lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NC1CC1)c1nc2cccnn2c1-c1ccc2ncnn2c1
InChIKey: KZFDLYSKEWBCTB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: The PDE4A3, PDE4B1, PDE4C1 and PDE4D3 assays: The PDE4A3, PDE4B1, PDE4C1 and PDE4D3 assays use the Scintillation Proximity Assay (SPA) technology to measure the inhibition of human recombinant PDE4A1, PDE4B3, PDE4C1, and PDE4D3 enzyme activity by compounds in vitro. The PDE4A1, PDE4B3, PDE4C1, and PDE4D3 assays are run in parallel using identical parameters, except for the concentration of enzyme (80 pM PDE4A3, 40 pM PDE4B3, 40 pM PDE4C1 and 10 pM PDE4D). The assays are performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE4A3, PDE4B1, PDE4C1, and PDE4D to convert ¿20% of substrate (1 μM cAMP consisting of 20 nM 3H-cAMP+980 uM cold cAMP) and a range of inhibitors. Reactions are incubated for 30 min at 25° C. The addition of 20 uL of 8 mg/ml yitrium silicate SPA beads (Perkin Elmer) stops the reaction. The plates are sealed (TopSeal, Perkin Elmer) and the beads are allowed to settle for 8 hrs, after which they are read on the Trilux Microbeta overnight.
Measurement: IC50 = 326 nM (pChEMBL 6.489999771118164)
Descriptors: MW 319.33, ALogP 1.33, HBA 7, HBD 1, PSA 89.48, QED 0.62
Compound (SMILES): COC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)Cc1nc2ccc(Cl)cc2s1
InChIKey: WJMOKQCSPRZIRW-HJOGWXRNSA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Inhibition of C-terminal fluorescein-labeled human TCF4 (7 to 51 residues) binding to wild-type C-terminal His6-tagged beta-catenin (138 to 781 residues) expressed in Escherichia coli BL21 DE3 measured after 2.5 hrs by fluorescence polarization assay
Measurement: Ki = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 683.14, ALogP 2.86, HBA 9, HBD 5, PSA 201.09, QED 0.12
Compound (SMILES): Nc1ncnc2c1c(OCc1ccccc1)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O
InChIKey: IRZWOFPUKRWUFQ-CNEMSGBDSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 452.45, ALogP -1.17, HBA 12, HBD 4, PSA 197.93, QED 0.34
Compound (SMILES): COCCOc1cc(-n2c(=O)[nH]c(=O)n(-c3ccc(Cl)cc3)c2=O)ccc1Oc1ccccc1
InChIKey: KJPZOWZQDKAVHY-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Agonist activity at TrkB (unknown origin) in expressed in U2OS cells incubated for 3 hrs and measured after 60 hrs in presence of BDNF by fluorescence complementation assay
Measurement: EC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 481.89, ALogP 3.15, HBA 8, HBD 1, PSA 104.55, QED 0.39
Compound (SMILES): CCc1sc2ncnc(N[C@H](CC3CCCCC3)C(=O)O)c2c1-c1cccc(Oc2ccc(F)cc2)c1
InChIKey: LAZOEPNCOREUPV-HSZRJFAPSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Displacement of N-terminal fluorescein labelled Puma-BH3 peptide from human N-terminal thrombin cleavage site-fused/His6-tagged Bcl-2 expressed in Escherichia coliBL21(DE3) pLysS cells by fluorescence polarization assay
Measurement: Ki = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 519.64, ALogP 7.69, HBA 6, HBD 2, PSA 84.34, QED 0.24
Compound (SMILES): COC(=O)[C@@H]1CC(=O)N(c2ccc(S(N)(=O)=O)cc2)[C@H]1c1ccc(F)cc1
InChIKey: GOMKLKMHMLKMDT-WBVHZDCISA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 392.41, ALogP 1.74, HBA 5, HBD 1, PSA 106.77, QED 0.8
Compound (SMILES): CCOc1ccc(Cc2ccccc2)cc1CNC(=O)[C@@H](N)Cc1c(C)cc(O)cc1C.O=C(O)C(F)(F)F
InChIKey: NULXATSSMPKLTD-UQIIZPHYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]-diprenorphine from rat delta-type opioid receptor expressed in rat C6 cell membranes incubated for 1 hr in shaker by liquid scintillation counting method
Measurement: Ki = 23.8 nM (pChEMBL 7.619999885559082)
Descriptors: MW 432.56, ALogP 4.18, HBA 4, HBD 3, PSA 84.58, QED 0.47
Compound (SMILES): CN1CC(NC(=O)c2ccncc2Nc2cc(-c3ccc4ccn(C)c4c3)c3nccnc3c2)CCC1=O
InChIKey: IZTXVFPCPZWGQY-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3 in human HCT116 cell lysates assessed as reduction in glycolytic-flux induced fructose-2,6-bisphosphate formation using fructose-6-phosphate as substrate treated with cells prior to glucose stimulation followed by PFK1 and substrate addition and measured at 0.5 mins interval for 45 mins
Measurement: IC50 = 96520 nM (pChEMBL 4.010000228881836)
Descriptors: MW 505.58, ALogP 4.28, HBA 7, HBD 2, PSA 105.04, QED 0.37
Compound (SMILES): O=C(c1cccc(Cl)c1)N1CCC(=CC#Cc2cccc(Cl)n2)CC1
InChIKey: AYGQZKNIHLPKOG-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6 using 3-[2-(N,N-diethylamino)ethyl]-7-methoxy-4-methylcoumarin as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 371.27, ALogP 4.6, HBA 2, HBD 0, PSA 33.2, QED 0.54
