lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H](C(=O)NCc1cc(C(F)(F)F)nn1-c1cccc(Cl)c1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: REFSKWWRGFCGDO-LBPRGKRZSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the rat-species vanilloid receptor 1 (VR1/TRPV1) can be determined using the following assay. In this assay, the influx of Ca2+ through the receptor channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Complete medium: 50 ml HAMS F12 nutrient mixture (Gibco Invitrogen GmbH, Karlsruhe, Germany) with10% by volume of FCS (foetal calf serum, Gibco Invitrogen GmbH, Karlsruhe, Germany, heat-inactivated);2 mM L-glutamine (Sigma, Munich, Germany);1% by weight of AA solution (antibiotic/antimyotic solution, PAA, Pasching, Austria) and 25 ng/ml NGF medium (2.5 S, Gibco Invitrogen GmbH, Karlsruhe, Germany).
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 93.09, QED 0.45
Compound (SMILES): COc1cc(C(C)C(=O)NCc2cc(C(C)(C)C)nn2-c2cccc(Cl)c2)ccc1NS(C)(=O)=O
InChIKey: VPVQGKJHURIMIH-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 519.07, ALogP 4.62, HBA 6, HBD 2, PSA 102.32, QED 0.45
Compound (SMILES): COc1cc(C(C)C(=O)NCc2cc(C(F)(F)F)nn2-c2cccc(Cl)c2)ccc1NS(C)(=O)=O
InChIKey: BJOHMPNMJMXUFX-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 530.96, ALogP 4.34, HBA 6, HBD 2, PSA 102.32, QED 0.45
Compound (SMILES): O=C(Cc1cccc(F)c1)NCc1cc(C(F)(F)F)nn1-c1cccc(Cl)c1
InChIKey: FHOABVDHYAEXMO-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: Ki = 51.8 nM (pChEMBL 7.289999961853027)
Descriptors: MW 411.79, ALogP 4.54, HBA 3, HBD 1, PSA 46.92, QED 0.63
Compound (SMILES): CC(C(=O)NCc1cc(C(F)(F)F)nn1-c1cccc(Cl)c1)c1ccc(C(F)(F)F)c(F)c1
InChIKey: JVEMIXUBIITKHD-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: FLIPR Assay: The agonistic or antagonistic effect of the substances to be tested on the vanilloid receptor 1 (VR1) can also be determined using the following assay. In this assay, the influx of Ca2+ through the channel is quantified with the aid of a Ca2+-sensitive dye (type Fluo-4, Molecular Probes Europe BV, Leiden, the Netherlands) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA).Method:Chinese hamster ovary cells (CHO K1 cells, European Collection of Cell Cultures (ECACC) United Kingdom) are stably transfected with the VR1 gene. For functional testing, these cells are plated out on poly-D-lysine-coated black 96-well plates having a clear base (BD Biosciences, Heidelberg, Germany) at a density of 25,000 cells/well. The cells are incubated overnight at 37 C. and 5% CO2 in a culture medium (Ham's F12 nutrient mixture, 10% by volume of FCS (foetal calf serum), 18 ug/ml of L-proline). The next day the cells are incubated with Fluo-4.
Measurement: Ki = 13.6 nM (pChEMBL 7.869999885559082)
Descriptors: MW 493.81, ALogP 6.12, HBA 3, HBD 1, PSA 46.92, QED 0.44
Compound (SMILES): COc1cc(N2CCNCC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: UAFDWTTZIJTWGE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 514.55, ALogP 3.47, HBA 7, HBD 3, PSA 105.4, QED 0.4
Compound (SMILES): COc1cc(C2CCNCC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: FJMPEQKEWCBVKU-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 3685 nM (pChEMBL 5.429999828338623)
Descriptors: MW 513.56, ALogP 4.53, HBA 6, HBD 3, PSA 102.16, QED 0.39
Compound (SMILES): COc1cc(C2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: AWJVIOYPZZZYAX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 538 nM (pChEMBL 6.269999980926514)
Descriptors: MW 527.59, ALogP 4.87, HBA 6, HBD 2, PSA 93.37, QED 0.41
Compound (SMILES): CCN1CCC(c2ccc(Nc3ncc(C(F)(F)F)c(CCc4ccccc4CC(N)=O)n3)c(OC)c2)CC1
InChIKey: UVFVNHXQBCTBNE-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Biacore SPR Assay: In running buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 0.005% Surfactant P20, mM MgCl2, and 1% DMSO)N-terminally GST-fused purified FAK enzyme was captured on both spot 1 and 2. Spot 1 was subsequently blocked by loading with 30 nM PF-562,271 at the beginning of each cycle. Concentration series' of the test compounds were injected over the spots at 25° C.
