lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(=O)c1c(OCCCC2CCN(C(=O)OC(C)(C)C)CC2)c2ccccc2n(C)c1=O
InChIKey: MOCCCNQSZJLIKX-UHFFFAOYSA-N
Target: Phosphatidylcholine:ceramide cholinephosphotransferase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D4B1
Assay: Inhibition of mouse recombinant C-terminal FLAG-tagged SMS2 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay
Measurement: IC50 = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 683.69, ALogP 7.65, HBA 6, HBD 0, PSA 81.08, QED 0.18
Compound (SMILES): O=C(N[C@@H](CSCc1cc(=O)oc2cc(O)ccc12)C(=O)O)OCC1c2ccccc2-c2ccccc21
InChIKey: TZLYIRRLSAYOFA-DEOSSOPVSA-N
Target: Sialin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRA2
Assay: Non-competitive inhibition of human recombinant-Sialin expressed in HEK293 cells assessed as reduction in [3H]Neu5Ac uptake incubated for 15 mins by liquid scintillation counting method
Measurement: Ki = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 517.56, ALogP 4.72, HBA 7, HBD 3, PSA 126.07, QED 0.29
Compound (SMILES): Cn1cc(-c2cnc(N)c(Oc3ccc(C(=O)Nc4ccccc4)cc3)n2)cn1
InChIKey: PYIBJGHLGTVZLN-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora kinase B (unknown origin) incubated for 30 mins by Kinase Glo luminescent assay
Measurement: IC50 = 164 nM (pChEMBL 6.789999961853027)
Descriptors: MW 386.42, ALogP 3.5, HBA 7, HBD 2, PSA 107.95, QED 0.54
Compound (SMILES): CN(C)[C@@H]1CCc2c(cccc2-c2cccs2)C1
InChIKey: ZXVKQUORIGSESV-CYBMUJFWSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-5-carboxamidotryptamine from human 5-HT1A receptor expressed in HEK293T cell membranes incubated for 90 mins by scintillation counting method
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 257.4, ALogP 3.83, HBA 2, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2COCC[C@H]2Cn2ccc(-c3ccc(F)cn3)n2)c1
InChIKey: LFPIOOYGMXHBRI-SFHVURJKSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human recombinant OX2R expressed in CHOK1 cells assessed as inhibition of orexin A-induced intracellular Ca2+ release preincubated for 30 mins followed by orexin-A stimulation by Fluo-4AM dye based fluorescence analysis
Measurement: IC50 = 3.41 nM (pChEMBL 8.470000267028809)
Descriptors: MW 447.47, ALogP 2.86, HBA 8, HBD 0, PSA 90.96, QED 0.47
Compound (SMILES): O=c1sn(-c2cccc3ccccc23)c(=O)n1CCc1ccccc1
InChIKey: CUSWRYUULFULAK-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus SrtA delta N24 mutant expressed in Escherichia coli BL21 (DE3) using Abz-LPATG-Dnp substrate incubated for 20 mins by FRET-based assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 348.43, ALogP 3.46, HBA 5, HBD 0, PSA 44, QED 0.57
Compound (SMILES): C=CC(=O)NCCOc1cc(Cc2cccc(C(F)(F)F)c2)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: FQEVROYETXSXEO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 256 nM (pChEMBL 6.590000152587891)
Descriptors: MW 554.52, ALogP 6.94, HBA 3, HBD 3, PSA 82.8, QED 0.1
Compound (SMILES): Nc1nccc2cc(CNC(=O)[C@@H]3CCCN3C(=O)[C@H](NC3CCCCC3)C3CCOCC3)ccc12
InChIKey: LPSWZZASPZFANL-LOSJGSFVSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 493.65, ALogP 3.14, HBA 6, HBD 3, PSA 109.58, QED 0.55
Compound (SMILES): CC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1
InChIKey: QWEBSYDRFXZQMF-GHIUXRNCSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of Beta1 subunit in human 20S proteasome using Ac-nLPnLD-AMC as substrate after 1 hr by fluorescence based microplate reader analysis
Measurement: IC50 = 206.7 nM (pChEMBL 6.679999828338623)
Descriptors: MW 514.62, ALogP 0.73, HBA 6, HBD 3, PSA 137.21, QED 0.35
Compound (SMILES): Clc1cccc2c(-n3cnc4c(-c5nnc[nH]5)cc(N5CCOCC5)cc43)ccnc12