Compound (SMILES): Cl.O=S1(=O)c2cccc3cccc(c23)N1CCCCCCN1CCN(c2ccccc2Cl)CC1
InChIKey: RUYPKJLDKNPSBZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1AR expressed in HEK293 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 484.07, ALogP 5.38, HBA 4, HBD 0, PSA 43.86, QED 0.4
Compound (SMILES): Cc1ncc(C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](/C=C/S(C)(=O)=O)Cc2ccc(CN)cc2)C2CCCCC2)s1
InChIKey: DXOAAWKCOREWGR-GMFYUHATSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of 20S constitutive proteasome beta 2 trypsin-like activity (unknown origin) by cell based ABPP assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 631.86, ALogP 3.41, HBA 8, HBD 4, PSA 160.35, QED 0.25
Compound (SMILES): CCCN1C(=O)/C(=N\Nc2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: XQNYORMJZQLZGB-SILNSSARSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 71.6 nM (pChEMBL 7.139999866485596)
Descriptors: MW 358.42, ALogP 1.91, HBA 5, HBD 2, PSA 104.86, QED 0.8
Compound (SMILES): O=C(NCc1cccs1)c1csc(CCNCc2nc3ccccc3[nH]2)n1
InChIKey: SBDWEFWBEATLNK-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 397.53, ALogP 3.34, HBA 6, HBD 3, PSA 82.7, QED 0.4
Compound (SMILES): O=C(O)c1ccc2nc(-c3ccccc3)c(N3CCN(c4ncccc4C(F)(F)F)CC3)nc2c1
InChIKey: JGEZDSXGEXKMGW-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: Radiochemical Assay: Purified PASK (UniProt # Q96RG2; human recombinant N-terminal GST tagged construct, residues 879-1323) from insect cells (final concentration 5 nM) is added to freshly prepared Base Reaction Buffer containing 20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO and Myelin Basic Protein (20 μM final). Test compounds in DMSO are then added and the mixture, followed by delivery of 33P-ATP (specific activity 0.01 μCi/μl final) to initiate the reaction. The kinase reaction is incubated for 120 min at room temperature. The entire reaction mixture is washed through onto a P81 Phosphocellulose paper and washed three times for 10 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 479.46, ALogP 4.74, HBA 6, HBD 1, PSA 82.45, QED 0.45
Compound (SMILES): Nc1ncnc2c(C(=O)Nc3cccc4c3c(Br)nn4Cc3cccnc3)csc12
InChIKey: RNSPJNIKRAJKOU-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 480.35, ALogP 4.08, HBA 8, HBD 2, PSA 111.61, QED 0.4
Compound (SMILES): Cc1cc(-c2ccccc2)cc(C(=O)NNS(=O)(=O)c2ccccc2)c1F
InChIKey: PHHZKBMVRPULAW-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Mus musculus
UniProt: Q8BZ21
Assay: Inhibition of KAT6A in C57BL/6 mouse embryonic fibroblasts assessed as reduction in cell proliferation after 10 days
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 384.43, ALogP 3.42, HBA 3, HBD 2, PSA 75.27, QED 0.66
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2cccc(-c3cccc(Cl)c3)c2)cc1
InChIKey: NMYYLDWVJNVYLJ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human biotinylated HN-Avi-MBPS-TCS-RORC2 (258 to 518 residues) assessed as recruitment of SRC-1-derived coactivator measured after 15 mins by FRET assay
Measurement: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 413.93, ALogP 4.98, HBA 3, HBD 1, PSA 63.24, QED 0.62
Compound (SMILES): CN1CCN(c2ccc(-c3nc4ccc(F)cc4c(=O)[nH]3)cc2)CC1
InChIKey: ZQAMFUHPGNZLHA-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of GST tagged-TEV cleavage site-fused human recombinant TNKS1 (1023 to 1327 residues) expressed in baculovirus infected sf9 cells assessed as reduction in auto-PARsylation incubated for 1 hr in presence of bio-NAD as co-substrate by ELISA
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 338.39, ALogP 2.48, HBA 4, HBD 1, PSA 52.23, QED 0.78
Compound (SMILES): CC(=O)N1CC[C@H]2c3ccccc3N(c3ccccc3)C[C@]21C
InChIKey: NLHAPFNRLLWFGD-AZUAARDMSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H]-Pentazocine from human recombinant sigma1 receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 306.41, ALogP 3.93, HBA 2, HBD 0, PSA 23.55, QED 0.8
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: USBUUOOWXGOCJM-QURZBVGQSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1608.8
Compound (SMILES): CC[C@H](Nc1nc(N)nc(C)c1C#N)c1nc2cccc(NCc3ccc(C(=O)NO)cc3)c2c(=O)n1-c1ccccc1
InChIKey: OUFOTOLRWBQNQU-QHCPKHFHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 575.63, ALogP 4.23, HBA 11, HBD 5, PSA 183.87, QED 0.13
Compound (SMILES): Cc1noc(-c2ccc3nc(Nc4cc(C(C)N5CCN(C(=O)CC(F)(F)F)CC5)ccn4)[nH]c3c2)n1
InChIKey: SYMILEXMAHCATG-UHFFFAOYSA-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 = 829 nM (pChEMBL 6.079999923706055)
