lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C#CCN1CCC(/C=C/c2ccc(F)cc2)CC1
InChIKey: IMLUTNFPMZSEGM-ONEGZZNKSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Reversible inhibition of recombinant human MAOB expressed in Pichia pastoris using varying levels of kynuramine as substrate measured after 5 mins by Michaelis-Menten equation analysis
Measurement: Ki = 1920 nM (pChEMBL 5.71999979019165)
Descriptors: MW 243.32, ALogP 3.18, HBA 1, HBD 0, PSA 3.24, QED 0.74
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1ccc(C(c2ccccc2)c2ccccc2)s1)C(=O)O
InChIKey: XYFDAJRUBYOTRD-SFHVURJKSA-N
Target: C3a anaphylatoxin chemotactic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16581
Assay: Antagonist at C3a receptor in human LAD2 cells assessed as inhibition of C3a-induced beta-hexosaminidase release preincubated for 30 mins followed by C3a addition
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 450.56, ALogP 3.37, HBA 4, HBD 5, PSA 128.3, QED 0.18
Compound (SMILES): C/C=C/C(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: MAEVSXHQLPMRFL-SNAWJCMRSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in vitamin D3 differentiated human THP1 cells assessed as inhibition of FCgammaR-induced IL8 production measured after 24 hrs by HTRF assay
Measurement: IC50 = 263 nM (pChEMBL 6.579999923706055)
Descriptors: MW 521.57, ALogP 4.86, HBA 6, HBD 2, PSA 110.44, QED 0.39
Compound (SMILES): OC(CC1c2c(F)cccc2-c2cncn21)C1CCC(F)(F)CC1
InChIKey: FPKRCRNJVIHTNG-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using midazolam as substrate
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 336.36, ALogP 4.17, HBA 3, HBD 1, PSA 38.05, QED 0.91
Compound (SMILES): Fc1ccccc1-c1cc(Nc2ccncc2)c2cc[nH]c2n1
InChIKey: ICADYKQQHFVDME-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 304.33, ALogP 4.51, HBA 3, HBD 2, PSA 53.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(CN2CCN(S(=O)(=O)Nc3ccc(SCCc4ccccc4)cc3C(=O)O)CC2)cc1
InChIKey: WIWNZUYJVZDDEH-UHFFFAOYSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Inhibition of N-terminal His6-tagged human Bfl-1 (1 to 151 residues), expressed in Escherichia coli Rosetta2 DE3 by fluorescent labeled FAM-Bid peptide based fluorescence polarization assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 567.78, ALogP 5.49, HBA 5, HBD 2, PSA 89.95, QED 0.32
Compound (SMILES): Cc1ccc(-c2c(C(=O)N(CCC(N)=O)Cc3ccc(OC(C)C)cc3)cnn2Cc2ccccc2)cc1
InChIKey: SCOFDRPTZSMXDV-UHFFFAOYSA-N
Target: Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl-diphosphate specific) (SINGLE PROTEIN), Acinetobacter baumannii
UniProt: V5VCK8
Assay: Inhibition of hexa-histidine tagged Acinetobacter baumannii UppS expressed in Escherichia coli assessed as reduction in IPP condensation to growing prenyl chain by measuring pyrophosphate production
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 510.64, ALogP 5.21, HBA 5, HBD 1, PSA 90.45, QED 0.3
Compound (SMILES): Cc1nc(C(=O)Nc2cc(-c3cnc(Cl)c(NS(=O)(=O)c4ccccc4)c3)cc3[nH]ncc23)cs1
InChIKey: BIFBJBYMVYPTPW-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin)
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 525.02, ALogP 5.1, HBA 7, HBD 3, PSA 129.73, QED 0.26
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3cccc(B(O)O)c3)S(C)(=O)=O)c(C3CC3)cc12
InChIKey: BCJAXELMGXMCGE-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1b NS5B RNA dependent RNA polymerase C316N mutant infected in human HuH7 Lunet replicon cells assessed as reduction in viral replication after 48 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 522.36
Compound (SMILES): OCc1cccc(-c2ccc3nc(-c4ccc(Cl)cc4)cn3c2)c1
InChIKey: IHUPABWARJLUMA-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 334.81, ALogP 4.81, HBA 3, HBD 1, PSA 37.53, QED 0.58
Compound (SMILES): N#Cc1ccc2c([C@@H](CC(F)(F)F)c3cccs3)c(-c3ccccc3)[nH]c2c1
InChIKey: ZQTJTBWIFLKGEE-KRWDZBQOSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulation of human Gi/Go-coupled CB1 receptor expressed in CHOK1 cells assessed as increase in CP55940-induced inhibition of forskolin-stimulated cAMP production preincubated for 30 mins followed by CP55940 addition and measured after 30 to 60 mins by Hit-hunter assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 396.44, ALogP 6.85, HBA 2, HBD 1, PSA 39.58, QED 0.4
