lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H]1C[C@H]2CSC(N)=N[C@@]2(c2nc(NC(=O)c3ccc(OC(F)F)cn3)cs2)CO1
InChIKey: ZLZUHACSRMOLLV-RAALSFIWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Patch Clamp Assay: All testing was carried out in CHO cells transfected with the hERG gene purchased from Millipore (PrecisION hERG-CHO Recombinant Cell Line CYL3038). The cell line was grown in DMEM/F-12, GlutaMAX with 10% fetal bovine serum, 1% Penicillin-Streptomycin, 1% Geneticin and 1% of 1M HEPES buffer solution, and maintained at approximately 37 °C. in a humidified atmosphere containing 5% carbon dioxide. The cells were passaged every 3-5 days based on confluency. On the day of the experiment, 50%-80% confluent cells were harvested from a 175 cm2 culture flask using Detachin. After 10 minutes of exposure to Detachin at 37 °C., the cells were centrifuged for 1 minute at 1000 RPM. The supernatant was removed and the cell pellet was reconstituted in 5-8 mL of serum free media with 2.5% of 1M HEPES, placed on the Qstirrer, and allowed to recover. After a 30 minute recovery period, experiments were initiated.
Measurement: IC50 = 9900 nM (pChEMBL 5)
Descriptors: MW 455.51, ALogP 3.07, HBA 9, HBD 2, PSA 111.72, QED 0.71
Compound (SMILES): CC1CCN(C(=O)C(CCn2cccc2C#N)NS(=O)(=O)c2cc(Cl)c(N)c(Cl)c2)CC1
InChIKey: ZYSPBBJRIQHKDF-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Antagonist activity at human histamine H4 receptor assessed as inhibition of histamine-induced calcium flux
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.44, ALogP 3.24, HBA 6, HBD 2, PSA 121.22, QED 0.57
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2OC)CCC[C@H](N2CCN(CCO)CC2)C3)ncc1Cl
InChIKey: BCSHRERPHLTPEE-NRFANRHFSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Binding affinity to human ALK (1088 to 1409 residues) L1196M mutant expressed in mammalian system by KINOMEscan assay
Measurement: Kd = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 580.13, ALogP 3.84, HBA 9, HBD 4, PSA 114.88, QED 0.28
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
InChIKey: KCVWGCOBGFLUEB-UHFFFAOYSA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: In Vitro Affinity Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the β-arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 β-arrestin line results in the recruitment of β-arrestin (Richardson, R. M., R. J. Marjoram, L. S. Barak, R. Snyderman. 2003. Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with β-arrestin 2, a β-arrestin 2 recruitment test for CXCR2 or CXCR1 based on β-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44), as established by DiscoveRx Corporation was used. The stimulation of these two cell lines with CXCL8 (10 nM) induces β-arrestin 2 recruitment, as indicated by a significant increase in the induction factor. All the CXCR2 antagonists were tested in a dose-dependent manner and the concentration corresponding to 50% inhibition of the response was determined (IC50=half inhibition concentration).
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 455.54, ALogP 3.38, HBA 8, HBD 3, PSA 111.88, QED 0.37
Compound (SMILES): C[C@H]1C[C@H]2CSC(N)=N[C@@]2(c2nc(NC(=O)c3ccc(OC(F)F)cn3)cs2)CO1
InChIKey: ZLZUHACSRMOLLV-RAALSFIWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Patch Clamp Assay: All testing was carried out in CHO cells transfected with the hERG gene purchased from Millipore (PrecisION hERG-CHO Recombinant Cell Line CYL3038). The cell line was grown in DMEM/F-12, GlutaMAX with 10% fetal bovine serum, 1% Penicillin-Streptomycin, 1% Geneticin and 1% of 1M HEPES buffer solution, and maintained at approximately 37 °C. in a humidified atmosphere containing 5% carbon dioxide. The cells were passaged every 3-5 days based on confluency. On the day of the experiment, 50%-80% confluent cells were harvested from a 175 cm2 culture flask using Detachin. After 10 minutes of exposure to Detachin at 37 °C., the cells were centrifuged for 1 minute at 1000 RPM. The supernatant was removed and the cell pellet was reconstituted in 5-8 mL of serum free media with 2.5% of 1M HEPES, placed on the Qstirrer, and allowed to recover. After a 30 minute recovery period, experiments were initiated.
