lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1c(Br)cc(Cl)c2nc(CCc3nc(N4CCCC4)nn3C)nn12
InChIKey: YSHVXPJMAINWHF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat # SE-534) with or without a specific test compound. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC50, the concentration of the competitor inhibiting PDE10A activity by 50%). Non-specific activity was tested without the enzyme. The reaction was initiated by the addition of the substrate solution (cGMP and [3H]-cGMP) and allowed to progress for 20 minutes at room temperature. The reaction was terminated by adding 25 μl of YSi-SPA scintillation beads (GE Healthcare, cat. # RPNQ0150) in 18 mM zinc sulphate solution (stop reagent). After 1 h under shaking, the plate was centrifuged one minute at 170 g to allow beads to settle. Afterwards, radioactive counts were measured on a Perkin Elmer Top-Count Scintillation plate reader.
Measurement: IC50 = 1.22 nM (pChEMBL 8.90999984741211)
Descriptors: MW 424.73, ALogP 2.97, HBA 7, HBD 0, PSA 64.14, QED 0.64
Compound (SMILES): CN[C@H]1c2ccc3c(ccn3S(=O)(=O)c3ccccc3)c2[C@@H]1CCO
InChIKey: LXQQHMVSKDDSKV-LPHOPBHVSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methyl-spiperone from human dopamine D2L receptor expressed in HEK293 cell membranes after 1 hr by radioligand binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 356.45, ALogP 2.62, HBA 5, HBD 2, PSA 71.33, QED 0.74
Compound (SMILES): CC(C)NS(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(OC(F)(F)F)cc2)nc2c1CCN2
InChIKey: VIEFXBYMSANHKZ-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biochemical Assay: To measure inhibitory activity of FAK/PYK2 inhibitors, compounds were first prepare as a 1 mM stock in 100% DMSO and 3-fold serial dilution was performed in a 96-well plate (Corning, 3897) to generate 12 different concentration of 100× stock. A 5 μl of 100× stock of each concentration was added to wells containing 95 μl of 1× reaction buffer (40 mM Tris, pH7.5, mM MgCl2, 1 mM DTT and 1 mM CHAPS) to generate 5× stock. Then 2 μl of 5× stock of each concentration was added to a 384 wells-OptiPlate (PerkinElmer, 6007299). For FAK, 4 μl of 2.5 nM FAK, 1 μl of 8 μg/μl BSA and 1.5 μl of 666 nM ULight-poly Glu, Ala, Tyr (1:1:1) peptide substrate, prepared in above reaction buffer, were added to each well. The reaction was initiated by adding 1.5 μl of 33.3 μM ATP. The reaction was allowed to proceed for 120 min before being quenched with 5 μl of 40 mM EDTA stop buffer prepared in 1×LANCE detection buffer (PerkinElmer, CR97-100). For PYK2, 5 μl of 2 nM PYK2 and 1.5 μl of 666 nM ULight-poly Glu, Ala, Tyr (1:1:1) peptide substrate, prepared in above reaction buffer, were added to each well. The reaction was initiated by adding 1.5 μl of 46.6 μM ATP. The reaction was allowed to proceed for 40 min before being quenched with 5 μl of 40 mM EDTA stop buffer prepared in 1×LANCE detection buffer (PerkinElmer, CR97-100). Upon quenching of the reaction, 5 μl of 8 nM anti-phosphotyrosine antibody was added to each well and incubated for 60 minutes.
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 508.53, ALogP 4.52, HBA 8, HBD 4, PSA 117.27, QED 0.35
Compound (SMILES): COC(=O)CCC/C=C\C[C@H]1C(=O)C(C)(C)[C@@H](O)[C@@H]1/C=C/C(O)CCc1sc2ccccc2c1Cl
InChIKey: KXQYFWREBNFZKI-HFZQZZKLSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding: HEK-293 cells stably expressing the human or feline FP receptor, or EP1, EP2, EP3, or EP4 receptors were washed with TME buffer, scraped from the bottom of the flasks, and homogenized for 30 sec using a Brinkman PT 10/35 polytron. TME buffer was added to achieve a final 40 ml volume in the centrifuge tubes (the composition of TME is 100 mM TRIS base, 20 mM MgCl2, 2M EDTA; 10 N HCl is added to achieve a pH of 7.4).The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4 C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2 (5 nM) were performed in a 100 ul volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell.