InChIKey: GDZNVPWDBYHIJL-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length p110alpha/p85alpha using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 431.89, ALogP 3.85, HBA 7, HBD 1, PSA 84.75, QED 0.47
Compound (SMILES): Cc1cc(-c2cnc3c(NCC(C)C)nccn23)ccc1C(=O)NC1CC1
InChIKey: PVHCHYPHQLKTTA-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 483 nM (pChEMBL 6.320000171661377)
Descriptors: MW 363.47, ALogP 3.66, HBA 5, HBD 2, PSA 71.32, QED 0.7
Compound (SMILES): O=C(Cc1ccc(Nc2nccc(NC3CCCC3)n2)cc1)NC1CCCCC1
InChIKey: RIZUAVMTLJDZPO-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) after 1 hr in presence of ATP by Kinase-Glo reagent-based luminescence assay
Measurement: IC50 = 309 nM (pChEMBL 6.510000228881836)
Descriptors: MW 393.54, ALogP 4.57, HBA 5, HBD 3, PSA 78.94, QED 0.64
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)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
InChIKey: QFDKGMCHXMRSPL-DUGSHLAESA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [3H]UR-KK200 from human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ measured after 90 mins by scintillation counting analysis
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 990.18, ALogP -2.09, HBA 11, HBD 18, PSA 439.41, QED 0.02
Compound (SMILES): COC(=O)C1=Cc2ccc(OC)cc2OC(=O)C1
InChIKey: WAAJRGDCTPVMQO-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibitory constant incubated for 6 hrs by stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 248.23, ALogP 1.56, HBA 5, HBD 0, PSA 61.83, QED 0.59
Compound (SMILES): CCC[C@@]12C=C(C#N)C(=O)[C@H](C)[C@H]1CCc1c(-c3ccccc3F)nc(-c3ccnc(C4CC4)c3)nc12
InChIKey: FWKSAZKIHQOSIJ-IEEYFSLBSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 492.6, ALogP 6.49, HBA 5, HBD 0, PSA 79.53, QED 0.41
Compound (SMILES): CN1CCN(Cc2cnc(NC(=O)/C(=N/N3CCCC3)c3ccc(S(=O)(=O)C4CC4)cc3)s2)CC1
InChIKey: FETSDWZQMXCKMK-HPNDGRJYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 16900 nM (pChEMBL 4.769999980926514)
Descriptors: MW 516.69, ALogP 2.27, HBA 9, HBD 1, PSA 98.21, QED 0.54
Compound (SMILES): CC(C)c1cc(-c2ccc3c(c2)[C@H](N)CO3)cc(C(O)CN2CCc3cccc(C(=O)O)c32)c1
InChIKey: PKASBNFVFWUNOA-IKOFQBKESA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of N-terminal human plasma F11a catalytic domain expressed in Escherichia coli strain BL21(DE3) using D-Leu-Pro-Arg*Rh110-D-Pro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 458.56, ALogP 4.66, HBA 5, HBD 3, PSA 96.02, QED 0.5
Compound (SMILES): Nc1nc(-c2ccc(OCCO)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: YLFFYCSPRODDOW-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]-CCPA from human A1 receptor expressed in CHO cells
Measurement: Ki = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 363.38, ALogP 1.5, HBA 8, HBD 2, PSA 107.67, QED 0.56
Compound (SMILES): Nc1nc(N2CCC(CNC(=O)c3cccc(S(N)(=O)=O)c3)CC2)nc2sc(-c3ccco3)nc12
InChIKey: SPELWQPJKAETGH-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241383 from human A2AR expressed in CHO cells by competitive binding assay
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 513.61, ALogP 2.22, HBA 10, HBD 3, PSA 170.33, QED 0.35
Compound (SMILES): C=CC(=O)NC1CCN(c2ccc(C(N)=O)c3[nH]c(C)c(C)c23)C1
InChIKey: RESKELIYOIZFRG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 μM), ATP (20 μM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubating at room temperature for 60 min., the reaction was terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to control reactions with no enzyme (for 100% inhibition) and controls with no inhibitor (for 0% inhibition). Dose response curves were generated to determine the concentration required for inhibiting 50% of Btk activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations.