Measurement: IC50 = 23600 nM (pChEMBL 4.630000114440918)
Descriptors: MW 455.51, ALogP 3.07, HBA 9, HBD 2, PSA 111.72, QED 0.71
Compound (SMILES): CC1CCN(C(=O)C(CCn2cccc2C#N)NS(=O)(=O)c2cc(Cl)c(N)c(Cl)c2)CC1
InChIKey: ZYSPBBJRIQHKDF-UHFFFAOYSA-N
Target: C-C chemokine receptor type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P46092
Assay: Reversible inhibition of human CCL27-Fc binding to CCR10 expressed in HEK cell membranes by immunochemical binding assay
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 498.44, ALogP 3.24, HBA 6, HBD 2, PSA 121.22, QED 0.57
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2OC)CCC[C@H](N2CCN(CCO)CC2)C3)ncc1Cl
InChIKey: BCSHRERPHLTPEE-NRFANRHFSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK tyrosine phosphorylation in human NCI-H2228 cells
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 580.13, ALogP 3.84, HBA 9, HBD 4, PSA 114.88, QED 0.28
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
InChIKey: KCVWGCOBGFLUEB-UHFFFAOYSA-N
Target: C-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P51684
Assay: In Vitro Affinity Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the β-arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 β-arrestin line results in the recruitment of β-arrestin (Richardson, R. M., R. J. Marjoram, L. S. Barak, R. Snyderman. 2003. Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with β-arrestin 2, a β-arrestin 2 recruitment test for CXCR2 or CXCR1 based on β-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44), as established by DiscoveRx Corporation was used. The stimulation of these two cell lines with CXCL8 (10 nM) induces β-arrestin 2 recruitment, as indicated by a significant increase in the induction factor. All the CXCR2 antagonists were tested in a dose-dependent manner and the concentration corresponding to 50% inhibition of the response was determined (IC50=half inhibition concentration).
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 455.54, ALogP 3.38, HBA 8, HBD 3, PSA 111.88, QED 0.37
Compound (SMILES): CC1CCN(C(=O)C(CCn2cccc2C#N)NS(=O)(=O)c2cc(Cl)c(N)c(Cl)c2)CC1
InChIKey: ZYSPBBJRIQHKDF-UHFFFAOYSA-N
Target: C-C chemokine receptor type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P46092
Assay: Displacement of human CCL27-Fc from CCR10 expressed in HEK cell membranes by immunochemical binding analysis
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 498.44, ALogP 3.24, HBA 6, HBD 2, PSA 121.22, QED 0.57
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2OC)CCC[C@H](N2CCN(CCO)CC2)C3)ncc1Cl
InChIKey: BCSHRERPHLTPEE-NRFANRHFSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK tyrosine phosphorylation in human NCI-H3122 cells
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 580.13, ALogP 3.84, HBA 9, HBD 4, PSA 114.88, QED 0.28
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2CCCS2)o1
InChIKey: KCVWGCOBGFLUEB-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: In Vitro Affinity Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the β-arrestin recruitment after receptor activation type.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 β-arrestin line results in the recruitment of β-arrestin (Richardson, R. M., R. J. Marjoram, L. S. Barak, R. Snyderman. 2003. Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911).In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with β-arrestin 2, a β-arrestin 2 recruitment test for CXCR2 or CXCR1 based on β-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44), as established by DiscoveRx Corporation was used. The stimulation of these two cell lines with CXCL8 (10 nM) induces β-arrestin 2 recruitment, as indicated by a significant increase in the induction factor. All the CXCR2 antagonists were tested in a dose-dependent manner and the concentration corresponding to 50% inhibition of the response was determined (IC50=half inhibition concentration).