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 519.1, ALogP 5.9, HBA 6, HBD 2, PSA 83.83, QED 0.22
Compound (SMILES): Cc1nc(C)n(CC(=O)N2CCN(c3sc(C(F)(F)F)nc3-c3nc4ccc(N5CCOCC5)cc4[nH]3)C[C@H]2C)n1
InChIKey: XVZNCFNOCOZMAS-OAHLLOKOSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: FLIPR Assay: The bioactivity of compounds is tested in a fluorometric imaging plate reader (FLIPR: Molecular Devices) using engineered CHO-K1 cells expressing the human CXCR3A coupled to a G protein (Galpha(16)). Cells are plated the day prior to bioassay in F12 medium supplemented with 10% FBS and G418 and hygromycin antibiotics to maintain recombinant selection. At the day of bioassay, cells are washed and dye loaded for one hour with Fluo-4-AM (Invitrogen) in Hanks Balanced Salt Solution (Invitrogen), buffered with 20 mM Hepes at pH 7.4 and sodium bicarbonate (0.015%), containing 5 mM probenecid. This buffer, but lacking the dye and containing probenecid at a concentration of 2.5 nM, is also is used for washing steps (wash buffer); or lacking both dye and probenecid but supplemented with 0.1% BSA for compound dilution steps (dilution buffer). Cells are washed free of excess dye and 60 microliter of wash buffer is added. Stock solutions of test compounds are made up at a concentration of 10 mM in DMSO, and serially diluted in dilution buffer to concentrations required for inhibition dose response curves. After a 10 minute incubation period at 37° C., 10 microliters of each compound dilution are transferred from a compound plate to the plate containing the recombinant cells in the FLIPR instrument according to the manufacturer's instructions. Following basal readings, 10 microliter CXCL10 agonist at a concentration of 20 nM (from Peprotech) is added, again using the FLIPR instrument. Changes in fluorescence are monitored before and after addition of the test compounds.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 589.65, ALogP 3.49, HBA 10, HBD 1, PSA 108.3, QED 0.38
Compound (SMILES): Nc1ccccc1NC(=O)CCCCNC(=O)c1ccno1
InChIKey: RJPNUUOJSBLPJS-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: HDAC enzyme inhibitionAssay: HDAC enzyme inhibition assays were performed using purified HDACs 1-10 essentially as described in Beckers et al., 2007, Int. J. Cancer., 121:1138-48 and Perez-Balado et al., 2007, J. Med. Chem., 50:2497-2505. Inhibition assays using nuclear extract were performed essentially as described in Herman et al., 2006, Nat. Chem. Biol., 2:551-558. Briefly, the purified HDACs or nuclear extract were incubated with an acetylated substrate in the absence of the compound to be assayed and with increasing concentrations of the compound. The rate of substrate deacetylation was measured under each condition, and half-maximal inhibitory concentration with regard to each HDAC was determined by standard means.
Measurement: IC50 = 32850 nM (pChEMBL 4.480000019073486)
Descriptors: MW 302.33, ALogP 1.8, HBA 5, HBD 3, PSA 110.25, QED 0.53
Compound (SMILES): CC1(COC(=O)N2CC[C@@H](C#N)[C@H](n3cc(C(N)=O)c(Nc4ccc(F)cc4)n3)C2)CC1
InChIKey: FGNZGLOLAGQBCO-KBXCAEBGSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Biochemical HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 μL of 1.11× enzyme and 1.11× substrate in 1× assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 μL of 10×ATP in 1× assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at ambient temperature for 120 minutes. At the end of the incubation, 20 μL of 2× stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction. Plates were shaken and centrifuged and then incubated 60 minutes at ambient temperature and then read on a Perkin Elmer Envision (λex=337 nm, λem=665 and 615 nm, TRF delay time=20 μs). HTRF signal=10,000*665 nm reading/615 nm reading.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 440.48, ALogP 3.19, HBA 7, HBD 2, PSA 126.27, QED 0.71
Compound (SMILES): COCCNc1cc(NC(=O)N2CCCc3cc(N4CCC(C)C4=O)c(C=O)nc32)ncc1C#N
InChIKey: QDWHWMTWLHLMDN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Biochemical Kinase Assay: Liquid handling and incubation steps were done on an Innovadyne Nanodrop Express equipped with a robotic arm (Thermo CatX, Caliper Twister II) and an incubator (Liconic STX40, Thermo Cytomat 2C450). The assay plates were prepared by addition of 50 nl per well of compound solution in 90% DMSO. The kinase reactions were started by stepwise addition of 4.5 ul per well of peptide/ATP-solution (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% Tween20, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 uM sodium orthovanadate, 16 mM MgCl2, 1122 uM ATP, 4 uM peptide (5-Fluo-Ahx-KKKKEEIYFFFG-NH2, Biosyntan GmbH) and 4.5 ul per well of enzyme solution (50 mM HEPES, pH 7.5, 1 mM DTT, 0.02% Tween20, 0.02% BSA, 0.6% DMSO, 10 mM beta-glycerophosphate, and 10 uM sodium orthovanadate, 16 mM MgCl2, 6 nM FGFR4 (GST-FGFR4(388-802), produced in-house by expression in insect cells and affinity chromatography). Kinase reactions were incubated at 30° C. for 60 minutes and subsequently terminated by addition of 16 ul per well of stop solution (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35).
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 477.53, ALogP 2.58, HBA 8, HBD 2, PSA 140.55, QED 0.46
Compound (SMILES): Cc1cc(N)nc(C)c1CNC(=O)c1ccn(S(=O)(=O)c2ccc(-c3ccccc3)cc2)c1
InChIKey: UQGMQMRTUNUSCX-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: In-vitro Plasma Kallikrein Inhibition: Enzymatic reactions were conducted in â¿¿assay bufferâ¿¿, comprising 50 mM Hepes/NaOH at pH 7.8, 150 mM NaCl, 1 mM EDTA and 0.05% (w/v) CHAPS. For the determination of IC50 values, the assays were performed at room temperature in 384-well plates with a total assay volume of 25.25 ul per well. The test compound was dissolved in 90% (v/v) DMSO/water. For the assays, 250 nL of the 90% (v/v) DMSO/water solution or compound solution were added per well, followed by the addition of 12.5 ul protease solution (protease in assay buffer). The final assay concentration of the human plasma kallikrein was nominally 25 pM, the 11 compound concentrations in the dilution series were in the range form 1 nM to 100 uM. After 1 hour of pre-incubation at room temperature, the reactions were started by the addition of 12.5 ul substrate solution (in assay buffer, final assay concentration was 0.5 uM). After the addition of the substrate solution, the final DMSO concentration in the assay was 0.9% (v/v).