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 326.4, ALogP 1.76, HBA 3, HBD 3, PSA 91.22, QED 0.75
Compound (SMILES): Nc1ncnc2c1c(Oc1cc(C(F)(F)F)ccn1)nn2[C@@H]1CCCC[C@H]1O
InChIKey: QBGXAQUTKHIMNE-GHMZBOCLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells by patch-clamp electrophysiology assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 394.36, ALogP 3.09, HBA 8, HBD 2, PSA 111.97, QED 0.7
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4CCNCC4)cc3)c2C2CC2)cc(OC)c1OC
InChIKey: INODBUMZBVKPKI-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human ALK5 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay
Measurement: IC50 = 4658 nM (pChEMBL 5.329999923706055)
Descriptors: MW 445.56, ALogP 4.73, HBA 6, HBD 1, PSA 55.85, QED 0.57
Compound (SMILES): C[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccncc4)nc(Cc4ccccc4)c3CC[C@H]12
InChIKey: RKLFSSGRLFGJPY-UKPISFLSSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 420.52, ALogP 4.62, HBA 5, HBD 0, PSA 79.53, QED 0.62
Compound (SMILES): COC(=O)N[C@@H](C(=O)N1CCC[C@H]1c1ncc[nH]1)c1ccccc1
InChIKey: DKFDECDMJFWAFT-UONOGXRCSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in Hepatitis C virus subtype 1b replicon infected in human HuH7 cells assessed as reduction in viral replication
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 328.37, ALogP 2.17, HBA 4, HBD 2, PSA 87.32, QED 0.9
Compound (SMILES): CC1CN(CC(=O)NC2C3CC4CC2CC(C(N)=O)(C4)C3)S(=O)(=O)N(c2c(Cl)cc(-c3ccco3)cc2Cl)C1
InChIKey: OXMXAGRNIUSNGG-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P50172
Assay: Inhibition of mouse 11beta-HSD1 expressed in CHOK1 cells using XL665-labeled cortisol as substrate measured after 24 hrs by HTRF assay
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 595.55, ALogP 4.05, HBA 5, HBD 2, PSA 125.95, QED 0.52
Compound (SMILES): CN(C)C(=O)Oc1ccc(C(O)CNC(C)(C)C)cc1.Cl
InChIKey: VYBHMNJMPQBEKX-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using S-butyrylthiocholine iodide as substrate preincubated for 60 mins followed by substrate addition and measured for 5 mins by Ellman's method
Measurement: IC50 = 5370 nM (pChEMBL 5.269999980926514)
Descriptors: MW 280.37, ALogP 2.17, HBA 4, HBD 2, PSA 61.8, QED 0.89
Compound (SMILES): CC(C)(O)CNC(=O)c1nc(C(=O)N2CCC(F)CC2)c(-c2ccc(S(=O)(=O)N[C@@H](C(C)(C)C)C(F)(F)F)c(Cl)c2Cl)s1
InChIKey: SFNXQUTWLUEVKO-QHCPKHFHSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 0.07 nM (pChEMBL 10.149999618530273)
Descriptors: MW 691.6, ALogP 5.45, HBA 7, HBD 3, PSA 128.7, QED 0.32
Compound (SMILES): CN(C1CCCCC1)C1CCOCC1
InChIKey: DEZUHHGUZRMLAP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 197.32, ALogP 2.43, HBA 2, HBD 0, PSA 12.47, QED 0.67
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCCN2CCN(c3cccc(C)c3C)CC2)c(=O)c2cc(F)ccc12
InChIKey: XFZRXHPMALBAIJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 537.64, ALogP 2.93, HBA 8, HBD 1, PSA 96.77, QED 0.4
Compound (SMILES): COc1ccc(/C=C/C(=O)C(=O)NCCc2ccccc2)cc1
InChIKey: QZEDVYATOGNVJL-FMIVXFBMSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 309.37, ALogP 2.64, HBA 3, HBD 1, PSA 55.4, QED 0.63
Compound (SMILES): CC/C(=C\c1ccccc1)[C@@H]1C[C@H]1NC1CC2(C1)CN(CCO)C2
InChIKey: XOLYNCLYMBLPIW-ZVIVXHKUSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant N-terminal His-tagged LSD1 (unknown origin) expressed in Escherichia coli expression system using ART-K(Me1)-QTARKSTGGKAPRKQLAGGK(Biotin) as substrate incubated for 60 mins by TR-FRET assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 326.48, ALogP 2.91, HBA 3, HBD 2, PSA 35.5, QED 0.81
Compound (SMILES): COc1cccc(Cn2cnc3sc(-c4ccnc(Cl)c4)cc3c2=O)c1
InChIKey: HUGJKZRIYIWAGB-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of recombinant human ROCK2 (11 to 552 residues) using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate incubated for 40 mins in presence of [gamma-33P]ATP by radiometric scintillation assay
Measurement: IC50 = 501 nM (pChEMBL 6.300000190734863)
Descriptors: MW 383.86, ALogP 4.23, HBA 6, HBD 0, PSA 57.01, QED 0.49
Compound (SMILES): C[C@@H]1CN(c2nc(-c3cnn(C)c3)ncc2C#N)CCN1C(=O)C1(C)CC1
InChIKey: MSDVUBZPLFKQFG-CYBMUJFWSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3K delta in human whole blood assessed as inhibition of anti-IgE-stimulated CysLt release in basophils preincubated for 30 mins followed by anti-IgE stimulation and measured after 20 mins