Compound (SMILES): C=CC(=O)N1CC[C@H]1COc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: VNHKOUCVWYOOAC-IBGZPJMESA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human B cells assessed as reduction in anti-IgM/IL4-stimulated CD69 expression on B cells preincubated for 60 mins followed by anti-IgM antibody/IL4 stimulation and measured after 16 hrs by flow cytometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 519.55, ALogP 4.61, HBA 6, HBD 2, PSA 110.44, QED 0.42
Compound (SMILES): Nc1nc(N/N=C/c2ccc(OCc3ccc(F)cc3)cc2)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
InChIKey: UYHNVMOFUPUSHA-JKXQLKLBSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Agonist activity at human adenosine receptor A2A expressed in HEK293 cells assessed as cAMP accumulation incubated for 30 mins by Eu-cAMP tracer-based Envision plate reader analysis
Measurement: EC50 = 4.05 nM (pChEMBL 8.390000343322754)
Descriptors: MW 509.5, ALogP 1.18, HBA 12, HBD 5, PSA 173.16, QED 0.17
Compound (SMILES): COC1Cc2ccccc2[C@]2(CC[C@@H](N(C)CC3CCCCC3)CC2)O1
InChIKey: MBRMOGQHSBUGKH-FXCIWXGGSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H](+)-pentazocine from sigma 1 receptor in human RPMI8226 cell membranes incubated for 2 hrs under shaking by scintillation counting analysis
Measurement: Ki = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 357.54, ALogP 4.88, HBA 3, HBD 0, PSA 21.7, QED 0.77
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: VAGFPILJLLZTKR-ISSCZAFUSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Agonist activity at human amylin receptor expressed in BHK570 cells co-expressing RAMP3 assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.093 nM (pChEMBL 10.029999732971191)
Descriptors: MW 3736.23
Compound (SMILES): Cc1ccc(C)c(NC(=O)Nc2ccc(CCc3nc4ccccc4n3C)cc2)c1
InChIKey: AUYBBRVFPGVHFD-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human full length TRKB expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 398.51, ALogP 5.62, HBA 3, HBD 2, PSA 58.95, QED 0.46
Compound (SMILES): CCCCCn1/c(=N/C(=O)c2ccc(C(F)(F)F)cc2)sc2ccccc21
InChIKey: ZKQOBFAUDJCQMQ-CLCOLTQESA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at N-terminal Flag epitope tagged CB2 (unknown origin) expressed in HTLA cells assessed as increase of beta-arrestin recruitment by Tango assay
Measurement: EC50 = 2511.8 nM (pChEMBL 5.599999904632568)
Descriptors: MW 392.45, ALogP 5.65, HBA 3, HBD 0, PSA 34.36, QED 0.52
Compound (SMILES): CC1CCCc2c(-c3ccc(Cl)cc3)nc(N)nc21
InChIKey: UJEILDLSZCSTQA-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Agonist activity at recombinant human Gs-coupled H2 receptor expressed in HEK293T cells assessed as inhibition of forskolin-stimulated cAMP accumulation preincubated for 10 to 15 followed by forskolin-stimulation by Glo-sensor assay
Measurement: EC50 = 77.62 nM (pChEMBL 7.110000133514404)
Descriptors: MW 273.77, ALogP 3.82, HBA 3, HBD 1, PSA 51.8, QED 0.86
Compound (SMILES): Cc1c(C(=O)N2CCC(C3CC3)CC2)cnn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: MVNRRKJQPQGBDT-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 367.45, ALogP 2.01, HBA 5, HBD 1, PSA 83.88, QED 0.9
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3C(F)(F)F)c3c(F)cccc32)cc1
InChIKey: CWHKOHWOAVTDCW-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 22600 nM (pChEMBL 4.650000095367432)
Descriptors: MW 461.8, ALogP 6.37, HBA 3, HBD 1, PSA 59.3, QED 0.28
Compound (SMILES): C=CC(=O)Nc1ccc(CNc2cc(Nc3ccc(N4CCN(C)CC4)cc3)ncn2)cc1
InChIKey: PEKRZGDPNKNLBI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and further incubated for 30 mins and subsequently measured after 1 hr by HTRF assay
Measurement: IC50 = 731 nM (pChEMBL 6.139999866485596)
Descriptors: MW 443.56, ALogP 3.71, HBA 7, HBD 3, PSA 85.42, QED 0.46
Compound (SMILES): CO[C@H](CN1CC[C@@]2(C)c3cc(O)ccc3C[C@@H]1[C@@H]2C)c1ccccc1
InChIKey: CYJVECUASMVXNS-RAKGIWIYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from DOR in rat brain membranes incubated for 45 mins by liquid scintillation counting
Measurement: Ki = 2.59 nM (pChEMBL 8.59000015258789)
Descriptors: MW 351.49, ALogP 4.3, HBA 3, HBD 1, PSA 32.7, QED 0.89
Compound (SMILES): COc1ncc(-c2ccc3ncnc(NCCN4CCOCC4)c3c2)cc1C#N
InChIKey: GNJXDCIDKCOMEA-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) assessed as reduction in ATP depletion using lipid substrate after 40 mins by Kinase-Glo luminescent assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 390.45, ALogP 2.32, HBA 8, HBD 1, PSA 96.19, QED 0.68
Compound (SMILES): Cc1cc(NC(=O)c2nn(C3CCN(C(=O)NC(C)(C)C)CC3)c3ccccc23)ccc1NC(=O)c1cnn2ccccc12