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 460.56, ALogP 3.92, HBA 6, HBD 2, PSA 107.08, QED 0.45
Compound (SMILES): CC1CCCN1c1cccc(Nc2cc(-c3cccc(CNC4CCNCC4)c3)nn3ccnc23)n1
InChIKey: HZQSZSYYPVFONP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition Assay: Assay plates: 96-well MultiScreen 0.65 um filter plates (Millipore Cat. No.: MADVNOB10)Streptavidin coated beads: Streptavidin Sepharose, suspension 5.0 mL, in 50 mM EDTA/PBS diluted (1:100), (Amersham, Cat. No.: 17-5113-01)Compounds: 10 mM in 100% dimethylsulfoxide (DMSO), final conc.: compound 0.003-100 uM in 10% DMSOEnzyme: SYK RPA purified, truncated construct of Spleen Tyrosine Kinase aa 360-635, stock solution 1 mg/mL, MW: 31.2 KDa, final conc.:0.0005 uM. Peptide 1: biotinylated peptide is derived from a naturally occurring phosphor-acceptor consensus sequence (Biotin-EPEGDYEEVLE), special order from QCB, stock solution 20 mM, final conc.: 5.0 uM.ATP: Adenosine-5'-triphosphate 20 mM, (ROCHE Cat. No.: 93202720), final concentration: 20 uM Buffer: HEPES: 2-Hydroxyethyl piperazine-2-ethanesulfonic acid (Sigma, Cat. No.: H-3375)final concentration: 50 mM HEPES pH7.5BSA: Bovine Serum Albumin Fraction V, fatty acid free (Roche Diagnostics GmbH, Cat. No. 9100221).
Measurement: IC50 = 24.37 nM (pChEMBL 7.610000133514404)
Descriptors: MW 482.64, ALogP 4.37, HBA 8, HBD 3, PSA 82.41, QED 0.36
Compound (SMILES): O=c1[nH]c(-c2ccc(S(=O)(=O)N(CCCCC(F)(F)F)c3sc4ccccc4c3Br)cc2)ns1
InChIKey: HDEXUAMBROWRHJ-UHFFFAOYSA-N
Target: Transient receptor potential M8 protein (SINGLE PROTEIN), Canis lupus familiaris
UniProt: Q1A7N1
Assay: Functional Assay: The functional activity of compounds of the formula (I) was determined by measuring changes in intracellular calcium concentration using a Ca2+-sensitive fluorescent dye. The changes in fluorescent signal were monitored by a fluorescence plate reader, either a FLIPR (Molecular Devices) or FDSS (Hamamatsu). Increases in intracellular Ca2+ concentration were readily detected upon activation with icilin.At 24 hrs prior to assay, HEK293 cells stably expressing canine TRPM8 were seeded in culture medium in black wall, clear-base poly-D-lysine coated 384-well plates (BD Biosciences, NJ, USA) and grown overnight in 5% CO2 at 37° C. On assay day, growth media was removed and cells were loaded with Calcium 3 Dye (Molecular Devices) for 35 min at 37° C., under 5% CO2 and then for 25 min at room temperature and atmosphere. Subsequently, cells were tested for agonist-induced increases in intracellular Ca2+ levels using FLIPR or FDSS. Cells were challenged with a compound of the Formula (I) (at varying concentrations) and intracellular Ca2+ was measured for 5 min prior to the addition of icilin to all wells to achieve a final concentration that produces approximately an 80% maximal response. EC50 or IC50 values for compounds of the present invention were determined from eight-point dose-response studies.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 592.48, ALogP 6.4, HBA 6, HBD 1, PSA 83.13, QED 0.24
Compound (SMILES): NC(=O)C12CC3CC(C1)C(NC(=O)C1(NS(=O)(=O)c4ccccc4F)CC1)C(C3)C2
InChIKey: CGPSAYFSIYKTQP-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: HTRF Assay : The inhibiting activity of 11β-HSD1 derived from microsomal fractions was measured using the HTRF assay (62CO2PEB, Cisbio). Different concentrations of compounds were added to 96-well plates, followed by the addition of TE buffer (20 mM Tris buffer and 5 mM EDTA, pH 6.0) containing 200 μM NADPH (N1630, Sigma) and 160 nM cortisone (C2755, Sigma), The reactions were initiated by the addition of human microsomal fractions (M0317, Sigma), and were allowed to incubate for 2 h at 37° C. Europium (Eu3+) cryptate and XL665-conjugated cortisol were then added to each well and incubated for an additional 2 h at room temperature.