Measurement: IC50 = 5707 nM (pChEMBL 5.239999771118164)
Descriptors: MW 365.44, ALogP 1.59, HBA 7, HBD 0, PSA 90.94, QED 0.82
Compound (SMILES): CCN(CC(C)C)C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: ZLLJGRVCLRCMID-ZDUSSCGKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 647.57, ALogP 4.96, HBA 7, HBD 3, PSA 128.7, QED 0.32
Compound (SMILES): Cc1cccc(C(=O)N[C@@H](C(=O)N2CCC3(CC2)C(=O)N(C)CN3c2ccccc2)C2CCOCC2)c1
InChIKey: LEQNBKIUGXBMTP-RUZDIDTESA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 504.63, ALogP 2.82, HBA 5, HBD 1, PSA 82.19, QED 0.68
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(C4=CCN(C)CC4)cc3)c2C)cc(OC)c1OC
InChIKey: XIKOWUNWIVBZIV-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human ALK5 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay
Measurement: IC50 = 2520 nM (pChEMBL 5.599999904632568)
Descriptors: MW 430.55, ALogP 5.47, HBA 5, HBD 0, PSA 43.82, QED 0.52
Compound (SMILES): COc1cc([C@H]2CC[C@@H](C(N)=O)N2)ccc1OCc1ccccc1F
InChIKey: SNOYMERIIZYNOF-CVEARBPZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 344.39, ALogP 2.69, HBA 4, HBD 2, PSA 73.58, QED 0.84
Compound (SMILES): CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O
InChIKey: AWPNCYPNCSCZFL-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human CDK6/cyclin-D3 using RB protein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 831.94, ALogP 3.09, HBA 15, HBD 4, PSA 220.93, QED 0.08
Compound (SMILES): C[N+](C)(C)C[C@@H]1CO[C@H](c2ccccc2)[C@@H](c2ccccc2)O1.[I-]
InChIKey: HERDQXDYIAMKFW-DEXIKXDTSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 2238.72 nM (pChEMBL 5.650000095367432)
Descriptors: MW 312.43, ALogP 3.59, HBA 2, HBD 0, PSA 18.46, QED 0.8
Compound (SMILES): COc1ccccc1NC(=O)CN1[C@@H]2CCC[C@H]1C[C@H](NC(=O)c1cc(OC)c(OC)c(OC)c1)C2
InChIKey: CTHJPSUBSCTMHA-OWZKRDHZSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 14700 nM (pChEMBL 4.829999923706055)
Descriptors: MW 497.59, ALogP 3.48, HBA 7, HBD 2, PSA 98.36, QED 0.55
Compound (SMILES): Cc1cn(-c2cc(CN3CCCC[C@H]3C(N)=O)cc(NC(=O)c3ccc(C)c(Nc4nccc(-c5ccc(F)cc5)n4)c3)c2)cn1
InChIKey: RLBSTAFRIPOFEZ-YTTGMZPUSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of recombinant human N-terminal GST-tagged PDGFRbeta cytoplasmic domain (557 to 1106 residues) expressed in baculovirus expression system using FAM-labelled P22 peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 618.72, ALogP 5.92, HBA 8, HBD 3, PSA 131.06, QED 0.19
Compound (SMILES): N#Cc1cnc(-c2ccnc3[nH]ccc23)nc1N1C[C@@H]2C[C@H]1CN2c1cccc(F)c1
InChIKey: CUUSXHFSMFZOJP-ROUUACIJSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged p110delta/untagged full-length p85alpha expressed in baculovirus infected Sf21 cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 411.44, ALogP 3.5, HBA 6, HBD 1, PSA 84.73, QED 0.56
Compound (SMILES): OCCCCCCNc1cc(-c2ccc3c(c2)OCO3)nc2ccccc12
InChIKey: MJXWPWYXCVTZGQ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine chloride as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 4320 nM (pChEMBL 5.369999885559082)
Descriptors: MW 364.45, ALogP 4.6, HBA 5, HBD 2, PSA 63.61, QED 0.57
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccc(C#N)cc4)c(C)c3c2)CC1
InChIKey: KSEXEYIAEJTYMJ-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 7010 nM (pChEMBL 5.150000095367432)
Descriptors: MW 372.52, ALogP 4.41, HBA 3, HBD 2, PSA 54.85, QED 0.7
Compound (SMILES): COc1cccc2c1NC(C(=O)O)C1CCCC21
InChIKey: BGTVMDCLIVIRLC-UHFFFAOYSA-N
Target: Protein fosB/Transcription factor jun-D (PROTEIN COMPLEX), Homo sapiens
UniProt: P17535
Assay: Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5'-GTCGGTGACTCAAAACA-3' AP1 oligonucleotide measured after 15 mins by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 247.29, ALogP 2.46, HBA 3, HBD 2, PSA 58.56, QED 0.84
Compound (SMILES): COC(=O)C1CCCN1Cc1ccc2nc3n(c(=O)c2c1)-c1ccc(F)cc1C3=O
InChIKey: WGCWHZSIAJDMBO-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 407.4, ALogP 2.21, HBA 7, HBD 0, PSA 81.5, QED 0.48
Compound (SMILES): CO[C@H]1CCN(Cc2c(C)cc(C)c3[nH]ccc23)[C@H](c2ccc(C(=O)O)cc2)C1
InChIKey: SUWQILGSQSOVBF-UGKGYDQZSA-N
Target: Complement factor B (SINGLE PROTEIN), Homo sapiens
UniProt: P00751