Descriptors: MW 514.51, ALogP 4.22, HBA 8, HBD 2, PSA 116.07, QED 0.39
Compound (SMILES): NC[C@H]1O[C@@H](O[C@@H](Cn2cc(Cc3ccc(COc4ccc(C(=O)c5ccccc5)cc4)cc3)nn2)[C@H]2O[C@@H](n3ccc(=O)[nH]c3=O)[C@H](O)[C@@H]2O)[C@H](O)[C@@H]1O
InChIKey: IXVYVURINIITCR-NSBLWWESSA-N
Target: Phospho-N-acetylmuramoyl-pentapeptide-transferase (SINGLE PROTEIN), Aquifex aeolicus (strain VF5)
UniProt: O66465
Assay: Inhibition of MraY in Aquifex aeolicus
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 756.77, ALogP -0.36, HBA 16, HBD 6, PSA 246.5, QED 0.08
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(C)CC4)cc3)[nH]c2c1=O
InChIKey: KVYZSLYRTMOOQF-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX-2 from recombinant human A2A adenosine receptor expressed in CHO cell membranes measured after 30 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 432.51, ALogP 0.43, HBA 7, HBD 2, PSA 124.16, QED 0.6
Compound (SMILES): CCCCCCNCC(F)(P(=O)(O)O)P(=O)(O)O
InChIKey: WPVQOCGESLLUKB-UHFFFAOYSA-N
Target: Farnesyl diphosphate synthase (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q197X6
Assay: Inhibition of Toxoplasma gondii FPPS using DMAPP as substrate incubated for 30 mins measured by scintillation counting
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 307.2, ALogP 1.14, HBA 3, HBD 5, PSA 127.09, QED 0.32
Compound (SMILES): CCOc1ccc(-c2cc(C(=O)NCCCN3CCOCC3)nn2-c2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: UBRMHWUNHFUKKD-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P12527
Assay: Inhibition of Sprague-Dawley rat 5-LOX assessed as calcium ionophore A23187-stimulated LTB4 production preincubated for 30 mins followed by calcium ionophore A23187 addition and measured after 30 mins by ELISA
Measurement: IC50 = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 513.62, ALogP 2.04, HBA 8, HBD 2, PSA 128.78, QED 0.4
Compound (SMILES): CN1C(N)=N[C@]2(C)c3cc(NC(=O)c4ccc(C#N)cn4)ccc3OCC[C@H]2S1(=O)=O
InChIKey: WHPBHJQRLDCBOO-YLJYHZDGSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2 preincubated for 30 mins followed by QSY7- EISEVNLDAEFC-Eu-amide substrate addition and measured after 1.5 hrs by HTRF assay
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 440.49, ALogP 1.16, HBA 8, HBD 2, PSA 150.77, QED 0.71
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(N)=O)C(C)(C)C)C(C)C)C(C)C
InChIKey: BTMWOYGWMDFFEL-CQMSCVFFSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 22.4 nM (pChEMBL 7.650000095367432)
Descriptors: MW 2373.79
Compound (SMILES): Nc1nc(C(=O)N/N=C/c2ccccc2)nn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: KRBLCBPKAICODD-VXLYETTFSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase-2 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 86.4 nM (pChEMBL 7.059999942779541)
Descriptors: MW 385.41, ALogP 0.26, HBA 8, HBD 3, PSA 158.35, QED 0.42
Compound (SMILES): O=c1cc(Nc2ccc(-c3ccc(Cl)cc3)cc2)[nH]c(=O)n1O
InChIKey: LGFBJZJIXJDDDV-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of RNase H activity of full length recombinant HIV1 reverse transcriptase assessed as reduction in DNA 3'-end cleavage using HTS2 substrate
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 329.74, ALogP 2.84, HBA 5, HBD 3, PSA 87.12, QED 0.64
Compound (SMILES): C/C=C/c1nnn(Cc2ccc(C(F)(F)F)cc2)c1C(=O)NCc1ccc(C(=O)O)cc1
InChIKey: KIFOLGWAKJFARK-NSCUHMNNSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Mus musculus
UniProt: P32240
Assay: Antagonist activity at mouse EP4 expressed in CHO cells coexpressing G16-alpha assessed as intracellular calcium flux preincubated for 15 mins followed by addition of PGE2 by calcium flux assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 444.41, ALogP 4.01, HBA 5, HBD 2, PSA 97.11, QED 0.57
Compound (SMILES): COc1cccc(C(=O)Cn2cnc3ccccc32)c1
InChIKey: ORCOJUWYWLCLIJ-UHFFFAOYSA-N
Target: Chromodomain Y-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N8U2
Assay: Binding affinity to recombinant human N-terminal GST-tagged CDYL2 (1 to 70 residues) expressed in Escherichia coli BL2 by SPR analysis
Measurement: Kd = 56200 nM (pChEMBL 4.25)
Descriptors: MW 266.3, ALogP 2.93, HBA 4, HBD 0, PSA 44.12, QED 0.68
Compound (SMILES): Cc1cc(CNC(=O)c2csc(CCNCc3nc4ccccc4[nH]3)n2)ccn1
InChIKey: MNGVYJXTKAOVTA-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 4327 nM (pChEMBL 5.360000133514404)
Descriptors: MW 406.52, ALogP 2.99, HBA 6, HBD 3, PSA 95.59, QED 0.39
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3cncnc3)c(O)c(F)c2Br)C1=O