Measurement: IC50 = 24.7 nM (pChEMBL 7.610000133514404)
Descriptors: MW 435.52, ALogP 1.43, HBA 4, HBD 3, PSA 118.36, QED 0.63
Compound (SMILES): CCCCCCCCOCCOCCOCCOCCOCCOC(=O)NCCOCCOCCOCCNS(=O)(=O)c1cccc([C@@H]2CN(C)Cc3c(Cl)cc(Cl)cc32)c1
InChIKey: VOLGELITSVMUAE-FAIXQHPJSA-N
Target: Sodium/hydrogen exchanger 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P26433
Assay: Inhibition of rat NHE3-mediated sodium-dependant hydrogen ion antiport in Opossum kidney cells preincubated in NH4Cl-HEPES buffer containing BCECF-AM dye followed by washout with ammonium free HEPES and subsequent addition of compound in presence of NHE1 antagonist EIPA by fluorescence assay
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 923.01, ALogP 6.07, HBA 13, HBD 2, PSA 161.58, QED 0.08
Compound (SMILES): CCN1CCC(CCOc2ncc(-c3nc(C#N)nc4c3ccn4CC3CCOC3)cc2C(F)(F)F)CC1
InChIKey: XBZQPYJROWDGHL-UHFFFAOYSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition Assay: 5 μL of a human cathepsin S enzyme (R&D1183-CY-010) was added to a 96-well plate so as to be 20 ng/well. Next, 10-fold dilution of the test compound (a 10 mM DMSO solution) was serially performed with a buffer solution for assay (a solution of 50 mM sodium methoxide, 250 mM sodium chloride and 5 mM dithiothreitol (DTT), adjusted to pH=4.5 with 1 N hydrochloric acid) six times such that the final concentration becomes 0.1 nM to 10 μM then, 20 μL of each of the solutions was added to the wells (the final DMSO concentration was 0.1%), and 25 μL of synthetic substrate VVR-AMC (3211-V manufactured by PEPTIDE INSTITUTE, INC.) was added thereto such that the final concentration becomes 40 μM, thereby starting a enzyme reaction. A fluorescence intensity (an excitation wavelength: 380 nm and a fluorescent wavelength: 460 nm) was measured at 37° C. for 10 minutes immediately after the start of the reaction using a fluorescence spectrophotometer (SPECTRA MAX GEMINI, manu
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 528.58, ALogP 4.92, HBA 8, HBD 0, PSA 89.09, QED 0.41
Compound (SMILES): CN1Cc2c(Cl)cc(Cl)cc2[C@H](c2cccc(S(=O)(=O)N(CCO)CCOCCOCCNC(=O)NCCCN(CCCNC(=O)NCCOCCOCCN(CCO)S(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)CCCNC(=O)NCCOCCOCCN(CCO)S(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)c2)C1
InChIKey: BDNJBKSNSUVFFL-UCBZISERSA-N
Target: Sodium/hydrogen exchanger 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P26433
Assay: Inhibition of rat NHE3-mediated sodium-dependant hydrogen ion antiport in Opossum kidney cells preincubated in NH4Cl-HEPES buffer containing BCECF-AM dye followed by washout with ammonium free HEPES and subsequent addition of compound in presence of NHE1 antagonist EIPA by fluorescence assay
Measurement: IC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 1905.85
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)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)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)N[C@@H](CCCNC(N)=O)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
InChIKey: KXDAKPLYUGGQBD-KFJAGZKUSA-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 = 229 nM (pChEMBL 6.639999866485596)
Descriptors: MW 2448.86
Compound (SMILES): COc1nc(-c2cc(F)cc(F)c2)c(Cl)cc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ncccn3)ccc21
InChIKey: CPYMAVKGUXMXST-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Nav1.7 In Vitro PX Assay: HEK 293 cells stably transfected with human Nav1.7 were recorded in whole cell voltage clamp mode with the PatchXpress automated electrophysiology system (Molecular Devices, LLC, Sunnyvale, Calif.). Compound effects were measured on a partially inactivated state of the sodium channel. Cells were clamped to a holding potential yielding 20 to 50% inactivation. To elicit sodium current, channels were activated by pulsing to -10 mV for 20 msec. This voltage protocol was repeated at a rate of 0.1 Hz throughout the experiment. A single concentration of test compound was applied to cells for a duration of 3 minutes.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 555.95, ALogP 4.58, HBA 8, HBD 1, PSA 116.07, QED 0.33
Compound (SMILES): CS(=O)(=O)CC(=O)N(CCN1[C@@H]2CC[C@H]1C[C@@H](c1cccc(C(N)=O)c1)C2)Cc1ccc(C(F)(F)F)cc1.O=C(O)C(F)(F)F
InChIKey: NVSIHIFCHYAWLY-LLWNGYSHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]-diprenorphine from guinea pig kappa opioid receptor expressed in CHOK1 cell membranes
