lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4C(F)(F)F)C3C2)nnc1-c1cccnc1
InChIKey: UFUQIVBOXLXINJ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 488.58, ALogP 4.59, HBA 7, HBD 0, PSA 50.08, QED 0.36
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1cc[nH]c(=O)c1
InChIKey: CRAJXQNFXAOYDL-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 504.58, ALogP 3.88, HBA 7, HBD 1, PSA 70.05, QED 0.39
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant human CYP3A4 expressed in baculosomes preincubated for 10 mins followed by cofactor addition measured every minute for 10 mins using diethoxyflourescein as substrate by CYPEX assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4c(F)cc(F)cc4F)C3C2)nnc1-c1ccn(C)c(=O)c1
InChIKey: ZRQADOCXGLFZJC-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol. 266: 79-85.
Measurement: Ki = 7.59 nM (pChEMBL 8.119999885559082)
Descriptors: MW 504.58, ALogP 3.29, HBA 8, HBD 0, PSA 59.19, QED 0.36
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4)C3C2)nnc1C1CCOCC1
InChIKey: BGRFOPBDZYUOMJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at recombinant human muscarinic M1 receptor expressed in CHO-K1 cells assessed as inhibition of acetylcholine induced calcium mobilization preincubated for 10 mins followed by acetylcholine addition measured after 1 hr by fluo-4 AM dye-based FLIPR assay
Measurement: Ki = 1023.29 nM (pChEMBL 5.989999771118164)
Descriptors: MW 427.62, ALogP 3.4, HBA 7, HBD 0, PSA 46.42, QED 0.5
Compound (SMILES): CCn1cc(-c2cccc(C(F)(F)F)c2)c2sc(C(=N)NC3CCS(=O)(=O)CC3)cc2c1=O
InChIKey: WRUWGLUCNBMGPS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Affinity On-target Cellular interaction (Western Blot (chemoproteomic competition binding assay in HUT-78 cell lysate)) EUB0000247b BRD9
Measurement: IC50 = 79.4 nM (pChEMBL 7.099999904632568)
Descriptors: MW 497.56, ALogP 4.26, HBA 6, HBD 2, PSA 92.02, QED 0.42
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain and PHD finger-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULD4
Assay: Affinity Biochemical interaction (ITC) EUB0000323b BRPF3
Measurement: Kd = 2406 nM (pChEMBL 5.619999885559082)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cc1cc(C#N)ccc1N1CCN(S(=O)(=O)N[C@H](CCCNC(=O)OCc2ccccc2)C(=O)NO)CC1
InChIKey: FWILDXURZVZYSC-JOCHJYFZSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O14672
Assay: Inhibition of ADAM-10 in human L540 cells assessed as reduction in pervanadate-induced TNFalpha shedding after 24 hrs by ELISA
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 544.63, ALogP 1.4, HBA 8, HBD 4, PSA 164.1, QED 0.19
Compound (SMILES): Cc1cc(C#N)ccc1N1CCN(S(=O)(=O)N2CSC[C@@H]2C(=O)NO)CC1
InChIKey: UGVOWFLXYXPRQV-OAHLLOKOSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O14672
Assay: Inhibition of ADAM-10 in human L540 cells assessed as reduction in pervanadate-induced TNFalpha shedding after 24 hrs by ELISA
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 411.51, ALogP 0.11, HBA 7, HBD 2, PSA 116.98, QED 0.53
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3cccc4ccccc34)s2)n1
InChIKey: MENNDDDTIIZDDN-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of recombinant SIRT2 (unknown origin) using FAM-RHKK(Ac)LM as substrate measured after 60 mins by electrophoretic mobility shift assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 420.56, ALogP 5.02, HBA 6, HBD 1, PSA 67.77, QED 0.35
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4)C3C2)n1C
InChIKey: SBCYNHCFJBYRJY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 424.57, ALogP 3.47, HBA 8, HBD 0, PSA 63.22, QED 0.43
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4F)C3C2)n1C
InChIKey: YTXILLIRPDSLHZ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes after 120 mins by liquid scintillation counter method
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 510.56, ALogP 4.63, HBA 8, HBD 0, PSA 63.22, QED 0.26
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(F)cc4)C3C2)n1C
InChIKey: FZEUFNLUEJZENL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 442.56, ALogP 3.61, HBA 8, HBD 0, PSA 63.22, QED 0.41
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1cnccn1