InChIKey: ZLXUXNOXPKFKQF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ZAP-70 (SINGLE PROTEIN), Homo sapiens
UniProt: P43403
Assay: Effect on ZAP70 phosphorylation in human Jurkat cells pre-incubated for 30 mins followed by anti-CD3/CD28 stimulation measured after 10 mins
Measurement: EC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 592.7, ALogP 5.64, HBA 7, HBD 3, PSA 125.66, QED 0.24
Compound (SMILES): CC(=O)c1cccc(-c2ccc3c(c2)CCNC3=O)c1
InChIKey: DCVQXQUORFSGCT-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of full length human His-SUMO-tagged PARP11 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 265.31, ALogP 2.84, HBA 2, HBD 1, PSA 46.17, QED 0.85
Compound (SMILES): CC1(C)C(N)=Nc2cc(OCCCN3Cc4ccc(OCc5cn(CC(=O)N6CCC(CCN7CCCC7)CC6)nn5)cc4C3)c(OCC3CC3)cc21
InChIKey: UTRTZBSUZOWVCN-UHFFFAOYSA-N
Target: Spindlin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y657
Assay: Binding affinity to recombinant human His-tagged SPIN1 (49 to 262 residues) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry
Measurement: Kd = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 724.95, ALogP 5.44, HBA 11, HBD 1, PSA 123.57, QED 0.19
Compound (SMILES): COc1ccc(NC(=O)c2cccc(-c3nc(NC(P(=O)(O)O)P(=O)(O)O)c4ccsc4n3)c2)cc1F
InChIKey: XPPGEOUCUMGOGK-UHFFFAOYSA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: Inhibition of human N-terminal His6-tagged GGPPS Y246D mutant expressed in Escherichia coli BL21(DE3) using [14C]-IPP and FPP as substrates after 10 mins by scintillation counting
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 568.42, ALogP 3.81, HBA 8, HBD 6, PSA 191.2, QED 0.17
Compound (SMILES): Cc1cc(S(N)(=O)=O)c(C)cc1N1CC(C(=O)O)CC1=O
InChIKey: MTHLUECOFDPPBS-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human CA4 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 312.35, ALogP 0.39, HBA 4, HBD 2, PSA 117.77, QED 0.84
Compound (SMILES): O=C(/C=C/c1cccn(CCc2ccc3ccccc3c2)c1=O)NO
InChIKey: XQXZIMLBLPDARP-MDZDMXLPSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of recombinant full-length human HDAC3/NCOR2 using RHKK(Ac) as substrate measured after 2 hrs by fluorescence assay
Measurement: IC50 = 69.88 nM (pChEMBL 7.159999847412109)
Descriptors: MW 334.38, ALogP 2.76, HBA 4, HBD 2, PSA 71.33, QED 0.43
Compound (SMILES): CC(=O)C1=C(O)C(=O)N(c2ccc(Br)cc2F)C1C1CCCCC1
InChIKey: ARZUMHIABDHPTN-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Antagonist activity at human TEV protease site linked CCR1 expressed in human U20S cell membranes co-expressing Gal4-VP16 transcription factor assessed as reduction in CCL3-induced G-protein activation preincubated for 30 mins in presence of CCL3 followed by incubation of 90 mins by [35S]GTPgammaS binding assay
Measurement: IC50 = 549.54 nM (pChEMBL 6.260000228881836)
Descriptors: MW 396.26, ALogP 4.28, HBA 3, HBD 1, PSA 57.61, QED 0.83
Compound (SMILES): CC(C)(C)N1C(=O)C=C(c2cccs2)S1(=O)=O
InChIKey: ZEJXILZKNWYIPA-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibitory constant preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 220.8 nM (pChEMBL 6.659999847412109)
Descriptors: MW 271.36, ALogP 2.06, HBA 4, HBD 0, PSA 54.45, QED 0.79
Compound (SMILES): CCCN(CCCCNC(=O)c1cc2ccccc2[nH]1)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: XQXLIZUFYLRIQF-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D3 receptor (unknown origin) measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 468.04, ALogP 5.86, HBA 3, HBD 2, PSA 57.36, QED 0.33
Compound (SMILES): COC(=O)[C@@H]1CC(=O)N(c2ccc(S(N)(=O)=O)cc2)[C@H]1c1ccc(Cl)cc1
InChIKey: XLJGLKFOOZEQKH-WBVHZDCISA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 408.86, ALogP 2.25, HBA 5, HBD 1, PSA 106.77, QED 0.78
Compound (SMILES): CCn1ncc2c(NC3CCCCC3)c(C(=O)NCCNc3c4c(nc5cc(Cl)ccc35)CCCC4)cnc21
InChIKey: PUNJQTISEGWDHW-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of recombinant human PDE4D2 catalytic domain (86 to 413 residues) expressed in Escherichia coli BL21 codonplus cells using [3H]cAMP as substrate preincubated for 15 mins followed by substrate addition by liquid scintillation counting method
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 546.12, ALogP 6.12, HBA 7, HBD 3, PSA 96.76, QED 0.23
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(=O)N[C@H](CC(=O)O)C(=O)O)cc2)n1)[C@@H](CC)N(O)C=O.O=C(O)C(F)(F)F
InChIKey: MZWSNHXLAFIRCI-MZKZWTLCSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 599.64, ALogP 2.03, HBA 8, HBD 6, PSA 215.33, QED 0.05
