expressed in HEK293 cells coexpressing NFkappaB-SEAP reporter measured after 7 to 9 hrs by HEKBIue reporter assay
Measurement: IC50 = 523 nM (pChEMBL 6.28000020980835)
Descriptors: MW 480.63, ALogP 4.29, HBA 6, HBD 2, PSA 83.56, QED 0.52
Compound (SMILES): CN1CCC[C@H]1[C@H]1COc2ccc([N+](=O)[O-])cc2O1
InChIKey: KGERICSLPNAGOM-GXFFZTMASA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Displacement of [3H]-Epibatidine from alpha4beta2 nAChR in rat cerebral cortex membrane preincubated for 5 mins followed by [3H]-Epibatidine addition and measured after overnight incubation by liquid scintillation beta counter analysis
Measurement: Ki = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 264.28, ALogP 1.83, HBA 5, HBD 0, PSA 64.84, QED 0.6
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1nnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncc(C(C)(C)O)cn2)c1OC
InChIKey: JTHSHTJUGJKWSN-HPRDVNIFSA-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 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 477.53, ALogP 2.62, HBA 9, HBD 4, PSA 151.25, QED 0.38
Compound (SMILES): N#Cc1cn(C2CCCC2)c2ccc(-c3noc(=O)[nH]3)cc12
InChIKey: DLCGGKMVKHIBSQ-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P80457
Assay: Mixed type inhibition of bovine xanthine oxidase assessed as inhibitory constant using xanthine as substrate preincubated for 25 mins followed by substrate addition measured at first 2 mins by spectrophotometry based Lineweaver-Burk plot analysis
Measurement: Ki = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 294.31, ALogP 2.97, HBA 5, HBD 1, PSA 87.61, QED 0.79
Compound (SMILES): O=c1cc(-c2ccc(OCCCCN3CCc4ccccc4C3)cc2)oc2cc(OCCCCN3CCc4ccccc4C3)cc(O)c12
InChIKey: YNXCNTICEBIQKR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE in human erythrocytes by Ellman's method
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
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: 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 = 2313 nM (pChEMBL 5.639999866485596)
Descriptors: MW 463.52, ALogP 5.48, HBA 5, HBD 3, PSA 95.17, QED 0.3
Compound (SMILES): CC1c2ccccc2CCN1CCCCOc1ccc(-c2coc3cc(OCCCCN4CCc5ccccc5C4C)cc(O)c3c2=O)cc1
InChIKey: ZGXSCBBSDIABRW-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE by Ellman's method
Measurement: IC50 = 12400 nM (pChEMBL 4.909999847412109)
Descriptors: MW 672.87, ALogP 8.72, HBA 7, HBD 1, PSA 75.38, QED 0.13
Compound (SMILES): CC1(C)C(=O)C(C)(C)c2cc(C(=O)Nc3ccc(C(=O)O)cc3)ccc21
InChIKey: KFBPBWUZXBYJDG-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: Compounds were assessed for inhibition (IC50, n=2) of CYP2C8, CYP2C9 and CYP3A4 in pooled human liver microsomes using selective probe substrates at their previously determined Km values (CYP2C8: paclitaxel, 4 μM; CYP2C9: diclofenac, 5 μM; CYP3A4: midazolam, 0.5 μM). Incubations contained 0.1 mg/mL human liver microsomes, 3 mM MgCl2, probe substrate and various concentrations of inhibitor (12-point IC50 curve) in 100 mM potassium phosphate buffer (pH 7.4). Concentrations of organic solvents were kept to <1% (v/v). All incubations were pre-incubated at 37° C. for 5 minutes prior to addition of 1 mM NADPH (final concentration). Incubations were stopped after 5 (CYP3A4) or 15 minutes (CYP2C8 and CYP2C9) with one volume (v/v) of ice-cold acetonitrile containing 0.1 μM tolbutamide as an internal standard. All samples were vortexed and centrifuged prior to LC-MS/MS analysis.
