lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): [C-]#[N+]c1ccc(C2c3c(nn(-c4cnc(OC)nc4OC)c3C(C)C)C(=O)N2c2cc(Cl)c(=O)n(C)c2)c(F)c1
InChIKey: SBTIBAXZWFMNEF-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 = 4.058 nM (pChEMBL 8.390000343322754)
Descriptors: MW 563.98, ALogP 4.59, HBA 9, HBD 0, PSA 108.73, QED 0.32
Compound (SMILES): [C-]#[N+]c1ccc(C2c3c(nn(-c4cnc(OC)nc4OC)c3C(C)C)C(=O)N2c2cc(Cl)cn(C)c2=O)cc1F
InChIKey: LQQCZFNYHWBMBO-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 = 1.292 nM (pChEMBL 8.890000343322754)
Descriptors: MW 563.98, ALogP 4.59, HBA 9, HBD 0, PSA 108.73, QED 0.32
Compound (SMILES): [C-]#[N+]c1ccc(C2c3c(nn(-c4cnc(OC)nc4OC)c3C(C)C)C(=O)N2c2cc(Cl)cn(C)c2=O)c(F)c1
InChIKey: XQWVYYDDSOFRPG-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 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 563.98, ALogP 4.59, HBA 9, HBD 0, PSA 108.73, QED 0.32
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(C#N)c(F)c1)N(c1cc(Cl)cn(C)c1=O)C2=O
InChIKey: QCBBDTOZLNYFGQ-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 = 0.376 nM (pChEMBL 9.430000305175781)
Descriptors: MW 577.02, ALogP 3.97, HBA 10, HBD 0, PSA 122.17, QED 0.34
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(C#N)c(F)c1)N(c1cc(Cl)c(=O)n(C)c1)C2=O
InChIKey: OPHHVKUMEIMJFY-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 = 0.213 nM (pChEMBL 9.670000076293945)
Descriptors: MW 577.02, ALogP 3.97, HBA 10, HBD 0, PSA 122.17, QED 0.34
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(C#N)c(F)c1)N(c1cc(Cl)c[nH]c1=O)C2=O
InChIKey: UBDXCWOLGCQOJC-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 = 0.215 nM (pChEMBL 9.670000076293945)
Descriptors: MW 562.99, ALogP 3.96, HBA 9, HBD 1, PSA 133.03, QED 0.37
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(C#N)c(F)c1)N(c1c[nH]c(=O)c(Cl)c1)C2=O
InChIKey: NIQDSHQHXGATPM-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 = 0.197 nM (pChEMBL 9.710000038146973)
Descriptors: MW 562.99, ALogP 3.96, HBA 9, HBD 1, PSA 133.03, QED 0.37
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(Cl)c(F)c1)N(c1cc(Cl)cn(C)c1=O)C2=O
InChIKey: RNZZSMCPSZIPLM-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 = 0.128 nM (pChEMBL 9.890000343322754)
Descriptors: MW 586.46, ALogP 4.75, HBA 9, HBD 0, PSA 98.38, QED 0.32
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(Cl)c(F)c1)N(c1cc(Cl)c[nH]c1=O)C2=O
InChIKey: SPSDWBLEDCVGLA-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 = 0.165 nM (pChEMBL 9.779999732971191)
Descriptors: MW 572.43, ALogP 4.74, HBA 8, HBD 1, PSA 109.24, QED 0.36
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(Cl)c(F)c1)N(c1cc(Cl)c(=O)n(C)c1)C2=O
InChIKey: RKQCNVIHAFSPMO-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 = 0.155 nM (pChEMBL 9.8100004196167)
Descriptors: MW 586.46, ALogP 4.75, HBA 9, HBD 0, PSA 98.38, QED 0.32
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(Cl)c(F)c1)N(c1c[nH]c(=O)c(Cl)c1)C2=O
InChIKey: OZTFXLSOURVIGT-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 = 0.164 nM (pChEMBL 9.789999961853027)
Descriptors: MW 572.43, ALogP 4.74, HBA 8, HBD 1, PSA 109.24, QED 0.36
Compound (SMILES): COc1ncc(-n2nc3c(c2C(C)C)C(c2ccc(Cl)cc2)N(c2cc(C)cn(C)c2=O)C3=O)c(OC)n1
InChIKey: BQVXYVMHLPJQST-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 = 2.13 nM (pChEMBL 8.670000076293945)