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](C)NC(=O)CN2CCOCC2)C(=O)N[C@@H](CCC2CCCCC2)C(=O)[C@@]2(C)CO2)cc1
InChIKey: XOVCQLITIBRPQB-ZBCYONBYSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of 20S constitutive proteasome beta 2 trypsin-like activity in human Raji cell lysates after 1 hr by competitive ABPP assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 600.76, ALogP 1.76, HBA 8, HBD 3, PSA 138.6, QED 0.26
Compound (SMILES): Fc1ccc(SCCCN2CCCN(c3ccc(Cl)cn3)CC2)cc1
InChIKey: BLMUCJBVVUARNX-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement [3H]-Pentazocine from sigma 1 receptor (unknown origin) expressed in HEK cell membranes
Measurement: Ki = 7.244 nM (pChEMBL 8.140000343322754)
Descriptors: MW 379.93, ALogP 4.57, HBA 4, HBD 0, PSA 19.37, QED 0.54
Compound (SMILES): CSc1nn([C@@H]2O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: KSULIUAOMXPISB-RPKMEZRRSA-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 = 431 nM (pChEMBL 6.369999885559082)
Descriptors: MW 392.42, ALogP -2.03, HBA 12, HBD 4, PSA 188.7, QED 0.41
Compound (SMILES): C[C@@]1(Cc2ccc(C#N)cc2)C(=O)N(c2cc(Cl)cc(Cl)c2)c2ncc(C(=O)NC3(c4nc(C5CCC5)no4)CC3)n21
InChIKey: VATLFUUMDRXLTK-GDLZYMKVSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000549a TMEM97
Measurement: Ki = 557.65 nM (pChEMBL 6.25)
Descriptors: MW 602.48, ALogP 5.77, HBA 8, HBD 1, PSA 129.94, QED 0.28
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NC(=O)CCc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: MQDLMPVZWKXFOG-NYZPMSFKSA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Inhibition of bovine thrombin using Tos-Gly-Pro-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 8795 nM (pChEMBL 5.059999942779541)
Descriptors: MW 771.92, ALogP 2.18, HBA 8, HBD 7, PSA 201.85, QED 0.1
Compound (SMILES): CC(=O)O.CNc1nc(Nc2cnc(C#N)c(O[C@@H]3CCCNC3)c2)ncc1-c1cnn(C)c1
InChIKey: GZTCTVFBVJLJOM-XFULWGLBSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant human C-terminal His-tagged FLT3 (M1 to N541 residues) expressed in HEK293 cells using biotin-labelled STK substrate-1 as substrate incubated for 60 mins by HTRF assay
Measurement: IC50 = 100.45 nM (pChEMBL 7)
Descriptors: MW 405.47, ALogP 2.06, HBA 10, HBD 3, PSA 125.6, QED 0.56
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=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: PRPVVMSCQSOWKN-LWMCYQQMSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Antagonist activity at rat alpha3beta2 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 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 1652.88
Compound (SMILES): CNCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(N)=O)C(C)C
InChIKey: MJQQGUJPWJCFMO-PITCCTKHSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 904.04, ALogP -2.11, HBA 12, HBD 13, PSA 351.97, QED 0.03
Compound (SMILES): Cc1cc(C)nc(NS(=O)(=O)c2ccc(NC(=O)NC(=O)c3ccc(Cl)cc3Cl)cc2)n1
InChIKey: COTBDKMEUUNJTI-UHFFFAOYSA-N
Target: StAR-related lipid transfer protein 7, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQZ5
Assay: Inhibition of StarD7 (unknown origin) using NBD-PC and donor and acceptor small unilamellar vesicles by fluorescence quench assay
Measurement: IC50 = 63000 nM (pChEMBL 4.199999809265137)
Descriptors: MW 494.36, ALogP 4.16, HBA 6, HBD 3, PSA 130.15, QED 0.49
Compound (SMILES): C=CC(=O)N1CCC(Cn2nc(Br)c3c(N)ncnc32)CC1
InChIKey: QSWMNWOCZWNPPO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 catalytic domain (809 to 1153+9 residues) expressed in baculovirus expression system using TK-biotin as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 90.1 nM (pChEMBL 7.039999961853027)
Descriptors: MW 365.24, ALogP 1.6, HBA 6, HBD 1, PSA 89.93, QED 0.83
Compound (SMILES): COc1ccccc1NC(=O)Nc1nnc(SCc2cc(=O)n3cccc(C)c3n2)s1
InChIKey: UOUHOXFDGOKEPE-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of human full length TRKA expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 454.54, ALogP 3.8, HBA 9, HBD 2, PSA 110.51, QED 0.34
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)CS(=O)(=O)CC3)cc1
InChIKey: JTWSNIOCMRULQH-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 using fluorogenic HDAC substrate
Measurement: IC50 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 370.43, ALogP 2.28, HBA 5, HBD 2, PSA 88.4, QED 0.55
Compound (SMILES): COc1nc(C#N)ccc1N[C@@H](C)c1cc2cc(Cl)ccc2[nH]c1=O
