lovingscience/chembl-v37-raw-activities huggingface dataset:
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)N(C)CC(=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](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
InChIKey: BSWBCDUBCHDFSM-YTMVHBNOSA-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 = 10 nM (pChEMBL 8)
Descriptors: MW 2358.73
Compound (SMILES): CCNCc1cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)nc(C(F)(F)F)n1
InChIKey: LNADOZPWRKKIOA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 593.62, ALogP 2.97, HBA 10, HBD 2, PSA 144.54, QED 0.32
Compound (SMILES): COc1cc(N2CCC(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3cc(F)ccn23)n1
InChIKey: PGSWZQCCZKKHSP-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 785.85, ALogP 7.54, HBA 11, HBD 2, PSA 140.05, QED 0.13
Compound (SMILES): CCOc1cc(N2CCN(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: NEVZWMZAOSTPNR-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 752.85, ALogP 6.3, HBA 11, HBD 2, PSA 134.06, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)C3CCN(c4ncc(Cl)cc4F)CC3)CC2)C1
InChIKey: JNKOIMIJCLLCCZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 603.11, ALogP 3.84, HBA 9, HBD 1, PSA 122.86, QED 0.35
Compound (SMILES): COc1cn(C(C[C@H]2CC[C@H](OC)CC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: LARGKTWCHAEXEF-QDTYANCNSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition Assay: Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 564.04, ALogP 5.52, HBA 7, HBD 2, PSA 130.65, QED 0.35
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CCC(=O)NCC[C@@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(N)=O)NC(=O)CNC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: NMWVNUICWHDBJN-BWBQVKFQSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in a human melanoma cell line, HBL, that express hMCR-1 (see Kang, L., et al., A selective small molecule agonist of melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice, J. Leuk. Biol. 80:897-904 (2006)) or HEK-293 cells that express hMCR-4. Confluent HBL cells that express hMCR-1 or HEK-293 cells that express recombinant hMCR-4 were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.4Ã¿105 cells per well for HBL cells and 0.5x105 cells per well for HEK-293 cells and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a Perkin-Elmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. Maximum efficacy (Emax) values were determined for each test peptide of the present invention, compared to that achieved by the reference melanocortin agonist NDP-α-MSH.
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 911.03, ALogP -1.06, HBA 10, HBD 11, PSA 320.36, QED 0.07
Compound (SMILES): N#CCCNC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: MPZAIYOCKUDQCW-JOCQHMNTSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 323.4, ALogP 2.38, HBA 6, HBD 2, PSA 94.69, QED 0.7
Compound (SMILES): CCn1nc(C2CCN(C(=O)CCO)CC2)nc1-c1cnc(N)c(-c2nnc(C(C)(C)C)o2)n1
InChIKey: ZGRDYKFVDCFJCZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Cell Based Assay: ATR (Ataxia Telangiectasia+Rad3-related kinase) is a PI3-kinase-related kinase which phosphorylates multiple substrates on serine or threonine residues in response to DNA damage or replication blocks. Chk1, a downstream protein kinase of ATR, plays a key role in DNA damage checkpoint control. Activation of Chk1 involves phosphorylation of Ser317 and Ser345 (the latter regarded as the preferential target for phosphorylation/activation by ATR).This was a cell based assay to measure inhibition of ATR kinase, by measuring a decrease in phosphorylation of Chk1 (Ser 345) in HT29 cells, following treatment with compound and the UV mimetic 4NQO (Sigma #N8141). HT29 cells (ECACC #85061109) were seeded into 384 well assay plates (Costar #3712) at a density of 6000 cells/well in 40 ul EMEM medium containing 1% L glutamine and 10% FBS and allowed to adhere overnight. The following morning compounds in 100% DMSO were added to assay plates by acoustic dispensing.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 469.55, ALogP 1.77, HBA 11, HBD 2, PSA 161.97, QED 0.54