Assay: Inhibition of serine protease factor B in 50% human whole blood assessed as reduction in alternative pathway-mediated membrane attack complex formation pre-incubated for 15 mins before activated zymosan A stimulation for 50 mins by ELISA
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 392.5, ALogP 4.84, HBA 3, HBD 2, PSA 65.56, QED 0.65
Compound (SMILES): CC(C)(C)OC(=O)Nc1ccc(C#Cc2ccc(NC(=O)C(=O)O)cc2)cc1
InChIKey: ZDSKXOHRNJDALA-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 380.4, ALogP 3.46, HBA 4, HBD 3, PSA 104.73, QED 0.55
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccccc5)cc4C[C@@]4(OCCCC5CCCCC5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: GWROYBPWASJEAK-RJKGWOMYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 576.78, ALogP 7.54, HBA 5, HBD 1, PSA 54.82, QED 0.28
Compound (SMILES): CS(=O)(=O)n1cc2c(n1)CN([C@@H]1C[C@H](N)[C@@H](c3cc(F)ccc3F)O[C@@H]1C(F)(F)F)C2
InChIKey: GUBOXFWNNXSQNH-SVGFKBNWSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of recombinant human CYP2C8
Measurement: IC50 = 76300 nM (pChEMBL 4.119999885559082)
Descriptors: MW 466.43, ALogP 2.07, HBA 7, HBD 1, PSA 90.45, QED 0.7
Compound (SMILES): O=C(O)c1cc(-c2ccc(C34CCN(CC3)CC4)cc2)cc(-n2cc(-c3ccc(C(F)(F)F)cc3)nn2)c1
InChIKey: KWMPBNRKPTVPTE-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15391
Assay: Inhibition of MRS4174 binding to human P2Y14R expressed in CHO cells pre-incubated for 30 mins before MRS4174 addition and further incubated for 30 mins at pH 7.4 by flow cytomtery based competitive fluorescence assay
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 518.54, ALogP 6.06, HBA 5, HBD 1, PSA 71.25, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CCNC(=S)Nc1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(=O)N[C@@H](CCCC[N+](C)(C)C)C(=O)N[C@@H](CO)C(N)=O
InChIKey: SLIIQFIECPRWSD-KPZWOUCOSA-O
Target: Chromobox protein homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14781
Assay: Binding affinity to CBX2 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis
Measurement: Kd = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 1067.26
Compound (SMILES): O=[N+]([O-])c1ccc(-c2nc3ccccc3[nH]2)o1
InChIKey: GOUDVMWLWAFVMC-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 229.19, ALogP 2.73, HBA 4, HBD 1, PSA 84.96, QED 0.54
Compound (SMILES): C[N+](C)(C)C[C@@H]1CO[C@@H](c2ccc(Cc3ccccc3)cc2)CO1.[I-]
InChIKey: BPZCQQKODJNKRW-MUCZFFFMSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 326.46, ALogP 3.44, HBA 2, HBD 0, PSA 18.46, QED 0.78
Compound (SMILES): COc1cc(CN(C)C(=O)c2c(OCCCC3CCN(C(=O)OC(C)(C)C)CC3)c3cccnc3n(C)c2=O)cc(OC)c1
InChIKey: DSGMMOPUXYSDKE-UHFFFAOYSA-N
Target: Phosphatidylcholine:ceramide cholinephosphotransferase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D4B1
Assay: Inhibition of mouse recombinant C-terminal FLAG-tagged SMS2 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 608.74, ALogP 5.03, HBA 9, HBD 0, PSA 112.43, QED 0.29
Compound (SMILES): CC(=O)N1N=C(c2cc(O)c(O)c([N+](=O)[O-])c2)CC1c1ccoc1
InChIKey: PTMLGLYYKVHBQN-UHFFFAOYSA-N
Target: Catechol O-methyltransferase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P22734
Assay: Inhibition of rat liver COMT using esculetin as substrate by fluorescence based spectrophotometry
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 331.28, ALogP 2.3, HBA 7, HBD 2, PSA 129.41, QED 0.5
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CC3CC3C2)c(Cl)c1Cl)C(F)(F)F
InChIKey: ZVYHMKPFTBNVEA-UNXYVOJBSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 629.51, ALogP 3.94, HBA 7, HBD 3, PSA 128.7, QED 0.41
Compound (SMILES): Oc1ccc(C2CCN(c3ccn4c(CC5CC5)nnc4c3Cl)CC2)cc1
InChIKey: QYXZTBGZHFSRNA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Agonist activity at human mGlu2 receptor expressed in HEK293 cells co-expressing Gqo5 assessed as increase in intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: EC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 382.9, ALogP 4.42, HBA 5, HBD 1, PSA 53.66, QED 0.73
Compound (SMILES): O=C(NCCN1CCOCC1)c1ccc2c(c1)C(=O)c1ccc(Nc3ccc(F)c(NC(=O)c4ccc[se]4)c3)cc1CC2
InChIKey: WVDCLKDZJSPZRP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of NanoBRET kinase tracer K4 binding to full-length human C-terminal NanoLuc-tagged p38alpha MAPK expressed in HEK293T cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 645.59