Measurement: Kd = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 541.62, ALogP 5.26, HBA 6, HBD 2, PSA 93.37, QED 0.36
Compound (SMILES): COc1cc(C2CCNCC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2cccc(C(N)=O)c2)n1
InChIKey: UKXVRLBNBZAAIX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 5750 nM (pChEMBL 5.239999771118164)
Descriptors: MW 499.54, ALogP 4.6, HBA 6, HBD 3, PSA 102.16, QED 0.42
Compound (SMILES): COc1cc(C2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2cccc(C(N)=O)c2)n1
InChIKey: JAXOLKSOAOTUCK-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 10440 nM (pChEMBL 4.980000019073486)
Descriptors: MW 513.56, ALogP 4.94, HBA 6, HBD 2, PSA 93.37, QED 0.44
Compound (SMILES): CCN1CCC(c2ccc(Nc3ncc(C(F)(F)F)c(Cc4ccccc4C(N)=O)n3)c(OC)c2)CC1
InChIKey: OVSGTWVJEXAGQC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 13260 nM (pChEMBL 4.880000114440918)
Descriptors: MW 513.56, ALogP 5.14, HBA 6, HBD 2, PSA 93.37, QED 0.43
Compound (SMILES): CCc1cc(C2CCNCC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: JMXXELDLOUPZFT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 1176 nM (pChEMBL 5.929999828338623)
Descriptors: MW 511.59, ALogP 5.08, HBA 5, HBD 3, PSA 92.93, QED 0.37
Compound (SMILES): CCc1cc(C2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: SXMOIWLLBKAOGR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 1010 nM (pChEMBL 6)
Descriptors: MW 525.62, ALogP 5.42, HBA 5, HBD 2, PSA 84.14, QED 0.39
Compound (SMILES): NC(=O)Cc1ccccc1CCc1nc(Nc2ccc(C3CCNCC3)cc2OC(F)(F)F)ncc1C(F)(F)F
InChIKey: WEXDYWPJRYUSAD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 > 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 567.53, ALogP 5.42, HBA 6, HBD 3, PSA 102.16, QED 0.3
Compound (SMILES): CN1CCC(c2ccc(Nc3ncc(C(F)(F)F)c(CCc4ccccc4CC(N)=O)n3)c(OC(F)(F)F)c2)CC1
InChIKey: QSOOWIITUXDNSS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 59763 nM (pChEMBL 4.21999979019165)
Descriptors: MW 581.56, ALogP 5.76, HBA 6, HBD 2, PSA 93.37, QED 0.31
Compound (SMILES): Cc1cc(C2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(CCc2ccccc2CC(N)=O)n1
InChIKey: KAVPZFNKRGDVLL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 511.59, ALogP 5.17, HBA 5, HBD 2, PSA 84.14, QED 0.44
Compound (SMILES): CN1CCC(c2ccc(Nc3ncc(C(F)(F)F)c(CCc4ccccc4CC(N)=O)n3)c(F)c2)CC1
InChIKey: NOUVYWRJTCFRGO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Biochemical Assay: Compounds of the invention may be tested for in vitro activity in the following assay: A biotin labeled peptide is used as substrate (amino acid sequence: Biotin-Glu-Gly-Pro-Trp-Leu-Glu -Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) (SEQ ID NO: 1). VEGFR3 cytoplasmic domain (amino acids 798-1298) was purchased as N-terminal GST-fusion protein (the enzyme). The 15ul assay reactions are run in Greiner brand white 384-well low volume plates. All reactions contained 10 mM HEPES pH 7.4, 10mM MgCl2, 0.01% (v/v) Tween-20, 50uM Na3VO4, 0.01% (w/v) albumin from chicken egg white, 1mM Dithiothreitol, 111 nM peptide substrate, 500uM ATP, and 3.8ng/reaction enzyme, with the enzyme being omitted from negative control reactions. Compounds were added in a volume of 100nl from dilution series prepared in DMSO, positive and negative control reactions receiving the same volume DMSO without compound. The plates were sealed with adhesive seals and incubated for 90 minutes at 30 degree C.
