lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=CC(=O)Nc1cccc(-c2noc3ncnc(N[C@H](CO)c4ccccc4)c23)c1
InChIKey: RATDPSGRLABQHT-QGZVFWFLSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of GST-tagged human EGFR kinase domain (696 to 1022 residues) using poly(Glu, Tyr) 4:1 substrate incubated for 60 mins by kinase-Glo plus luminescent kinase assay
Measurement: IC50 = 416 nM (pChEMBL 6.380000114440918)
Descriptors: MW 401.43, ALogP 3.55, HBA 7, HBD 3, PSA 113.17, QED 0.41
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1ccc(OC)cc1C(C)C
InChIKey: KLTUDKDQTPDPQT-FZPFXXBJSA-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 808.88, ALogP 5.14, HBA 11, HBD 5, PSA 240.11, QED 0.03
Compound (SMILES): C[C@@H]1Cc2c([nH]c3ccccc23)[C@@](C)(c2c(F)cc(/C=C/C(=O)O)cc2F)N1CC(C)(C)F
InChIKey: QGICMPFWBJJTDL-OEFSXXAWSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of ERalpha degradation in human MCF7 cells assessed as downregulation of ER alpha receptor expression measured after 18 to 22 hrs by immunofluorescence assay
Measurement: IC50 = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 456.51, ALogP 5.8, HBA 2, HBD 2, PSA 56.33, QED 0.48
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2cncc(/C=C3\SC(=O)NC3=O)c2)cc1
InChIKey: IMUDILUTOPVIKR-AUWJEWJLSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of GST-tagged recombinant PI5P4Kalpha (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 375.43, ALogP 2.44, HBA 6, HBD 2, PSA 105.23, QED 0.8
Compound (SMILES): CC(C)c1cc2c(c(O)c1O)[C@@]1(c3nnc(N)o3)CCCC(C)(C)[C@@H]1CC2
InChIKey: OBTWNXPOBRZQLS-LHSJRXKWSA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged GGPPS expressed in Escherichia coli BL21 (DE3) using FPP and [14C] IPP as substrate preincubated for 15 mins with FPP followed by [14C] IPP addition and further incubated for 20 mins by scintillation counting method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 371.48, ALogP 4.25, HBA 6, HBD 3, PSA 105.4, QED 0.68
Compound (SMILES): CCCCc1nc(/C=N/Nc2nc(N)c3ncn([C@@H]4O[C@H](CO)[C@@H](O)[C@H]4O)c3n2)c(Cl)[nH]1
InChIKey: RURQHXBBEOQUIE-YIKSQJPDSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]CGS21680 from human cloned adenosine receptor A2A expressed in HEK-293 cell membrane incubated for 60 mins by microbeta counting method
Measurement: Ki = 18 nM (pChEMBL 7.75)
Descriptors: MW 465.9, ALogP 0.19, HBA 12, HBD 6, PSA 192.61, QED 0.2
Compound (SMILES): CN(C)c1ccc(C(=O)N2CCN(C(=O)c3ccc(-c4cccc5[nH]nc(N)c45)cc3)CC2)cc1
InChIKey: AYDZFCTWPHMERG-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of BCR/ABL T315I mutant (unknown origin) measured after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 86060 nM (pChEMBL 4.070000171661377)
Descriptors: MW 468.56, ALogP 3.48, HBA 5, HBD 2, PSA 98.56, QED 0.48
Compound (SMILES): O=C(NO)c1ccc(N(Cc2ccc(C(F)(F)F)cc2)C(=O)CN(Cc2ccccc2C(F)(F)F)S(=O)(=O)c2ccc(F)cc2F)cc1
InChIKey: VRTCJQKSPYPQSY-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 expressed in SF9 baculoviral system using FAM-labeled acetylated peptide as substrate by EMSA
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 701.59, ALogP 6.55, HBA 5, HBD 2, PSA 107.02, QED 0.11
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c(C(N)=O)c2N)C1
InChIKey: WTLRSSATGYETCG-QGZVFWFLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human Ramos cells assessed as reduction in BTK phosphorylation at Tyr223 residue preincubated for 1 hr followed by pervanadate or Na3VO4 stimulation for 20 mins by HTRF assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 431.5, ALogP 3.37, HBA 6, HBD 2, PSA 116.47, QED 0.58
Compound (SMILES): COc1ccc(N2CCN(CCCCCCN3C(=O)c4cccc5cccc(c45)C3=O)CC2)cc1
InChIKey: UGOXZHALYQBPNO-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 = 3569 nM (pChEMBL 5.449999809265137)
Descriptors: MW 471.6, ALogP 4.83, HBA 5, HBD 0, PSA 53.09, QED 0.33
Compound (SMILES): CN(Cc1ccccc1)C(=O)Cn1c2ccccc2c2ccccc21
InChIKey: RWKVNMWWFYMFCH-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Displacement of [3H]PK11195 from human TSPO A147T mutant expressed in HEK293 cell membranes after 90 mins by scintillation counting method
Measurement: Ki = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 328.42, ALogP 4.45, HBA 2, HBD 0, PSA 25.24, QED 0.54