Compound (SMILES): COC(=N)c1nc2ccc3ncnc(Nc4ccc(OC)cc4F)c3c2s1
InChIKey: RYBNARZBIXTFJS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of DYRK2 (unknown origin)
Measurement: IC50 = 3.16 nM (pChEMBL 8.5)
Descriptors: MW 383.41, ALogP 4.1, HBA 8, HBD 2, PSA 93.01, QED 0.41
Compound (SMILES): N#C[C@H]1CS(=O)(=O)CC[C@H]1n1cc(C(N)=O)c(Nc2ccc(F)cc2)n1
InChIKey: UPXCRMVZJWXWNO-IINYFYTJSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 377.4, ALogP 1.36, HBA 7, HBD 2, PSA 130.87, QED 0.83
Compound (SMILES): C[C@@H]1C[C@@H]2C[C@H](C1)C[C@@H](N1[C@@H]3CCC[C@H]1C[C@@H](n1c(=O)c(N4CC[C@H]4C(=O)O)nc4ccccc41)C3)C2
InChIKey: MAXKZGKDZCVVLT-VUOXEJBVSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: In Vitro ORL-1 Receptor Functional Assay: ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 μg/μL ORL-1 membrane protein, 10 μg/mL saponin, 3 μM GDP and 0.20 nM [35S]GTPγS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 μL/well) was transferred to 96-shallow well polypropylene plates containing 10 μL of 20× concentrated stock solutions of agonist/nociceptin prepared in DMSO. Plates were incubated for 30 min at about 25 °C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 μL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 °C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in Packard Top-Count for 1 min/well.
Measurement: EC50 = 6.54 nM (pChEMBL 8.180000305175781)
Descriptors: MW 504.68, ALogP 4.83, HBA 6, HBD 1, PSA 78.67, QED 0.64
Compound (SMILES): CS(=O)(=O)N1CCC(C(=O)N2CC[C@](c3ccc(C(O)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC1
InChIKey: QVPVWDKIJLWWPO-QHCPKHFHSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at LXRbeta (unknown origin) expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 660.63, ALogP 3.71, HBA 6, HBD 1, PSA 112.06, QED 0.37
Compound (SMILES): CCOc1cc(N2CCN(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OCC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: IEQDZYFPBXQSDQ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 810.93, ALogP 7, HBA 12, HBD 2, PSA 143.29, QED 0.12
Compound (SMILES): Cc1ncccc1-n1c([C@H](C)Nc2nc(N)nc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: MODOHQQWQXQEQB-NSHDSACASA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length PI3K p110alpha/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 447.89, ALogP 2.74, HBA 10, HBD 3, PSA 161.42, QED 0.43
Compound (SMILES): CC(C)Oc1ccc(-c2nc(-c3cccc4c3CC[C@H]4NS(=O)(=O)CCO)no2)cc1C#N
InChIKey: LKTZGXNAMSPVAG-HXUWFJFHSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at human S1P5 expressed in bla TANGO U2OS cells assessed as inhibition of cAMP formation preincubated for 4 hrs followed by FRET-based beta-lactamase fluorescent substrate addition measured after 2 hrs
Measurement: EC50 = 32.28 nM (pChEMBL 7.489999771118164)
Descriptors: MW 468.54, ALogP 2.96, HBA 8, HBD 2, PSA 138.34, QED 0.51
Compound (SMILES): COc1ccc(/C=N/Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)cc1
InChIKey: DIWRJVJHXXZINL-WYMPLXKRSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using peptide as substrate after 60 mins by HTRF assay
Measurement: IC50 = 587 nM (pChEMBL 6.230000019073486)
Descriptors: MW 459.96, ALogP 4.51, HBA 8, HBD 2, PSA 105.57, QED 0.38
Compound (SMILES): Nc1nc2cc(-c3nn(C4CC(O)C4)c4ncnc(N)c34)ccc2o1
InChIKey: PMWLHKAWVMRQSC-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00459
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 337.34, ALogP 1.49, HBA 9, HBD 3, PSA 141.9, QED 0.5
Compound (SMILES): CCOc1ccnc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)n1
InChIKey: PRVGMAOUBRLMGU-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 521.58, ALogP 4.43, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(F)c(C(F)(F)F)c4F)cs3)onc2n(C)c1=O
InChIKey: NTFPIJYAGREYFB-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 501.39, ALogP 2.83, HBA 9, HBD 1, PSA 112.02, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(O)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JMBVTEKOAZJGIC-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.54, ALogP 3.92, HBA 10, HBD 2, PSA 127.52, QED 0.32
