lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2c(NC3CCN(C)CC3)nc(N3CCCN(C)CC3)nc2cc1CCc1ccccn1
InChIKey: WOQWCIZJPNZCIF-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of N-terminal GST tagged human recombinant EHMT1 (794 to 1294 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in conversion of SAH to AMP using histone H3 as substrate and SAH as cosubstrate incubated for 30 mins by AMP Glo detection assay
Measurement: IC50 = 1350 nM (pChEMBL 5.869999885559082)
Descriptors: MW 489.67, ALogP 3.47, HBA 8, HBD 1, PSA 69.65, QED 0.54
Compound (SMILES): CO[C@@H]1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3nc(N)n[nH]3)CC2)C1
InChIKey: CWVKUWZSIMMEOV-DLBZAZTESA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D7Q1
Assay: Inhibition of full-length C-terminal his-tagged mouse CHIT1 expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N\"-triacetylchitotrioside as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.81
Compound (SMILES): Cc1cc(NC(=O)Cn2nnc(-c3ccc(Cl)c(C)c3)n2)n(C2CCCCC2)n1
InChIKey: SDYACSNIJCNOEN-UHFFFAOYSA-N
Target: Kir3.1/Kir3.4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P48544
Assay: Activation of human GIRK1/4 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assay
Measurement: EC50 = 1510 nM (pChEMBL 5.820000171661377)
Descriptors: MW 413.91, ALogP 3.95, HBA 7, HBD 1, PSA 90.52, QED 0.68
Compound (SMILES): CCCN(c1cncnc1)[C@@H]1Cc2ccc(C(=O)Nc3cc(-n4cnc(C)c4)cc(C(F)(F)F)c3)cc2C1
InChIKey: DADUZDKFVWUYOP-RUZDIDTESA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Inhibition of GST-tagged recombinant human DDR2 expressed in baculovirus using fluorescein-poly GAT as substrate after 1 hr by FRET-based LanthaScreen Eu kinase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 520.56, ALogP 5.63, HBA 6, HBD 1, PSA 75.94, QED 0.34
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1cccnc1
InChIKey: BNAZYGXWPOFSKF-DMTNHVFBSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 767.75, ALogP 2.47, HBA 12, HBD 6, PSA 281.07, QED 0.03
Compound (SMILES): CNC(=O)Nc1cc(Oc2cncc(OC)c2)c([C@@H]2COCC[C@@H]2O)cn1
InChIKey: AWJLMQBGAXWQAK-GJZGRUSLSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Activation of human recombinant glucokinase using 5 mM glucose as substrate in presence of NAD+ and 4% HSA by glucose 6-phosphate dehydrogenase coupled assay
Measurement: EC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 374.4, ALogP 1.89, HBA 7, HBD 3, PSA 114.83, QED 0.73
Compound (SMILES): NC(=O)C[C@H]1COCc2cc(F)ccc2N1C(=O)c1ccc2c(c1)NC(=O)CO2
InChIKey: ABQVVHVLSBJBNE-AWEZNQCLSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Binding affinity to recombinant human GR LBD by fluormone GS red-fluorescence polarization assay
Measurement: Ki > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 399.38, ALogP 1.58, HBA 5, HBD 2, PSA 110.96, QED 0.81
Compound (SMILES): CN1CCCc2c1nc(N1CCC3(CC1)C(=O)N(CC(F)(F)F)c1cc(F)cc(F)c13)[nH]c2=O
InChIKey: ZBQDZIKGERQLAW-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of recombinant human N-terminal TEV cleavage site-fused/FLAG-poly his-tagged TNKS2 ARC5-SAM-PARP domain (613 to 1166 residues) expressed in Escherichia coli assessed as reduction in auto-PARylation preincubated for 10 mins followed by biotinylated-NAD+ addition and measured after 45 mins by ELISA
Measurement: IC50 = 32.4 nM (pChEMBL 7.489999771118164)
Descriptors: MW 483.44, ALogP 2.88, HBA 5, HBD 1, PSA 72.54, QED 0.67
Compound (SMILES): C[C@H]1NC(=O)c2cc(-c3cccc4c(=O)n(C5CCC5)c(NC5(C)CC5)nc34)[nH]c21
InChIKey: XIXPZKIRXUHXDD-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of full length recombinant PIM2 (unknown origin) assessed as reduction in BAD phosphorylation at Ser112 residues preincubated for 30 mins followed by biotinylated BAD addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 403.49, ALogP 3.89, HBA 5, HBD 3, PSA 91.81, QED 0.62
Compound (SMILES): CC(C)=CCc1cc(/C=C/C(=O)O)ccc1OC(=O)Cc1cccc2ccccc12
InChIKey: PQDDLPYXRPBFHH-NTCAYCPXSA-N
Target: Aldo-keto reductase family 1 member C2 (SINGLE PROTEIN), Homo sapiens
UniProt: P52895
Assay: Inhibition of recombinant human AKR1C2 expressed in Escherichia coli BL21 (D3) using S-tetralol as substrate in presence of NADP+ by UV-spectrophotometric method
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 400.47, ALogP 5.59, HBA 3, HBD 1, PSA 63.6, QED 0.24
Compound (SMILES): O=C1Nc2cccc(n2)-c2nncn2CCCOc2ccccc21
InChIKey: ZWAJXTZDBJPROT-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of V5 tagged human ASK1 expressed in HEK-293T cells assessed as reduction in T838 autophosphorylation incubated for 1 hr
Measurement: IC50 = 6065 nM (pChEMBL 5.21999979019165)
Descriptors: MW 321.34, ALogP 2.37, HBA 6, HBD 1, PSA 81.93, QED 0.69
