lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(Cl)cccn2c1=O
InChIKey: RXHAROKPHMWUME-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human Ramos B cells assessed as reduction in goat anti human IgM-stimulated calcium flux preincubated for 1 hr followed by goat anti human IgM addition and measured for 180 secs by FLIPR assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 553.02, ALogP 5.04, HBA 6, HBD 3, PSA 122.59, QED 0.28
Compound (SMILES): Cc1cc(C)c(C#Cc2cccc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)c2)s1
InChIKey: OKHHETWNMVDAIU-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 = 218 nM (pChEMBL 6.659999847412109)
Descriptors: MW 646.79, ALogP 6.1, HBA 8, HBD 2, PSA 128.17, QED 0.2
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(C)(C)F
InChIKey: LXPLSZAVQYCVGQ-CLYVBNDRSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Binding Assay: hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials [Sanguinetti et al., Nature, 2006, 440, 463-469.] and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 497.63, ALogP 5.11, HBA 5, HBD 2, PSA 56.42, QED 0.43
Compound (SMILES): CCCCCCCC/C=C1\C=C(C(F)(F)F)c2cc(O)c(O)cc21
InChIKey: OWYMWLCFHDHVAH-UKTHLTGXSA-N
Target: Thioredoxin domain-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NBS9
Assay: Inhibition of TXNDC5 (unknown origin)
Measurement: IC50 = 12100 nM (pChEMBL 4.920000076293945)
Descriptors: MW 340.39, ALogP 6.19, HBA 2, HBD 2, PSA 40.46, QED 0.46
Compound (SMILES): COc1ccc(-c2ccnc3c(/N=N/c4ccc(S(N)(=O)=O)cc4)c(N)nn23)cc1
InChIKey: BMZCHLZLVYKQMW-WCWDXBQESA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 29.3 nM (pChEMBL 7.53000020980835)
Descriptors: MW 423.46, ALogP 3.05, HBA 9, HBD 2, PSA 150.32, QED 0.47
Compound (SMILES): COc1ccc2occc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: GEXUHNGZLUQIMG-SCYNACPDSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 109.65 nM (pChEMBL 6.960000038146973)
Descriptors: MW 217.27, ALogP 2.5, HBA 3, HBD 1, PSA 48.39, QED 0.86
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@@H]2COP(=O)(S)O[C@H]3[C@@H](F)[C@H](n4cnc5c(O)ncnc54)O[C@@H]3COP(=O)(S)O[C@H]2[C@H]1F
InChIKey: WBEHEZDHRLNQIK-IRYAPSAPSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of STING in human THP-1-Dual cells assessed as induction of type I IFNs by measuring stimulation of NF-kappaB pathway incubated for 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 695.52, ALogP 2.32, HBA 18, HBD 4, PSA 222.97, QED 0.17
Compound (SMILES): N=c1c2c(-c3ccc(Cl)cc3)cn(-c3ccc(S(N)(=O)=O)cc3)c2ncn1N
InChIKey: YLDDYPASMRPXAV-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 149.9 nM (pChEMBL 6.820000171661377)
Descriptors: MW 414.88, ALogP 1.99, HBA 7, HBD 3, PSA 132.78, QED 0.44
Compound (SMILES): CCNNC(=O)c1ccc(CNC(=O)c2ccccc2)cc1
InChIKey: XFDKMPCSDVCXCQ-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant HDAC1 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 = 399 nM (pChEMBL 6.400000095367432)
Descriptors: MW 297.36, ALogP 1.87, HBA 3, HBD 3, PSA 70.23, QED 0.71
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1-c1cccc(Cl)c1Cl
InChIKey: IKUYEYLZXGGCRD-ORAYPTAESA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant human SHP2 using IRS1 peptide and DiFMUP as substrate incubated for 30 mins followed by DiFMUP addition and measured after 30 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 437.37, ALogP 3.58, HBA 6, HBD 2, PSA 84.5, QED 0.76