Measurement: IC50 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 351.4, ALogP 3.78, HBA 3, HBD 2, PSA 83.47, QED 0.88
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc(C)ccc2OC)[nH]1
InChIKey: BMBFIGDBLWWCBK-RPBOFIJWSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 < 0.2 nM (pChEMBL 9.699000358581543)
Descriptors: MW 508.71, ALogP 5.6, HBA 5, HBD 2, PSA 87.32, QED 0.34
Compound (SMILES): FC1(F)CCN(Cc2cncc(-c3ccc4[nH]nc(-c5cc6cccnc6[nH]5)c4n3)c2)C1
InChIKey: ZGWXWDROUNEVKW-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 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 431.45, ALogP 4.4, HBA 5, HBD 2, PSA 86.38, QED 0.44
Compound (SMILES): CC1CCC(=O)C(C2CC(=O)N(Cc3ccccc3)C2=O)C1
InChIKey: TXMRIYTVMYYHRE-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5LOX expressed in baculovirus infected Sf insect cells using linoleic acid as substrate preincubated for 5 mins followed by substrate addition
Measurement: IC50 = 56200 nM (pChEMBL 4.25)
Descriptors: MW 299.37, ALogP 2.57, HBA 3, HBD 0, PSA 54.45, QED 0.81
Compound (SMILES): O=C(Nc1ccc([N+](=O)[O-])cc1)C(c1ccccc1)N(C(=O)c1ccccc1I)c1ccccc1
InChIKey: MIENZPZOHXCZQM-UHFFFAOYSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of MMP-1 (unknown origin) by colorimetric assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
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: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells using [ethanolamine-1-3H]AEA 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): COc1ccc(C(=O)NO)cc1NCc1ccc(OCCCCC(=O)Nc2ccc3c(c2)cc(C)c(=O)n3C)cc1
InChIKey: XYUDJKAHHUJQBC-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to BRPF1 (unknown origin) by Isothermal titration calorimetry
Measurement: Kd = 4080 nM (pChEMBL 5.389999866485596)
Descriptors: MW 558.64, ALogP 4.77, HBA 8, HBD 4, PSA 130.92, QED 0.11
Compound (SMILES): NC(=O)c1n[nH]c2ccc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: DTCMONXKIUJLND-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: Wnt activity assay: Reporter cell lines were generated by stably transducing cells of cancer cell lines (e.g., colon cancer) with a lentiviral construct that include a Wnt-responsive promoter driving expression of the firefly luciferase gene.Lentiviral constructs were made in which the SP5 promoter, a promoter having eight TCF/LEF binding sites derived from the SP5 promoter, was linked upstream of the firefly luciferase gene. The lentiviral constructs included a hygromycin resistance gene as a selectable marker. The SP5 promoter construct was used to transduce SW480 cells, a colon cancer cell line having a mutated APC gene that generates a truncated APC protein, leading to de-regulated accumulation of β-catenin. A control cell line was generated using another lentiviral construct containing the luciferase gene under the control of the SV40 promoter which does not require β-catenin for activation.Cultured SW480 cells bearing a reporter construct were distributed at approximately 10,000 cells per well into 384 well multiwell plates. Compounds were then added to the wells in half-log dilutions using a three micromolar top concentration. A series of control wells for each cell type received only buffer and compound solvent. Twenty-four hours after the addition of compound, reporter activity for luciferases was assayed, for example, by addition of the BrightGlo luminescence reagent (Promega) and the Victor3 plate reader (Perkin Elmer). Readings were normalized to DMSO only treated cells, and normalized activities were then used for the IC50 calculations.
Measurement: IC50 = 1960 nM (pChEMBL 5.710000038146973)
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: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 24300 nM (pChEMBL 4.610000133514404)
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 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Agonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as stimulation of cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay
Measurement: EC50 = 66 nM (pChEMBL 7.179999828338623)
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 = 5.8 nM (pChEMBL 8.239999771118164)
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: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Inhibition of recombinant GST-tagged CARM1 (unknown origin) expressed in Escherichia coli using histone H3.3 peptide as substrate incubated for 120 mins in presence of [3H]-SAM cofactor by radioactive filter plate assay
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
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: 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 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: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition by Ellman's method
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): CCN(C)C(=O)OCC1CCCN(C2Cc3ccccc3C2)C1
InChIKey: JTNNREFXLZRASL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 9390 nM (pChEMBL 5.03000020980835)
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 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 36.6 nM (pChEMBL 7.440000057220459)
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: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of GST-tagged human recombinant PI3Kgamma catalytic domain (468 to 1203 residues) expressed in insect cells using PIP2 peptide as substrate incubated for 1 hr in presence ATP by ADP-Glo Kinase Assay
Measurement: IC50 = 204 nM (pChEMBL 6.690000057220459)
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: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]astemizole from human ERG expressed in HEK293 cells by radioligand binding assay
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
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 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 by stopped-flow CO2 hydration assay
Measurement: Ki = 83.9 nM (pChEMBL 7.079999923706055)
Descriptors: MW 422.94, ALogP 1.43, HBA 5, HBD 2, PSA 95.74, QED 0.73