Compound (SMILES): CCn1ncc(-c2nc3c(N4CCC(n5c(=O)[nH]c6ncccc65)CC4)ncnc3n2C)c1C
InChIKey: WRPLWRLROFHFJF-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged recombinant full length human p110delta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 458.53, ALogP 2.43, HBA 10, HBD 1, PSA 115.34, QED 0.44
Compound (SMILES): CC1=C(c2cccc(O)c2)[C@H](c2ccc(OCCN3CC(CF)C3)cc2)Oc2ccc(O)cc21
InChIKey: KJAAPZIFCQQQKX-NDEPHWFRSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Competitive inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 461.53, ALogP 5.44, HBA 5, HBD 2, PSA 62.16, QED 0.49
Compound (SMILES): CC(C)c1ccc2c(c1)CC[C@H]1[C@](C)(CNC(=O)Nc3ccc(Cl)cc3)CCC[C@]21C
InChIKey: BBKLOKKZPCGLMA-DOEKTCAHSA-N
Target: Tyrosyl-DNA phosphodiesterase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NUW8
Assay: Inhibition of recombinant TDP1 H493R mutant (unknown origin) using 5'-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3' as substrate measured every 55 secs for 8 mins by fluorescence based assay
Measurement: IC50 = 34100 nM (pChEMBL 4.46999979019165)
Descriptors: MW 439.04, ALogP 7.3, HBA 1, HBD 2, PSA 41.13, QED 0.52
Compound (SMILES): COC1=CC(=O)N(C(=O)/C=C/[C@H](Cc2ccccc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)OC(=O)[C@H](C(C)C)N(C)C)[C@H]1CC(C)C
InChIKey: GVIHWZBKUKQYMN-GPSXOSEWSA-N
Target: Cruzipain (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P25779
Assay: Inhibition of recombinant Trypanosoma cruzi Cruzain expressed in Pichia pastoris using Z-Phe-Arg-AMC substrate incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 696.93, ALogP 4.66, HBA 8, HBD 2, PSA 134.35, QED 0.16
Compound (SMILES): O=C(/C=C/c1cc(O)c(O)c([N+](=O)[O-])c1)OCc1ccccc1
InChIKey: PNWJBLQUWZHYLS-VOTSOKGWSA-N
Target: Catechol O-methyltransferase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P22734
Assay: Inhibition of S-COMT in Wistar rat liver assessed as metanephrine formation preincubated for 20 mins followed by addition of adrenaline as substrate and SAM measured after 5 mins by chromatographic analysis
Measurement: IC50 = 52.47 nM (pChEMBL 7.28000020980835)
Descriptors: MW 315.28, ALogP 2.76, HBA 6, HBD 2, PSA 109.9, QED 0.29
Compound (SMILES): O=C(Cn1c(=O)c(-c2ccc(O)c(O)c2)nc2ccccc21)NS(=O)(=O)C(F)(F)F
InChIKey: HZOODCNHERLJMF-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of Wistar rat lens ALR2 using L-glyceraldehyde as substrate preincubated for 10 mins followed by substrate addition and measured for 4 mins by spectrophotometric method
Measurement: IC50 = 4636 nM (pChEMBL 5.329999923706055)
Descriptors: MW 443.36, ALogP 1.44, HBA 8, HBD 3, PSA 138.59, QED 0.52
Compound (SMILES): COc1ccc(F)c(-c2ccc3c(c2F)CC[C@H]3Oc2cccc([C@H](C3CC3)[C@H](C)C(=O)O)c2)c1
InChIKey: PXPSGIAUKBQQGA-GENHPLMOSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Positive allosteric modulation of recombinant human GPR40 expressed in HEK293 cells assessed as increase in [3H]-myo-inositol phosphate accumulation measured after 60 mins in absence of human serum by microbeta counting method
Measurement: EC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 478.54, ALogP 6.92, HBA 3, HBD 1, PSA 55.76, QED 0.38
Compound (SMILES): COCCN1CCN(c2ccc(C(=O)Nc3n[nH]c4nc(-c5c(Cl)c(OC)cc(OC)c5Cl)ccc34)cc2)CC1
InChIKey: CTUHAAWNNBQIDY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 585.49, ALogP 4.97, HBA 8, HBD 2, PSA 104.84, QED 0.28
Compound (SMILES): C[C@@H](O)[C@@H](CO)Nc1c(C(N)=O)cnn2cc(-c3ccccc3)cc12
InChIKey: PRWQQLFMBINSAW-IAQYHMDHSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of GST-tagged JAK1 (unknown origin) using fluoresceinated peptide as substrate measured after 3 hrs by electrophoresis method
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 340.38, ALogP 1.25, HBA 6, HBD 4, PSA 112.88, QED 0.54
Compound (SMILES): CC(C)c1ccc(/C=C/c2nc(NCCN(C)C)c3cc(F)ccc3n2)cc1
InChIKey: GIVPIMDNDFCLHM-KPKJPENVSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin) using TAMRA-Src-tide as substrate measured after 1 hr in presence of ATP at its Km concentration by IMAP-FP assay
Measurement: IC50 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 378.5, ALogP 5.04, HBA 4, HBD 1, PSA 41.05, QED 0.63