Compound (SMILES): O=S1(=O)CCN2CCNCc3ccc(Cl)c1c32
InChIKey: UIMCSPQRYWSTCR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at 5HT2B receptor (unknown origin)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 272.76, ALogP 1.04, HBA 4, HBD 1, PSA 49.41, QED 0.77
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)ccc(C(F)(F)F)n3n2)sn1
InChIKey: OEAFCPTWSOXDBU-DRXBFXEBSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Binding affinity to PIK4CB (unknown origin)
Measurement: Kd >= 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 506.48, ALogP 4.78, HBA 8, HBD 1, PSA 67.58, QED 0.5
Compound (SMILES): NS(=O)(=O)c1cc(Nc2cc(Oc3cn(C4CC4)nc3C3CCOCC3)ccn2)ccc1F
InChIKey: WDKDULZYHWXVIZ-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) expressed in mouse NIH/3T3 cells by cell-based luciferase assay
Measurement: IC50 = 126.4 nM (pChEMBL 6.900000095367432)
Descriptors: MW 473.53, ALogP 3.83, HBA 8, HBD 2, PSA 121.36, QED 0.53
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2cc(Cl)ccc2Cl)cc(OC)c1OC
InChIKey: SFSFYCBCVSQIDZ-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 536.46, ALogP 4.77, HBA 6, HBD 2, PSA 89.13, QED 0.51
Compound (SMILES): COC(=O)[C@H](Cc1c[nH]c2ccccc12)n1cc(COc2nc(Cl)nc(N3CCOCC3)n2)nn1
InChIKey: VRPQHRSATFUUKX-SFHVURJKSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate incubated for 10 mins followed by substrate addition and measured after 2 mins by EIA assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.93, ALogP 1.97, HBA 11, HBD 1, PSA 133.17, QED 0.36
Compound (SMILES): FC(F)(F)CC1CN2CCNCc3ccc(Br)c1c32
InChIKey: SDJMEHUUEVLBHX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2C receptor (unknown origin)
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 335.17, ALogP 3.41, HBA 2, HBD 1, PSA 15.27, QED 0.85
Compound (SMILES): Cc1cc(-c2ccc3nc(NC(=O)c4cccs4)nn3c2)cc(C)c1O
InChIKey: MEIUUTQJPQBJPZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 10 uM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 364.43, ALogP 4.03, HBA 6, HBD 2, PSA 79.52, QED 0.58
Compound (SMILES): N.Nc1nc([O-])c2c(n1)n([C@@H]1O[C@H](COP(=O)(O)NCCc3c[nH]c4ccccc34)[C@@H](O)[C@H]1O)c[n+]2Cc1ccccc1
InChIKey: DIICMVWIQKIYQM-DGUBOJIQSA-N
Target: m7GpppX diphosphatase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96C86
Assay: Inhibition of human DcpS using pyrene labeled 7-methylguanosine triphosphate as substrate preincubated for 15 mins followed by enzyme addition by fluorescence assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 595.55, ALogP 0.47, HBA 10, HBD 6, PSA 207.71, QED 0.1
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@@H]1CCC12CCN(CC)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: PGTVKKLHFBLXOX-XCZPVHLTSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 559.76, ALogP 6.23, HBA 6, HBD 2, PSA 100.21, QED 0.24
Compound (SMILES): CN(C)[C@H]1CCc2c(cccc2-c2cccn2C)C1
InChIKey: PNJROLLRVMVIDM-AWEZNQCLSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-carboxamidotryptamine from human 5-HT7A receptor expressed in HEK293 cell membranes incubated for 90 mins by scintillation counting method
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 254.38, ALogP 3.11, HBA 2, HBD 0, PSA 8.17, QED 0.8
Compound (SMILES): NC(=O)[C@@H]1CCCCn2cc(nn2)C[C@H](N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1
InChIKey: YQXDFRDKAUUILW-YJXWTMGESA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Binding affinity to N-terminal (His6)-MBP tagged full-length human proMMP2 expressed in Escherichia coli BL21(DE3) RIL assessed as reduction in Rhod-cy(WPHPY binding incubated for 30 mins by fluorescence polarization assay
Measurement: Kd = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 947.07, ALogP -0.62, HBA 13, HBD 9, PSA 321.54, QED 0.1
Compound (SMILES): CCc1cccc(NC(=O)c2cc3cccc(O)c3oc2=N)c1
InChIKey: KJSIIAIZHJYKDK-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of recombinant AKR1C4 (unknown origin) assessed as reduction in S-tetralol-induced dehydrogenase activity by measuring NADPH level
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 308.34, ALogP 3.43, HBA 4, HBD 3, PSA 86.32, QED 0.69
Compound (SMILES): COC(=O)NC1(C(=O)N[C@@H](Cc2ccccc2)[C@@H](O)C[C@H](Cc2ccccc2)NC(=O)O[C@H]2CO[C@H]3OCC[C@H]32)CCCC1