Compound (SMILES): CNC(=O)c1c(-c2ccccn2)c([C@H](C)Nc2ncnc(N)c2C#N)nc2ccc(F)cc12
InChIKey: OLJXUPJOUSFYSX-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of polyHis tagged full length recombinant PI3Kalpha (unknown origin) expressed in Sf9 cells co-expressing p85 incubated for 20 mins by alpha screen assay
Measurement: IC50 = 17600 nM (pChEMBL 4.75)
Descriptors: MW 442.46, ALogP 3.21, HBA 8, HBD 3, PSA 142.5, QED 0.43
Compound (SMILES): CC(O)c1nn([C@@H]2O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: TVOCSXIMZVTDKB-LBGUGVGYSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 390.38, ALogP -2.7, HBA 12, HBD 5, PSA 208.93, QED 0.35
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1cc(N2CCC[C@H](C(=O)NCc3ccc(OC(F)(F)F)cc3)C2)ccn1
InChIKey: YUFYDDHGCLTQIH-MHZLTWQESA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human N-terminal GST-tagged ALK (catalytic domain 1058 - 1620 residues) expressed in baculovirus system assessed as decrease in substrate phosphorylation using TK peptide as substrate preincubated with enzyme for 30 mins followed by substrate addition by HTRF method
Measurement: IC50 = 413 nM (pChEMBL 6.380000114440918)
Descriptors: MW 681.8, ALogP 5.48, HBA 9, HBD 2, PSA 85.44, QED 0.29
Compound (SMILES): O=C1NCCc2c(Br)cccc21
InChIKey: LYXUIQHDUVHEMZ-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of human PARP10 catalytic domain assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 10232.93 nM (pChEMBL 4.989999771118164)
Descriptors: MW 226.07, ALogP 1.74, HBA 1, HBD 1, PSA 29.1, QED 0.72
Compound (SMILES): O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2ncccn2)CC1
InChIKey: VJGYBRVHAUSTAR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OHDPAT from recombinant human 5HT1A receptor expressed in HEK293 cells measured after 1 hr by microbeta counting method
Measurement: Ki = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 415.54, ALogP 3.97, HBA 5, HBD 0, PSA 52.57, QED 0.52
Compound (SMILES): C=CC(=O)N1CCN(c2ccc(Cl)c(C3=C(c4c[nH]c5ccccc45)C(=O)NC3=O)c2)CC1
InChIKey: MJIDTPJXUZUOJN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 6 uM ATP by HTRF assay
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 460.92, ALogP 3.22, HBA 4, HBD 2, PSA 85.51, QED 0.46
Compound (SMILES): CSc1nnc2ccc(N3CCC(c4ccc(OCCN5CCN(C)C(=O)[C@H]5C)cc4)CC3)nn12
InChIKey: KTXYHHWRRROJQB-GOSISDBHSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa647-labeled JQ1 derivative from wild type BRD4 bromodomain 1 (44 to 460 residues) N140A mutant (unknown origin) incubated for 1 hr by fluorescence polarization assay
Measurement: Ki = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 495.65, ALogP 2.77, HBA 9, HBD 0, PSA 79.1, QED 0.46
Compound (SMILES): c1ccc(CCCN2CCC(Nc3nc(N4CCN(c5ccccc5)CC4)nc4ccccc34)CC2)cc1
InChIKey: BCPIMHRORICBDU-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6K1
Assay: Inhibition of recombinant human DNMT3a C-terminal catalytic domain (623 to 908 residues) using 5'-biotinylated/3'-FAM-oligonucleotide as substrate measured after 1 hr in presence of Adomet by fluorescence assay
Measurement: EC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 506.7, ALogP 5.47, HBA 6, HBD 1, PSA 47.53, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(C[Se]c2ccc(NC(=O)CN3C(=O)NC4(CCCCC4)C3=O)cc2)cc1
InChIKey: FHBDNRMYKOVBPS-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 19.6 nM (pChEMBL 7.710000038146973)
Descriptors: MW 549.51
Compound (SMILES): OC1(c2ccc(Cl)cc2)CCN(CCCC#Cc2ccc(F)cc2)CC1
InChIKey: SOPRISPDLYSDTL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of PPHT-red from SNAP-tagged human D2LR expressed in CHOK1 cell membranes by TR-FRET assay
Measurement: Ki = 19.05 nM (pChEMBL 7.71999979019165)
Descriptors: MW 371.88, ALogP 4.59, HBA 2, HBD 1, PSA 23.47, QED 0.63
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)NCc2cn(Cc3cccc([N+](=O)[O-])c3)nn2)C[C@H](N)[C@H]1NC(C)=O
InChIKey: YZZKFHVPCJVMPM-YTFSRNRJSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus (A/Memphis/1/1971(H3N2))
UniProt: P03471
Assay: Inhibition of Influenza A virus (A/Chicken/Hebei/LZF/2014(H5N2)) Neuraminidase N2 preincubated for 10 mins followed by MUNANA substrate addition and measured after 40 mins by fluorescence method
Measurement: IC50 = 1190 nM (pChEMBL 5.920000076293945)
Descriptors: MW 499.57, ALogP 1.59, HBA 9, HBD 3, PSA 167.3, QED 0.31
Compound (SMILES): Cc1nc2cnc3[nH]ccc3c2n1[C@H]1CC[C@H](CC#N)CC1
InChIKey: OETPUWNRYNOSLM-JOCQHMNTSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was <0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of enzyme and ATP mixture to 10 μL of substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat#06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction.