Compound (SMILES): CS(=O)(=O)O.Cc1c(Cc2c(CO)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: IJKRASZDCNSORU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to human MTOR (1382 to 2549 residues) expressed in mammalian expression system by KINOMEscan assay
Measurement: Kd = 6761 nM (pChEMBL 5.170000076293945)
Descriptors: MW 421.42, ALogP 2.56, HBA 7, HBD 2, PSA 88.91, QED 0.67
Compound (SMILES): CN1C(=O)c2c(ncn2CC(=O)Nc2nc(-c3ccc(C(C)(C)C)cc3)cs2)N2CCN=C12
InChIKey: OOZCYHFVKYNNLY-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 463.57, ALogP 3.2, HBA 8, HBD 1, PSA 95.72, QED 0.64
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1ccc(C(=O)OCCCCCC(=O)NO)c(F)c1
InChIKey: MMGBYDCIOWTBCJ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) assessed as inhibition of fluorogenic peptide deacetylation
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 580.56, ALogP 4.86, HBA 7, HBD 2, PSA 122.97, QED 0.11
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccn(C)c(=O)c1
InChIKey: JVGDBVAGMMZAGB-YKSBVNFPSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG transfected in HEK293 cells assessed as reduction in tail current by patch clamp assay
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 503.59, ALogP 4.56, HBA 7, HBD 0, PSA 55.95, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4cc5n(c4n3)C3(CCCCC3)CNC5=O)nc2)CC1
InChIKey: PDGKHKMBHVFCMG-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 446.56, ALogP 2.72, HBA 8, HBD 2, PSA 91.21, QED 0.64
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4cccc(F)c4)ccc3o2)cc1)c1cccc(F)c1
InChIKey: JGAPJICEYAQHGJ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTPN1 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 36000 nM (pChEMBL 4.440000057220459)
Descriptors: MW 541.56, ALogP 5.37, HBA 6, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC(C)C)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: VUGSVMNPSQXIRQ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 851.98, ALogP 7.07, HBA 12, HBD 2, PSA 146.53, QED 0.13
Compound (SMILES): COc1cc(OC)c(F)c(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: GLLVJFAKHOOPKT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 536.51, ALogP 5.01, HBA 8, HBD 1, PSA 77.33, QED 0.23
Compound (SMILES): O=C(Nc1ccc(F)cc1)N1N=C(c2ccncc2)CC1c1ccc(F)cc1
InChIKey: RDQXNTXNNZITKD-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of human T-type calcium channel Cav3.2 expressed in CHO cells assessed as inhibition of calcium tail current at -60 mV holding potential measured after 150 secs by QPatch assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 378.38, ALogP 4.74, HBA 3, HBD 1, PSA 57.59, QED 0.72
Compound (SMILES): COC/C(CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)=N/O
InChIKey: YIDCCLXYFLNYHA-OGLMXYFKSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 462.51, ALogP 3.66, HBA 10, HBD 1, PSA 107.12, QED 0.23
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(S(=O)(=O)C3CCCC3)CC2)C1
InChIKey: MVGIEAHSBOJVAK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 10 nM (pChEMBL 8)
Descriptors: MW 494.63, ALogP 2.48, HBA 8, HBD 1, PSA 123.8, QED 0.56
Compound (SMILES): COc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1OC
InChIKey: MHHANWALJYYOEO-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 344.41, ALogP 2.83, HBA 5, HBD 1, PSA 63.79, QED 0.85
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: MMGNRRUXETXMDE-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.54, ALogP 4.61, HBA 8, HBD 1, PSA 85.53, QED 0.4
Compound (SMILES): Cc1nnc(C)n1-c1ccc(O[C@H]2c3cc(Cl)cc(Cl)c3C[C@@H]2N2CC[C@@H](O)C2)c(F)c1.Cl
InChIKey: MDJADLPQDRFYIJ-SIVZDDAJSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in pooled human hepatic microsomes using diclofenac substrate in presence of NADPH
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 477.37, ALogP 4.44, HBA 6, HBD 1, PSA 63.41, QED 0.6