InChIKey: YTBBVCQPJXFQBH-VEIVPZTASA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-106 cells using EDANS/DABCYL-labelled 10-amino acid containing protease cleavage site as substrate preincubated for 1 hr followed by substrate addition and measured for 60 mins by FRET assay
Measurement: Ki = 236 nM (pChEMBL 6.630000114440918)
Descriptors: MW 609.72, ALogP 3.23, HBA 8, HBD 4, PSA 144.45, QED 0.29
Compound (SMILES): CCNC(=O)N1C[C@@H]2C[C@H]1CN2c1nc(-c2cnn(C)c2)ncc1C#N
InChIKey: CCUFTWMGUUIZJE-KBPBESRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: This assay was developed and further optimized from a kit produced by Upstate (Millipore catalog #33-047) (Millipore Sigma, Billerica Mass., USA) and has been configured for high throughput screening (HTS) and structure-activity relationship (SAR) screening. Briefly, this procedure exploits the exquisite specificity and high affinity binding of enzyme reaction substrate phosphatidyl(3,4,5)triphosphate (PIP3) to the GRP1 pleckstrin homology (PH) domain to generate the signal. In the absence of PIP3, an HTRF (Homogeneous Time-Resolved Fluorescence energy transfer) complex is formed consisting of europium (u)-labeled anti-GST, GST tagged GRP1-PH domain, biotin-PIP3 (biotinylated-PIP3) and streptavidin conjugated APC (Allophycocyanin). The native PIP3 produced by PI3-Kinase activity disrupts in a competitive manner the biotin-PIP3 from the pleckstrin homology (PH) domain, resulting in the loss of energy transfer (HTRF complex) and a decrease in the signal. The format of this assay is the same for all 4 isoforms of PI3K; the differences lie in the concentration of enzyme used to achieve robust assay window. The alpha, beta, and delta assays are run at 0.5, 1, and 0.3 nM enzymes and the gamma assay is run at 5 nM enzyme. The ATP concentration is 100 uM in the alpha, beta, and delta assays and 50 uM adenosine triphosphate (ATP) in the gamma assay. All reactions are run at 5 uM PIP2.
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 352.4, ALogP 0.74, HBA 7, HBD 1, PSA 102.97, QED 0.87
Compound (SMILES): COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)C1CC1
InChIKey: UAUIISPUXGSUCV-DMVQEWIISA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-106 cells using EDANS/DABCYL-labelled 10-amino acid containing protease cleavage site as substrate preincubated for 1 hr followed by substrate addition and measured for 60 mins by FRET assay
Measurement: Ki = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 595.69, ALogP 2.7, HBA 8, HBD 4, PSA 144.45, QED 0.28
Compound (SMILES): Cc1cc(-c2ccc(=O)n(C)c2C)cc2cn(C3CCCN(CC(F)(F)F)C3)nc12
InChIKey: OZZZXYNMOPESRV-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at TLR8 in human PBMC assessed as inhibition of DOTAP-ssRNA40 induced TNFalpha production preincubated for 30 mins followed by ssRNA40 addition measured after 20 hrs by HTRF assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 418.46, ALogP 4.22, HBA 5, HBD 0, PSA 43.06, QED 0.64
Compound (SMILES): NCCCN(CCc1ccccc1)CC(=O)N(CCc1ccccc1)CCc1ccc(S(N)(=O)=O)cc1
InChIKey: IZHCFMDCLZJGQJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 367.3 nM (pChEMBL 6.429999828338623)
Descriptors: MW 522.72, ALogP 2.84, HBA 5, HBD 2, PSA 109.73, QED 0.32
Compound (SMILES): Clc1cc2c3c(c1)CNCCN3CC2
InChIKey: MDQPGZXLZQAZJJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at 5HT2B receptor (unknown origin)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 208.69, ALogP 1.81, HBA 2, HBD 1, PSA 15.27, QED 0.7
Compound (SMILES): CCS(=O)(=O)N[C@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: RZCOAAMJHKLYHQ-UXHICEINSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 475.62, ALogP 1.78, HBA 6, HBD 3, PSA 134.49, QED 0.51
Compound (SMILES): Cc1ccc2c3c1C(C)CN3CCNC2
InChIKey: MOBZMLUSNDWIQT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2C receptor (unknown origin)
Measurement: Ki = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 202.3, ALogP 2.02, HBA 2, HBD 1, PSA 15.27, QED 0.69
Compound (SMILES): CC(C)CNc1cccn2c(-c3ccc(C(=O)NC4CC4)cc3)cnc12
InChIKey: VYVCVQBNQXWFAL-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 364 nM (pChEMBL 6.440000057220459)
Descriptors: MW 348.45, ALogP 3.96, HBA 4, HBD 2, PSA 58.43, QED 0.71
Compound (SMILES): COCC(C)(C)NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)(F)CC2)c(Cl)c1Cl