Measurement: IC50 < 0.2 nM (pChEMBL 9.699000358581543)
Descriptors: MW 293.37, ALogP 3.87, HBA 4, HBD 1, PSA 70.29, QED 0.78
Compound (SMILES): C#CCSc1nc(Sc2nccs2)c(C#N)c(-c2ccc(Cl)cc2)n1
InChIKey: RZWYLWWXGROEFD-UHFFFAOYSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Binding affinity to N-terminal GST tagged recombinant human DCN1 (58 to 259 residues) expressed in Escherichia coli BL21(DE3) assessed as reduction in DCN1-FAM-labelled N-terminal acetylated UBE2M (1 to 21 residues) protein-protein interaction after 30 mins by HTRF assay
Measurement: IC50 = 96.05 nM (pChEMBL 7.019999980926514)
Descriptors: MW 400.94, ALogP 5, HBA 7, HBD 0, PSA 62.46, QED 0.26
Compound (SMILES): Cc1cncc(Nc2cc(NC3CCN(c4ccc(C#N)cn4)CC3)c(C(N)=O)cn2)n1
InChIKey: RTQDAHIOCNGMNZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 assessed as reduction in phosphorylation of Biotin-Lyn-Substrate-2 after 1 hr in presence of ATP by ELISA
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 429.49, ALogP 2.37, HBA 9, HBD 3, PSA 145.74, QED 0.54
Compound (SMILES): Nc1nc2[nH]cc(Cc3ccc(C(=O)Nc4cccc(C(=O)O)c4)cc3)c2c(=O)[nH]1
InChIKey: JNRSKWXVEYVQFX-UHFFFAOYSA-N
Target: Thymidylate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P04818
Assay: Inhibition of recombinant human His6-tagged TS using dUMP and 5,10-methylenetetrahydrofolate as substrate by spectrometry
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 403.4, ALogP 2.37, HBA 5, HBD 5, PSA 153.96, QED 0.34
Compound (SMILES): CS(=O)(=O)c1cc(-c2cccnc2)cc(S(=O)(=O)c2ccc(CN)s2)c1.Cl.Cl
InChIKey: IAHZBAGMZRBYSF-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB expressed in baculovirus infected BTI insect cells incubated for 1 hr by luminescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 408.53, ALogP 2.51, HBA 7, HBD 1, PSA 107.19, QED 0.69
Compound (SMILES): COC(=O)c1ccc2nc(-c3nc[nH]c3C)c(NCCN3CCOCC3)n2c1
InChIKey: QHUTYZUGNYJCEG-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase TRIM33 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPN9
Assay: Inhibition of recombinant TRIM33 PHD bromodomain (unknown origin) using biotinylated H3 peptide (H3K9me3K18ac) by AlphaScreen assay
Measurement: IC50 = 1934 nM (pChEMBL 5.710000038146973)
Descriptors: MW 384.44, ALogP 1.56, HBA 8, HBD 2, PSA 96.78, QED 0.62
Compound (SMILES): NS(=O)(=O)CCNC(=O)/C(Cc1ccccc1)=N/OCc1ccccc1
InChIKey: SSXSONMYXMTUAR-HEHNFIMWSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 expressed in Escherichia coli BL21 (DE3) by stopped-flow CO2 hydration assay
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 375.45, ALogP 1.21, HBA 5, HBD 2, PSA 110.85, QED 0.51
Compound (SMILES): CC1=C(C(=O)Nc2cccc(C)c2)C(c2ccco2)C2=C(CCCC2=O)N1
InChIKey: LVGNCHBAIBJZCL-UHFFFAOYSA-N
Target: Free fatty acid receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14843
Assay: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay
Measurement: EC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 362.43, ALogP 4.19, HBA 4, HBD 2, PSA 71.34, QED 0.86
Compound (SMILES): O=C(NO)c1cc(F)c(Cn2nnc(-c3ncccn3)n2)c(F)c1
InChIKey: IAJVLFQKWJCAML-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC1 expressed in Sf9 insect cells using Fluor de Lys deacetylase or Fluor de Lys Green deacetylase as substrate by fluorescent microplate reader assay
Measurement: IC50 = 3960 nM (pChEMBL 5.400000095367432)
Descriptors: MW 333.26, ALogP 0.58, HBA 8, HBD 2, PSA 118.71, QED 0.53
Compound (SMILES): Cn1c(=O)[nH]c2cccc(Oc3cc(Cl)cc(C#N)c3)c21
InChIKey: HOBUPBKXAJVBGV-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase K103N mutant in HIV1 infected HEK293T cells harboring luciferase gene assessed as reduction in viral infection after 48 hrs by Bright-Glo luciferase assay
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 299.72, ALogP 3.18, HBA 4, HBD 1, PSA 70.81, QED 0.79
Compound (SMILES): Cc1cc(C(c2ccc(O)cc2)c2ccc(O)cc2)sc1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: BNVBUQDHZMGUKI-IBGZPJMESA-N
Target: C3a anaphylatoxin chemotactic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16581
Assay: Agonist activity at C3a receptor in human MDM cells assessed as induction of intracellular calcium release measured at 1 sec interval for => 200 secs by Fluo-3 AM dye-based FLIPR assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 496.59, ALogP 3.09, HBA 6, HBD 7, PSA 168.76, QED 0.13
Compound (SMILES): Cc1cc(CN2CCn3c(nc4c3c(=O)n(C)c(=O)n4C)C2)n(C)n1