Compound (SMILES): CCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: NGKFLYGSJDSBQC-QSVWIEALSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Agonist activity at human recombinant EP4 receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 431.55, ALogP 4.77, HBA 5, HBD 2, PSA 87.07, QED 0.5
Compound (SMILES): COc1ccc2[nH]c3c(c2c1)C[C@H]1c2cc4c(cc2CCN1C3)OCO4
InChIKey: HOTTYHVEFWTDND-IBGZPJMESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 13200 nM (pChEMBL 4.880000114440918)
Descriptors: MW 348.4, ALogP 3.56, HBA 4, HBD 1, PSA 46.72, QED 0.73
Compound (SMILES): Cc1ccc(CN2CC[C@@H](N3CC[C@@H](c4ccc(O)cc4)[C@H](F)C3)C2=O)cc1
InChIKey: UNVYDSCXINFREZ-BHDDXSALSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 382.48, ALogP 3.63, HBA 3, HBD 1, PSA 43.78, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: WPAMXPNNWJGKNP-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.51, ALogP 3.02, HBA 9, HBD 2, PSA 105.76, QED 0.38
Compound (SMILES): NC(=O)c1cccc(-c2c[nH]c3ncnc(N4CCOCC4)c23)c1
InChIKey: NCXSLSJEOUOJBB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Binding affinity to recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli assessed as inhibition constant
Measurement: Ki = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 323.36, ALogP 1.56, HBA 5, HBD 2, PSA 97.13, QED 0.76
Compound (SMILES): O=C(O)CC1CCC2(CC1)CCN(c1cc(Cl)cc(Cl)c1)CC2
InChIKey: LTCCGKRFGBBEHR-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human GPR40 expressed in HEK293 cells assessed as induction of IP1 accumulation after 60 mins by HTRF assay
Measurement: EC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 356.29, ALogP 5.24, HBA 2, HBD 1, PSA 40.54, QED 0.8
Compound (SMILES): CC(=O)Nc1nc2cc(-c3nn(C(C)C)c4ncnc(N)c34)ccc2o1
InChIKey: ZZRAXLZGRQLFFU-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00459
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.37, ALogP 2.76, HBA 8, HBD 2, PSA 124.75, QED 0.58
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BXMUZNHPFQUNSZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 472.59, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.39
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1c(-c2c(Cl)cccc2Cl)noc1C
InChIKey: AHIOWTSQFILAEW-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 576.27, ALogP 8.54, HBA 7, HBD 1, PSA 82.3, QED 0.21
Compound (SMILES): c1cnc2c(N3CCN(CCCCc4ccc(OCCCN5CCCCCC5)cc4)CC3)cccc2c1
InChIKey: HKPKDTNLXGOYIC-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Antagonist activity at human Histamine H1 receptor expressed in CHO cells assessed as inhibition of histamine-induced calcium flux at 100 nM preincubated for 30 mins followed by histamine addition by Fluo-4-AM dye based FLIPR assay
Measurement: Kd = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 500.73, ALogP 6.02, HBA 5, HBD 0, PSA 31.84, QED 0.3
Compound (SMILES): C[C@@H](c1nc2ccc(N3CCC[C@@H](C(=O)N4CCCC4)C3)nc2[nH]1)n1cc(Cl)cn1
InChIKey: NOSUIOGIJKVTAO-LSDHHAIUSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5FVP8
Assay: Inhibition of rat DGAT2
Measurement: IC50 = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 427.94, ALogP 3.26, HBA 6, HBD 1, PSA 82.94, QED 0.69
Compound (SMILES): CCC(=O)NC1CCCc2c(-c3ccc(F)c(C)c3)cncc21
InChIKey: QZVUORKNBRDTPK-UHFFFAOYSA-N
Target: Cytochrome P450 11B2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P19099
Assay: Cellular Enzyme Assay: G-402 cells expressing CYP11 constructs were established as described above and maintained in McCoy's 5a Medium Modified, ATCC Catalog No. 30-2007 containing 10% FCS and 400 ug/ml G418 (Geneticin) at 37° C. under an atmosphere of 5% CO2/95% air. Cellular enzyme assays were performed in DMEM/F12 medium containing 2.5% charcoal treated FCS and appropriate concentration of substrate (0.3-10 uM 11-Deoxycorticosterone, 11-Deoxycortisol or Corticosterone). For assaying enzymatic activity, cells were plated onto 96 well plates and incubated for 16 h. An aliquot of the supernatant is then transferred and analyzed for the concentration of the expected product (Aldosterone for CYP11B2; Cortisol for CYP11B1). The concentrations of these steroids can be determined using HTRF assays from CisBio analyzing either Aldosterone or Cortisol.