InChIKey: IEANUCBEHWUTGX-JYOAFUTRSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with interferon stimulatory DNA and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 440.25, ALogP 3.33, HBA 7, HBD 1, PSA 92.62, QED 0.73
Compound (SMILES): Cl.O=C(O)C1CCCN(CCO/N=C/c2ccccc2-c2ccc(Cl)cc2Cl)C1
InChIKey: AILJISZBVRATFZ-KEJAMGHHSA-N
Target: GABA transporter 3 (SINGLE PROTEIN), Mus musculus
UniProt: P31649
Assay: Inhibition of mouse GAT-2 expressed in HEK293 cells assessed as decrease in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 10 mins by scintillation counting analysis
Measurement: IC50 = 45708.82 nM (pChEMBL 4.340000152587891)
Descriptors: MW 421.32, ALogP 4.81, HBA 4, HBD 1, PSA 62.13, QED 0.4
Compound (SMILES): Cc1ccc(NC(=O)c2ccnc(C(F)(F)F)c2)cc1-c1cc(NCCO)nc(N2CCOCC2)c1
InChIKey: PXMHFJJONBKRDM-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of CRAF Y340E/Y341E mutant (unknown origin) using human MEK1 K97R mutant as substrate pretreated for 30 mins followed by substrate addition measured after 40 mins by alphascreen assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 501.51, ALogP 3.96, HBA 7, HBD 3, PSA 99.61, QED 0.45
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)nc2ccccc12)c1cccc([N+](=O)[O-])c1
InChIKey: INIHDUJEBIVBBD-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of GFP-fused human ABCG2 expressed in MDCK2 cells assessed as potentiation of mitoxantrone-induced cytotoxicity after 72 hrs by MTT assay
Measurement: IC50 = 47.3 nM (pChEMBL 7.329999923706055)
Descriptors: MW 370.37, ALogP 4.46, HBA 5, HBD 1, PSA 98.02, QED 0.42
Compound (SMILES): CCCN(CCCCNC(=O)c1cc2ccccc2[nH]1)CC1CC1c1cccc(Cl)c1Cl.Cl
InChIKey: SUJXBDJLOIDKBO-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D2 receptor stably expressed in fibroblast cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 1502 nM (pChEMBL 5.820000171661377)
Descriptors: MW 472.46, ALogP 6.5, HBA 2, HBD 2, PSA 48.13, QED 0.31
Compound (SMILES): CC(=O)/C=C/[C@H](CCc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc2c(c1)OCCO2
InChIKey: VTRSKGWSVOGHRX-KIWHWNASSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human Cathepsin L assessed as inhibition constant using Cbz-Phe-Arg-AMC as substrate by fluorescence assay
Measurement: Ki = 78.2 nM (pChEMBL 7.110000133514404)
Descriptors: MW 512.61, ALogP 4.06, HBA 5, HBD 2, PSA 93.73, QED 0.38
Compound (SMILES): CCCn1cc(-c2cc3c4c(ccc(NS(=O)(=O)c5ccccc5OC)c4c2)N(C)C3=O)cn1
InChIKey: VQSCASYQNZDOTF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of tetra-acetylated histone H4 peptide (1-21) from recombinant human N-terminal His-tagged BRD4 BD2 (349 to 460 residues) expressed in Escherichia coli incubated for 30 mins followed by further incubation with tetra-acetylated histone H4 peptide (1-21) for 30 mins by Alphascreen assay
Measurement: IC50 = 265.6 nM (pChEMBL 6.579999923706055)
Descriptors: MW 476.56, ALogP 4.51, HBA 6, HBD 1, PSA 93.53, QED 0.42
Compound (SMILES): COc1ccc2c(c1)[C@]13CCN(S(=O)(=O)c4ccccc4)[C@H](C2)[C@@H]1CC[C@H](N(C)C(=O)/C=C/c1ccoc1)C3
InChIKey: CHLAMJXRDIVYQK-LLJBSZEZSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human OX2 receptor expressed in CHOK1 cells assessed as inhibition of orexin-A-induced calcium mobilization preincubated for 15 mins followed by orexin-A addition and measured by FURA 2-AM dye based fluorescence assay
Measurement: Ki = 79.9 nM (pChEMBL 7.099999904632568)
Descriptors: MW 546.69, ALogP 4.89, HBA 5, HBD 0, PSA 80.06, QED 0.41
Compound (SMILES): Cc1nn(-c2ccc(CN)cc2)c(C)c1-c1ccc(Cl)cc1
InChIKey: ZXZCYOIIQYFCCB-UHFFFAOYSA-N
Target: Acid-sensing ion channel 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q925H0
Assay: Inhibition of pH 5.5-stimulated mouse ASIC2a homomer expressed in CHOK1 cells assessed as reduction in channel activation by VSD fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 311.82, ALogP 4.27, HBA 3, HBD 1, PSA 43.84, QED 0.78
Compound (SMILES): Cn1cc(-c2cc(C(=O)N[C@@H]3CCN(C#N)C3)ccc2F)cn1
InChIKey: JIQQUTLHGNCQEO-CYBMUJFWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 313.34, ALogP 1.51, HBA 5, HBD 1, PSA 73.95, QED 0.87
Compound (SMILES): CC(C)CCc1c(OCCOc2cccc(/C=C/C(=O)NO)c2)ccc2c1OC(=O)CC2
InChIKey: WANCIXSROFZVFM-KPKJPENVSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human His-tagged HDAC6 expressed in baculovirus infected insect cells using Boc Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 439.51, ALogP 4.1, HBA 6, HBD 2, PSA 94.09, QED 0.14
Compound (SMILES): Cc1nnc2n1-c1ccc(-c3ccc(N)nc3)cc1C(Nc1ccc(C#N)cc1)CC2
InChIKey: JYYLBPCIPZULEH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human recombinant BRD4 BD1 (44 to 168 residues) by fluorescence polarization assay