InChIKey: DKVXOVRMMQRGLB-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]MSX from A2A receptor in rat brain striatum membranes measured after 30 mins by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 343.39, ALogP -0.51, HBA 9, HBD 0, PSA 82.88, QED 0.63
Compound (SMILES): O=C1CC(c2c[nH]c3ccc(F)cc23)C(=O)N1CCCN1CCC(c2c[nH]c3ccc(F)cc23)CC1
InChIKey: ZLXDHMZRGGRDJS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor expressed in CHO-K1 cell membranes incubated for 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 336 nM (pChEMBL 6.46999979019165)
Descriptors: MW 490.55, ALogP 5.04, HBA 3, HBD 2, PSA 72.2, QED 0.37
Compound (SMILES): O=C1c2ccccc2S(=O)(=O)N1C[C@H]1CC(c2cccs2)=NO1
InChIKey: YPMBTZWFMDTVIO-SNVBAGLBSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 358 nM (pChEMBL 6.449999809265137)
Descriptors: MW 348.41, ALogP 2.09, HBA 6, HBD 0, PSA 76.04, QED 0.85
Compound (SMILES): Cc1ccc(-n2nc(C(=O)N3CCC4(CCCC4)CC3)nc2-c2ccc3c(c2)N(C2CCCC2)[C@H](C)C(=O)N3C)cc1
InChIKey: SWGFAVICDXWFGW-XMMPIXPASA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of 5-FITC labelled (+)-JQ1 from His6-tagged human BRD4 bromodomain 1 expressed in Escherichia coli BL21(DE3) )-codon plus-RIL cells incubated for 4 hrs in dark condition by fluorescence anisotropy binding assay
Measurement: IC50 = 27.2 nM (pChEMBL 7.570000171661377)
Descriptors: MW 566.75, ALogP 6.15, HBA 6, HBD 0, PSA 74.57, QED 0.38
Compound (SMILES): COc1ccc(-c2ccc(Cn3cc(-c4ccccc4)nn3)cc2)cn1
InChIKey: DHCIMAVXPHVRLC-UHFFFAOYSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 342.4, ALogP 4.06, HBA 5, HBD 0, PSA 52.83, QED 0.55
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)CCCc2ccccc2)CC1
InChIKey: NGFSRVTVKPMWBP-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 = 14400 nM (pChEMBL 4.840000152587891)
Descriptors: MW 322.45, ALogP 3.67, HBA 2, HBD 0, PSA 23.55, QED 0.84
Compound (SMILES): CCCC(=O)Oc1ccc(C2Oc3cc(OC(=O)CCC)cc(O)c3C(=O)C2c2c(OC(=O)CCC)cc(O)c3c(=O)cc(-c4ccc(OC(=O)CCC)c(OC(=O)CCC)c4)oc23)cc1
InChIKey: ZWQBXMCOZWYXPE-UHFFFAOYSA-N
Target: Cruzipain (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P25779
Assay: Inhibition of Trypanosoma cruzi cruzain (unknown origin) using Z-FR-MCA as substrate by spectrofluorimetric method
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 906.93, ALogP 9.5, HBA 16, HBD 2, PSA 228.47, QED 0.06
Compound (SMILES): NS(=O)(=O)c1ccc(N2N=C(c3ccc(Cl)c(Cl)c3)CCC2=O)cc1
InChIKey: RCMFZCLVTRBJDF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of membrane bound human CA 9 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 398.27, ALogP 3.17, HBA 4, HBD 1, PSA 92.83, QED 0.86
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1ccncc1C.N.N.N
InChIKey: JZMFFFDSTBEIPT-BCWYDYJVSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 781.77, ALogP 2.78, HBA 12, HBD 6, PSA 281.07, QED 0.03
Compound (SMILES): CC1OC2(CCN(CCc3ccccc3)CC2)CN(c2cncc(F)c2)C1=O
InChIKey: HJJBGZORBJLFRB-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHOK1 cells assessed as stimulation of cAMP accumulation incubated for 45 mins by HTRF assay
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 383.47, ALogP 3.05, HBA 4, HBD 0, PSA 45.67, QED 0.81
Compound (SMILES): CCc1ncncc1-c1nc2cc(F)c(F)cc2n1C1CC1
InChIKey: BPAROTGKULTHJV-UHFFFAOYSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human recombinant CYP11B1 using deoxycortisol as substrate incubated for 60 mins by cell-based HPLC analysis
Measurement: IC50 = 3330 nM (pChEMBL 5.480000019073486)
Descriptors: MW 300.31, ALogP 3.67, HBA 4, HBD 0, PSA 43.6, QED 0.74
Compound (SMILES): O=c1c(-c2ccccc2F)c2n(c(=O)n1CCCCN1CCCC(c3c[nH]c4ccccc34)C1)CCCC2
InChIKey: SIUHBRWYHJOWBX-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]-citalopram from SERT in rat cortex tissue incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 514.65, ALogP 5.29, HBA 5, HBD 1, PSA 63.03, QED 0.34
Compound (SMILES): CCCN(CCCCNC(=O)c1ccc(-c2ccccn2)cc1)CC1CC1c1ccc(C(F)(F)F)cc1.Cl
InChIKey: ZPFCVRSVVBBMQM-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D2 receptor stably expressed in fibroblast cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 509.62, ALogP 6.79, HBA 3, HBD 1, PSA 45.23, QED 0.27
Compound (SMILES): Cc1noc(C)c1-c1cc(S(=O)(=O)NC2CCCC2O)c2cc(N)c(=O)[nH]c2c1
InChIKey: PCHQDIJCHWUSLF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of biotin-labelled tetra-acetylated Histone H4 peptide binding to recombinant human N-terminal TEV-cleavable hexa-histidine tagged BRD4 bromodomain1 after 60 mins by HTRF assay