Descriptors: MW 535, ALogP 4.21, HBA 9, HBD 0, PSA 104.37, QED 0.36
Compound (SMILES): COc1nc(N(C)C)ncc1-n1nc2c(c1C(C)C)C(c1ccc(Cl)cc1)N(c1cc(C)cn(C)c1=O)C2=O
InChIKey: IKDAKUWICQIDSR-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 = 0.528 nM (pChEMBL 9.279999732971191)
Descriptors: MW 548.05, ALogP 4.27, HBA 9, HBD 0, PSA 98.38, QED 0.36
Compound (SMILES): Cn1cc(Cc2nn(CC(=O)O)c(=O)c3ccccc23)c2ccccc21
InChIKey: JUBNTJHSYUBGEB-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 347.37, ALogP 2.56, HBA 5, HBD 1, PSA 77.12, QED 0.62
Compound (SMILES): Cc1cccc2c1c(Cc1nn(CC(=O)O)c(=O)c3ccccc13)cn2C
InChIKey: ANCZYUBQVBTXII-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 361.4, ALogP 2.87, HBA 5, HBD 1, PSA 77.12, QED 0.61
Compound (SMILES): O=C(O)Cn1nc(Cc2cccc3ccccc23)c2ccccc2c1=O
InChIKey: VYEOVMUBOFHZPC-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 344.37, ALogP 3.23, HBA 4, HBD 1, PSA 72.19, QED 0.62
Compound (SMILES): Cc1cccc2c1c(Cc1nn(CCC(=O)O)c(=O)c3ccccc13)cn2C
InChIKey: SRWLFOUYCJTYKD-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 375.43, ALogP 3.26, HBA 5, HBD 1, PSA 77.12, QED 0.58
Compound (SMILES): O=C(O)C(c1ccccc1)n1nc(Cc2cccc3ccccc23)c2ccccc2c1=O
InChIKey: VEJXCOIVBQLOOM-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 420.47, ALogP 4.81, HBA 4, HBD 1, PSA 72.19, QED 0.44
Compound (SMILES): CCCC(C(=O)O)n1nc(Cc2cccc3ccccc23)c2ccccc2c1=O
InChIKey: KOFDKPAWXNMYGX-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 386.45, ALogP 4.57, HBA 4, HBD 1, PSA 72.19, QED 0.53
Compound (SMILES): Cn1cc(Cc2nn(C(C(=O)O)c3ccccc3)c(=O)c3ccccc23)c2ccccc21
InChIKey: JXEAVXZALMHYOT-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 423.47, ALogP 4.15, HBA 5, HBD 1, PSA 77.12, QED 0.46
Compound (SMILES): CCCC(C(=O)O)n1nc(Cc2cn(C)c3cccc(C)c23)c2ccccc2c1=O
InChIKey: CFWPPIWGODXVHI-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 403.48, ALogP 4.21, HBA 5, HBD 1, PSA 77.12, QED 0.52
Compound (SMILES): Cc1cccc2c1c(Cc1nn(C(C(=O)O)c3ccccc3)c(=O)c3ccccc13)cn2C
InChIKey: UAYYAAIBVQDTIU-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 437.5, ALogP 4.46, HBA 5, HBD 1, PSA 77.12, QED 0.44
Compound (SMILES): CCCC(C(=O)O)n1nc(Cc2cn(C)c3ccccc23)c2ccccc2c1=O
InChIKey: ALXLWMJOACABSO-UHFFFAOYSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: In Vitro Assay: Chymase assays were performed in a total volume of 15 uL in Corning black opaque 384-well microtiter plates with a non-binding surface (Corning, N.Y.). The assay buffer was comprised of 20 mM Tris HCl pH 8.0, 50 mM NaCl, 0.01% CHAPS. The test compounds were serially diluted 3-fold with neat DMSO in a 96-well polypropylene plate from a 10 mM DMSO stock to give the 10 point dose response curve. 3 uL of the resulting DMSO solution were transferred to a 384-well polypropylene plate in duplicate, and 37 uL of assay buffer was added. Chymase was added to the assay plate in 3 uL of assay buffer followed by 2 uL of the appropriate compound dilution using a PlateMate Plus (Matrix Technologies Corp., Hudson, N.H.). The reaction was initiated by the addition of 10 uL rhodamine 110, bis-(succinoyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanylamide) (American Peptides, Sunnyvale, Calif.) in assay buffer containing 150 uM tris(2-carboxyethyl)phosphine.