Measurement: Ki = 508 nM (pChEMBL 6.289999961853027)
Descriptors: MW 407.48, ALogP 4.19, HBA 7, HBD 2, PSA 105.44, QED 0.53
Compound (SMILES): Cc1c(NC(=O)[C@H](c2ccc(-c3cncc(Cl)c3)cc2)C2CCCC2)cccc1[C@H](C)CC(=O)O
InChIKey: ZMPUWAPOGIXWRT-WRHNGFHOSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Mus musculus
UniProt: Q9JM51
Assay: Inhibition of mouse recombinant FLAG-tagged PTGES expressed in baculovirus infected Hi-5 insect cells using prostaglandin H2 as substrate incubated for 20 mins followed by substrate addition and incubated for 60 sec by TR-FRET assay
Measurement: IC50 = 3080 nM (pChEMBL 5.510000228881836)
Descriptors: MW 491.03, ALogP 7.2, HBA 3, HBD 2, PSA 79.29, QED 0.35
Compound (SMILES): COc1nc(-c2cccc3c2OCCO3)ccc1Nc1ccc(CN(C)C)cc1
InChIKey: MJHHFDJNRRCUOB-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Binding affinity to GST-tagged GppNHp bound KRas G12V mutant (unknown origin) expressed in Escherichia coli C41(DE3) by 1H-CPMG NMR spectroscopy
Measurement: Kd = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 391.47, ALogP 4.33, HBA 6, HBD 1, PSA 55.85, QED 0.67
Compound (SMILES): COc1cccc(N2CCN(CCCCCCN3C(=O)c4ccccc4S3(=O)=O)CC2)c1
InChIKey: PBVURPVGJYNWJV-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]raclopride from full length human cloned D2L receptor expressed in HEK293 cells incubated for 1 hr by radioligand displacement assay
Measurement: Ki = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 457.6, ALogP 3.22, HBA 6, HBD 0, PSA 70.16, QED 0.54
Compound (SMILES): O=C(OCCc1ccc2c(c1)OCO2)N(c1ccccc1)C1CN2CCC1CC2
InChIKey: MYODZQJNSSBKEB-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]NMS from human M3 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 394.47, ALogP 3.7, HBA 5, HBD 0, PSA 51.24, QED 0.77
Compound (SMILES): Oc1ccc(CCNc2nc(C#Cc3ccccc3)nc3c2ncn3[C@H]2[C@H](O)[C@H](O)[C@@H]3C[C@@H]32)cc1F
InChIKey: KGGHGIFVNOZTSG-LJWFOBJUSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I]I-AB-MECA from recombinant mouse A3AR expressed in HEK293 cell membranes measured after 60 mins by liquid scintillation counting method
Measurement: Ki = 61.6 nM (pChEMBL 7.210000038146973)
Descriptors: MW 485.52, ALogP 2.64, HBA 8, HBD 4, PSA 116.32, QED 0.32
Compound (SMILES): COc1ccc(CNC(=O)N2CCN(c3ccc(C(C)=O)cc3)CC2)cn1
InChIKey: IWZIKMPFQUSSMX-UHFFFAOYSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Inhibition of C-terminal His6-tagged MLLT1 YEATS domain (1 to 148 residues) (unknown origin) expressed in Escherichia coli Rosetta by alphascreen assay
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 368.44, ALogP 2.32, HBA 5, HBD 1, PSA 74.77, QED 0.82
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)nc2sc(-c3ccco3)nc12)c1ccccc1
InChIKey: BTDPUZHZCQINFZ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]NECA from human adenosine A2A receptor expressed in CHO cells after 3 hrs by scintillation counting method
Measurement: Ki = 1144 nM (pChEMBL 5.940000057220459)
Descriptors: MW 398.45, ALogP 5.27, HBA 6, HBD 1, PSA 80.91, QED 0.45
Compound (SMILES): COc1c(-c2cncc(-c3ccc(N4CCNCC4)cc3)c2C)csc1C(N)=O
InChIKey: QISPCHIVQPQHBT-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 10 uM [gamma33P] ATP by radioactive assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 408.53, ALogP 3.3, HBA 6, HBD 2, PSA 80.48, QED 0.68
Compound (SMILES): O=C(NCC1CC1)c1ccc2nc(Nc3cc(CN4CCN(C(=O)CC(F)(F)F)CC4)ccn3)[nH]c2c1
InChIKey: BYGZCGOGQACGKA-UHFFFAOYSA-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 10 uM of ATP by TR-FRET assay
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 515.54, ALogP 3.44, HBA 6, HBD 3, PSA 106.25, QED 0.42
Compound (SMILES): Cc1ccc(-c2cc(S(C)(=O)=O)cc(S(=O)(=O)c3cnc(CN)s3)c2)cc1.Cl.Cl
InChIKey: NGEBQJGZUQUJHR-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAOA expressed in yeast incubated for 1 hr by luminescence based assay
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 422.55, ALogP 2.81, HBA 7, HBD 1, PSA 107.19, QED 0.68
Compound (SMILES): Cl.N=C(N)c1ccc(NCC2Cc3ccccc3B(O)O2)cc1
InChIKey: IEUHBWQCKSZKCU-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibition of human recombinant N-terminal His-tagged and enterokinase cleavage site-fused KLK1 (19 to 262 residues) expressed in baculovirus infected Sf9 insect cells using R110 labelled GSK3162232A as substrate measured at 30 secs interval for 5 mins by FLINT assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 295.15
Compound (SMILES): CSCC[C@H](NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(N)=O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O