Compound (SMILES): C[C@H](CO)n1cnnc1-c1cccc(NC(=O)Nc2ncc3ccccc3n2)n1
InChIKey: FOTUGUOSNRAFAQ-GFCCVEGCSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of TAK1 (unknown origin)
Measurement: IC50 = 5769 nM (pChEMBL 5.239999771118164)
Descriptors: MW 390.41, ALogP 2.48, HBA 8, HBD 3, PSA 130.74, QED 0.48
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc(C(C)C)c(F)cc2OC)[nH]1
InChIKey: BQWFIIWFCIDPNV-VPUSJEBWSA-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 554.75, ALogP 6.56, HBA 5, HBD 2, PSA 87.32, QED 0.26
Compound (SMILES): CS(=O)(=O)Nc1cccc(CC(=O)Nc2nc(-c3c[nH]c4ncc(F)cc34)cs2)c1
InChIKey: PTZWBJZYUKABMZ-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition of ROCK1 (unknown origin)
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 445.5, ALogP 3.38, HBA 6, HBD 3, PSA 116.84, QED 0.42
Compound (SMILES): Cc1cccc(Cc2cn(CCCCCCC(=O)NO)c3ccc(-c4c(C)noc4C)cc23)c1
InChIKey: KPYXYHJFASGCDD-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 using human HeLa cell nuclear extract at 1 uM measured after 60 mins by fluorescence assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 459.59, ALogP 6.27, HBA 5, HBD 2, PSA 80.29, QED 0.17
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4c(OC)ncnc4C4CC4)nc3n([C@@H](C)C(F)(F)F)c2=O)nc1
InChIKey: ZGCBUHCNTNDCGG-ZDUSSCGKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human PBMC assessed as reduction in anti-CD3/IL-23 stimulated IL-17 level measured after 3 days by MSD assay
Measurement: IC50 = 9.9 nM (pChEMBL 8)
Descriptors: MW 590.59, ALogP 3.45, HBA 12, HBD 1, PSA 154.74, QED 0.3
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: LHQONNLUWUCJOW-NHMULKRUSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at kappa opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 2456 nM (pChEMBL 5.610000133514404)
Descriptors: MW 1117.33
Compound (SMILES): COc1cc(OC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC1(F)CC1
InChIKey: MRUYVXJFVOSZEV-CLYVBNDRSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding Assay : hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.The assay was conducted as follows with all reagents used at room temperature unless otherwise stated.Reagent Preparations Include:1. Internal IC700 solution used to perfuse the underside of chip (in mM), KF 130, KCl 20, MgCl2 1, EGTA 10 and HEPES 10, (all Sigma-Aldrich; pH 7.2-7.3 using 10 M KOH, 320 mOsm) and supplemented with 25 □M escin.2. External and cell buffer (in mM), NaCl 137, KCl 4, HEPES 10, D-glucose 10, CaCl2 2, MgCl2 1 (pH7.4, NaOH)3. NMDG reference buffer used to establish a stable baseline prior to the addition of test compounds, NaCl 80, KCl 4, CaCl2 2, MgCl2 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 NaOH 298 mOsm)4. Seal enhancer used to improve seal quality of cells, NaCl 80, KCl 3, CaCl2 10, HEPES 10, MgCl2 1 (pH7.4 NaOH)
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 496.6, ALogP 4.83, HBA 5, HBD 1, PSA 53.62, QED 0.46
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2cccnc2OC)nc1C#N
InChIKey: WKXRYMCWFRFGGI-YADHBBJMSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 34.8 nM (pChEMBL 7.460000038146973)
Descriptors: MW 506.65, ALogP 4.17, HBA 7, HBD 2, PSA 124, QED 0.41
Compound (SMILES): CCCCCCCC/C=C\CCCCCCCC(=O)OC[C@H](COC)OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: AWVXRDOQCOHYDO-NXDWNWMYSA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 < 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 537.63, ALogP 5.13, HBA 8, HBD 3, PSA 154.61, QED 0.06