Compound (SMILES): CC(C)c1cc(-c2cccc(NC(=O)Nc3cccc(C(F)(F)F)c3)c2)[nH]n1
InChIKey: KMRSFOJOOJIQHU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant (unknown origin)
Measurement: IC50 = 5320 nM (pChEMBL 5.269999980926514)
Descriptors: MW 388.39, ALogP 5.86, HBA 2, HBD 3, PSA 69.81, QED 0.52
Compound (SMILES): CCCn1c(NC(=O)c2cc(C)nn2CC)nc2cc(C(=O)OC)cc(OC)c21
InChIKey: JCECLLWDLSRHBH-UHFFFAOYSA-N
Target: Interferon regulatory factor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14653
Assay: Induction of IRF3 pathway in STING knockout human THP1 cells measured after 20 hrs by luciferase reporter gene assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 399.45, ALogP 3.02, HBA 8, HBD 1, PSA 100.27, QED 0.61
Compound (SMILES): CC(C)Sc1nn([C@@H]2O[C@H](COS(N)(=O)=O)[C@@H](O)[C@@H]2F)c2ncnc(N)c12
InChIKey: GXZMWGQFGQGFLM-GURMABIDSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of ATG7 in human 293HEK cells assessed as inhibition of ATG7:ATG8 thioester formation after 4 hrs by Western blot analysis
Measurement: IC50 = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 422.46, ALogP -0.27, HBA 11, HBD 3, PSA 168.47, QED 0.53
Compound (SMILES): C[C@@H]1CN2c3c(cc4c(N5C[C@H](C)SC5=O)noc4c3F)CC3(C(=O)NC(=O)NC3=O)[C@H]2[C@H](C)O1
InChIKey: VKPFEBWUNOHCOZ-ILMIYZIASA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA gyrase supercoiling activity using relaxed pHOT-1 DNA as substrate after 60 mins by ethidium bromide-based gel electrophoresis
Measurement: IC50 = 12600 nM (pChEMBL 4.900000095367432)
Descriptors: MW 503.51, ALogP 1.92, HBA 9, HBD 2, PSA 134.08, QED 0.56
Compound (SMILES): CC(C)c1cc2c(c(O)c1O)[C@@]1(C(=O)NC(=O)c3ccc(Br)cc3)CCCC(C)(C)[C@@H]1CC2
InChIKey: QEFHCTJPYXRZCQ-CCLHPLFOSA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged GGPPS expressed in Escherichia coli BL21 (DE3) using FPP and [14C] IPP as substrate preincubated for 15 mins with FPP followed by [14C] IPP addition and further incubated for 20 mins by scintillation counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 514.46, ALogP 5.95, HBA 4, HBD 3, PSA 86.63, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cnn5c4CCCC5)n3)nc2)CC1
InChIKey: PDAGDCQXFVQYJZ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human full length GST-tagged CDK6 (1 to 326(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay
Measurement: Ki = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 390.5, ALogP 2.57, HBA 8, HBD 1, PSA 75, QED 0.73
Compound (SMILES): Cc1cccc(-c2[nH]c(CNc3ccccc3)nc2-c2cc3cnccc3s2)n1
InChIKey: MCBWWEZTLDGOCP-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human recombinant GST-tagged ALK5 expressed in Sf9 insect cells using casein as substrate incubated for 60 mins in presence of [33P]-ATP by scintillation counting method
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 397.51, ALogP 5.67, HBA 5, HBD 2, PSA 66.49, QED 0.4
Compound (SMILES): O=C(Nc1n[nH]c2cc(-c3cccc(CNS(=O)(=O)CCC(F)(F)F)c3)ccc12)C1CC1
InChIKey: NTOMZGNNDKIPEH-UHFFFAOYSA-N
Target: BMP-2-inducible protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSY1
Assay: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged BMP2K kinase domain (38 to 345 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assay
Measurement: Ki = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 466.49, ALogP 3.95, HBA 4, HBD 3, PSA 103.95, QED 0.47
Compound (SMILES): Cl.O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1cc2ccccc2o1
InChIKey: RNUVMAJSKKQEHU-XQLHXREKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Displacement of [3H]-Naltrindole from mouse kappa opioid receptor expressed in CHO cells incubated for 1.5 hrs by competitive radioligand binding assay
Measurement: Ki = 1.67 nM (pChEMBL 8.779999732971191)
Descriptors: MW 486.57, ALogP 3.5, HBA 6, HBD 3, PSA 95.17, QED 0.52
Compound (SMILES): CCCCCCCCCCc1ccc(NC(=O)C(=O)N2C[C@@H](Oc3ccc(/C=C/S(=O)(=O)OCC)cc3)[C@H](Oc3ccc(CCS(=O)(=O)OCC)cc3)C2)cc1
InChIKey: CRUPUHJUVOOKRI-RJMOTYGGSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of TCPTP (unknown origin) using pNPP as substrate after 30 mins
Measurement: IC50 = 2160 nM (pChEMBL 5.670000076293945)