Measurement: IC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 455.54, ALogP 3.38, HBA 8, HBD 3, PSA 111.88, QED 0.37
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2OC)CCC[C@H](N2CCN(CCO)CC2)C3)ncc1Cl
InChIKey: BCSHRERPHLTPEE-NRFANRHFSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin)
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 580.13, ALogP 3.84, HBA 9, HBD 4, PSA 114.88, QED 0.28
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCN(CCN4CCOCC4)CC3)cc12
InChIKey: DCGPJAOHTGLEOK-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 438.55, ALogP 3.89, HBA 5, HBD 1, PSA 53.62, QED 0.63
Compound (SMILES): COc1ccc(-c2cc3c(C(=O)O)n[nH]c3cc2Cl)cc1
InChIKey: WXDKLJLSBMTTFY-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P54619
Assay: Binding affinity to recombinant human AMPK alpha1/beta1/gamma1 by SPR binding assay
Measurement: Kd = 1776 nM (pChEMBL 5.75)
Descriptors: MW 302.72, ALogP 3.59, HBA 3, HBD 2, PSA 75.21, QED 0.78
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cccc(O)c4)c4c(N)ncnc43)n(C3CCCCC3)c(=O)c12
InChIKey: KJURAXOPBFNIBP-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 480.57, ALogP 4.96, HBA 8, HBD 2, PSA 111.85, QED 0.38
Compound (SMILES): CCOC(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cc3)nc2n(C2CCCC2)c1=O.Cl
InChIKey: FJRMZRFQOLFFKE-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of Cdk2/Cyclin A (unknown origin) using retinoblastoma protein substrate and [gamma32P]ATP incubated for 15 mins by beta plate counter based assay
Measurement: IC50 = 5950 nM (pChEMBL 5.21999979019165)
Descriptors: MW 462.55, ALogP 3.24, HBA 9, HBD 2, PSA 101.38, QED 0.54
Compound (SMILES): Cc1ccccc1S(=O)(=O)Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccccc4C)ccc3o2)cc1
InChIKey: NXCWWLTWLQEIKK-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P10809
Assay: Inhibition of human mitochondrial HSP60/HSP10 expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 40 to 60 mins by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 533.63, ALogP 5.71, HBA 6, HBD 2, PSA 118.37, QED 0.28
Compound (SMILES): CN1CCc2cccc(c2)[C@@H](Nc2ccc3c(N)ncc(F)c3c2)C(=O)N(C)Cc2cc(ccc2S(=O)(=O)C2CC2)NC1=O
InChIKey: BCCZSVOMVPSNRH-GDLZYMKVSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins at 37 degC
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 616.72, ALogP 4.72, HBA 7, HBD 3, PSA 137.73, QED 0.3
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(C#C[C@@H](C)O)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: MTSIDIMIRBATAB-GOSISDBHSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 464.53, ALogP 3.11, HBA 8, HBD 2, PSA 111.85, QED 0.4
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc5ncsc5c4)ccc3o2)cc1)c1ccc2ncsc2c1
InChIKey: JTUYIPCRQVQRHO-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q548M1
Assay: Inhibition of Escherichia coli GroEL/GroES-ATPase activity expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 20 to 40 mins by malachite green dye based fluorescence assay
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 619.73, ALogP 6.32, HBA 10, HBD 2, PSA 144.15, QED 0.21
Compound (SMILES): O=C(CCCNC1=NCCN1)Nc1ccc(C[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)cc1
InChIKey: AJZHUKFTTKIGAR-GOTSBHOMSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay
Measurement: IC50 = 0.13 nM (pChEMBL 9.890000343322754)
Descriptors: MW 570.67, ALogP 0.92, HBA 8, HBD 5, PSA 169.3, QED 0.23
Compound (SMILES): Fc1c(O[C@H]2CC[C@](Cc3cccc(Nc4cc[nH]n4)n3)(c3n[nH]c(=S)o3)CC2)cccc1C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: VRSSRQLGTAIPQJ-IGVGDGLPSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human full-length N-terminal GST-tagged Aurora B/His-tagged INCENP (803 to 916 residues) using kemptide as substrate and [gamma33P]ATP after 45 mins by liquid scintillation counting method
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 534.54, ALogP 6.25, HBA 7, HBD 3, PSA 104.65, QED 0.19
Compound (SMILES): COC(=O)c1ccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5ccc(C(=O)OC)cc5)ccc4o3)cc2)cc1
InChIKey: QVXVRRFDGPIAJS-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q548M1
Assay: Inhibition of Escherichia coli GroEL/GroES-ATPase activity expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 20 to 40 mins by malachite green dye based fluorescence assay
Measurement: IC50 = 91000 nM (pChEMBL 4.039999961853027)