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 551.63, ALogP 3.59, HBA 5, HBD 1, PSA 100.78, QED 0.51
Compound (SMILES): CN[C@@H](C)C(=O)N[C@H](C(=O)N1Cc2ccccc2[C@H]1C(=O)Nc1c(Cl)cccc1Cl)C(C)C
InChIKey: UXSNKCGXQFHARH-JBYOLUDKSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: TR-FRET Assay: The peptide AVPIAQKSEK-(ε-biotin)-OH 1:2 TFA ("Peptide A") was identified as a substrate for the TR-FRET assay by screening the 6× Histidine-tagged BIR2 domain and BIR3 domain of XIAP against a set of 29 peptides synthesized based on sequences reported by Sweeny et al. (Biochemistry, 2006, 45, 14740 14748). The peptides were labeled with the fluorescent tags FITC or TAMRA and Kd values were determined by fluorescence polarization assay. The sequence AVPIAQKSEK was identified as optimal for using in an assay. The peptide sequence was derivatized with biotin to provide AVPIAQKSEK-(Îµ-biotin)-OH 1:2 TFA as the substrate for the TR-FRET assay. Ten nanomolar of 6× Histidine-tagged BIR2 domain, corresponding to amino acids 124-240 of XIAP, or BIR3 domain, corresponding to amino acids 241-356 of XIAP, was mixed with 20 nM of the peptide AVPIAQKSEK-(ε-biotin)-OH 1:2 TFA, in the presence of 50 mM Tris-Cl, pH 7.5, 100 mM NaCl, 1 mM dithiothreitol (DTT) and 0.1 mg/mL bovine serum albumin (BSA). Following a 45 min. incubation at 37° C., Europium-Streptavidin and Allophycocyanin conjugated anti-Histidine antibody were added to a final concentration of 1.5 nM and 15 nM, respectively. Time-resolved fluorescence resonance energy transfer (TR-FRET) signals were measured 1 hour later at room temperature. Test compound potency was assessed at 10 serially diluted concentrations.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 491.42, ALogP 3.76, HBA 4, HBD 3, PSA 90.54, QED 0.55
Compound (SMILES): COc1cc(CN(CC2CC2)C(CC(=O)O)c2ccc(Cl)c(F)c2)ccc1SCCN1C(=O)CCC1=O
InChIKey: MZQYPJCDZAIFRC-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Radioligand Binding Assay: The composition of the binding assay buffer is determined in a course of detailed optimization procedure. This resulted in a binding assay buffer constituted by the following components: 25 mM Hepes (pH=7.4), 5 mM MgCl2, 1 mM CaCl2, 100 mM NaCl, supplemented with 0.1% of protease free BSA (as a final concentration). Competition binding assay is performed using 125I-CXCL10 (PerkinElmer, NEX348, specific activity 2200 Ci/mmol) radioligand in a final concentration of 50-70 pM. The nonspecific binding is defined by 150 pM of hr-CXCL10 (R&D Systems, Cat No 266-IP). The total assay volume is equal to 150 ul and contained 1% of DMSO (final concentration). Binding reaction is initiated by adding of membranes (10-20 ug proteins, approximately 5x105 cell equivalents) to the reaction mixture. After 60 minutes of incubation at 25° C. the reaction is terminated by rapid filtration over GF/B glass fibre filters that are pre-soaked with 0.5% polyethyleneimine (Fluka Analytical, P3143) for 1 hour, using a Skatron cell harvester device. Filters then are washed with 8 ml of ice-cold wash buffer (modified binding buffer in which BSA is omitted and the concentration of NaCl is adjusted to 500 mM concentration). The radioactivity retained on the filters is measured by a Wizard 1470 Automatic Gamma counter.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 549.06, ALogP 5.16, HBA 6, HBD 1, PSA 87.15, QED 0.27
Compound (SMILES): c1ccc(Cn2cc(-c3ccc4[nH]nc(N5CCOCC5)c4c3)nn2)cc1
InChIKey: UYDSPNGPTPODBJ-UHFFFAOYSA-N
Target: Cell division cycle 7-related protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O00311
Assay: Inhibition Assay: 11 data point. Cdc7 kinase assays were carried out in 25 mM HEPES, pH 7.5, 1 mM DTT, 10 mM MgCl2, 100 μM Na3VO4, and 0.075 mg/ml Triton X-100 using 12 ng baculovirus-expressed Cdc7/Dbf4 and 2 μM Jerini peptide substrate A-A11 (biotin-C6linker-TPSDSLIYDDGLS) (SEQ ID NO:5). Reactions were initiated with λ-[33P]-ATP (1 μM, 20 mCi/μmol) and quenched after 1 hour with 5 volumes of stop buffer (50 mM EDTA, 2 M NaCl). The reactions were incubated for 30 minutes on streptavidin-coated plates, washed, and quantified using a TopCount scintillation plate reader (Packard). IC50 values are determined via non-linear regression fitting of the data. Ki values are generated assuming ATP-competitive (equilibrium) inhibition and using the experimentally determined apparent ATP Km of Cdc7 (0.7 μM).