InChIKey: ZAEUKWQDCRNREI-RJIAEONKSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 1931 nM (pChEMBL 5.710000038146973)
Descriptors: MW 3104.73
Compound (SMILES): O=C(/C=C/c1ccc(OCCCCN2CCCCC2)cc1)c1ccc(OCCCCN2CCCCC2)cc1O
InChIKey: AYQQQEJLVLPUBT-QGOAFFKASA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine butyrylcholinesterase using butyrylthiocholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 534.74, ALogP 6.58, HBA 6, HBD 1, PSA 62.24, QED 0.16
Compound (SMILES): CCCCCCCOc1ccc(S(=O)(=O)Nc2ccc(F)c(C(=O)O)c2)c2ccccc12
InChIKey: XSRNBQDPCPRAAE-UHFFFAOYSA-N
Target: Fatty acid-binding protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01469
Assay: Displacement of 1,8-ANS from human recombinant full length N-terminal his-tagged FABP5 expressed in Escherichia coli BL21 (DE3) incubated for 3 mins by fluorescence based assay
Measurement: IC50 = 2760 nM (pChEMBL 5.559999942779541)
Descriptors: MW 459.54, ALogP 5.83, HBA 4, HBD 2, PSA 92.7, QED 0.35
Compound (SMILES): CCOc1ccc(Cc2nc3cc(C(=O)N(CC)CC)ccc3n2CCCCCCNc2c3c(nc4ccccc24)CCCC3)cc1
InChIKey: UTGZBXOXPAIMOK-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured for 3 mins by spectrophotometry based Ellman's method
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 631.87, ALogP 8.61, HBA 6, HBD 1, PSA 72.28, QED 0.12
Compound (SMILES): NC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SCc1ccccc1
InChIKey: ANNKSEHPPUSPLF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 356.86, ALogP 2.38, HBA 4, HBD 2, PSA 103.25, QED 0.8
Compound (SMILES): COc1ccc(Oc2cc(NCCC(F)(F)F)c3ncc(-c4ccc(C(=O)NC5CC5)c(C)c4)n3n2)c(F)c1F
InChIKey: WNEILUNVMHVMPH-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 = 1 nM (pChEMBL 9)
Descriptors: MW 561.51, ALogP 6.04, HBA 7, HBD 2, PSA 89.78, QED 0.24
Compound (SMILES): O=C(O)CC(CCc1ccccc1)O[C@H]1O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: HRYIDVZLDQBLFF-HURARVKQSA-N
Target: Synaptojanin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43426
Assay: Inhibition of C-Myc/DDK-tagged human recombinant SYNJ1 expressed in HEK293T cells assessed as reduction in 5'-phosphatase activity incubated for 8 mins using fluorescently-labeled PI(3,4)P2 probe and Tapp1 PH-domain as detector protein by fluorescence polarization competitive assay
Measurement: IC50 <= 15900 nM (pChEMBL 4.798999786376953)
Descriptors: MW 356.37, ALogP -0.72, HBA 7, HBD 5, PSA 136.68, QED 0.41
Compound (SMILES): CN1CCc2ccc(OCCCN3CCCC3)cc2C1=O
InChIKey: WEWYQJLCNKLTRV-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P31389
Assay: Displacement of [3H]-mepyramine from histamine H1 receptor in guinea pig cerebellum homogenates incubated for 60 mins by Cheng and Prusoff equation analysis by scintillation counting analysis
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 288.39, ALogP 2.18, HBA 3, HBD 0, PSA 32.78, QED 0.78
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(c5cccc(OC)c5)CC4)cc3)[nH]c2c1=O
InChIKey: YKOORYUATMJZNO-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX-2 from recombinant human A2A adenosine receptor expressed in CHO cell membranes measured after 30 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 197 nM (pChEMBL 6.710000038146973)
Descriptors: MW 524.6, ALogP 2.01, HBA 8, HBD 2, PSA 133.39, QED 0.38
Compound (SMILES): CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C4CCN(C)CC4)cc3OC)nc2N1C1CCCC1
InChIKey: WCMQEPUDHFATFM-JOCHJYFZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 (unknown origin) by isothermal calorimetry
Measurement: Kd = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 478.64, ALogP 4.54, HBA 7, HBD 1, PSA 73.83, QED 0.65
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: SXIFJSHGLQMOET-GECFALDLSA-N
Target: Kallikrein-14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0G3
Assay: Inhibition of recombinant KLK14 (unknown origin) expressed in Spodoptera frugiperda Sf9 cells using pNA peptide as susbtrate measured every 10 secs for 300 secs by spectrophotometric analysis
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1512.83
Compound (SMILES): COc1ccccc1Nc1c([N+](=O)[O-])cnc2cc(OCCCN(C)Cc3ccccc3)c(OC)cc12
InChIKey: QZKXJNZGOOPXEI-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 502.57, ALogP 5.8, HBA 8, HBD 1, PSA 98.99, QED 0.15
Compound (SMILES): CS(=O)(=O)c1cc(C2(NC(=O)c3cncc4c3cnn4-c3ccc(F)cc3)CC2)ccn1
InChIKey: PXQATVYJKMMHAU-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Ca flux
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 451.48, ALogP 2.78, HBA 7, HBD 1, PSA 106.84, QED 0.5