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 389.46, ALogP 3.9, HBA 5, HBD 1, PSA 77.12, QED 0.54
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1CC2CC(Oc3cnc(C(F)(F)F)cn3)C1C2
InChIKey: CWZJPIYFFDDMCP-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 430.39, ALogP 2.76, HBA 7, HBD 0, PSA 86.03, QED 0.63
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CC3CC(Oc4cnc(C(F)(F)F)cn4)C2C3)n1
InChIKey: CKWUPZSHHCLQII-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 342 nM (pChEMBL 6.46999979019165)
Descriptors: MW 445.4, ALogP 2.46, HBA 8, HBD 0, PSA 98.92, QED 0.61
Compound (SMILES): CCOc1ncc2ccccc2c1C(=O)N1CC2CC(Oc3cnc(C(F)(F)F)cn3)C1C2
InChIKey: VCKIIVINGOZJPM-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 458.44, ALogP 4.12, HBA 6, HBD 0, PSA 77.44, QED 0.57
Compound (SMILES): Cc1cnc(C(=O)N2CC3CC(Oc4cnc(C(F)(F)F)cn4)C2C3)c(-n2nccn2)c1
InChIKey: YLFJSQKDYGUXAW-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 837 nM (pChEMBL 6.079999923706055)
Descriptors: MW 445.41, ALogP 2.46, HBA 8, HBD 0, PSA 98.92, QED 0.61
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: PSWAVZZVHYHQBT-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 429.4, ALogP 3.36, HBA 6, HBD 0, PSA 73.14, QED 0.64
Compound (SMILES): CCOc1ncc2ccccc2c1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: WORAHSUSUFAEIQ-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: Receptor Radioligand Binding Assay: Human Orexin 2 Receptor:HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol), diluted to a 5 nM concentration in PBS (2 nM final concentration). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentration (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 1450 nM (pChEMBL 5.840000152587891)
Descriptors: MW 457.45, ALogP 4.73, HBA 5, HBD 0, PSA 64.55, QED 0.55
Compound (SMILES): Cc1cnc(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)c(-n2nccn2)c1
InChIKey: OAQRBSBYWFGTPG-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 444.42, ALogP 3.07, HBA 7, HBD 0, PSA 86.03, QED 0.61
Compound (SMILES): CCOc1ccc2cccnc2c1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: TWCLRHNSMBRHHR-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: Receptor Radioligand Binding Assay: Human Orexin 2 Receptor:HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol), diluted to a 5 nM concentration in PBS (2 nM final concentration). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentration (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 526 nM (pChEMBL 6.28000020980835)
Descriptors: MW 457.45, ALogP 4.73, HBA 5, HBD 0, PSA 64.55, QED 0.55
Compound (SMILES): O=C(c1cccc(F)c1-c1ncccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: HUKWIAXQBOHZIX-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Human Orexin 1 Receptor Ca2+ Mobilization Assay: CHO cells stably transfected with the human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12, 10% FBS, 1×pen-strep, 400 μg/ml G418. Cells were seeded on to 384-well Packard viewplates at a density of 10,000 cells/well and incubated overnight at 37° C., 5% CO2. The cells were dye-loaded with BD Calcium Assay kit (BD, cat #640178) in HBSS (Gibco, cat #14025-092) with 2.5 mM probenecid and incubated at 37° C., 5% CO2 for 45 min. Cells were pre-incubated with compounds (diluted in DMEM/F-12) for 15-30 minutes before agonist (orexin A, 10 nM) stimulation. Ligand-induced Ca2+ release was measured using a Fluorometric Imaging Plate Reader (FLIPR, Molecular Devices, Sunnyvale, Calif.). Functional responses were measured as peak fluorescence intensity minus basal. The concentration of agonist that produced a half-maximal response is represented by the EC50 value. Antagonistic potency values were converted to apparent pKB values using a modified Cheng-Prusoff correction. Apparent pKB=−log IC50/1+[conc agonist/EC50].
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 458.42, ALogP 4.38, HBA 5, HBD 0, PSA 68.21, QED 0.54
Compound (SMILES): COc1ccc(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)c(-c2ncccn2)c1
InChIKey: DSTQNGFYZOHDRW-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Human Orexin 1 Receptor Ca2+ Mobilization Assay: CHO cells stably transfected with the human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12, 10% FBS, 1×pen-strep, 400 μg/ml G418. Cells were seeded on to 384-well Packard viewplates at a density of 10,000 cells/well and incubated overnight at 37° C., 5% CO2. The cells were dye-loaded with BD Calcium Assay kit (BD, cat #640178) in HBSS (Gibco, cat #14025-092) with 2.5 mM probenecid and incubated at 37° C., 5% CO2 for 45 min. Cells were pre-incubated with compounds (diluted in DMEM/F-12) for 15-30 minutes before agonist (orexin A, 10 nM) stimulation. Ligand-induced Ca2+ release was measured using a Fluorometric Imaging Plate Reader (FLIPR, Molecular Devices, Sunnyvale, Calif.). Functional responses were measured as peak fluorescence intensity minus basal. The concentration of agonist that produced a half-maximal response is represented by the EC50 value. Antagonistic potency values were converted to apparent pKB values using a modified Cheng-Prusoff correction. Apparent pKB=−log IC50/1+[conc agonist/EC50].
Measurement: Ki = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 470.45, ALogP 4.25, HBA 6, HBD 0, PSA 77.44, QED 0.56
Compound (SMILES): COc1ccc(C(=O)N2CC3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)c(-n2nccn2)c1
InChIKey: JAACBBVXXQKQLD-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 459.43, ALogP 3.37, HBA 7, HBD 0, PSA 82.37, QED 0.58
Compound (SMILES): O=C(c1cc(F)ccc1-n1nccn1)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: PSMGZVKVWYLIHB-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 447.39, ALogP 3.5, HBA 6, HBD 0, PSA 73.14, QED 0.57
Compound (SMILES): COc1cccc(-n2nccn2)c1C(=O)N1CC2CC(Oc3ccc(C(F)(F)F)cn3)C1C2
InChIKey: XSMDMCQWMREAHT-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM 001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1x Pen/Strep, 1x sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1x Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1x with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2Kx G, 5 min at 4 C.), the supernatant was aspirated and the pellets frozen and stored at -80 C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 459.43, ALogP 3.37, HBA 7, HBD 0, PSA 82.37, QED 0.58