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 418.48, ALogP 1.57, HBA 7, HBD 4, PSA 151.31, QED 0.5
Compound (SMILES): Cc1c(C)c2ccc(OCC3CCN(Cc4cccc(OCCCO)c4)CC3)cc2oc1=O
InChIKey: QLFPNOYDCBXGNI-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected insect cell microsomes using kynuramine as substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 451.56, ALogP 4.46, HBA 6, HBD 1, PSA 72.14, QED 0.38
Compound (SMILES): CC(=O)Nc1nc(-c2ccc(Cl)c(Cl)c2)cs1
InChIKey: KQRLIWILHIFHRX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Displacement of Myr-GQQPGKVLGDQRRPSL(K-TAMRA)G-amide from N-terminal-truncated human c-ABL D382N mutant (46 to 534 residues) after 30 mins by fluorescence polarization binding assay
Measurement: IC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 287.17, ALogP 4.08, HBA 3, HBD 1, PSA 41.99, QED 0.9
Compound (SMILES): C[C@H]1CCN(S(=O)(=O)c2cc(NC(=O)Cc3noc4ccccc34)ccc2Br)C1
InChIKey: DBZGKTULFWRCIP-ZDUSSCGKSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of Alexa Fluor 647-labeled GSK tracer from FLAG-6His-Tev-fused CECR2 (424 to 543 residue) (unknown origin) measured after 15 mins by TR-FRET assay
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 478.37, ALogP 3.8, HBA 5, HBD 1, PSA 92.51, QED 0.6
Compound (SMILES): O=C(Nc1ccc(OCc2nc3ccccc3s2)cc1)Nc1cccc(Cl)c1
InChIKey: YUJUWTKAAYMVNM-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of recombinant human sEH preincubated for 10 mins followed by PHOME substrate addition and measured after 60 mins by fluorescence-based assay
Measurement: IC50 = 25.9 nM (pChEMBL 7.590000152587891)
Descriptors: MW 409.9, ALogP 6.17, HBA 4, HBD 2, PSA 63.25, QED 0.41
Compound (SMILES): CN(CCN)Cc1ccccc1
InChIKey: LIUGRXFEJOSPIA-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of PRMT6 (unknown origin)
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 164.25, ALogP 1.08, HBA 2, HBD 1, PSA 29.26, QED 0.72
Compound (SMILES): O=C1c2ccccc2S(=O)(=O)N1CCCCCCN1CCN(c2ncccn2)CC1
InChIKey: OUHWYWVRNFHIJL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]raclopride from full length human cloned D2L receptor expressed in HEK293 cells incubated for 1 hr by radioligand displacement assay
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 429.55, ALogP 2, HBA 7, HBD 0, PSA 86.71, QED 0.59
Compound (SMILES): CSc1ccccc1[C@H]1CCCN1C(=O)CNC(=O)NCc1ccc2c(c1)[C@H]1C[C@@H](N2)[C@H](O)CO1
InChIKey: BICVGZIZTMOLHN-SSGKUCQKSA-N
Target: Peptidyl-prolyl cis-trans isomerase D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08752
Assay: Displacement of fluorescein labelled cyclosporine A derivative from human recombinant CypD (30 to 207 residues) expressed in Escherichia coli cells incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 496.63, ALogP 3.19, HBA 6, HBD 4, PSA 102.93, QED 0.46
Compound (SMILES): COc1ccc2[nH]cc(C3CCCN(CCCCn4c(=O)c(-c5ccccc5OC)c5ccccn5c4=O)C3)c2c1
InChIKey: BDUNEIZTJAOINC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from recombinant human 5HT1A receptor expressed in CHO cell membranes measured after 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 552.68, ALogP 5.29, HBA 7, HBD 1, PSA 80.97, QED 0.25
Compound (SMILES): Fc1cccc2c1C(C1CCN(c3ccccc3)CC1)n1cncc1-2
InChIKey: DURRNOMJUBJEMB-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in Escherichia coli Rosetta measured after 1 hr microplate reader analysis
Measurement: IC50 = 338 nM (pChEMBL 6.46999979019165)
Descriptors: MW 333.41, ALogP 4.51, HBA 3, HBD 0, PSA 21.06, QED 0.69
Compound (SMILES): NC1=CC(N)=C2C=CC(=O)N=C2C1=O
InChIKey: MNCJAIOYOIRYJW-UHFFFAOYSA-N
Target: Tyrosyl-DNA phosphodiesterase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95551
Assay: Inhibition of recombinant human TDP2 using T5PNP as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 189.17, ALogP -0.84, HBA 4, HBD 2, PSA 98.54, QED 0.49
Compound (SMILES): COC(=O)[C@@H]1OCC(=O)N(c2ccc(S(N)(=O)=O)cc2)[C@H]1c1ccc(C)cc1
InChIKey: OWICWGWYCBDTEH-ZWKOTPCHSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 404.44, ALogP 1.29, HBA 6, HBD 1, PSA 116, QED 0.77
Compound (SMILES): COc1cccc(-c2csc(N3N=C(c4ccc(F)cc4)CC3c3ccccc3O)n2)c1
InChIKey: AJOKYPUUKHXYKB-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of recombinant human MMP-2 preincubated for 10 mins followed by Mca-PLGL-Dpa-AR-NH2 substrate addition and measured for 5 mins by fluorescence assay
Measurement: IC50 = 6760.83 nM (pChEMBL 5.170000076293945)
Descriptors: MW 445.52, ALogP 6.02, HBA 6, HBD 1, PSA 57.95, QED 0.41