Descriptors: MW 621.65, ALogP 4.67, HBA 10, HBD 2, PSA 170.97, QED 0.22
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cccc(O)c4)c4c(N)ncnc43)n(C3CCCCC3)c(=O)c12
InChIKey: KJURAXOPBFNIBP-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 480.57, ALogP 4.96, HBA 8, HBD 2, PSA 111.85, QED 0.38
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4ccc(F)c(O)c4)c4c(N)ncnc43)n(C3CCCC3)c(=O)c12
InChIKey: WVEJQTWCILMLIC-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 484.54, ALogP 4.71, HBA 8, HBD 2, PSA 111.85, QED 0.38
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3ncnc4[nH]c(Cl)nc34)n(-c3ccccc3)c(=O)c12
InChIKey: CVXMSDSLWRSIBG-AWEZNQCLSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 430.9, ALogP 4.79, HBA 6, HBD 2, PSA 88.49, QED 0.4
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc5ncsc5c4)ccc3o2)cc1)c1ccc2ncsc2c1
InChIKey: JTUYIPCRQVQRHO-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P10809
Assay: Inhibition of human mitochondrial HSP60/HSP10 expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 40 to 60 mins by fluorescence based assay
Measurement: IC50 = 49000 nM (pChEMBL 4.309999942779541)
Descriptors: MW 619.73, ALogP 6.32, HBA 10, HBD 2, PSA 144.15, QED 0.21
Compound (SMILES): O=C(CCCNC1=NCCN1)Nc1ccc(C[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)cc1
InChIKey: AJZHUKFTTKIGAR-GOTSBHOMSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08648
Assay: Cell Adhesion Assay : A panel of cell lines and integrin ligands were developed to allow rapid examination of potency and specificity of inhibitors against all 8 integrins that recognize RGD sequences in ligands. A subset of these was used to generate the very encouraging data about 8 shown above. These cell lines were used to calculate IC50 concentrations for each inhibitor synthesized to rapidly generate structure activity information to drive subsequent modification and synthesis. Inhibitors were evaluated for showing better potency/selectivity in CCl4-induced liver fibrosis.
Measurement: IC50 = 505 nM (pChEMBL 6.300000190734863)
Descriptors: MW 570.67, ALogP 0.92, HBA 8, HBD 5, PSA 169.3, QED 0.23
Compound (SMILES): Cc1cccc2cc(Cn3nc(C#CCO)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: OVIAKYKLZHEINE-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 454.47, ALogP 2.55, HBA 8, HBD 2, PSA 111.85, QED 0.41
Compound (SMILES): Cc1cccnc1-n1c(Cn2nc(-c3ccc(Cl)c(O)c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: CCLCQKWJVPVSIQ-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 523.98, ALogP 4.8, HBA 9, HBD 2, PSA 124.74, QED 0.34
Compound (SMILES): COC(=O)c1ccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5ccc(C(=O)OC)cc5)ccc4o3)cc2)cc1
InChIKey: QVXVRRFDGPIAJS-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P10809
Assay: Inhibition of human mitochondrial HSP60/HSP10 expressed in Escherichia coli DH5alpha/BL21 (DE3) assessed as inhibition of denatured MDH refolding preincubated for 10 mins followed by ATP addition measured after 40 to 60 mins by fluorescence based assay
Measurement: IC50 = 87000 nM (pChEMBL 4.059999942779541)
Descriptors: MW 621.65, ALogP 4.67, HBA 10, HBD 2, PSA 170.97, QED 0.22
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4ccc(F)c(O)c4)c4c(N)ncnc43)n(C3CCCC3)c(=O)c12
InChIKey: WVEJQTWCILMLIC-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 484.54, ALogP 4.71, HBA 8, HBD 2, PSA 111.85, QED 0.38
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3ncnc4[nH]c(Cl)nc34)n(-c3ccccc3)c(=O)c12
InChIKey: CVXMSDSLWRSIBG-AWEZNQCLSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 430.9, ALogP 4.79, HBA 6, HBD 2, PSA 88.49, QED 0.4
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(C#C[C@@H](C)O)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: MTSIDIMIRBATAB-GOSISDBHSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 464.53, ALogP 3.11, HBA 8, HBD 2, PSA 111.85, QED 0.4
Compound (SMILES): O=C(CCCNC1=NCCN1)Nc1ccc(C[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)cc1
InChIKey: AJZHUKFTTKIGAR-GOTSBHOMSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08648