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CSC(=S)N2CCN(c3ncccn3)CC2)cc1
InChIKey: ZVNONGKMYAONBZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human erythrocyte CA2 using 4-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 452.59, ALogP 0.9, HBA 8, HBD 2, PSA 121.52, QED 0.64
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)NC2COC2)[C@@H](O)[C@H]1O
InChIKey: JQZXCSIXUVOYDD-QRIDJOKKSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 336.31, ALogP -2.46, HBA 10, HBD 4, PSA 157.64, QED 0.48
Compound (SMILES): CN1CCN(CCCCCOc2cccc(N3C(=O)S/C(=C\c4ccc(Oc5ccc([N+](=O)[O-])cc5)cc4)C3=O)c2)CC1
InChIKey: JUFHVPKDACFHKK-SWKFRHMKSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Allosteric inhibition of IKKbeta (unknown origin) using 5FAM-GRHDSGLDSMK-NH2 as substrate incubated for 10 mins followed by substrate addition and measured after 40 mins by TR-FRET assay
Measurement: IC50 = 218.78 nM (pChEMBL 6.659999847412109)
Descriptors: MW 602.71, ALogP 6.42, HBA 9, HBD 0, PSA 105.46, QED 0.1
Compound (SMILES): CC(=O)[C@]12C[C@H]1[C@@](C)(c1cc(/C=C(\F)c3ccc(C#N)cn3)ccc1F)N=C(N)S2
InChIKey: BXVBTUULDWOVOF-FQRJWFRCSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: In Vitro Enzymatic BACE1 and BACE2 FRET (Fluorescence Resonance Energy Transfer) Assays: The cDNAs for both human recombinant BACE1 and 2 with C-terminal 6-His Tags were cloned into transient protein expression vectors, which were subsequently transfected into mammalian cell lines. These recombinant proteins were further purified using Ni-NTA affinity chromatography (Qiagen). The assay buffer used in these screens was 0.05M acetate, pH 4.5, 8% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.02 nM for BACE1 and 0.64 nM for BACE2) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 590 nm).
Measurement: IC50 = 12.1 nM (pChEMBL 7.920000076293945)
Descriptors: MW 424.48, ALogP 4.18, HBA 6, HBD 1, PSA 92.13, QED 0.79
Compound (SMILES): Cc1cc(-c2ccc3c(c2)-c2nnc(Nc4cccc(Cl)c4)n2CCO3)ccn1
InChIKey: PKCYBFPHVFQMSI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells assessed as reduction in S35-MK-0499 binding
Measurement: IC50 = 428 nM (pChEMBL 6.369999885559082)
Descriptors: MW 403.87, ALogP 5.1, HBA 6, HBD 1, PSA 64.86, QED 0.51
Compound (SMILES): C/C=C/C(=O)Nc1ccc(-c2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)cc1
InChIKey: FWVUYTUHMNSOTK-NSCUHMNNSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 cytoplasmic domain (809 to 1153+9 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 1412 nM (pChEMBL 5.849999904632568)
Descriptors: MW 415.5, ALogP 4.24, HBA 6, HBD 2, PSA 79.38, QED 0.59
Compound (SMILES): O=C(Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1)c1cc([N+](=O)[O-])ccc1F
InChIKey: CSLQALGLKKWBBK-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 using dextromethorphan as substrate
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 598.99, ALogP 5.57, HBA 9, HBD 2, PSA 131.75, QED 0.14
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@H](C(=O)O)C3CCCCC3)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: COJPQLLOMWBEEN-ZCHKNENCSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 5.33 nM (pChEMBL 8.270000457763672)
Descriptors: MW 456.58, ALogP 2.82, HBA 6, HBD 3, PSA 91.26, QED 0.63