Compound (SMILES): Cc1ccc(Nc2c(F)cccc2Cl)c(CNc2nnn[nH]2)c1
InChIKey: MMAPSODFYGLEJI-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX2 in lympho-monocytes (unknown origin) preincubated for 30 mins followed by LPS challenged measured after 24 hrs by EIA
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 332.77, ALogP 3.66, HBA 5, HBD 3, PSA 78.52, QED 0.66
Compound (SMILES): COc1cccc(C(=O)Nc2c(Cl)cccc2Cl)c1
InChIKey: HWHWKIBZNCDDSK-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylcholine chloride as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins under dark condition by Ellman's method
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 296.15, ALogP 4.25, HBA 2, HBD 1, PSA 38.33, QED 0.92
Compound (SMILES): CC(=O)NCCN(C(=O)c1nn(C)c2c1COc1ccc(Cl)cc1-2)C(C)c1ccccc1
InChIKey: ITYKUKROJSDLOX-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR transfected in human HEK293T cells o-expressing pGL3/hBSEP/luc incubated for 24 hrs by Steady-Glo reagent based luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 452.94, ALogP 3.97, HBA 5, HBD 1, PSA 76.46, QED 0.61
Compound (SMILES): O=C(NCCc1c[nH]c2ccccc12)c1cc(Cl)ccc1O
InChIKey: DTYKSCYNZQVRKE-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 assessed as reduction in PGF2alpha formation using arachidonic acid as substrate incubated for 10 mins by ELISA
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 314.77, ALogP 3.5, HBA 2, HBD 3, PSA 65.12, QED 0.69
Compound (SMILES): CC(C)(C)CNc1nccc(NCCCc2c[nH]cn2)n1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: PDBCSXJPJFHIMZ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of 2 nM [3H]UR-PI294 from human H3R expressed in Sf9 cell membranes co-expressing Gia2 and beta1gamma2 by competition binding assay
Measurement: Ki = 9.333 nM (pChEMBL 8.029999732971191)
Descriptors: MW 288.4, ALogP 2.7, HBA 5, HBD 3, PSA 78.52, QED 0.68
Compound (SMILES): COc1cc(N2CCN(CCN(C)C)C2=O)ccc1Nc1ncc(Cl)c(Nc2ccccc2S(=O)(=O)C(C)C)n1
InChIKey: SSPYHBZSDDTSFN-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ALK L1196M mutant cytoplasmic domain (1058 to 1620 residues) expressed in baculovirus expression system using srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 = 0.73 nM (pChEMBL 9.140000343322754)
Descriptors: MW 588.13, ALogP 4.61, HBA 9, HBD 2, PSA 120, QED 0.33
Compound (SMILES): COc1ccc2c(c1)OCc1c([C@H](C)Nc3nccc(N4C(=O)OC[C@@H]4[C@H](C)F)n3)ncn1-2
InChIKey: CYAFWASBLFLKTQ-HEHGZKQESA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of recombinant human C-terminal His8-tagged IDH1 R132C mutant expressed in Escherichia coli BL21 assessed as reduction in NADPH consumption using alpha-ketoglutarate as substrate preincubated for 60 mins followed by substrate addition and measured for 60 mins in presence of NADPH by diaphorase/resazurin-based fluorescence assay
Measurement: IC50 = 153.8 nM (pChEMBL 6.809999942779541)
Descriptors: MW 454.46, ALogP 3.42, HBA 9, HBD 1, PSA 103.63, QED 0.6
Compound (SMILES): COc1cc(NC(=O)Nc2ccc(Oc3ncnc4cc(OC)c5c(c34)OCCO5)cc2)ccn1
InChIKey: FALKRMALMYZZJE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Test of Small Molecule Compounds for Inhibiting the Activity of VEGFR-2 Kinase: 1. Dilution of the compound: a total of 12 concentrations were obtained using a 4-fold gradient dilution from the highest concentration of 10000 nM (the maximum final concentration of the drug used in this experiment is 10000 nM, and the minimum final concentration is 0.002384 nM),2. 2.5 μl of the gradient-diluted compounds was taken with a transfer pipette to a 384-well plate,3. Addition of enzyme: 5 μl of 2×VEGFR-2 kinase was taken with a transfer pipette to the corresponding reaction well of the 384-well plate, which was mixed and pre-reacted at room temperature for 30 min,4. 2.5 μl of 4× substrate/ATP Mix was taken with a transfer pipette to the corresponding reaction well of the 384-well plate,5. Negative control: 2.5 μl/well 4× substrate/ATP Mix and 7.5 μl 1× Kinase Assay Buffer were added to the wells of the 384-well plate,Positive control: 2.5 μl/well 4× substrate/ATP Mix, 2.5 μl/well 1× Kinase Assay Buffer containing 4% DMSO, and 5 μl/well 2×VEGFR-2 solution were added to the 384-well plate. The final concentration of DMSO in the reaction system is 4%,6. The mixture was mixed well and then centrifuged and reacted at room temperature in dark for 60 min,7. Termination of the enzymatic reaction: 5 μl of 4× Stop solution was taken with a transfer pipette to the wells