Measurement: IC50 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 515.56, ALogP 5, HBA 5, HBD 2, PSA 84.14, QED 0.41
Compound (SMILES): Cc1cc(NC2CCc3ccccc3C2)n2nc(C(F)(F)F)nc2n1
InChIKey: SEOYKFZOPSMBHI-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: Q08210
Assay: Inhibiton Assay: For studying inhibition of Plasmodium or human DHODH enzyme, two assays that are in routine use are described, for example, in Baldwin, et al. (2002) JBiol Chem., 277, 41827-41834, and Baldwin, et al. (2005) J. Biol. Chem., 280. 21847-21853.Briefly, this colorimetric assay monitors the reduction of 2,6-dichloroindophenol (DCIP) at 600 nm (e = 18.8 mM-1cm-1) for measuring DHOD inhibition. The assay was carried out using a solution containing 100 mM HEPES, pH 8.0, 150 mM NaCl, 10% glycerol, 0.1% Triton X-100, 20 micro molar CoQD (coenzyme QD), 200 micro molar L-dihydroorotate, and 120 micro molar DCIP. Reactions are initiated by addition of enzyme to a final concentration in the range of about 5 nM to about 50 nM while maintaining the temperature of a circulating water bath at 25Â° C. Alternatively, for potent compounds, activity was determined by directly measuring the production of orotic acid at 296 nm (Îµ = 4.3 mM-1 cm-1).
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 347.34, ALogP 3.42, HBA 5, HBD 1, PSA 55.11, QED 0.77
Compound (SMILES): Cn1cc(-c2nc(C3(c4ccc(-c5cnc(N)nc5)nc4)CCC3)no2)cn1
InChIKey: DNIONESFABVQQY-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Inhibition of FLAP in calcimycin-stimulated human whole blood assessed as reduction in LTB4 production pretreated for 15 mins followed by calcimycin addition after 30 mins by ELISA
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 374.41, ALogP 2.37, HBA 9, HBD 1, PSA 121.43, QED 0.58
Compound (SMILES): Cc1cc(-c2nc(C3(c4ccc(-c5cnc(N)nc5)cn4)CCC3)no2)[nH]n1
InChIKey: IICYJPSPLINCAL-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Inhibition of FLAP in calcimycin-stimulated human whole blood assessed as reduction in LTB4 production pretreated for 15 mins followed by calcimycin addition after 30 mins by ELISA
Measurement: IC50 = 342 nM (pChEMBL 6.46999979019165)
Descriptors: MW 374.41, ALogP 2.67, HBA 8, HBD 2, PSA 132.29, QED 0.56
Compound (SMILES): Cn1cc(-c2nc(C3(c4ccc(-c5cnc(N)nc5)cn4)CCC3)no2)cn1
InChIKey: NCKPUAHDRNNIHZ-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Inhibition of FLAP in calcimycin-stimulated human whole blood assessed as reduction in LTB4 production pretreated for 15 mins followed by calcimycin addition after 30 mins by ELISA
Measurement: IC50 = 787 nM (pChEMBL 6.099999904632568)
Descriptors: MW 374.41, ALogP 2.37, HBA 9, HBD 1, PSA 121.43, QED 0.58
Compound (SMILES): CN(C(=O)Cn1cc(-c2nc(C3(c4ccc(-c5cnc(N)nc5)nc4)CCC3)no2)cn1)C(C)(C)C
InChIKey: HTELJZKEPOOTIK-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Inhibition of FLAP in calcimycin-stimulated human whole blood assessed as reduction in LTB4 production pretreated for 15 mins followed by calcimycin addition after 30 mins by ELISA
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 487.57, ALogP 3.09, HBA 10, HBD 1, PSA 141.74, QED 0.43
Compound (SMILES): CC(C)(C)NC(=O)Cn1cc(-c2nc(C3(c4ccc(-c5cnc(N)nc5)nc4)CCC3)no2)cn1
InChIKey: MGQUKLBZFFHVLX-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: Compounds area assessed for the ability to bind to FLAP in a binding assay that measures compound-specific displacement of an iodinated (125I) FLAP inhibitor via a scintillaion proximity assay format (adapted from S. Charleson et. al., Mol. Pharmacol., 1992,41 873-879).