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)NCc2ccccc2)cc1
InChIKey: GRFLMRGGHAVHMQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 694.5 nM (pChEMBL 6.159999847412109)
Descriptors: MW 412.49, ALogP 0.58, HBA 5, HBD 4, PSA 147.46, QED 0.5
Compound (SMILES): O=S(=O)(c1ccc(Nc2ncc(N3CCOCC3)c(Nc3ccccc3)n2)cc1)N1CCCCC1
InChIKey: RWUOCYNYQYDGGU-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of His6/TEV fused-GST-tagged Flt3 (unknown origin) (H564 to S993 residues) using Axltide (CKKSRGDYMTMQJ-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 75 mins by RapidFire LC-MS analysis
Measurement: IC50 > 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 494.62, ALogP 3.98, HBA 8, HBD 2, PSA 99.69, QED 0.51
Compound (SMILES): COc1ccc(S(=O)(=O)N2CCC[C@@H]2C(=O)NO)cc1
InChIKey: FRNDBEYBKGOTNX-LLVKDONJSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of MMP9 (unknown origin) using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 5 min followed by substrate addition and measured for 30 mins by fluorescence based assay
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 300.34, ALogP 0.35, HBA 5, HBD 2, PSA 95.94, QED 0.62
Compound (SMILES): CO[C@@H]1O[C@H](CNC(=O)c2cc(Br)c(C)n(Cc3ccc(F)cc3)c2=O)[C@H](O)[C@H](O)[C@H]1O
InChIKey: SKRSGLPHCNLKFU-BWZHCXAASA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL in human U937 cells using [glycerol-1,2,3-3H]2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 515.33, ALogP 0.29, HBA 8, HBD 4, PSA 130.25, QED 0.44
Compound (SMILES): COc1ccc(C2N=C(C(N)=O)c3ncn(-c4ccc(N5CCN(C)CC5)c([N+](=O)[O-])c4)c3N2)cc1OC
InChIKey: GREQUBMKQXGAHX-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/Cyclin D1 (unknown origin) using Rb protein as substrate incubated for 1 hr
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 520.55, ALogP 1.95, HBA 11, HBD 2, PSA 153.38, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(N/N=C(\CS(=O)(=O)c2ccccc2)c2cc3cc(Br)ccc3oc2=O)cc1
InChIKey: FGYZFLSKWNJOCH-SZXQPVLSSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 36.2 nM (pChEMBL 7.440000057220459)
Descriptors: MW 576.45, ALogP 3.49, HBA 8, HBD 2, PSA 148.9, QED 0.19
Compound (SMILES): CCN(C)C(=O)Oc1ccc(/C=C/C(=O)N2CCN(Cc3ccccc3)CC2)cc1
InChIKey: FQGOWPYBNKSIRG-SDNWHVSQSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 14800 nM (pChEMBL 4.829999923706055)
Descriptors: MW 407.51, ALogP 3.49, HBA 4, HBD 0, PSA 53.09, QED 0.69
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCC4O)c(Cl)cn2)C1
InChIKey: BRQSWVAJJNFGEP-IODPJOFQSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (1.5 nM CDK9/CycT1, 5 mM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 431.92, ALogP 3.06, HBA 6, HBD 3, PSA 109.14, QED 0.69
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(-c3cnc4c(c3)[C@](C)(NCC(C)(C)F)C(=O)N4)ncnc21
InChIKey: YYXYTTPRFNUTKT-DEOSSOPVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 475.53, ALogP 3.18, HBA 9, HBD 2, PSA 123.4, QED 0.44
Compound (SMILES): CNCC[C@H](Oc1cccc(N2CCN(C)c3nc(SC)ncc3C2=O)c1)c1cccs1
InChIKey: LRBRSWLNUGPGBK-IBGZPJMESA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Binding Assay: α2δ-1: Binding Assay to Human α2δ-1 Subunit of Cav2.2 Calcium Channel.Human α2δ-1 enriched membranes (2.5 μg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10 mM, pH 7.4.NSB (non specific binding) was measured by adding 10 μM pregabalin. After 60 min incubation at 27° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).