Assay: Cell Adhesion Assay : A panel of cell lines and integrin ligands were developed to allow rapid examination of potency and specificity of inhibitors against all 8 integrins that recognize RGD sequences in ligands. A subset of these was used to generate the very encouraging data about 8 shown above. These cell lines were used to calculate IC50 concentrations for each inhibitor synthesized to rapidly generate structure activity information to drive subsequent modification and synthesis. Inhibitors were evaluated for showing better potency/selectivity in CCl4-induced liver fibrosis.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 570.67, ALogP 0.92, HBA 8, HBD 5, PSA 169.3, QED 0.23
Compound (SMILES): Cc1cccc2cc(Cn3nc(C#CCO)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: OVIAKYKLZHEINE-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.47, ALogP 2.55, HBA 8, HBD 2, PSA 111.85, QED 0.41
Compound (SMILES): Cc1cccnc1-n1c(Cn2nc(-c3ccc(Cl)c(O)c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: CCLCQKWJVPVSIQ-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 523.98, ALogP 4.8, HBA 9, HBD 2, PSA 124.74, QED 0.34
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(-c3ccnn3C)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)nccc2c1
InChIKey: RRNRMCAVLZYWDN-JCOAXYOVSA-N
Target: Coagulation factor VII/tissue factor (PROTEIN COMPLEX), Homo sapiens
UniProt: P08709
Assay: Inhibition of full-length human TF/recombinant human factor 7a assessed as decrease in conversion of factor 10 to factor 10a by measuring S2765 hydrolysis after 15 mins
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 589.7, ALogP 6, HBA 8, HBD 3, PSA 127.4, QED 0.24
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Inhibition of gamma-secretase (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Inhibition of gamma secretase derived from human Hela cell membrane assessed as reduction in amyloid beta (1 to 40) production by ELISA
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): COc1ccc(-c2cc3c(C(=O)O)n[nH]c3cc2Cl)cc1
InChIKey: WXDKLJLSBMTTFY-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y478
Assay: Binding affinity to recombinant human AMPK alpha1/beta1/gamma1 by SPR binding assay
Measurement: Kd = 1776 nM (pChEMBL 5.75)
Descriptors: MW 302.72, ALogP 3.59, HBA 3, HBD 2, PSA 75.21, QED 0.78
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Inhibition of gamma-secretase (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Inhibition of gamma secretase derived from human Hela cell membrane assessed as reduction in amyloid beta (1 to 40) production by ELISA
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Inhibition of gamma-secretase (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Inhibition of gamma secretase derived from human Hela cell membrane assessed as reduction in amyloid beta (1 to 40) production by ELISA
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Inhibition of gamma-secretase (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Inhibition of gamma secretase derived from human Hela cell membrane assessed as reduction in amyloid beta (1 to 40) production by ELISA
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of gamma-secretase (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN([C@@H](C)[C@@H]2CC[C@H](c4cc(F)c(Cl)cc4C(F)(F)F)O2)C3=O)cn1
InChIKey: AKCDDYGYIGPEKL-JQOQJDEVSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of gamma secretase derived from human Hela cell membrane assessed as reduction in amyloid beta (1 to 40) production by ELISA
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 538.93, ALogP 4.92, HBA 6, HBD 0, PSA 69.36, QED 0.44
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@H]2CCC[C@@H]1c1nnc(-c3ccc(F)cn3)n1C2
InChIKey: KAXAHUBBXCYPAA-BLLLJJGKSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 = 14825.2 nM (pChEMBL 4.829999923706055)
Descriptors: MW 465.84, ALogP 4.9, HBA 5, HBD 0, PSA 63.91, QED 0.5
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@@H]2CCC[C@H]1c1nnc(-c3ccc(F)cn3)n1C2
InChIKey: KAXAHUBBXCYPAA-WBMJQRKESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: IC50 = 14825 nM (pChEMBL 4.829999923706055)
Descriptors: MW 465.84, ALogP 4.9, HBA 5, HBD 0, PSA 63.91, QED 0.5
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@H]2CCC[C@@H]1c1nnc(-c3cccnc3)n1C2
InChIKey: HIHBQMZMGKEOHM-XJKSGUPXSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding: Human or rat P2X7-1321N1 cells were collected and frozen @-80.degree. C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 .mu.l:10 .mu.l compound (10.times.)+(b) 40 .mu.l tracer (2.5.times.)+50 .mu.l membrane (2.times.). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2009, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4.degree. C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 17.4 nM (pChEMBL 7.760000228881836)