InChIKey: LXAVQRJBWNUBTP-JTQLQIEISA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Cellular 2-HG Assay Using HCT116 Mutant IDH1 Cells: HCT116 isogenic IDH1-R132H and IDH1-R132C mutant cells were cultured in growth media (McCoy's 5 A, 10% fetal bovine serum, 1× antibiotic-antimycotic solution and 0.3 mg/mL G418) in 5% CO2 in an incubator at 37° C. To prepare the assay, cells were trypsinized and resuspended in assay media (McCoy's 5 A with no L-glutamine, 10% fetal bovine serum, 1× antibiotic-antimycotic solution and 0.3 mg/mL G418). An aliquot of 10,000 cells/100 μL was transferred to each well of a clear 96-well tissue culture plate. The cells were incubated in 5% CO2 at 37° C. in an incubator overnight to allow for proper cell attachment. An aliquot of 50 μL of compound containing assay media were then added to each well and the assay plate was kept in 5% CO2 at 37° C. in an incubator for 24 hours. The media was then removed from each well and 150 μL of a methanol/water mixture (80/20 v/v) was added to each well. The plates were kept at −80° C. freezer overnight to allow for complete cell lysis. An aliquot of 125 μL of extracted supernatant was analyzed by RapidFire high-throughout-mass spectrometry (Agilent) to determine the cellular 2-HG level. The IC50 of a given compound was calculated by fitting the dose response curve of cellular 2-HG inhibition at a given concentration with the four parameter logistic equation.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 354.8, ALogP 3.63, HBA 5, HBD 2, PSA 90.8, QED 0.75
Compound (SMILES): Cc1ccc(N2C(=O)COc3ccc(-c4ccc(O)cc4)cc32)cc1
InChIKey: MTHIHJSNXDLNIF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human N-terminal FLAG-tagged mTOR (1362 to end residues) using Ulight-4E-BP1 as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 331.37, ALogP 4.42, HBA 3, HBD 1, PSA 49.77, QED 0.76
Compound (SMILES): CCC1(CC)c2ccc(-c3cnc([C@@H]4CCCN4C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]3)cc2Oc2cc3ccc(-c4cnc([C@@H]5CCCN5C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]4)cc3cc21
InChIKey: CITBIKHEQYOEMB-MXAOVZPPSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 2b assessed as decrease in viral replication
Measurement: EC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 873.07, ALogP 8.92, HBA 9, HBD 4, PSA 183.87, QED 0.1
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)C(N)CCCCC(N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: HHGDUTJHZKFJND-NHMXRAEOSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [3H](2R,7R)-10 from human NPY Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ by liquid scintillation counting
Measurement: Kd = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 1706.04
Compound (SMILES): C[C@H](Nc1c(-c2nc3cnc(N4CCOCC4)cc3[nH]2)c(=O)[nH]c2cn(C)nc12)c1ncccn1
InChIKey: QZYPCCCTXSBCNE-ZDUSSCGKSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of wild-type FGFR3 (unknown origin) expressed in mouse NIH/3T3 cells overexpressing wild type FGFR3-TACC3 assessed as inhibition of cell proliferation measured after 72 hrs by celltiter-glo assay
Measurement: IC50 = 5.896 nM (pChEMBL 8.229999542236328)
Descriptors: MW 472.51, ALogP 2, HBA 10, HBD 3, PSA 142.53, QED 0.35
Compound (SMILES): CCC(c1ccccc1)n1c(=O)[nH]c2ccc(Cl)cc21
InChIKey: URKZMNUSADOUAO-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 reverse transcriptase in HIV1 infected HEK293T cells harboring luciferase gene assessed as reduction in viral infection after 48 hrs by Bright-Glo luciferase assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 286.76, ALogP 3.98, HBA 2, HBD 1, PSA 37.79, QED 0.78
Compound (SMILES): COc1nn(C)cc1Nc1ncc(Br)c(-c2c[nH]c3c(NC(=O)[C@@H](C)N4CCN(C)CC4)cccc23)n1
InChIKey: PCJQEPKPLJLWMX-OAHLLOKOSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: JAK Enzymatic Assay: Enzyme inhibition studies were performed using recombinant JAK1 (amino acids 866-1154, Life Technologies, #PV4774, Carlsbad, Calif.), JAK2 (amino acids 831-1132), or JAK3 (amino acids 781-1124) under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween® 20, 50 μg/mL BSA, and 10 mM MgCl2. JAK enzyme was expressed as an N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes were assayed both at their respective ATP Km (JAK1: 55 μM, JAK2: 15 μM, JAK3: 3 μM) and the approximated high end of physiological ATP concentration of 5 mM, in the presence of inhibitor dosed at 30, 3, 0.3, 0.03, 0.003 and 0 μM final test concentrations. For JAK1, 6 nM of enzyme (for Km ATP