Measurement: Ki = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 469.64, ALogP 4.09, HBA 8, HBD 1, PSA 70.59, QED 0.39
Compound (SMILES): c1ccc(-c2c3c(nn2-c2ccccc2)CCNCC3)cc1
InChIKey: MXOUMFAGXNVEAJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]-CT from rat 5-HT7 receptor expressed in HEK293 cells by competitive radioligand binding assay
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 289.38, ALogP 3.23, HBA 3, HBD 1, PSA 29.85, QED 0.78
Compound (SMILES): c1ccc2cc(-c3coc4ccc(-c5cn[nH]c5)nc34)ccc2c1
InChIKey: KLYOYEDXPDCWAL-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86Z02
Assay: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 311.34, ALogP 5.04, HBA 3, HBD 1, PSA 54.71, QED 0.5
Compound (SMILES): COc1ccc(-n2cc(-c3ccc4ccc(=O)oc4c3)c3cc(-c4ccc(C(=O)O)cc4)cnc32)cc1
InChIKey: CQHDXEWKDCKMHF-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase A (SINGLE PROTEIN), Homo sapiens
UniProt: P62937
Assay: Inhibition of PPIA (unknown origin) pre-incubated for 20 mins followed by fluorescence substrate addition and measured after 120 mins by DiFMUP assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 488.5, ALogP 6.17, HBA 6, HBD 1, PSA 94.56, QED 0.29
Compound (SMILES): NC(=O)c1ccccc1OCCNCC1(F)CCN(C(=O)c2ccc(F)c(Cl)c2)CC1
InChIKey: PFQWJWAFVWGWKC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 451.9, ALogP 3.19, HBA 4, HBD 2, PSA 84.66, QED 0.6
Compound (SMILES): N#CC[C@]1(n2cc(-c3nc(-c4cc[nH]n4)cn4nccc34)cn2)C[C@H](C#N)C1
InChIKey: CCSVAVWZJWQMCI-HJGJAMNPSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 catalytic domain (781 to 1124 residues) expressed in baculovirus expression system using FITC-KGGEEEEYFELVKK as substrate in presence of ATP at Km by microfluidic assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 369.39, ALogP 2.53, HBA 8, HBD 1, PSA 124.27, QED 0.59
Compound (SMILES): CC(Sc1nc2cnccc2n1-c1ccc(C2CC2)c2ccccc12)C(=O)O
InChIKey: NSXLFTWTIDIJIC-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsome using probe substrate measured after 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 2390 nM (pChEMBL 5.619999885559082)
Descriptors: MW 389.48, ALogP 5.02, HBA 5, HBD 1, PSA 68.01, QED 0.49
Compound (SMILES): COc1ccccc1C1c2c(C(C)(C)C)n[nH]c2C(=O)N1c1ccc(-c2cc(C)no2)cc1
InChIKey: AOMNZFWIRFJLQR-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 442.52, ALogP 5.43, HBA 5, HBD 1, PSA 84.25, QED 0.46
Compound (SMILES): Cn1cc(-c2ccccc2Oc2ccccc2)c2cc(C(=O)NCCCCCC(=O)Nc3ccccc3N)[nH]c2c1=O
InChIKey: ICPNDBHZFPANIZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 563.66, ALogP 5.84, HBA 6, HBD 4, PSA 131.24, QED 0.12
Compound (SMILES): C/C(=N\Nc1ccc(S(N)(=O)=O)cc1)c1sc2nc3ccccc3n2c1C
InChIKey: AHCARNVWNXRULP-SRZZPIQSSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 31.3 nM (pChEMBL 7.5)
Descriptors: MW 399.5, ALogP 3.34, HBA 7, HBD 2, PSA 101.85, QED 0.41
Compound (SMILES): O=c1c2ccccc2oc2ccc(OCCCCCN3CCCCC3)cc12
InChIKey: HIDZMCKONDQZSV-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 BTI cells using p-tyramine as substrate by fluorometric assay
Measurement: IC50 = 1498 nM (pChEMBL 5.820000171661377)
Descriptors: MW 365.47, ALogP 4.98, HBA 4, HBD 0, PSA 42.68, QED 0.44
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCN(S(N)(=O)=O)CC3)cc2)nc2ccsc12
InChIKey: JLPPMVVFVQHWGQ-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 561.69, ALogP 4.71, HBA 9, HBD 2, PSA 137.47, QED 0.31
Compound (SMILES): COc1ccc(N2CCN(Cc3cc(=O)oc4cc(OCc5ccc([N+](=O)[O-])cc5)ccc34)CC2)cc1
InChIKey: LMPGUAQELTXXCR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 4830 nM (pChEMBL 5.320000171661377)
Descriptors: MW 501.54, ALogP 4.61, HBA 8, HBD 0, PSA 98.29, QED 0.2