Descriptors: MW 813.05, ALogP 7.29, HBA 10, HBD 1, PSA 154.61, QED 0.06
Compound (SMILES): CC(Oc1ccccc1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: CSWAXADHPUYFGC-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L receptor expressed in human HEK293 cells incubated for 1 hr by radioligand binding assay
Measurement: Ki = 1001 nM (pChEMBL 6)
Descriptors: MW 348.84, ALogP 2, HBA 7, HBD 1, PSA 80.4, QED 0.9
Compound (SMILES): CN(CCOc1ccccc1)c1nc(-c2ccncc2)nc2ccccc12
InChIKey: UPJYMERFIKQLSP-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 = 3980 nM (pChEMBL 5.400000095367432)
Descriptors: MW 356.43, ALogP 4.21, HBA 5, HBD 0, PSA 51.14, QED 0.52
Compound (SMILES): COc1cc2c(cc1OC1CCCC1)CC(C(=O)Nc1c(F)cccc1F)N=C2c1ccccc1
InChIKey: FVWDHVVLBZFRFO-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of PDE4D in human U937 cells using [3H]cAMP as substrate incubated for 30 mins
Measurement: IC50 = 26160 nM (pChEMBL 4.579999923706055)
Descriptors: MW 476.52, ALogP 5.7, HBA 4, HBD 1, PSA 59.92, QED 0.5
Compound (SMILES): Nc1cccc(Cl)c1Oc1ccc(CNc2ccc(Cl)cc2)cc1
InChIKey: CSBUGJYMOMQGFR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition and measured for 6 mins by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.26, ALogP 5.98, HBA 3, HBD 2, PSA 47.28, QED 0.55
Compound (SMILES): COCCN1CCN(CCNc2nonc2/C(=N/O)Nc2ccc(F)c(Br)c2)S1(=O)=O
InChIKey: NQGJIPSSKWDBFO-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 expressed in HEK293 cells assessed as N-formylkynurenine formation by measuring kynurenine level incubated for 12 hrs by microplate reader analysis
Measurement: IC50 = 22.2 nM (pChEMBL 7.650000095367432)
Descriptors: MW 522.36, ALogP 1.14, HBA 9, HBD 3, PSA 145.42, QED 0.19
Compound (SMILES): NCc1ncc(S(=O)(=O)c2cccc(-c3ccccc3)c2)s1
InChIKey: ZIFBHKQLIVUBDJ-UHFFFAOYSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 1 hr followed by substrate addition by ROS-Glo assay
Measurement: IC50 = 342 nM (pChEMBL 6.46999979019165)
Descriptors: MW 330.43, ALogP 3.1, HBA 5, HBD 1, PSA 73.05, QED 0.8
Compound (SMILES): COc1ccc(Cl)cc1S(=O)(=O)Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Cl)s4)ccc3o2)cc1
InChIKey: LLRZSRNUUGTTEW-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTPN1 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 610.52, ALogP 6.47, HBA 8, HBD 2, PSA 127.6, QED 0.21
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccccc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC1
InChIKey: SXKKMGOPECZXNY-JJMBJGOUSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at full length human RORgammat expressed in human Jurkat cells assessed as inhibition of constitutive receptor activity incubated for 18 hrs by Gal4-Luc reporter gene assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 635.6, ALogP 6.08, HBA 4, HBD 1, PSA 91.75, QED 0.4
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](Cc3cnc[nH]3)NC(=O)[C@H](CC(=O)O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: XLKCNEKRHSDUDI-HSSWSOOJSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta2/beta3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12391
Assay: Antagonist activity at rat alpha6alpha3beta2beta3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 19.9 nM (pChEMBL 7.699999809265137)
Descriptors: MW 1716.98
Compound (SMILES): CC1=C[C@@]2(C)C(=C(C)[C@H]3[C@@H]4C[C@H](C)C[C@H](C)[C@H]4[C@@H]4Oc5ccc(cc5)C[C@@]5(O)C=C(C(=O)N5)C(=O)[C@@H]2[C@@H]43)[C@H]1C
InChIKey: LLDBYBFRGSYHAF-YSCVJVDNSA-N
Target: Receptor-type tyrosine-protein phosphatase S (SINGLE PROTEIN), Homo sapiens
UniProt: Q13332
Assay: Inhibition of human PTPsigma
Measurement: IC50 = 8400 nM (pChEMBL 5.079999923706055)
Descriptors: MW 527.71, ALogP 5.4, HBA 4, HBD 2, PSA 75.63, QED 0.35
Compound (SMILES): CS(=O)(=O)c1ccc(C(CCCO)=C(c2ccc(F)cc2)c2ccc(F)cc2)cc1
InChIKey: SMXNOJXGSQHUFP-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at human full-length ERbeta expressed in non-human mammalian expression system assessed as inhibition of 17beta-estradiol-induced response measured after 22 to 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 428.5, ALogP 5.1, HBA 3, HBD 1, PSA 54.37, QED 0.53
Compound (SMILES): CCc1cc(-c2cc(C(=O)Nc3cccc(C(F)(F)F)c3)ccc2CC)cc(-c2cnc3cnccn23)c1