Measurement: Ki = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 360.42, ALogP 2.71, HBA 6, HBD 1, PSA 71.86, QED 0.61
Compound (SMILES): COc1ccccc1N1CCN(CCCOc2c(C)cccc2C)CC1.Cl
InChIKey: AIVAMIDHQVBRBJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from recombinant human 5-HT7 receptor after 60 mins by liquid scintillation counting method
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 354.49, ALogP 3.9, HBA 4, HBD 0, PSA 24.94, QED 0.7
Compound (SMILES): CC(C)(O)C(=O)N1CCC(c2ccc(C(OCc3c(F)cccc3F)(C(F)(F)F)C(F)(F)F)cc2)(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: OYNHZXSXTMTGAB-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Scintillation Proximity Assay (SPA): The binding of potential ligands to RORγ is measured by competition with [3H] 25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA) binding assay. The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 ug/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 uM to 0.28 nM for 10 min at room temperature in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% Glycerol (Sigma Cat#G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat #RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce [3H] 25-hydroxycholesterol specific binding by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 683.59, ALogP 6.31, HBA 5, HBD 1, PSA 83.91, QED 0.22
Compound (SMILES): COc1cc2c(Nc3ccc(NC(=O)Nc4ccccc4)c(Cl)c3)ncnc2cc1OCCCN1CCN(C)CC1
InChIKey: HQHBKFFDVBPVBM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human EGFR cytoplasmic domain (669 to 1210 residues) expressed in baculovirus expression system preincubated for 10 mins followed by FAM-labelled peptide substrate addition by caliper mobility shift assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 576.1, ALogP 5.7, HBA 8, HBD 3, PSA 103.88, QED 0.21
Compound (SMILES): OC(COc1cccc(OCc2ccccc2)c1)CN1CCc2ccccc2C1
InChIKey: WYHHSWYAZANDKQ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 389.5, ALogP 4.06, HBA 4, HBD 1, PSA 41.93, QED 0.63
Compound (SMILES): N#Cc1c(N)ncnc1N1CCC[C@H]1c1nn2cccc2c(=O)n1-c1ccccc1
InChIKey: QOGPJIWCEKLLOE-INIZCTEOSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of full length recombinant human N-terminal His6-tagged PI3K p110delta/human p85alpha expressed in baculovirus infected sf21 cells using PIP2 as substrate preincubated for 30 mins followed by substrate addition by HTRF assay
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 398.43, ALogP 2.07, HBA 9, HBD 1, PSA 118.13, QED 0.56
Compound (SMILES): NC(=O)[C@]1(Cc2cccc(Nc3cc[nH]n3)n2)CC[C@@H](Oc2cccc(Cl)c2F)CC1
InChIKey: GABKCBKPNYHAJC-VVONHTQRSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human full-length N-terminal GST-tagged Aurora B/His-tagged INCENP (803 to 916 residues) using kemptide as substrate and [gamma33P]ATP after 45 mins by liquid scintillation counting method
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 443.91, ALogP 4.38, HBA 5, HBD 3, PSA 105.92, QED 0.5
Compound (SMILES): Nc1nc(-c2ccc(-n3c(Cl)cc4[nH]c(=O)n(-c5cccc(C(=O)O)c5)c(=O)c43)cc2)cs1
InChIKey: XJJWJDXENZWLAZ-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P54619
Assay: Activation of full length human His/GST-tagged AMPK alpha1/beta1/gamma1 expressed in baculovirus expression system after 1 hr by Z'Lyte assay
Measurement: EC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 479.91, ALogP 3.53, HBA 8, HBD 3, PSA 136, QED 0.36
Compound (SMILES): CN1CC[C@H](c2c(O)cc(O)c3c(=O)cc(-c4ccncc4)oc23)[C@H](O)C1
InChIKey: MPBLVVMMAMGCPJ-BLLLJJGKSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin A using histone H1 as substrate after 10 mins by [gamma-32P]ATP based binding assay
Measurement: IC50 = 208.2 nM (pChEMBL 6.679999828338623)
Descriptors: MW 368.39, ALogP 2.05, HBA 7, HBD 3, PSA 107.03, QED 0.64
Compound (SMILES): COC(=O)c1ccc2nc(N(C)C)nc(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)c2c1
InChIKey: LTMRAHNMLFYWGG-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 1476 nM (pChEMBL 5.829999923706055)
Descriptors: MW 473.51, ALogP 4.49, HBA 7, HBD 2, PSA 96.45, QED 0.38
Compound (SMILES): CCOCc1cc2cnc(Nc3ccc(N4CCOCC4)cn3)nc2n(C2CCCC2)c1=O
InChIKey: AFNOMJNGXFOVCJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of Cdk4/Cyclin D (unknown origin) using retinoblastoma protein substrate and [gamma32P]ATP incubated for 15 mins by beta plate counter based assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 450.54, ALogP 3.42, HBA 9, HBD 1, PSA 94.4, QED 0.59
Compound (SMILES): Cn1cnc2ccc(-c3cccc(OCC(O)CN4CCc5ccccc5C4)c3)cc21
InChIKey: XOQLCVLZWLEHOX-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 413.52, ALogP 4.04, HBA 5, HBD 1, PSA 50.52, QED 0.52
Compound (SMILES): CC(=O)c1ccc(-c2cccc(OCC(O)CN3CCc4ccccc4C3)c2)cc1