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 473.54, ALogP 2.75, HBA 10, HBD 2, PSA 150.53, QED 0.43
Compound (SMILES): CC(C)(C#N)n1cc(-c2nc(C3(c4ccc(-c5cnc(N)nc5)nc4)CCC3)no2)cn1
InChIKey: CBZQTDDFYHAQDT-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: Compounds area assessed for the ability to bind to FLAP in a binding assay that measures compound-specific displacement of an iodinated (125I) FLAP inhibitor via a scintillaion proximity assay format (adapted from S. Charleson et. al., Mol. Pharmacol., 1992,41 873-879).
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 427.47, ALogP 3.1, HBA 10, HBD 1, PSA 145.22, QED 0.51
Compound (SMILES): Nc1ncc(-c2ccc(C3(c4noc(N5CCC(O)CC5)n4)CCC3)cn2)cn1
InChIKey: UBBBCORMCZKJOS-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Inhibition of FLAP in calcimycin-stimulated human whole blood assessed as reduction in LTB4 production pretreated for 15 mins followed by calcimycin addition after 30 mins by ELISA
Measurement: IC50 = 595 nM (pChEMBL 6.21999979019165)
Descriptors: MW 393.45, ALogP 1.93, HBA 9, HBD 2, PSA 127.08, QED 0.68
Compound (SMILES): Cc1n[nH]cc1-c1nc(C2(c3ccc(-c4cnc(N)nc4)nc3)CCC2)no1
InChIKey: UQAOJVOXRQBBJW-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: Compounds area assessed for the ability to bind to FLAP in a binding assay that measures compound-specific displacement of an iodinated (125I) FLAP inhibitor via a scintillaion proximity assay format (adapted from S. Charleson et. al., Mol. Pharmacol., 1992,41 873-879).
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 374.41, ALogP 2.67, HBA 8, HBD 2, PSA 132.29, QED 0.56
Compound (SMILES): COC(=O)CCC1(c2ccc(Cl)cc2)c2c(nn(-c3ccccc3OC)c2C(C)C)C(=O)N1c1ccc(F)c(Cl)c1
InChIKey: OATMHJTYDZFHJL-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Time Resolved Fluorescence Energy Transfer (TR-FRET) Assay: The inhibition of p53-MDM2 and p53-MDM4 interactions is measured by time resolved fluorescence energy transfer (TR-FRET). Fluorescence energy transfer (or Foerster resonance energy transfer) describes an energy transfer between donor and acceptor fluorescent molecules. For this assay, human MDM2 protein (amino acids 2-188) and human MDM4 protein (amino acids 2-185), tagged with a C-terminal biotin moiety, are used in combination with a Europium labeled streptavidin (Perkin Elmer, Inc., Waltham, MA, USA) serving as the donor fluorophore. The p53 derived, Cy5 labeled peptide Cy5-TFSDLWKLL (p53 aa18-26) is the energy acceptor. Upon excitation of the donor molecule at 340nm, binding interaction between MDM2 or MDM4 and the p53 peptide induces energy transfer and enhanced response at the acceptor emission wavelength at 665 nm.