assay) or 4 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2 (SEQ ID NO:1), Intonation, Boston, Mass.). For JAK2, 0.8 nM of enzyme (for Km ATP assay) or 0.3 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). For JAK3, 0.2 nM of enzyme (for Km ATP assay) or 0.1 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). Phosphorylated and unphosphorylated peptides were separated and quantified by a Caliper LC3000 system (Caliper Life Sciences, MA) for calculating percent inhibition. The results of this assay are shown in Table 16 and indicate that the compounds of Formula (I), (Ia), (Ib) and Table 1 exhibit preferential inhibition of JAK1 over JAK2 (in many cases demonstrating over 100 times selectivity for inhibition of JAK1 vs. JAK2).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 568.48, ALogP 3.45, HBA 9, HBD 3, PSA 116.23, QED 0.31
Compound (SMILES): O[C@@H]1c2ccccc2CC[C@H]1[C@H]1c2ccccc2-c2cncn21
InChIKey: VKUCRVDZHQWVKF-DFQSSKMNSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 302.38, ALogP 3.75, HBA 3, HBD 1, PSA 38.05, QED 0.74
Compound (SMILES): NS(=O)(=O)c1ccc(N2C(=O)C[C@H](C(=O)NCCCO)[C@H]2c2ccc(Cl)cc2)cc1
InChIKey: HEHPEFQHZKOOLK-PKOBYXMFSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 451.93, ALogP 1.58, HBA 5, HBD 3, PSA 129.8, QED 0.55
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3C(F)(F)F)c3c(F)cccc32)c(F)c1
InChIKey: RXFPAAYTOMUIII-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 20300 nM (pChEMBL 4.690000057220459)
Descriptors: MW 479.79, ALogP 6.51, HBA 3, HBD 1, PSA 59.3, QED 0.27
Compound (SMILES): CCc1cccc(N2CCN(CCCCNC(=O)c3nc4sccn4c3C)CC2)c1Cl
InChIKey: VDXPHDCGJBDTON-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human dopamine D4.4 receptor expressed in HEK293 cell membranes incubated for 1 hr by liquid scintillation counting analysis
Measurement: Ki = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 460.05, ALogP 4.25, HBA 6, HBD 1, PSA 52.88, QED 0.51
Compound (SMILES): Cc1cc(Oc2nccc3ccccc23)ccc1-c1c(C)ncc2nccn12
InChIKey: FGRWNIHWCDTJQF-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at recombinant C-terminal RLuc8-fused human D1 receptor expressed in HEK29T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 15 mins in presence of coelenterazine H by BRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.42, ALogP 5.35, HBA 5, HBD 0, PSA 52.31, QED 0.43
Compound (SMILES): O=C(Nc1ccccc1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: YQNFLDBZFLCLLR-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using midazolam as substrate
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 402.5, ALogP 4.15, HBA 4, HBD 2, PSA 70.39, QED 0.69
Compound (SMILES): O=C(OCCCc1ccc(F)c(F)c1)N(c1ccccc1)C1CN2CCC1CC2
InChIKey: DGWWXFCHEOPTQT-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 400.47, ALogP 4.63, HBA 3, HBD 0, PSA 32.78, QED 0.66
Compound (SMILES): O=C(O)c1ccc(CNc2ccc(-c3ccc(-c4nc5cc(Cl)ccc5[nH]4)cn3)cn2)cc1
InChIKey: KMRKVWIQPVPEED-UHFFFAOYSA-N
Target: Sterol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35610
Assay: Inhibition of human ACAT1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 455.91, ALogP 5.65, HBA 5, HBD 3, PSA 103.79, QED 0.31
Compound (SMILES): CN1CCc2c(nnn2CC(=O)Nc2ccc(Cl)c(S(=O)(=O)N3CC[C@H](C4CC4)C3)c2)C1
InChIKey: DBLNLPCEKQBLAI-HNNXBMFYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647-labeled ligand from BRD4 BD1 Y390A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 479.01, ALogP 1.98, HBA 7, HBD 1, PSA 100.43, QED 0.68
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCOCCOCCN)c1nnc(C)n1-2
InChIKey: WTJMHBMWPMTETL-FQEVSTJZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin) by TR-FRET assay
Measurement: IC50 = 2480 nM (pChEMBL 5.610000133514404)
Descriptors: MW 531.08, ALogP 3.3, HBA 9, HBD 2, PSA 116.65, QED 0.37
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc3c(F)c4oc5ccc(-c6cnc([C@@H]7CCCN7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]6)cc5c(=O)c4cc3c2)[nH]1)C(C)C
InChIKey: LYOZUKZKCWAPEP-SEXBWERRSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 3a assessed as decrease in viral replication
Measurement: EC50 > 1 nM (pChEMBL 9)
Descriptors: MW 848.93, ALogP 7.11, HBA 10, HBD 4, PSA 204.85, QED 0.1
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cccc(P(=O)(O)O)c2)o1
InChIKey: JOIBYGMUKZLFQR-MRXNPFEDSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 481.44, ALogP 1.6, HBA 6, HBD 5, PSA 169.41, QED 0.07