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 312.39, ALogP 4.1, HBA 2, HBD 1, PSA 41.99, QED 0.93
Compound (SMILES): C#CC(=O)Nc1cc(-c2cnc3[nH]cc(C)c3c2)ccc1F
InChIKey: IEVQOCMRVHKNMW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Biochemical Inhibition Assay: 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2,3-b]pyrazine series of compounds exhibited over >100 fold selective against Janus and TEC family of kinases except for the BMX and TXK it had activity of 30 and 45 nM respectively.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 293.3, ALogP 3.25, HBA 2, HBD 2, PSA 57.78, QED 0.71
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2cccnc2)c1F)c1c[nH]c2nccc(Cl)c12
InChIKey: UGHOYILAXQCULM-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.84, ALogP 3.92, HBA 5, HBD 2, PSA 104.81, QED 0.45
Compound (SMILES): CCOc1cc(C2CCN(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: VWWDKFOSAHCQHN-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 751.86, ALogP 7.36, HBA 10, HBD 2, PSA 130.82, QED 0.13
Compound (SMILES): CC(C(=O)Nc1ccc(C(=O)O)cc1)n1cc(Cl)c(-c2cc(Cl)ccc2C#N)cc1=O
InChIKey: MYLKJUSMRUADNT-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 456.29, ALogP 4.59, HBA 5, HBD 2, PSA 112.19, QED 0.58
Compound (SMILES): CCn1cc(-c2cnc3ccc(N(CCNC)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: ZNKBNXVWLPQHKJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 432.53, ALogP 3.89, HBA 8, HBD 1, PSA 77.33, QED 0.43
Compound (SMILES): CCCc1cc(N2CCC(N3CCCCC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: IJBMUUYVEUCISL-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 726.88, ALogP 9.14, HBA 8, HBD 2, PSA 90.69, QED 0.15
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCO)c3)nc2c1
InChIKey: CQDXYQFRLSRPQH-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.53, ALogP 2.86, HBA 9, HBD 2, PSA 97.56, QED 0.38
Compound (SMILES): CCSC[C@@](O)([C@@H](Nc1cccc2nc(C)ccc12)c1ccc(OC)c(F)c1Cl)C(F)(F)F
InChIKey: NVBRVAKHESDYFE-FCHUYYIVSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding affinity to recombinant human progesterone receptor expressed in baculovirus infected sf9 cells
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 502.96, ALogP 6.54, HBA 5, HBD 2, PSA 54.38, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCNS(=O)(=O)N(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HONWIFHKRIBHLZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.64, ALogP 2.97, HBA 9, HBD 1, PSA 114.71, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC
InChIKey: VENHPOQTVRCHJV-JXBRRONGSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant human N-terminal GST-tagged factor 10a cleavage site-fused Flt1 (K784 to I1338 residues) expressed in baculovirus infected insect Sf9 cells using poly-EY as substrate after 120 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 492.36, ALogP 4.5, HBA 8, HBD 1, PSA 83.96, QED 0.52
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccccn3)c2c(=O)n1-c1ccccc1