Compound (SMILES): O=S(=O)(N[C@H]1CCN(CCCc2noc3ccccc23)C1)c1ccc(F)c(Cl)c1
InChIKey: KGCZEOUXHSFHJT-AWEZNQCLSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from recombinant human D2 receptor expressed in CHOK1 cell membranes measured after 60 mins by microbeta counting method
Measurement: Ki = 169.82 nM (pChEMBL 6.769999980926514)
Descriptors: MW 437.92, ALogP 3.61, HBA 5, HBD 1, PSA 75.44, QED 0.61
Compound (SMILES): COc1ccc(N2CCN(CCC(=O)NCc3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: IABRHLSKVMKCOD-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped-flow CO2 hydration assay
Measurement: Ki = 136.2 nM (pChEMBL 6.869999885559082)
Descriptors: MW 432.55, ALogP 1.17, HBA 6, HBD 2, PSA 104.97, QED 0.65
Compound (SMILES): O=C(C1CCS(=O)(=O)CC1)N1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)nc3CC[C@@H]12
InChIKey: UPHISCDXGJDADQ-FYYLOGMGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 660.61, ALogP 4.55, HBA 6, HBD 0, PSA 101.48, QED 0.35
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NC1CCN(Cc2cccc(Cl)c2)C1
InChIKey: XJKMJRZBVBOXHX-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 597 nM (pChEMBL 6.21999979019165)
Descriptors: MW 383.88, ALogP 3.26, HBA 4, HBD 3, PSA 73.05, QED 0.63
Compound (SMILES): OC(Cc1ccccc1)CN1CCC(NCCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: LEPYGHSZGURSOB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from human D2L receptor expressed in HEK293 cell membranes measured after 60 mins by microbeta scintillation counting method
Measurement: Ki = 4020 nM (pChEMBL 5.400000095367432)
Descriptors: MW 496.67, ALogP 5.45, HBA 4, HBD 2, PSA 35.5, QED 0.35
Compound (SMILES): CCC(NC(=O)[C@H](Cc1ccc(O)c([N+](=O)[O-])c1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](N)CC(N)=O)C(N)=O
InChIKey: LKQQKKQSOSJUFO-QOWIWEFOSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of [125I-Tyr11]-SS14 from human SSTR2 expressed in HEK293-A cells incubated for 30 mins by gamma counting based competition radioligand binding assay
Measurement: IC50 = 37500 nM (pChEMBL 4.429999828338623)
Descriptors: MW 925.02, ALogP -0.06, HBA 12, HBD 12, PSA 378.67, QED 0.02
Compound (SMILES): CN1CCN(c2cc(C(=O)Nc3cc4cc(-c5cnn(C6CC6)c5)ccc4cn3)ccn2)CC1
InChIKey: KITGSDROWQMUKJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 453.55, ALogP 3.83, HBA 7, HBD 1, PSA 79.18, QED 0.49
Compound (SMILES): CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2sc(CN3CCN(C4CCCC4)C(=O)C3)cc2n1
InChIKey: WVTWODVINWUSDE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin)
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 545.71, ALogP 4.02, HBA 9, HBD 0, PSA 79.62, QED 0.36
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: DFZXNMRSOUHRAB-AJUYTZQHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]diprenorphine from human MOR expressed in mouse NG108-15 cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 9549.93 nM (pChEMBL 5.019999980926514)
Descriptors: MW 1022.22
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3NCCC4)c(Cl)cn2)C1
InChIKey: HGTYXDXGMWEQPT-UONOGXRCSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (ATP Concentration at Km): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (3 nM CDK9/CycT1, 6 μM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 416.91, ALogP 3.05, HBA 6, HBD 3, PSA 100.94, QED 0.71
Compound (SMILES): C[C@]1(O)CCC[C@@H]1n1c(=O)c(CC(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: GUFBYMCWKSZUBS-KKSFZXQISA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: CDK2/Cyclin E1 Mobility Shift Assay : The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (±inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 1.87 nM (pChEMBL 8.729999542236328)