InChIKey: XQRIKSVCIIZMIM-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Inhibition of recombinant human GST-tagged DDR2 cytoplasmic domain (427 to 855 residues) expressed in baculovirus expression system using Fluorescein-poly GAT as substrate incubated for 1 hr in presence of ATP by LanthaScreen Eu kinase assay
Measurement: IC50 = 3227 nM (pChEMBL 5.489999771118164)
Descriptors: MW 514.55, ALogP 7.46, HBA 4, HBD 1, PSA 59.29, QED 0.26
Compound (SMILES): CSc1cccc(Nc2nc(-c3ccccc3)nc3ccccc23)c1
InChIKey: HQOYRLKAIJOQPD-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of ABCC1 in human H69AR cells preincubated for 30 mins before calcein AM addition by calcein AM assay
Measurement: IC50 = 3730 nM (pChEMBL 5.429999828338623)
Descriptors: MW 343.46, ALogP 5.76, HBA 4, HBD 1, PSA 37.81, QED 0.48
Compound (SMILES): COc1ccc(NC(=O)/C=C/c2sc(N3CCOCC3)nc2-c2ccc(Cl)cc2)cc1
InChIKey: ALAOOALTZDJNPS-ZHACJKMWSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase2 preincubated for 10 mins followed by CO2 solution addition by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 50400 nM (pChEMBL 4.300000190734863)
Descriptors: MW 455.97, ALogP 4.96, HBA 6, HBD 1, PSA 63.69, QED 0.53
Compound (SMILES): COc1nnc2ccc(N3CCC(c4ccc(CCN5CCN(C)C(=O)[C@H]5C)cc4)CC3)nn12
InChIKey: VKNADHXUWBBIPI-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 463.59, ALogP 2.22, HBA 8, HBD 0, PSA 79.1, QED 0.55
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(CC#N)C3)n(C)c1=O
InChIKey: COFGPVTTZHNCPH-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 274.28, ALogP -1.23, HBA 8, HBD 0, PSA 88.85, QED 0.61
Compound (SMILES): CC[C@@H]1C(=O)N(C)c2cnc(Nc3cc(F)c(C(=O)NCCN4CCN(C)CC4)cc3OCCO)nc2N1C1CCCC1
InChIKey: QMGCOLHGTKYVOP-XMMPIXPASA-N
Target: Serine/threonine-protein kinase PLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYY3
Assay: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 167.3 nM (pChEMBL 6.78000020980835)
Descriptors: MW 598.72, ALogP 2.21, HBA 10, HBD 3, PSA 126.4, QED 0.35
Compound (SMILES): COc1cc(NCc2cc3cc(Cl)ccc3[nH]c2=O)cc(OC)c1C#N
InChIKey: QMMJQMZFINBAFK-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 μM Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 369.81, ALogP 3.68, HBA 5, HBD 2, PSA 87.14, QED 0.72
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)NC34CCC(C(N)=O)(CC3)CC4)nc3cnc4[nH]ccc4c32)CC1
InChIKey: VGQGFYCOZCNACG-RWSJPRBTSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2/JAK2 in human PBMC assessed as reduction in GM-CSF-induced STAT5 phosphorylation pre-incubated for 30 mins before GM-CSF stimulation for 30 mins AlphaLISAassay
Measurement: IC50 = 1962 nM (pChEMBL 5.710000038146973)
Descriptors: MW 487.61, ALogP 3.79, HBA 6, HBD 3, PSA 142.48, QED 0.48
Compound (SMILES): NS(=O)(=O)c1cccc(NC(=S)NC(=O)c2ccc([N+](=O)[O-])cc2)c1
InChIKey: ROYDNDHSEWMZDS-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human erythrocyte carbonic anhydrase-1 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: IC50 = 60.46 nM (pChEMBL 7.21999979019165)
Descriptors: MW 380.41, ALogP 1.37, HBA 6, HBD 3, PSA 144.43, QED 0.41
Compound (SMILES): Cc1c(C)c2ccc(OCC3CCCN(Cc4cccc(Cl)c4)C3)cc2oc1=O.Cl
InChIKey: DVHSQXOMDRSHCZ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB expressed in microsomes of baculovirus-infected insect cell using kynuramine as substrate preincubated for 20 mins followed by protein addition measured after 30 mins by fluorescence assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 411.93, ALogP 5.35, HBA 4, HBD 0, PSA 42.68, QED 0.53
Compound (SMILES): Fc1ccc(Cl)cc1-c1cc(Nc2ccncc2)c2cc[nH]c2n1
InChIKey: OCAIEQPVLOKCDM-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) using fluorescein-labeled peptide substrate incubated for 90 mins by TR-FRET assay
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 338.77, ALogP 5.16, HBA 3, HBD 2, PSA 53.6, QED 0.54
Compound (SMILES): Oc1ccccc1CNC1CCN(Cc2ccccc2)CC1
InChIKey: PEZATUMKVOFZTR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine iodide as substrate pre-incubated for 10 mins followed by substrate addition and measured for 6 mins by Ellman's method
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 296.41, ALogP 3.15, HBA 3, HBD 2, PSA 35.5, QED 0.89