InChIKey: WERHDSCRDSDMLI-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 401.51, ALogP 4.35, HBA 4, HBD 1, PSA 49.77, QED 0.6
Compound (SMILES): NS(=O)(=O)OC[C@@H]1C[C@@H](Oc2ncnc3c2ncn3Cc2ccccc2)C[C@@H]1O
InChIKey: LIJMFHOBJCEVMH-ZNMIVQPWSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAEalpha/N-terminal His-tagged NAEbeta expressed in baculovirus infected insect Sf9 cells using N-terminal FLAG tagged Nedd8 as substrate incubated for 105 mins in presence of N-terminal GST-tagged Ubc12 by FRET assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 419.46, ALogP 0.61, HBA 9, HBD 2, PSA 142.45, QED 0.57
Compound (SMILES): CCN(CC)c1nc(NCc2ccc(NC(=O)C3CCN(Cc4ccc(F)cc4)CC3)cc2)c2cc(C(F)(F)F)ccc2n1
InChIKey: FMQIPZPIEGHYNH-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 3850 nM (pChEMBL 5.420000076293945)
Descriptors: MW 608.68, ALogP 7.1, HBA 6, HBD 2, PSA 73.39, QED 0.19
Compound (SMILES): CCCC(=O)NC(Cc1ccc2cc(OCc3ccc(C(=N)N)cc3)ccc2c1)C(=O)O.Cl
InChIKey: NHUSPQRLJQTSLY-UHFFFAOYSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Antagonist activity at GP2b/GP3a receptor in human platelet rich plasma assessed as inhibition of ADP-induced platelet aggregation preincubated for 1 min followed by ADP addition by aggregometric method
Measurement: IC50 = 1080 nM (pChEMBL 5.96999979019165)
Descriptors: MW 433.51, ALogP 3.61, HBA 4, HBD 4, PSA 125.5, QED 0.29
Compound (SMILES): O=C(Nc1cc(-c2ccc(F)c(NCC3CCOCC3)n2)c(Cl)cn1)[C@@H]1CCCNC1
InChIKey: OETJRQWLHMSDMD-OAHLLOKOSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using cdk7tide peptide as substrate
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 447.94, ALogP 3.71, HBA 6, HBD 3, PSA 88.17, QED 0.63
Compound (SMILES): CC(C)(O)CN1C[C@H](c2cccc(F)c2F)CC[C@@H](NC(=O)c2ccc3c(c2)CC2(C3)C(=O)Nc3ncccc32)C1=O
InChIKey: WAZDMGGJAWEMTD-ZKUVRKPUSA-N
Target: Calcitonin-gene-related peptide receptor, CALCRL/RAMP1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60894
Assay: Displacement of [125I]hCGRP from human recombinant CGRP receptor expressed in HEK293 cell membranes incubated for 3 hrs by scintillation counting method
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 574.63, ALogP 3.62, HBA 5, HBD 3, PSA 111.63, QED 0.43
Compound (SMILES): COc1ccc2c(c1)[C@@H](Nc1cc(O[C@@H]3C[C@@H](COS(N)(=O)=O)[C@@H](O)C3)ncn1)[C@@H](OC)CC2
InChIKey: MCALKOUCNUORLI-BVFBRMCBSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAEalpha/N-terminal His-tagged NAEbeta expressed in baculovirus infected insect Sf9 cells using N-terminal FLAG tagged Nedd8 as substrate incubated for 105 mins in presence of N-terminal GST-tagged Ubc12 by FRET assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 494.57, ALogP 1.34, HBA 10, HBD 3, PSA 155.12, QED 0.46
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)Nc4ccc(F)cc4)cc3)nc(N(C)C)nc2c1
InChIKey: OYUPNTBJUKVCPL-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 2025 nM (pChEMBL 5.690000057220459)
Descriptors: MW 444.51, ALogP 5.4, HBA 5, HBD 3, PSA 82.18, QED 0.37
Compound (SMILES): COC(=O)Nc1ccc(S(=O)(=O)C(C)C)c([C@H]2CCCN2C(=O)[C@H](Nc2ccc3c(F)c[nH]c(=O)c3c2)c2ccc(OC)c(OC)c2)c1
InChIKey: OWZJHFYKSGTIJZ-DLFZDVPBSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 680.75, ALogP 5.56, HBA 9, HBD 3, PSA 156.13, QED 0.2
Compound (SMILES): OC(COCc1cccnc1)CN1CCc2ccccc2C1
InChIKey: IIAYQMJYZOAFAF-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 10001 nM (pChEMBL 5)
Descriptors: MW 298.39, ALogP 2.02, HBA 4, HBD 1, PSA 45.59, QED 0.89
Compound (SMILES): Cc1ccc2nc(N3CCN[C@@H](C)C3)nc(NCc3ccc(NC(=O)c4ccc(F)cc4)cc3)c2c1
InChIKey: DCXKFVRAFWMNLE-IBGZPJMESA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 987 nM (pChEMBL 6.010000228881836)
Descriptors: MW 484.58, ALogP 4.74, HBA 6, HBD 3, PSA 82.18, QED 0.37
Compound (SMILES): O=C(NCC(O)CN1CCc2ccccc2C1)c1cccc(N2CCNCC2)c1
InChIKey: FCEZIJXSGGPYAD-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 394.52, ALogP 1.25, HBA 5, HBD 3, PSA 67.84, QED 0.69
Compound (SMILES): Cl.O=C(O)[C@]1(Cc2cccc(Nc3nccs3)n2)CC[C@@H](Oc2cccc(Cl)c2)CC1
InChIKey: HQENAOPPXAWIEA-UBTQVQQGSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human full-length N-terminal GST-tagged Aurora B/His-tagged INCENP (803 to 916 residues) using kemptide as substrate and [gamma33P]ATP after 45 mins by liquid scintillation counting method
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 443.96, ALogP 5.57, HBA 6, HBD 2, PSA 84.34, QED 0.5
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(Br)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: VBXHOCIRRABFDD-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 475.35, ALogP 4.14, HBA 7, HBD 1, PSA 91.62, QED 0.42
Compound (SMILES): O=C(Nc1ccc(CNc2nc(N3CCCC3)nc3ccc(C(F)(F)F)cc23)cc1)c1ccc(Cl)cc1