Descriptors: MW 485.56, ALogP 1.91, HBA 8, HBD 2, PSA 117.42, QED 0.64
Compound (SMILES): [O-][S+](CCNC1CCN(Cc2ccc(F)cc2)CC1)C(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: FECGZFUZXKQCAY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from human D2L receptor expressed in HEK293 cell membranes measured after 60 mins by microbeta scintillation counting method
Measurement: Ki = 12400 nM (pChEMBL 4.909999847412109)
Descriptors: MW 486.6, ALogP 5.2, HBA 3, HBD 1, PSA 38.33, QED 0.42
Compound (SMILES): Cc1cccc(S(=O)(=O)N[C@@H]2CCN(CCCc3noc4ccccc34)C2)c1
InChIKey: SYYIAXPMUWTBLV-QGZVFWFLSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from recombinant human D2 receptor expressed in CHOK1 cell membranes measured after 60 mins by microbeta counting method
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 399.52, ALogP 3.12, HBA 5, HBD 1, PSA 75.44, QED 0.66
Compound (SMILES): O=C(NC1CC1)c1cnc2[nH]ccc2c1NC1CCN(Cc2ccccc2)CC1
InChIKey: GFKFPDJIWVGACL-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 1346 nM (pChEMBL 5.869999885559082)
Descriptors: MW 389.5, ALogP 3.53, HBA 4, HBD 3, PSA 73.05, QED 0.6
Compound (SMILES): COc1ccc(N2CCN(Cc3cc(=O)oc4cc(OCc5cccc(Cl)c5)ccc34)CC2)cc1
InChIKey: NGWJIKSRKHNZLF-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 4580 nM (pChEMBL 5.340000152587891)
Descriptors: MW 490.99, ALogP 5.36, HBA 6, HBD 0, PSA 55.15, QED 0.33
Compound (SMILES): CN(C)c1ccc(CC(=O)N[C@@H]2CNC[C@H]2c2ccc(C(F)(F)F)cc2)cc1
InChIKey: XORRDVHOURHODX-RBUKOAKNSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 expressed in baculovirus infected insect cells using phenacetin as substrate incubated for 30 mins in presence of NADPH-regenerating system by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 391.44, ALogP 3.19, HBA 3, HBD 2, PSA 44.37, QED 0.82
Compound (SMILES): Cc1cc(Cl)cc(N2C=Nc3cc(C)c(-c4cc(O)cc(F)c4)cc3C2C(=O)N(C)C[C@@H]2CCCN2)c1
InChIKey: DGZBUPNCYZBICZ-XYXHBKGXSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Agonist activity at SST5 (unknown origin)
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 521.04, ALogP 5.9, HBA 5, HBD 2, PSA 68.17, QED 0.44
Compound (SMILES): O=C(NO)c1ccc(NC(=O)c2c(F)c(F)c(F)c(F)c2F)cc1
InChIKey: REYWGPFBFQEPPD-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 346.21, ALogP 2.75, HBA 3, HBD 3, PSA 78.43, QED 0.26
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCF)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: JEIIPIFVEMKMLA-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulation of gamma secretase in human SH-SY5Y cells overexpressing wild type APP751 assessed as effect on amyloid beta42 level by meso scale discovery
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 453.55, ALogP 4.5, HBA 9, HBD 1, PSA 82.68, QED 0.44
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(O)cc3)cc2)CC1.Cl
InChIKey: WKVWXDMJXHFGCP-FJISBNMDSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 = 4371 nM (pChEMBL 5.360000133514404)
Descriptors: MW 455.64, ALogP 6.71, HBA 3, HBD 2, PSA 43.7, QED 0.37
Compound (SMILES): CC(C)(C)c1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: XGIJNCDMAVBREM-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 90.7 nM (pChEMBL 7.039999961853027)
Descriptors: MW 454.57, ALogP 2.19, HBA 5, HBD 4, PSA 147.46, QED 0.51
Compound (SMILES): CC(C)(O)C(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)nc3CC[C@@H]12
InChIKey: AMFWGZXIWGMBRF-REDKUUPNSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 600.53, ALogP 4.79, HBA 5, HBD 2, PSA 96.36, QED 0.38
Compound (SMILES): Cl.O=C(Cc1ccc(Cl)c(Cl)c1)N1CCCC[C@H]1CN1CCCC1