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5cccc(F)c5)CC4)cn3)nccc12
InChIKey: FJLXFYHDLHZPQK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: O94953
Assay: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 418.48, ALogP 3.07, HBA 6, HBD 1, PSA 79.7, QED 0.54
Compound (SMILES): CCCOc1cc(NC(=O)C2CN(C#N)CCO2)ccc1-c1ccn[nH]1
InChIKey: BLLSNBWUWXCFJQ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: USP30 Biochemical IC50 Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 355.4, ALogP 1.99, HBA 6, HBD 2, PSA 103.27, QED 0.77
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)C(=O)N1CCOCC1
InChIKey: BFQMUXBMPJZLIR-QPWGPPCNSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of 20S proteosome beta 2 purified from human HCT116 cells using Boc-LRR-AMC as substrate incubated for 30 to 120 mins by fluorimetry
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 590.76, ALogP 2.61, HBA 7, HBD 4, PSA 146.3, QED 0.25
Compound (SMILES): COc1cccc(CNC(=O)c2ccc(-c3ccncc3)cc2)c1OC
InChIKey: JQMRBDRBWNQOMI-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of GST-fused human recombinant ROCK2 (11 to 552 residues) expressed in Spodoptera frugiperda insect cells using STK S2 peptide substrate and 33P-ATP after 60 mins by HTRF assay
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 348.4, ALogP 3.7, HBA 4, HBD 1, PSA 60.45, QED 0.74
Compound (SMILES): COc1ccc(-n2c(-c3ccc(C#N)c(F)c3)nc(C(=O)N3CCC[C@@H](N)C3)c2C)cc1
InChIKey: UYHUORYPWSIYFP-GOSISDBHSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 in human THP1 cells assessed as induction of CD11b expression after 4 days by LIVE/DEAD violet staining based FACS analysis
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 433.49, ALogP 3.43, HBA 6, HBD 1, PSA 97.17, QED 0.68
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@](C)(NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)CNC(C)=O)C(C)C)CCC/C=C/CCC[C@@](C)(C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: UKXNLIZYDHRVRB-UZYBZMBHSA-N
Target: Relaxin-3 receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSD7
Assay: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay
Measurement: EC50 = 11.75 nM (pChEMBL 7.929999828338623)
Descriptors: MW 2544.01
Compound (SMILES): C[C@@H]1[C@H](NC(=O)c2ccc(-c3ccc(F)cc3)cn2)CCN1C#N
InChIKey: SBWGJUSHWMJPLJ-MLGOLLRUSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 324.36, ALogP 2.56, HBA 4, HBD 1, PSA 69.02, QED 0.88
Compound (SMILES): N#CN1CC[C@@H](NS(=O)(=O)N2CCc3cc(-c4ccccc4)ccc32)C1
InChIKey: CQXJRHUVXHVCBE-GOSISDBHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 368.46, ALogP 2.11, HBA 4, HBD 1, PSA 76.44, QED 0.84
Compound (SMILES): CC1(C)CCc2cc3c(cc2N1)NC(C#N)C=C3C(F)(F)F
InChIKey: MYOJSDYCLRRKBG-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Inhibition of human androgen receptor
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 307.32, ALogP 4.09, HBA 3, HBD 2, PSA 47.85, QED 0.76
Compound (SMILES): CCOC(=O)NC(=O)c1ccsc1NC(=O)c1nc2cnccc2s1
InChIKey: JCOQDKZVKXILLW-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate after 30 mins by in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 376.42, ALogP 2.89, HBA 8, HBD 2, PSA 110.28, QED 0.72
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)NCc2cn(Cc3cccc(Br)c3)nn2)C[C@H](N)[C@H]1NC(C)=O
InChIKey: FCYBBKDNJLIMKE-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 = 2320 nM (pChEMBL 5.630000114440918)
Descriptors: MW 533.47, ALogP 2.44, HBA 7, HBD 3, PSA 124.16, QED 0.43
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: QFFQWBOXUYJESF-JHGPBYKISA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1805.05
Compound (SMILES): Cc1c(N2CCN(Cc3cnccn3)CC2)c(=O)n(C[C@H](N)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
InChIKey: OSDZSMPBICHFGX-SANMLTNESA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Displacement of [125I]D-Trp6-LHRH from human GnRH receptor expressed in CHO-K1 cell membranes incubated for 1 hr by competitive binding assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 597.62, ALogP 3.34, HBA 9, HBD 1, PSA 102.28, QED 0.31
Compound (SMILES): Clc1cccc(-c2cn(Cc3ccc(-c4cccnc4)cc3)nn2)c1