InChIKey: RYAQYDFEDXGXQC-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: PI3K-gamma Selective Assay: A compound's ability in selectively inhibiting PI3K-γ can be assessed using RAW264.7 macrophages. Briefly, serum-starved RAW264.7 cells are stimulated with a known GPCR agonist C5a. See, e.g., Camps et al., Nature Medicine (2005) 11(9):936-943. Cells can be treated with test compounds prior to, simultaneously with, or subsequent to the stimulation by C5a. RAW 264.7 cells respond to the complement component fragment C5a through activation of the C5a receptor, and the C5a receptor activates macrophages and induces cell migration. Test compounds' ability to inhibit C5a-mediated AKT phosphorylation is indicative of selective inhibition of PI3K-γ. Thus, by monitoring the reduction of phospho-AKT in stimulated RAW 264.7 cells (using for example, phospho-AKT antibodies), a compound's potential efficacy in selectively inhibiting PI3Kγ can be assessed.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 525.57, ALogP 3.9, HBA 8, HBD 2, PSA 120.2, QED 0.34
Compound (SMILES): O=C(c1ccc2cc(Oc3ccc(C(F)F)cn3)ccc2n1)N1CCNCC1
InChIKey: XJNLQAUECWCBNY-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav 1.5 expressed in HEK293 cells at -90 mV holding potential by Whole cell voltage clamp electrophysiology assay
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 384.39, ALogP 3.41, HBA 5, HBD 1, PSA 67.35, QED 0.75
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IHZFSYQVOKXLQL-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(C2CCCNC2)n1
InChIKey: HFTHZTJJBJKTGD-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 516.45, ALogP 6.19, HBA 8, HBD 2, PSA 81.19, QED 0.3
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCc4cccc(C)c4)[C@@H](C2)N(C)CC[C@]315
InChIKey: WHNASSKNNOILQR-CLRRHZRJSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Binding Assay: Binding assay of certain compounds of this invention to the opioid receptor was determine using radioligand binding assay (screening and dose-displacement).
Measurement: Ki = 23.97 nM (pChEMBL 7.619999885559082)
Descriptors: MW 475.63, ALogP 4.66, HBA 5, HBD 0, PSA 40.16, QED 0.61
Compound (SMILES): COc1ccc(NC(=O)C2=C(c3ccc(C)cc3)C[C@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)NC2=O)cc1
InChIKey: FBBPRPJENPWDPL-LJAQVGFWSA-N
Target: Diacylglycerol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75907
Assay: Inhibition of human DGAT1
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 606.56, ALogP 7.09, HBA 4, HBD 2, PSA 76.66, QED 0.15
Compound (SMILES): Fc1cncc(-c2nc3ccc(F)cn3c2C2CC2)c1
InChIKey: VEYOJFZFZMQFIJ-UHFFFAOYSA-N
Target: Steroid 21-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: P08686
Assay: Inhibition of human CYP21 expressed in African green monkey COS7 cells using 17-hydroxypregnenolone as substrate preincubated for 1 hr followed by substrate addition after 3 hrs by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 271.27, ALogP 3.55, HBA 3, HBD 0, PSA 30.19, QED 0.71
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3sc(C(F)(F)F)cc3O)CC2)C1
InChIKey: ZBYPMXBGBCGFAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 556.57, ALogP 3.84, HBA 9, HBD 2, PSA 126.96, QED 0.38
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ZXPUNZSPQJIHJB-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 432.53, ALogP 3.88, HBA 8, HBD 2, PSA 88.33, QED 0.44
Compound (SMILES): CCN(C)Cc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PVNKKQPQLLGLMA-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 8912.51 nM (pChEMBL 5.050000190734863)
Descriptors: MW 456.59, ALogP 5.04, HBA 7, HBD 0, PSA 59.31, QED 0.35
Compound (SMILES): N=C(N)Nc1cccc(C(=O)Nc2ccc(C[C@H](NC(=O)[C@@H]3CCCN3S(=O)(=O)c3ccccc3)C(=O)O)cc2)c1
InChIKey: KXYAXQVLPNBUFO-ZEQRLZLVSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay
Measurement: IC50 = 0.0631 nM (pChEMBL 10.199999809265137)
Descriptors: MW 578.65, ALogP 2.21, HBA 6, HBD 6, PSA 194.78, QED 0.16