of the 384-well plate, mixed and then centrifuged, and reacted at room temperature for 5 min,8. Development of the reaction: 5 μl of 4× Detection Mix was taken with a transfer pipette to the wells of the 384-well plate for color development, and the mixture was mixed and then centrifuged and reacted at room temperature for 60 min,9. The 384-well plate was placed into the Envision plate reader and the signal was detected using the appropriate program,10. Analysis and processing of the raw data:The drug concentrations and the corresponding inhibition rates were input into GraphPad Prism5 for calculation, and the inhibition rate of the compound was calculated as follows: inhibition rate (%)=[1−(experimental well reading value−negative control well reading value)/(positive control well reading value−negative control well reading value)]×100%. Processing with GraphPad Prism5 software yielded the corresponding IC50 value (the concentration of the compound at which 50% of the highest inhibition of the enzyme is achieved).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 475.46, ALogP 4.25, HBA 9, HBD 2, PSA 125.95, QED 0.42
Compound (SMILES): Cc1cc(O)cc2c(/C=N/NC(=N)NCCc3ccc(Cl)c(Cl)c3)c[nH]c12
InChIKey: YNHKFRKBWWGVCP-KIBLKLHPSA-N
Target: Relaxin-3 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU9
Assay: Agonist activity at human RXFP4 expressed in CHOK1 cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation preincubated for 30 mins followed by forskolin-stimulation and measured after 30 mins by HTRF assay
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 404.3, ALogP 4.18, HBA 3, HBD 5, PSA 96.29, QED 0.25
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)Nc1ccccc1
InChIKey: WYAIOWMAXROAKX-FXVJXKIMSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 781.77, ALogP 3.47, HBA 11, HBD 7, PSA 280.21, QED 0.03
Compound (SMILES): CCCN1CCc2cccc3c2[C@H]1Cc1ccc2c(c1-3)OCO2
InChIKey: YSONYEIWWIFWEV-MRXNPFEDSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at C-terminal RLuc8-fused D1R (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay
Measurement: EC50 = 1949 nM (pChEMBL 5.710000038146973)
Descriptors: MW 307.39, ALogP 3.95, HBA 3, HBD 0, PSA 21.7, QED 0.84
Compound (SMILES): O=[N+]([O-])CC(c1ccc(F)cc1)c1c(-c2ccccc2)[nH]c2c(F)cccc12
InChIKey: HBLVFFQTZCTIRO-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulatory activity at human CB1R expressed in CHO-K1 cells assessed as increase in CP55940-induced inhibition of forskolin-stimulated cAMP production after 30 mins in presence of CP55940 at EC20 concentration by hit-hunter cAMP assay
Measurement: EC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 378.38, ALogP 5.52, HBA 2, HBD 1, PSA 58.93, QED 0.37
Compound (SMILES): COc1ccc(CC(=O)n2nc(OCCN3CCCC3)c3ccccc32)cc1
InChIKey: CMPZCYYEUVTKFE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using butyrylthiocholine as substrate by Ellman's assay
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 379.46, ALogP 3.4, HBA 6, HBD 0, PSA 56.59, QED 0.63
Compound (SMILES): Nc1ncnc2c3c(n(-c4ccc(NC(=O)Cc5cc(C(F)(F)F)ccn5)cc4)c12)CCC3
InChIKey: OQLKITGDQKDPKR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Displacement of kinase tracer 236 from recombinant human His-tagged KDR cytoplasmic domain (789 to 1356 residues) expressed in baculovirus-infected insect cells measured after 5 hrs by TR-FRET based LanthaScreen assay
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 452.44, ALogP 4.09, HBA 6, HBD 2, PSA 98.72, QED 0.49
Compound (SMILES): O=C(NC1CC(F)(F)C1)[C@@H](c1ccccc1Cl)N(C(=O)[C@H](CO)Nc1ncccn1)c1cccc(F)c1
InChIKey: FBGANBCVYJNYRD-LEWJYISDSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) assessed as reduction in NADPH consumption by diaphorase/resazurin-based assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 533.94, ALogP 3.73, HBA 6, HBD 3, PSA 107.45, QED 0.39
Compound (SMILES): COc1ccc(Cc2nc3cc(C(C)=O)ccc3n2C[C@@H]2CCCN3CCCC[C@H]23)cc1
InChIKey: UESORWCQFPYQSQ-WIOPSUGQSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membranes measured after 90 mins
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 431.58, ALogP 5.1, HBA 5, HBD 0, PSA 47.36, QED 0.51
Compound (SMILES): CC1(C#Cc2c(Cl)c3c(Cl)cc(C(N)=O)nc3n2[C@H]2CCCNC2)COC1
InChIKey: XNQLYGHTCMOZRQ-NSHDSACASA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of PIM1 (unknown origin) assessed as reduction in BAD phosphorylation at Ser-112 residue by TR-FRET assay