InChIKey: CKSVXBHBHLTQQY-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 657.59, ALogP 4.19, HBA 8, HBD 3, PSA 137.93, QED 0.35
Compound (SMILES): CN(C)c1cc(-c2ccncc2)c(-c2cccc3ccccc23)nn1
InChIKey: GEAPHVHHVPDTKQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human p38alpha
Measurement: Ki = 180 nM (pChEMBL 6.75)
Descriptors: MW 326.4, ALogP 4.42, HBA 4, HBD 0, PSA 41.91, QED 0.56
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NCCc4ccccc4)n3)nc2)CC1
InChIKey: VBACZDJYOLHJGZ-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.95, ALogP 3.68, HBA 7, HBD 2, PSA 69.21, QED 0.6
Compound (SMILES): COc1c(S(C)(=O)=O)ccc(O[C@@H](C)C(F)(F)F)c1C(=O)N1CC(c2ccc(C(F)(F)F)cc2)C1
InChIKey: JCXDGAMFXUHQBI-LBPRGKRZSA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48067
Assay: Inhibition of human GlyT1 expressed in human HEK cells assessed as reduction in radiolabeled glycine uptake by scintillation proximity assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 525.47, ALogP 4.69, HBA 5, HBD 0, PSA 72.91, QED 0.51
Compound (SMILES): C#CC(=O)N1CCC(Nc2ccc(C(N)=O)c3[nH]c(C)c(C)c23)CC1
InChIKey: RRVWOHOZIVWEIW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Btk Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 μM), ATP (20 μM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubating at room temperature for 60 min., the reaction was terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to control reactions with no enzyme (for 100% inhibition) and controls with no inhibitor (for 0% inhibition). Dose response curves were generated to determine the concentration required for inhibiting 50% of Btk activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations.
Measurement: IC50 = 0.85 nM (pChEMBL 9.069999694824219)
Descriptors: MW 338.41, ALogP 1.92, HBA 3, HBD 3, PSA 91.22, QED 0.75
Compound (SMILES): O=C1c2cc(F)ccc2-n2c1nc1ccc(CN3CCC(C(=O)O)CC3)cc1c2=O
InChIKey: DYFMZPVPJQIGOC-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 407.4, ALogP 2.37, HBA 6, HBD 1, PSA 92.5, QED 0.56
Compound (SMILES): O=C(NC1CCN(Cc2ccccc2)CC1)c1ccc(CO[N+](=O)[O-])cc1
InChIKey: CCNCSTVEOVJYEZ-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor (unknown origin) incubated for 1 hr in presence of (+)SKF10047 by liquid scintillation counting method
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 369.42, ALogP 2.79, HBA 5, HBD 1, PSA 84.71, QED 0.6
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2C[C@H](O)C2)cc2c1O[C@H](CF)[C@H]2c1ccccc1
InChIKey: LOGHPTLVAZULOZ-RGCFKVTRSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD2 (1 to 477 residues)/BD1 Y97A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 398.43, ALogP 2.16, HBA 4, HBD 3, PSA 87.66, QED 0.72
Compound (SMILES): Nc1cccc(C(=O)N2CCN(C(=O)c3ccc(S(N)(=O)=O)cc3)CC2)c1
InChIKey: KBEVPEAJPAROJU-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 51.1 nM (pChEMBL 7.289999961853027)
Descriptors: MW 388.45, ALogP 0.51, HBA 5, HBD 2, PSA 126.8, QED 0.74
Compound (SMILES): Cc1nnc(-c2cnc3c(c2)C[C@@]2(OCCCc4ccccc4)[C@H]4Cc5ccc(O)c6c5[C@@]2(CCN4CC2CC2)[C@H]3O6)o1
InChIKey: VPJPODNUIYHZFU-XCQSDYEBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 8.12 nM (pChEMBL 8.09000015258789)
Descriptors: MW 576.7, ALogP 5.5, HBA 8, HBD 1, PSA 93.74, QED 0.27
Compound (SMILES): CNC(=O)CN1CN(c2ccccc2)C2(CCN(C(=O)c3ccc4[nH]ncc4c3)CC2)C1=O
InChIKey: QDMKAQVMVBLGFR-UHFFFAOYSA-N
Target: Epithelial discoidin domain-containing receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q08345
Assay: Inhibition of recombinant GST-tagged human DDR1 by FRET assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 446.51, ALogP 1.59, HBA 5, HBD 2, PSA 101.64, QED 0.63
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccccc5)cc4C[C@@]4(OCCCc5ccccn5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: LQSLTLGPDRWAJR-RXJSGBQWSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 5.89 nM (pChEMBL 8.229999542236328)
Descriptors: MW 571.72, ALogP 6.21, HBA 6, HBD 1, PSA 67.71, QED 0.25
Compound (SMILES): c1ccc(CCCCNC2CCc3ccsc3CC2)cc1
InChIKey: VZUAQJKJAFSNFL-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membranes incubated for 120 mins by scintillation counting method
Measurement: Ki = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 299.48, ALogP 4.61, HBA 2, HBD 1, PSA 12.03, QED 0.61