Measurement: IC50 = 0.499 nM (pChEMBL 9.300000190734863)
Descriptors: MW 596.49, ALogP 7.31, HBA 6, HBD 0, PSA 73.66, QED 0.2
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@H]1n1ccnn1
InChIKey: DTOJGRXBNXZBHP-LCNIEQOASA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 2.53 nM (pChEMBL 8.600000381469727)
Descriptors: MW 507.52, ALogP 4.49, HBA 7, HBD 2, PSA 111.61, QED 0.41
Compound (SMILES): COCC(=O)N[C@@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: SCIFRMHWIBCWPT-LCNIEQOASA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 30.07 nM (pChEMBL 7.519999980926514)
Descriptors: MW 527.55, ALogP 3.79, HBA 6, HBD 3, PSA 119.23, QED 0.43
Compound (SMILES): CC(C)C(=O)N[C@@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: RXIVHKXXRWBNDH-CSMVMILBSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 525.58, ALogP 4.79, HBA 5, HBD 3, PSA 110, QED 0.43
Compound (SMILES): C[C@H]1CN(c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@H]1n1cc(-c2ccsc2)nn1
InChIKey: QMBLOFSJYILYLC-SYWSQECDSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.06 nM (pChEMBL 10.220000267028809)
Descriptors: MW 590.64, ALogP 5.16, HBA 9, HBD 2, PSA 114.85, QED 0.28
Compound (SMILES): C[C@H]1CN(c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)[C@H]1n1ccnn1
InChIKey: MYFHTAWVDSNJJK-IKGLDXFJSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 1.24 nM (pChEMBL 8.90999984741211)
Descriptors: MW 508.51, ALogP 3.43, HBA 8, HBD 2, PSA 114.85, QED 0.42
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)/C1=N\O
InChIKey: ZRNYLUKSHWKQCV-RELFCZETSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 6.81 nM (pChEMBL 8.170000076293945)
Descriptors: MW 469.47, ALogP 4.48, HBA 6, HBD 3, PSA 113.49, QED 0.39
Compound (SMILES): Cc1cn([C@@H]2[C@H](N)CN(c3ccncc3NC(=O)c3ccc(F)c(-c4c(F)cccc4F)n3)C[C@@H]2C)nn1
InChIKey: WRZSMTVCYOXUQT-FSKGLPCWSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.04 nM (pChEMBL 10.399999618530273)
Descriptors: MW 522.54, ALogP 3.74, HBA 8, HBD 2, PSA 114.85, QED 0.41
Compound (SMILES): CCOC(=O)N[C@@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: XELTWQUXHGQCGM-JWGOKDHHSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 14.23 nM (pChEMBL 7.849999904632568)
Descriptors: MW 527.55, ALogP 4.77, HBA 6, HBD 3, PSA 119.23, QED 0.43
Compound (SMILES): CC(C)OC(=O)N[C@@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: UPIKPYVJDQBIIJ-CSMVMILBSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 17.78 nM (pChEMBL 7.75)
Descriptors: MW 541.57, ALogP 5.16, HBA 6, HBD 3, PSA 119.23, QED 0.4
Compound (SMILES): COC(=O)N[C@@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: GXSHWBSAHCQKFV-OEDDDKJZSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 13.88 nM (pChEMBL 7.860000133514404)
Descriptors: MW 513.52, ALogP 4.38, HBA 6, HBD 3, PSA 119.23, QED 0.47
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](N)C1=O
InChIKey: QJTHIJNIWCBEOX-VEVIJQCQSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 454.45, ALogP 4.22, HBA 5, HBD 2, PSA 97.97, QED 0.62
Compound (SMILES): CO/N=C1/[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: IGYTYDLTGAZLER-KLPFSRNGSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 15.72 nM (pChEMBL 7.800000190734863)
Descriptors: MW 483.49, ALogP 4.66, HBA 6, HBD 2, PSA 102.49, QED 0.51
Compound (SMILES): CO/N=C1\[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: IGYTYDLTGAZLER-OLBDUGHSSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 4.82 nM (pChEMBL 8.319999694824219)
Descriptors: MW 483.49, ALogP 4.66, HBA 6, HBD 2, PSA 102.49, QED 0.51