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 407.3, ALogP 2.75, HBA 5, HBD 2, PSA 82.17, QED 0.75
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1cc(N2CCC[C@H](C(=O)NCc3ccc(OC(F)(F)F)cc3)C2)ccn1
InChIKey: OBAHAQPVDNQTSJ-QHCPKHFHSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human N-terminal GST-tagged ALK (catalytic domain 1058 - 1620 residues) expressed in baculovirus system assessed as decrease in substrate phosphorylation using TK peptide as substrate preincubated with enzyme for 30 mins followed by substrate addition by HTRF method
Measurement: IC50 = 492 nM (pChEMBL 6.309999942779541)
Descriptors: MW 598.67, ALogP 5.02, HBA 8, HBD 2, PSA 82.2, QED 0.36
Compound (SMILES): CC(C)(O)c1cnc(N2C[C@@]3(CCC[C@](C)(Cn4cnc5ccc(C#N)cc54)C3)OC2=O)cn1
InChIKey: URCMKDJBULWNAI-DQEYMECFSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Antagonist activity at human TRPV4
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 460.54, ALogP 3.9, HBA 8, HBD 1, PSA 117.16, QED 0.63
Compound (SMILES): CN(C)[C@H]1CCN(c2ccc3c(C(=O)NCC4CCC(F)(F)CC4)c(Cl)ccc3n2)C1
InChIKey: PUYAVUFSDFVGJW-INIZCTEOSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at P2X7R in LPS-stimulated human THP1 cells assessed as inhibition of BzATP-induced IL-1beta release preincubated for 30 mins followed by BzATP stimulation and measured after 30 mins by sandwich ELISA
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 450.96, ALogP 4.58, HBA 4, HBD 1, PSA 48.47, QED 0.72
Compound (SMILES): O=C1COc2ccc(-c3cnc4ccccc4c3)cc2N1C1CCCCC1
InChIKey: JTASMHQNPIGCLV-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human full length N-terminal GST-tagged PI3Kdelta (1 to 1044 residues)/PIK3R1 (1 to 724 residues) expressed in baculovirus expression system using PIP2 as substrate incubated for 2 hrs by ADP-Glo assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 358.44, ALogP 4.96, HBA 3, HBD 0, PSA 42.43, QED 0.65
Compound (SMILES): COc1ccccc1/C=N/NC(=O)c1cc2cc(Cl)ccc2o1
InChIKey: IJWWCDLTYUXQTO-VXLYETTFSA-N
Target: Anoctamin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQ90
Assay: Inhibition of YFP-fused ANO2 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 328.75, ALogP 3.86, HBA 4, HBD 1, PSA 63.83, QED 0.58
Compound (SMILES): CCCCCCCCNCC(F)(P(=O)(O)O)P(=O)(O)O
InChIKey: ORKXJWRZJCHYDN-UHFFFAOYSA-N
Target: Farnesyl diphosphate synthase (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q197X6
Assay: Inhibition of Toxoplasma gondii FPPS using DMAPP as substrate incubated for 30 mins measured by scintillation counting
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 335.25, ALogP 1.92, HBA 3, HBD 5, PSA 127.09, QED 0.29
Compound (SMILES): CN(CCOCc1ccccc1)c1nc(-c2cccnc2)nc2ccccc12
InChIKey: SIPGZEAUCVNPPT-UHFFFAOYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: High Throughput Screening (HTS) by Fluorescence Polarization (pH = 7.2): The enzyme in GCase enzyme activity buffer (25 μL/well) was added to a 384-well black plate. The fluorescent probe 3 (25 nL/well, 50 nM final concentration) was transferred to a 384-well black plate using a Labcyte Echo 550 Liquid Handler system. Compounds in DMSO stock solution (50 nL) were transferred to the plate. The plate was shaken at room temperature in dark for 20 min. The final concentration was 19.5 nM to 10 μM, 10 concentrations, 2 times dilution. The fluorescence polarization was measured in a Molecular Devices Analyst GT with Ex=535 nm and Em=580 nm, G Factor=1.05. To the recombinant wild type enzyme (22 μM, 95 μL, 1 equiv) in 0.1 M phosphate buffer (pH 7.2) was added 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(4-(4-(2,4-dimethylpyrrolo [1,2-a]pyrimidine-8-carboxamido)phenyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)propanoate (4) in DMSO (0.89 mM, 5 μL, 2 equiv) in one portion, and was vortexed for 5 sec immediately. At indicated time points, the reaction solution (2 μL) was sampled and diluted (1:3125 dilution) into the assay buffer (50 mM citric acid, 176 mM K2HPO4, and 0.01% Tween-20 at pH 5.9). After 2 h the reaction solution was dialyzed three times with 0.1 M phosphate buffer (pH 7.2). The enzyme was adjusted to the same concentration and sampled for activity. The dilution solutions were assayed with three substrates, resorufin substrate, 4-MU substrate, and natural substrate using the methods described in the examples above without adding compounds.
Measurement: IC50 = 11220 nM (pChEMBL 4.949999809265137)
Descriptors: MW 370.46, ALogP 4.34, HBA 5, HBD 0, PSA 51.14, QED 0.45