Descriptors: MW 447.85, ALogP 4.76, HBA 5, HBD 0, PSA 63.91, QED 0.57
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@@H]2CCC[C@H]1c1nnc(-c3ncc(F)cn3)n1C2
InChIKey: OKEUHBTYCIUVSL-RISCZKNCSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: IC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 466.83, ALogP 4.3, HBA 6, HBD 0, PSA 76.8, QED 0.53
Compound (SMILES): O=C(c1ccc(Cl)cc1Cl)N1[C@@H]2CCC[C@H]1c1nnc(-c3ncc(F)cn3)n1C2
InChIKey: OFEDUVRGSIXSPB-DOMZBBRYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 = 3349.7 nM (pChEMBL 5.46999979019165)
Descriptors: MW 433.27, ALogP 3.93, HBA 6, HBD 0, PSA 76.8, QED 0.61
Compound (SMILES): Cc1cccc(-c2nnc3n2C[C@@H]2CCC[C@H]3N2C(=O)c2cccc(C(F)(F)F)c2Cl)n1
InChIKey: NBZULESLUAZFRE-SUMWQHHRSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding: Human or rat P2X7-1321N1 cells were collected and frozen @-80.degree. C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 .mu.l:10 .mu.l compound (10.times.)+(b) 40 .mu.l tracer (2.5.times.)+50 .mu.l membrane (2.times.). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2009, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4.degree. C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 461.88, ALogP 5.07, HBA 5, HBD 0, PSA 63.91, QED 0.53
Compound (SMILES): Cc1cccc(-c2nnc3n2C[C@H]2CCC[C@@H]3N2C(=O)c2cccc(C(F)(F)F)c2Cl)n1
InChIKey: NBZULESLUAZFRE-DYVFJYSZSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 461.88, ALogP 5.07, HBA 5, HBD 0, PSA 63.91, QED 0.53
Compound (SMILES): COc1ccnc(-c2nnc3n2C[C@H]2CCC[C@@H]3N2C(=O)c2cccc(C(F)(F)F)c2Cl)c1
InChIKey: SDWUWEKAOFIYDK-PXAZEXFGSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 = 1541.7 nM (pChEMBL 5.809999942779541)
Descriptors: MW 477.87, ALogP 4.77, HBA 6, HBD 0, PSA 73.14, QED 0.54
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@@H]2CCC[C@H]1c1nnc(-c3ccc(Cl)cn3)n1C2
InChIKey: KBSSPWAWZCWGIR-WBMJQRKESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 = 2773.3 nM (pChEMBL 5.559999942779541)
Descriptors: MW 482.29, ALogP 5.42, HBA 5, HBD 0, PSA 63.91, QED 0.49
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@H]2CCC[C@@H]1c1nnc(-c3ccccn3)n1C2
InChIKey: GJFWSWDCNPBEIO-BLLLJJGKSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 = 11.3 nM (pChEMBL 7.949999809265137)
Descriptors: MW 447.85, ALogP 4.76, HBA 5, HBD 0, PSA 63.91, QED 0.57
Compound (SMILES): O=C(c1ccnc(C(F)(F)F)c1Cl)N1[C@@H]2CCC[C@H]1c1nnc(-c3cccs3)n1C2
InChIKey: WDRCRSCGFCTTSL-PWSUYJOCSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: Ca.sup.2+flux: 1321N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 .mu.l volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl.sub.2, 1 MgCl.sub.2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250.times. the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 .mu.L of the compound into 300 .mu.L of assay buffer. A further 3.times. dilution occurred when transferring 50 .mu.L/well of the compound plate to 100 .mu.L/well in the cell plate.
Measurement: IC50 = 36.5 nM (pChEMBL 7.440000057220459)
Descriptors: MW 453.88, ALogP 4.82, HBA 6, HBD 0, PSA 63.91, QED 0.56
Compound (SMILES): Cc1ccc(-c2nnc3n2C[C@H]2CCC[C@@H]3N2C(=O)c2ccnc(C(F)(F)F)c2Cl)s1
InChIKey: WVKYIOZRKRHELJ-YPMHNXCESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding Assay: human or rat P2X7-1321N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: IC50 = 338 nM (pChEMBL 6.46999979019165)
Descriptors: MW 467.9, ALogP 5.13, HBA 6, HBD 0, PSA 63.91, QED 0.52
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1[C@H]2CC[C@@H]1c1nnc(-c3ccc(F)cc3)n1C2
InChIKey: JLCZWQQYVOECLS-XJKSGUPXSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Radioligand Binding: Human or rat P2X7-1321N1 cells were collected and frozen @-80.degree. C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 .mu.l:10 .mu.l compound (10.times.)+(b) 40 .mu.l tracer (2.5.times.)+50 .mu.l membrane (2.times.). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2009, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4.degree. C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM).
Measurement: Ki = 35.5 nM (pChEMBL 7.449999809265137)
Descriptors: MW 450.82, ALogP 5.12, HBA 4, HBD 0, PSA 51.02, QED 0.51