InChIKey: NGVLSOWJSUUYDE-RSAXXLAASA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: PDSP Secondary Binding target: SLC6A3 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 4855.11 nM (pChEMBL 5.309999942779541)
Descriptors: MW 355.31, ALogP 4.01, HBA 2, HBD 0, PSA 23.55, QED 0.81
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CN2CCN(c3ncccn3)CC2)cc1
InChIKey: VAFHHCSJIKYKHM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped-flow CO2 hydration assay
Measurement: Ki = 2230.8 nM (pChEMBL 5.650000095367432)
Descriptors: MW 390.47, ALogP -0.44, HBA 7, HBD 2, PSA 121.52, QED 0.69
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1N[C@@H]1CCN(Cc2cccc(OC)c2)[C@@H](C)C1
InChIKey: JUDOWCMPQBMECF-DOTOQJQBSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 407.52, ALogP 3.4, HBA 5, HBD 3, PSA 82.28, QED 0.58
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N2Cc3ccc(O)cc3C[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: VZDNJIOWZQXYGZ-ZJSCUCBRSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]-neurotensin from human recombinant NTS1 stably expressed in CHO-K1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 6830 nM (pChEMBL 5.170000076293945)
Descriptors: MW 1350.68
Compound (SMILES): CCN1CCN(CCS(=O)(=O)c2ccc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)c(OC)c2)CC1
InChIKey: GPAQVHTXRUBATF-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK L1196M mutant (unknown origin) using peptide substrate incubated for 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 637.23, ALogP 4.22, HBA 11, HBD 2, PSA 133.83, QED 0.3
Compound (SMILES): COc1cc(OC)c(Cl)c(COc2cnc(Nc3c(C)cccc3NC#N)nc2)c1Cl
InChIKey: TYZARYXVJAAWDV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human His-tagged FGFR3 (399 to 806 residues) cytoplasmic domain expressed in baculovirus expression system using Tyr 04 peptide as substrate after 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 460.32, ALogP 5.32, HBA 8, HBD 2, PSA 101.32, QED 0.34
Compound (SMILES): C=CC(=O)Nc1ccc(-c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2)cc1
InChIKey: TYKQKTWRESGLLK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) assessed as reduction in ATP-dependent phosphorylation of ULight-myelin basic protein substrate peptide incubated for 60 mins by LANCE TR-FRET assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 400.48, ALogP 4.82, HBA 3, HBD 3, PSA 86.88, QED 0.5
Compound (SMILES): CC(C)c1noc(-c2cnc(Nc3ccc4c(c3)C(C)(C)OC4=O)nc2N[C@H](CO)c2ccccc2)n1
InChIKey: VQYASORGHMGXQV-OAQYLSRUSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in anti-CD3/anti-CD28-stimulated human T-cells assessed as inhibition of SLP76 phosphorylation preincubated for 1 hr followed by anti-CD3/CD28 stimulation for 30 mins by AlphaLISA assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 500.56, ALogP 4.94, HBA 10, HBD 3, PSA 135.29, QED 0.29
Compound (SMILES): COc1ccc2nc3cc(Cl)ccc3c(Nc3ccc(C(=O)NO)cc3)c2n1
InChIKey: RLHSWYLCHQWPQD-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC9 (604 to 1066 residues) expressed in baculovirus infected Sf9 cells using fluorogenic HDAC 2A substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 394.82, ALogP 4.31, HBA 6, HBD 3, PSA 96.37, QED 0.27
Compound (SMILES): Cc1ccc2c(c1)C(=O)C(O)(O)C2=O
InChIKey: YSFDBEXXZHVVAE-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 2460 nM (pChEMBL 5.610000133514404)
Descriptors: MW 192.17, ALogP 0.05, HBA 4, HBD 2, PSA 74.6, QED 0.45
Compound (SMILES): CCCCCCCCC1CCc2cc(CCC(N)(CO)CO)ccc2C1
InChIKey: SQKXCOAPPIICFR-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 361.57, ALogP 4.16, HBA 3, HBD 3, PSA 66.48, QED 0.49