InChIKey: DTIBDUZHSDASKY-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 = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 346.82, ALogP 4.71, HBA 4, HBD 0, PSA 43.6, QED 0.54
Compound (SMILES): O=C(O)[C@H]1CNC[C@@H](N/N=C/c2cc(F)ccc2-c2ccc(Cl)cc2)C1
InChIKey: MATCLQIZQUZJIL-GOUPHMKNSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK cells assessed as reduction in [3H]GABA uptake by measuring remaining [3H]GABA uptake levels preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by microbeta liquid scintillation counting analysis
Measurement: IC50 = 5370.32 nM (pChEMBL 5.269999980926514)
Descriptors: MW 375.83, ALogP 3.13, HBA 4, HBD 3, PSA 73.72, QED 0.55
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)C[C@H](C)N(Cc2cccc(C(=O)O)c2)C3=O)cc(C)c1Cl
InChIKey: SBXXUMARFCZQCG-QFIPXVFZSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of FITC-labeled Bim peptide binding to His6-tagged MBP-fused Mcl-1 (unknown origin) by fluorescence polarization assay
Measurement: Ki = 9.9 nM (pChEMBL 8)
Descriptors: MW 673.64, ALogP 8.34, HBA 6, HBD 1, PSA 89.59, QED 0.16
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)c1cncc(N2CC3CC(C2)N3)c1
InChIKey: GMZBJZZVVRFIAN-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Displacement of [125I]alpha-bungarotoxin from alpha7nAChR in rat hippocampus membrane
Measurement: Ki = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 328.8, ALogP 2.54, HBA 4, HBD 2, PSA 57.26, QED 0.91
Compound (SMILES): C#CCOc1ccc(/C=C2\SC(=S)NC2=O)cc1
InChIKey: QREKGPHPIGGKCE-FLIBITNWSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX1 catalytic activity using arachidonic acid as substrate pre-incubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA method
Measurement: IC50 = 11600 nM (pChEMBL 4.940000057220459)
Descriptors: MW 275.35, ALogP 2.19, HBA 4, HBD 1, PSA 38.33, QED 0.52
Compound (SMILES): Cc1ccc(C(SCC(=O)NO)P(=O)(O)O)cc1
InChIKey: FBMPGIWVPZIABL-UHFFFAOYSA-N
Target: 1-deoxy-D-xylulose 5-phosphate reductoisomerase (SINGLE PROTEIN), Escherichia coli
UniProt: W8T2T2
Assay: Inhibition of recombinant Escherichia coli IspC expressed in Escherichia coli M15 using 1-deoxy-D-xylulose 5-phosphate as substrate by photometric assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 291.26, ALogP 1.41, HBA 4, HBD 4, PSA 106.86, QED 0.37
Compound (SMILES): CCOc1ccc(-c2ccc(CCCc3nn(-c4ccc(C(F)(F)F)cc4)c(=O)n3-c3cccnc3)cc2)cc1CC(=O)O
InChIKey: KXHPLSHTOABRTL-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Antagonist activity at recombinant human PPARalpha assessed as inhibition of GW7647-induced receptor activation after overnight incubation by cell-based luciferase reporter gene assay
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 602.61, ALogP 6.31, HBA 7, HBD 1, PSA 99.24, QED 0.19
Compound (SMILES): COc1ccc(Cn2cc(CCC(=O)Nc3ccc(CCCCc4nnc(NC(=O)Cc5ccccn5)s4)nn3)nn2)cc1OC
InChIKey: XADHNQXCNDZIKP-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of human GLS1 expressed in Escherichia coli strain BL21 (DE3)pLysS pre-incubated for 10 mins before glutamine addition and measured after 60 mins by bovine liver glutamate dehydrogenase based coupled enzyme assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 642.75, ALogP 3.7, HBA 13, HBD 2, PSA 171.82, QED 0.15
Compound (SMILES): Cc1c(C#Cc2cnc3cnc(-c4ccc(N)cc4)cn23)cccc1C(=O)Nc1cc(CN2CCN(C)CC2)cc(C(C)C)c1
InChIKey: KDFREDAEEQQCFD-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of recombinant human His-tagged TrkB catalytic domain (526 to 838 residues) expressed in baculovirus expression system using tyr 01 as substrate incubated for 1 hr by Z'-Lyte assay
Measurement: IC50 = 10.47 nM (pChEMBL 7.980000019073486)
Descriptors: MW 597.77, ALogP 5.81, HBA 7, HBD 2, PSA 91.79, QED 0.19
Compound (SMILES): Cc1cc(-c2ccc(C(F)(F)F)cn2)[nH]c1C(=O)N[C@@H](CN)c1ncc(CO)s1
InChIKey: BILBXEUAJZPBIW-AWEZNQCLSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by NADPH addition and measured for 10 to 30 mins by LC-MS/MS analysis
Measurement: IC50 = 85400 nM (pChEMBL 4.070000171661377)
Descriptors: MW 425.44, ALogP 2.78, HBA 6, HBD 4, PSA 116.92, QED 0.48
Compound (SMILES): COc1ccc2nc(C)cc(NNC(=O)c3ccc(F)cc3)c2c1
InChIKey: DRVAZFUNEVUHRZ-UHFFFAOYSA-N