InChIKey: KBTMSHBWOZXTIL-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 6554 nM (pChEMBL 5.179999828338623)
Descriptors: MW 525.96, ALogP 6.77, HBA 5, HBD 2, PSA 70.15, QED 0.29
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cc(O)cc(F)c4)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: LAYNQKZCFROFGL-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 510.5, ALogP 4.72, HBA 8, HBD 2, PSA 111.85, QED 0.36
Compound (SMILES): O=C(O)c1ccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5ccc(C(=O)O)cc5)ccc4o3)cc2)cc1
InChIKey: GIICLPRKARRCTF-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q548M1
Assay: Inhibition of Escherichia coli GroEL/GroES expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 20 to 40 mins by fluorescence based assay
Measurement: IC50 = 83000 nM (pChEMBL 4.079999923706055)
Descriptors: MW 593.6, ALogP 4.49, HBA 8, HBD 4, PSA 192.97, QED 0.19
Compound (SMILES): C=Cc1ccc2nc(N(C)C)nc(NCc3ccc(NC(=O)C4CCN(Cc5ccccc5)CC4)cc3)c2c1
InChIKey: SNCNFKSRYUUHAW-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 287 nM (pChEMBL 6.539999961853027)
Descriptors: MW 520.68, ALogP 5.8, HBA 6, HBD 2, PSA 73.39, QED 0.29
Compound (SMILES): COc1ccc2cc1[C@@H](C)CN(C)C(=O)Nc1ccc(S(=O)(=O)C3CC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)ncc(F)c2c1
InChIKey: DRLAOAUSFABNAU-QPHCHLROSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins at 25 degC
Measurement: Ki < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 660.77, ALogP 5.29, HBA 8, HBD 3, PSA 146.96, QED 0.26
Compound (SMILES): CCOC(=O)c1nn(-c2ccc(OOSN)cc2)c2c1SCc1ccccc1-2
InChIKey: VKDVPWWTCOUXJI-UHFFFAOYSA-N
Target: Inhibitor of NF-kappa-B kinase alpha/beta (PROTEIN COMPLEX), Homo sapiens
UniProt: O14920
Assay: Inhibition of human recombinant N-terminal His6-tagged IKK1/C-terminal FLAG-epitope-tagged IKK2 expressed in baculovirus infected insect cells using biotinylated IkappaBalpha peptide as substrate in presence of [gamma-33P]-ATP after 30 mins by resin-based scintillation counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 415.5, ALogP 4.15, HBA 9, HBD 1, PSA 88.6, QED 0.21
Compound (SMILES): C[C@H]1CC(=O)Nc2ccc(S(=O)(=O)C3CC3)c(c2)CN(C)C(=O)[C@H](Nc2ccc3c(N)ncc(F)c3c2)c2ccc(OCC(F)F)c1c2
InChIKey: UWAQLEGUXYPPDC-HYHKQLJDSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins at 37 degC
Measurement: Ki = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 681.74, ALogP 5.79, HBA 8, HBD 3, PSA 143.72, QED 0.22
Compound (SMILES): CC(=O)Nc1nc2cc(-c3nn(Cc4cc5cccc(C)c5c(=O)n4-c4ccccc4)c4ncnc(N)c34)ccc2o1
InChIKey: AGZWRHMGHQGYHA-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 556.59, ALogP 4.84, HBA 10, HBD 2, PSA 146.75, QED 0.31
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3cc(N)nc(Cl)n3)n(-c3ccccc3)c(=O)c12
InChIKey: FUGXOIKZLQQLKY-AWEZNQCLSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 405.89, ALogP 4.5, HBA 6, HBD 2, PSA 85.83, QED 0.49
Compound (SMILES): CNc1nc(NCc2ccc(NC(=O)c3ccc(C#N)cc3)cc2)c2cc(C)ccc2n1
InChIKey: RTCXEIPGGCCRLN-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 2965 nM (pChEMBL 5.53000020980835)
Descriptors: MW 422.49, ALogP 4.72, HBA 6, HBD 3, PSA 102.73, QED 0.42
Compound (SMILES): C[C@H](NC(=O)c1cncc2cccnc12)c1cc2cccc(Cl)c2c(=O)n1-c1ccccc1
InChIKey: AGZPGVIJBUSPBO-INIZCTEOSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human recombinant full length N-terminal GST-tagged PI3K p110delta/p85alpha coexpressed in baculovirus infected Sf9 insect cells using diC8PIP2 as substrate incubated for 15 mins followed by substrate addition measured after 2 hr by ADP-Glo luminescence assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 454.92, ALogP 5.08, HBA 5, HBD 1, PSA 76.88, QED 0.41
Compound (SMILES): Cc1cccc2cc(C(C)Nc3ncnc4[nH]cnc34)n(C3CC3)c(=O)c12
InChIKey: XKHASMAALGBCSO-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 360.42, ALogP 3.48, HBA 6, HBD 2, PSA 88.49, QED 0.58
Compound (SMILES): CN(C)CCOc1cccc(C(=O)NCC(O)CN2CCc3ccccc3C2)c1
InChIKey: JGIHPUJYYYKYIG-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 397.52, ALogP 1.78, HBA 5, HBD 2, PSA 65.04, QED 0.68
Compound (SMILES): NSOOc1ccc(-n2nc(C(N)=O)c3c2-c2ccccc2CS3)cc1
InChIKey: BHHBQBJDTDRJFL-UHFFFAOYSA-N
Target: Inhibitor of NF-kappa-B kinase alpha/beta (PROTEIN COMPLEX), Homo sapiens
UniProt: O14920
Assay: Inhibition of human recombinant N-terminal His6-tagged IKK1/C-terminal FLAG-epitope-tagged IKK2 expressed in baculovirus infected insect cells using biotinylated IkappaBalpha peptide as substrate in presence of [gamma-33P]-ATP after 30 mins by resin-based scintillation counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 386.46, ALogP 3.08, HBA 8, HBD 2, PSA 105.39, QED 0.3