Compound (SMILES): C=CC(=O)N1CC(NC(=O)Cn2cc(C(=O)N3CCc4cc(F)ccc4C3)c3cc(Br)ccc32)C1
InChIKey: SGFLLRQDMOQUFI-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of GDP bound N terminal His-tagged KRAS G12C/C118A mutant (unknown origin) (1 to 169 residues) assessed as reduction in SOS-mediated guanine nucleotide exchange preincubated for 2 hrs followed by addition of SOS and GTP and measured after 1 hr by alphascreen assay
Measurement: IC50 = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 539.41, ALogP 3.25, HBA 4, HBD 1, PSA 74.65, QED 0.51
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CCCCNC(=O)CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: NVUJLWOOQCRILM-QQVIFTEYSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1733.97
Compound (SMILES): C=CC(=O)NCc1ccc(OC)c(Nc2nc(Nc3ccccc3C(=O)NC)c3cc[nH]c3n2)c1
InChIKey: LBDQNZXQCZAHPP-UHFFFAOYSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Bos taurus
UniProt: P21146
Assay: Inhibition of bovine GRK2 using tubulin as substrate measured after 4 hrs by [gamma-32P]-ATP assay
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 471.52, ALogP 3.62, HBA 7, HBD 5, PSA 133.06, QED 0.24
Compound (SMILES): C[C@H]1CC2(CCN(C[C@@H](O)c3ccc4c(ccc5nnnn54)c3)CC2)C(=O)N1C1=CC(=O)OC1
InChIKey: SUFBPVQFOFQPFD-MGPUTAFESA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Thallium Flux Assay: A Thallium Flux Assay was performed on the compounds of the Examples. This assay has been described previously; see, e.g., PCT Published Application WO 2013/062900.Data collected for compounds in the Examples of the present invention using the Thallium Flux Assay are shown in Table 3 below. All of the tested final product compounds in the Examples (diastereomeric mixtures and individual diastereomers) had IC50 potencies less than 1 μM in the Thallium Flux Assay.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 462.51, ALogP 1.45, HBA 9, HBD 1, PSA 113.16, QED 0.58
Compound (SMILES): NC(=O)c1ccc(-c2cccnc2)cc1OC1CCCCC1
InChIKey: RRMZWSJUDDSFBE-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition of N-terminal GST-tagged MNK2 (unknown origin) (72 to 385 residues) expressed in Escherichia coli BL21 (DE3) cells using 5-FAM-TATKSGSTTKNRFVV-NH2 peptide as substrate preincubated with enzyme for 10 mins followed by substrate addition after 60 mins in presence of ATP by caliper mobility shift assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 296.37, ALogP 3.56, HBA 3, HBD 1, PSA 65.21, QED 0.94
Compound (SMILES): O=C(O)CC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)c1cc2cc(Cl)ccc2[nH]1)C(=O)Nc1cccc(Cl)c1
InChIKey: OTFLOKLOTVOQMO-QMOZSOIISA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Inhibition of C-terminal fluorescein-labeled human TCF4 (7 to 51 residues) binding to wild-type C-terminal His6-tagged beta-catenin (138 to 781 residues) expressed in Escherichia coli BL21 DE3 measured after 2.5 hrs by fluorescence polarization assay
Measurement: Ki = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 746.6, ALogP 4.92, HBA 6, HBD 7, PSA 206.79, QED 0.08
Compound (SMILES): CC(C)CCCCc1ccc(S(=O)(=O)C2C3CCC(N3)C2NCc2ccc3ccccc3c2)cc1
InChIKey: BAUBQOTWYPOLPN-UHFFFAOYSA-N
Target: Plasmepsin 4 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q17SB2
Assay: Inhibition of Plasmodium falciparum plasmepsin 4 using fluorescently labeled peptide substrate by fluorescence method
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 490.71, ALogP 5.64, HBA 4, HBD 2, PSA 58.2, QED 0.36
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)OC(C)(C)C
InChIKey: AYHIIPXNEIYSCP-YFNKSVMNSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 762.77, ALogP 3.17, HBA 12, HBD 6, PSA 277.41, QED 0.03
Compound (SMILES): Cc1nc(-c2ccc(N3C(=O)C(O)=C(C(=O)C(C)(C)C)C3c3ccccc3OCCO)cc2)no1
InChIKey: QJLZVQJRDNURDX-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 477.52, ALogP 3.93, HBA 8, HBD 2, PSA 125.99, QED 0.52
Compound (SMILES): CC1=C(N2CCC3(CCN(CCc4ccc5c(c4)Cn4nnnc4-5)CC3)C2=O)COC1=O
InChIKey: BSQXZHQSWBZCSM-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Thallium Flux Assay: A Thallium Flux Assay was performed on the compounds of the Examples. This assay has been described previously; see, e.g., PCT Published Application WO 2013/062900.Data collected for compounds in the Examples of the present invention using the Thallium Flux Assay are shown in Table 3 below. All of the tested final product compounds in the Examples (diastereomeric mixtures and individual diastereomers) had IC50 potencies less than 1 μM in the Thallium Flux Assay.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 434.5, ALogP 1.39, HBA 8, HBD 0, PSA 93.45, QED 0.57