Target: Ribosyldihydronicotinamide dehydrogenase [quinone] (SINGLE PROTEIN), Homo sapiens
UniProt: P16083
Assay: Inhibition of NQO2 in human SKOV3 cells assessed as reduction in cell viability in presence of 1 uM CB1954 and EPR incubated for 24 hrs measured after 72 hrs by MTT assay
Measurement: IC50 = 74000 nM (pChEMBL 4.130000114440918)
Descriptors: MW 325.34, ALogP 3.45, HBA 4, HBD 2, PSA 63.25, QED 0.72
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)NC(C)(C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: TUIBDAKMRHWAJO-IQXXSZHYSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1577.74
Compound (SMILES): CC(C)(C)NC(=O)[C@H](c1c(C(=O)O)[nH]c2cc(Cl)ccc12)N(C=O)Cc1ccc(OCc2ccc(Cl)cc2)cc1
InChIKey: PESUUIPTWNTJKA-MHZLTWQESA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of p53 protein binding to MDM2 (unknown origin) by western blot analysis
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 582.48, ALogP 6.37, HBA 4, HBD 3, PSA 111.73, QED 0.19
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)C(CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(=O)NCC(=O)NCC(=O)N[C@H](C(=O)O)C(C)C
InChIKey: PUQKXRYUFLFLJY-BHGPCQQHSA-N
Target: BTB/POZ domain-containing protein KCTD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96CX2
Assay: Displacement of TAMRA-AAG-SLQLPILHHAYLPSIGGV from recombinant human 6X His-tagged KCTD12 T1 domain (27 to 131 residues) expressed in Escherichia coli BL21 DE3 cells by fluorescence polarization assay
Measurement: Ki = 37500 nM (pChEMBL 4.429999828338623)
Descriptors: MW 1958.3
Compound (SMILES): Cl.O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2cccc(C(F)(F)F)c2)CC1
InChIKey: XZXOYWCOHDIXNL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1AR expressed in HEK293 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 481.56, ALogP 6.2, HBA 3, HBD 0, PSA 26.79, QED 0.36
Compound (SMILES): COc1ccccc1C1CCN(c2nc(C3CC3)nc3ccc(N4CC[C@@H](O)C4)cc23)CC1
InChIKey: SQSASMLYFCBHPV-OAQYLSRUSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: NTR1 Ca2+ Flux Dose Response: NTSR1 (NTR1) CHO cells are plated in 20 uL of assay media containing Ham's F12 supplemented with 10% fetal bovine serum and 0.4 mg/mL G418 at a concentration of 1.0×106 cells per mL into black, 384-well assay plates with clear bottoms using a Multidrop liquid handler. Assay plates are incubated at 37° C. in 5% CO2. The next day, the assay plates are aspirated to remove growth media and washed once with 20 uL of DPBS. The DPBS is then aspirated from the assay plate and replaced with 25 uL of Fluo-4 NW calcium dye prepared according to the manufacturer's recommendations then the plates are incubated for 1 hour at 37° C. Following the incubation in the presence of dye, the assay is run on a Molecular Devices FlexStation-III using 494 excitation and 516 emission wavelengths set to read for 90 seconds with the addition at 18 seconds of 5 uL of 6× final concentration of test compounds and peptide control diluted in assay media containing 0.1% BSA and no more than 9% DMSO to yield a maximum final DMSO concentration of 1.5%. Percent activation is calculated based on the maximum response minus the minimum value over the time course relative to the neurotensin 1 control peptide at 100 pM. EC50 values were calculated for those compounds tested in 8-point dose dependent response.
Measurement: EC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 444.58, ALogP 4.47, HBA 6, HBD 1, PSA 61.72, QED 0.63
Compound (SMILES): CCOC(=O)c1cccc(Nc2cc(OC)cc3ccccc23)c1
InChIKey: UCMCQFKDMRVNDS-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of N-terminal His6-tagged human CDC25A (336 to 508 residues) expressed in Escherichia coli BL21(DE3) cells using OMFP as substrate by double reciprocal Lineweaver-Burk plot analysis
Measurement: Ki = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 321.38, ALogP 4.77, HBA 4, HBD 1, PSA 47.56, QED 0.69
Compound (SMILES): O=S(=O)(Nc1ccc2oc(-c3ccccc3)nc2c1)c1ccc(F)cc1
InChIKey: ZWOGDTJABZSCJD-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTPN1 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 78000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 368.39, ALogP 4.43, HBA 4, HBD 1, PSA 72.2, QED 0.58