Compound (SMILES): Cc1noc(-c2ccc3nc(Nc4cc([C@H](C)N5CCN(C(=O)CC(F)(F)F)CC5)ccn4)[nH]c3c2)n1
InChIKey: SYMILEXMAHCATG-AWEZNQCLSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Inhibition of recombinant full length human N-terminal His-tagged TBK1 using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 1 mM of ATP by TR-FRET assay
Measurement: IC50 = 2490 nM (pChEMBL 5.599999904632568)
Descriptors: MW 514.51, ALogP 4.22, HBA 8, HBD 2, PSA 116.07, QED 0.39
Compound (SMILES): COc1nn(C)cc1Nc1nccc(-c2c[nH]c3c(NC(=O)[C@@H](C)N4CCN(C)CC4)cccc23)n1
InChIKey: CVCVOSPZEVINRM-MRXNPFEDSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: JAK Enzymatic Assay: Enzyme inhibition studies were performed using recombinant JAK1 (amino acids 866-1154, Life Technologies, #PV4774, Carlsbad, Calif.), JAK2 (amino acids 831-1132), or JAK3 (amino acids 781-1124) under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween® 20, 50 μg/mL BSA, and 10 mM MgCl2. JAK enzyme was expressed as an N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes were assayed both at their respective ATP Km (JAK1: 55 μM, JAK2: 15 μM, JAK3: 3 μM) and the approximated high end of physiological ATP concentration of 5 mM, in the presence of inhibitor dosed at 30, 3, 0.3, 0.03, 0.003 and 0 μM final test concentrations. For JAK1, 6 nM of enzyme (for Km ATP assay) or 4 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2 (SEQ ID NO:1), Intonation, Boston, Mass.). For JAK2, 0.8 nM of enzyme (for Km ATP assay) or 0.3 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). For JAK3, 0.2 nM of enzyme (for Km ATP assay) or 0.1 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). Phosphorylated and unphosphorylated peptides were separated and quantified by a Caliper LC3000 system (Caliper Life Sciences, MA) for calculating percent inhibition. The results of this assay are shown in Table 16 and indicate that the compounds of Formula (I), (Ia), (Ib) and Table 1 exhibit preferential inhibition of JAK1 over JAK2 (in many cases demonstrating over 100 times selectivity for inhibition of JAK1 vs. JAK2).
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 489.58, ALogP 2.69, HBA 9, HBD 3, PSA 116.23, QED 0.36
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(C(F)F)C[C@@H]34)c2)cn1
InChIKey: NURKHPHCXJUBHN-DLPLYFIVSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 479.46, ALogP 3.32, HBA 7, HBD 2, PSA 102.49, QED 0.49
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](F)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: VSWSFOHKUMIXAS-XBNNLADJSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of recombinant human STING haplotype R71H/G230A/R293Q mutant expressed in 293T cells measured after 30 mins in presence of digitonin A by bright Glo-luciferase reporter gene assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 676.41, ALogP -1.36, HBA 19, HBD 6, PSA 309.42, QED 0.13
Compound (SMILES): NS(=O)(=O)c1ccc(-n2ncc(N3CCOCC3)cc2=O)cc1
InChIKey: YHEYJRUKOHDDDT-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic CA 2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 336.37, ALogP -0.28, HBA 7, HBD 1, PSA 107.52, QED 0.83
Compound (SMILES): CCCCCn1c(=O)n(CCCCN2CCN(c3ccc(F)cc3)CC2)c2ccccc21
InChIKey: CYNRAFPHCBCEFW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]ketanserin from 5-HT2 receptor in rat brain membranes after 120 mins by radioligand binding assay
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 438.59, ALogP 4.73, HBA 5, HBD 0, PSA 33.41, QED 0.43
Compound (SMILES): CCNC(=O)Nc1ccc(-c2nc(N3CCOC[C@@H]3C)c3c(n2)C(C)(C)S(=O)(=O)C3)cc1
InChIKey: IZLPVLBNRGPOHA-AWEZNQCLSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BPZ7
Assay: Inhibition of mTORC2 in HEK293T/17 cells assessed as reduction in Akt phosphorylation at Ser-473 residue after 2 hrs by sandwich immunoassay
Measurement: IC50 = 14.8 nM (pChEMBL 7.829999923706055)
Descriptors: MW 459.57, ALogP 2.67, HBA 7, HBD 2, PSA 113.52, QED 0.72
Compound (SMILES): Nc1ncnc2c1c(Sc1ccccc1)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O
InChIKey: YHRJIUXBQBEGPM-UBEDBUPSSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 454.49, ALogP -0.6, HBA 12, HBD 4, PSA 188.7, QED 0.37
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)/C(Cl)=N/Nc2ccc(Cl)cc2)cc1
InChIKey: WOTQNSVSISRUJF-MOSHPQCFSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 906.5 nM (pChEMBL 6.039999961853027)
Descriptors: MW 387.25, ALogP 2.59, HBA 5, HBD 3, PSA 113.65, QED 0.54