Compound (SMILES): CC(C)(C)c1cc(C(c2ccccn2)N2CCN(C(C)(C)C)CC2)cc(C(C)(C)C)c1O
InChIKey: UDNYKXHBXWUVQU-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of N-terminal 6-His-tagged IDH1 R132C mutant (unknown origin) expressed in Escherichia coli BL21 cells using alpha-KG as substrate in presence of NADPH incubated for 40 mins by fluorescence assay
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 437.67, ALogP 5.89, HBA 4, HBD 1, PSA 39.6, QED 0.65
Compound (SMILES): COc1cc(F)cc2c1nnc1c2c(-c2ccncc2C)nn1C
InChIKey: BEHIYTQDLXFKJV-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of human PDE2A using cAMP as substrate measured after 60 mins
Measurement: IC50 = 3520 nM (pChEMBL 5.449999809265137)
Descriptors: MW 323.33, ALogP 3.03, HBA 6, HBD 0, PSA 65.72, QED 0.57
Compound (SMILES): N#Cc1ccc(Cn2nccc2-c2cc(Cl)c3nnn(-c4ccc5[nH]c(=O)[nH]c5c4)c3c2)nc1
InChIKey: GONXKSIPTDHRRR-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human liver microsome CYP1A2 using phenacetin as substrate incubated for 5 to 20 mins by LC-MS/MS analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 467.88, ALogP 3.42, HBA 8, HBD 2, PSA 133.86, QED 0.41
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C1=O
InChIKey: JOORNLXAAOZDNT-AKGHTDQDSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of LAP binding to human integrin alphavbeta6 receptor after 1 hr by solid-phase binding assay
Measurement: IC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 777.88, ALogP -3.65, HBA 10, HBD 10, PSA 314.42, QED 0.06
Compound (SMILES): O=c1[nH]c2ccc(Cl)cc2cc1CNc1cccn(C2CC2)c1=O
InChIKey: DHDHUTUALAFFMG-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Cell Based Assays: The cellular potency of Compound 1 in suppressing intracellular 2-HG levels was determined in cell lines expressing five different mutated IDH-1 proteins found in human cancers (R132H, R132C, R132G, R132L, R132S). The human fibrosarcoma cell line HT-1080 harbors a naturally occurring heterozygous IDH-1 R132C mutation. The human colorectal carcinoma cell line HCT 116 is wild type for IDH-1, but heterozygous mutations coding for IDH-1 R132H or R132C were introduced by knock-in into the endogenous IDH-1 gene locus. Finally, the human astrocytoma cell line U-87 MG is also wild type for IDH-1, but expression of five different mutated IDH-1 proteins was achieved by stable transfection.The parental HCT 116 line (colon) line does not produce high levels of 2-HG, but the variants used herein (X-MAN HCT-116 lines obtained from Horizon Discovery Ltd.) are engineered to knock-in a heterozygous mutation of either IDH-1 R132H or IDH-1 R132C. This recapitulates the cellular context in mIDH-1 cancer cells where there are both wild type and mutant IDH-1 subunits that together form a heterodimer that is responsible for the production of elevated levels of 2-HG. These modified lines can be used as models of IDH-1 mutant disease.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 341.8, ALogP 3.29, HBA 4, HBD 2, PSA 66.89, QED 0.76
Compound (SMILES): C[C@H]1NC(=O)c2cc(-c3cccc4c(=O)n(C5(C)CC5)c(NC(C)(C)C)nc34)[nH]c21
InChIKey: UMICCZFMUZBZJG-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of full length recombinant PIM2 (unknown origin) assessed as reduction in BAD phosphorylation at Ser112 residues preincubated for 30 mins followed by biotinylated BAD addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 405.5, ALogP 3.92, HBA 5, HBD 3, PSA 91.81, QED 0.62
Compound (SMILES): N#Cc1ccc(C[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)Nc2ccccc2)cc1
InChIKey: CGIRLPKWGZMBGL-NSVAZKTRSA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Inhibition of C-terminal fluorescein-labeled human TCF4 (7 to 51 residues) binding to wild-type C-terminal His6-tagged beta-catenin (138 to 781 residues) expressed in Escherichia coli BL21 DE3 measured after 2.5 hrs by fluorescence polarization assay
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 687.11, ALogP 2.98, HBA 7, HBD 7, PSA 230.58, QED 0.1
Compound (SMILES): CNC(=O)NC1CCN(Cc2cc3nc(-c4cccc5[nH]ncc45)nc(N4CCOCC4)c3s2)CC1
InChIKey: RCPUILDBAFKLMC-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 506.64, ALogP 2.96, HBA 8, HBD 3, PSA 111.3, QED 0.38
Compound (SMILES): CCO/C=N/c1nnc(-c2ccc(Cl)cc2)o1
InChIKey: XYPUMFPZCABHTQ-NTUHNPAUSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX-2 by EIA method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 251.67, ALogP 3.09, HBA 5, HBD 0, PSA 60.51, QED 0.62