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2c(C)cc(O)cc2C)cc2[nH]ncc12
InChIKey: HEHFJBTUIZUCRL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human His-tagged JAK2 expressed in baculovirus using biotin-synthetic peptide as substrate after 20 mins by HTRF assay
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 345.42, ALogP 3.31, HBA 4, HBD 3, PSA 95.08, QED 0.68
Compound (SMILES): CNCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)O)C(C)C)C(C)C
InChIKey: YGVLEJYAUJVGTO-NQPKZJONSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 840.98, ALogP -1.81, HBA 11, HBD 12, PSA 325.95, QED 0.03
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC)C(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(=O)O
InChIKey: OBBVCMGRQZZSDV-FMURTQEGSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 1083.88
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCCCNC(=N)Nc3ccc4[nH]c5c(c4c3)C[C@@]3(O)[C@H]4Cc6ccc(O)c7c6[C@@]3(CCN4CC3CC3)[C@H]5O7)c3ccc(S(=O)(=O)[O-])cc3C2(C)C)C(C)(C)c2cc(S(=O)(=O)O)ccc21
InChIKey: HCVZFSVJQSJQAZ-YRYQVCONSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-diprenorphine from recombinant human MOR transiently expressed in HEK293 cell membranes measured after 60 mins
Measurement: Ki = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 1381.65
Compound (SMILES): COC(=O)c1ccc(CSc2ccc3nc(N)sc3c2)cc1
InChIKey: CJRBTBVFIXNQRL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 330.43, ALogP 3.96, HBA 6, HBD 1, PSA 65.21, QED 0.58
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)O)C(C)C)[C@@H](C)O
InChIKey: JHGVKJZRAQPJTO-JHKJEGEHSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Antagonist activity at rat alpha3beta2 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 = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 3390.84
Compound (SMILES): COC(=O)c1cccc(-c2ccc(NC(=O)Nc3ccc(Cl)cc3)s2)c1
InChIKey: LCZPVSNAFBBHJI-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor expressed in CHO cells co-expressing Galpha16 assessed as inhibition of EC80 CP55,940-induced calcium mobilization preincubated for 15 mins followed by CP55,490 addition measured at 1 sec interval for 90 secs by calcium-5 dye based FLIPR assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 386.86, ALogP 5.5, HBA 4, HBD 2, PSA 67.43, QED 0.58
Compound (SMILES): COc1cc2c(cc1OC)CN(CCCCOc1ccc(C(C)=O)c(O)c1)CC2
InChIKey: GQORNNSDCGMJPS-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide incubated for 15 mins as substrate by Ellman's method
Measurement: IC50 = 15900 nM (pChEMBL 4.800000190734863)
Descriptors: MW 399.49, ALogP 3.83, HBA 6, HBD 1, PSA 68.23, QED 0.51
Compound (SMILES): Nc1n[nH]c(N2CCC(N(CCO)CCc3ccc(Cl)cc3)CC2)n1
InChIKey: WJUJBVLSGCCBRG-UHFFFAOYSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Mus musculus
UniProt: Q91XA9
Assay: Inhibition of full-length C-terminal his-tagged mouse acidic mammalian chitinase expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N'-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 364.88, ALogP 1.55, HBA 6, HBD 3, PSA 94.3, QED 0.69
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)Cc4ccc(Cl)c(C(F)(F)F)c4)cc3)c2cc1OC
InChIKey: YOHLRCOPRAVUCJ-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of recombinant human His-tagged CSF1R cytoplasmic domain (538 to 910 residues) expressed in baculovirus expression system by Z-lyte assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 516.9, ALogP 6.9, HBA 5, HBD 1, PSA 69.68, QED 0.29
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)Nc1ccnc(-c2ccccc2)c1
InChIKey: CZIALKPATQULIZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor expressed in CHO cells co-expressing Galpha16 assessed as inhibition of EC80 CP55,940-induced calcium mobilization preincubated for 15 mins followed by CP55,490 addition measured at 1 sec interval for 90 secs by calcium-5 dye based FLIPR assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 323.78, ALogP 5.05, HBA 2, HBD 2, PSA 54.02, QED 0.71
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(Cc2ccc3nc4n(c(=O)c3c2)-c2ccc(F)cc2C4=O)CC1
InChIKey: JPWWUFBCQPTXFF-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO expressed in Escherichia coli BL21 (DE3) assessed as reduction in conversion of L-tryptophan to N-formyl kynurenine using L-tryptophan as substrate after 30 mins by methylene blue assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 464.5, ALogP 3.12, HBA 7, HBD 0, PSA 84.74, QED 0.45