InChIKey: IYZBRQAAJGEDNI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 489.57, ALogP 3.98, HBA 8, HBD 0, PSA 62.97, QED 0.37
Compound (SMILES): CC(C)Oc1ccccc1N1CCC2CN(CCCSc3nnc(-c4cnccn4)n3C)CC21
InChIKey: QNDFBMWALLMDKL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 372 nM (pChEMBL 6.429999828338623)
Descriptors: MW 479.65, ALogP 3.75, HBA 9, HBD 0, PSA 72.2, QED 0.34
Compound (SMILES): CCC(=O)N1CCOc2c(cc(-c3ccc(OC)c(OC)c3)cc2OC[C@H]2CCCN(C)C2)C1
InChIKey: YKNAKDFZAWQEEO-IBGZPJMESA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Binding affinity to EP300 (unknown origin) by isothermal titration calorimetry
Measurement: Kd = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 468.59, ALogP 4.22, HBA 6, HBD 0, PSA 60.47, QED 0.61
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4C(F)(F)F)C3C2)nnc1-c1cccnc1
InChIKey: UFUQIVBOXLXINJ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 488.58, ALogP 4.59, HBA 7, HBD 0, PSA 50.08, QED 0.36
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1cc[nH]c(=O)c1
InChIKey: CRAJXQNFXAOYDL-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 504.58, ALogP 3.88, HBA 7, HBD 1, PSA 70.05, QED 0.39
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 expressed in baculosomes preincubated for 10 mins followed by cofactor addition measured every minute for 10 mins using ethoxyresorufin as substrate by CYPEX assay
Measurement: IC50 > 16000 nM (pChEMBL 4.796000003814697)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4c(F)cc(F)cc4F)C3C2)nnc1-c1ccn(C)c(=O)c1
InChIKey: ZRQADOCXGLFZJC-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 1202 nM (pChEMBL 5.920000076293945)
Descriptors: MW 504.58, ALogP 3.29, HBA 8, HBD 0, PSA 59.19, QED 0.36
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4)C3C2)nnc1C1CCOCC1
InChIKey: BGRFOPBDZYUOMJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Antagonist activity at recombinant human muscarinic M3 receptor expressed in CHO-K1 cells assessed as inhibition of acetylcholine induced calcium mobilization preincubated for 10 mins followed by acetylcholine addition measured after 1 hr by fluo-4 AM dye-based FLIPR assay
Measurement: Ki = 1445.44 nM (pChEMBL 5.840000152587891)
Descriptors: MW 427.62, ALogP 3.4, HBA 7, HBD 0, PSA 46.42, QED 0.5
Compound (SMILES): CCn1cc(-c2cccc(C(F)(F)F)c2)c2sc(C(=N)NC3CCS(=O)(=O)CC3)cc2c1=O
InChIKey: WRUWGLUCNBMGPS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Affinity Biochemical interaction (Time-Resolved FRET assay) EUB0000247b BRD9
Measurement: IC50 = 50.1 nM (pChEMBL 7.300000190734863)
Descriptors: MW 497.56, ALogP 4.26, HBA 6, HBD 2, PSA 92.02, QED 0.42
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95696
Assay: Selectivity interaction (AlphaScreen) EUB0000323b BRD1
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3cccc4ccccc34)s2)n1
InChIKey: MENNDDDTIIZDDN-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of SIRT2 deacetylation activity (unknown origin) using H3K9Ac ( 4 to 15 residues) as substrate by HPLC analysis
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 420.56, ALogP 5.02, HBA 6, HBD 1, PSA 67.77, QED 0.35
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4)C3C2)n1C
InChIKey: SBCYNHCFJBYRJY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 424.57, ALogP 3.47, HBA 8, HBD 0, PSA 63.22, QED 0.43
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4F)C3C2)n1C
InChIKey: YTXILLIRPDSLHZ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 510.56, ALogP 4.63, HBA 8, HBD 0, PSA 63.22, QED 0.26
Compound (SMILES): CCC(=O)N1CCOc2c(cc(-c3ccc(OC)c(OC)c3)cc2OC[C@H]2CCCN(C)C2)C1
InChIKey: YKNAKDFZAWQEEO-IBGZPJMESA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Binding affinity to C-terminally biotinylated N-terminal His10-tagged human CBP bromodomain (R1081 to G1198 residues) expressed in Escherichia coli BL21(DE3) by isothermal titration calorimetry
Measurement: Kd = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 468.59, ALogP 4.22, HBA 6, HBD 0, PSA 60.47, QED 0.61
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4C(F)(F)F)C3C2)nnc1-c1cccnc1
InChIKey: UFUQIVBOXLXINJ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 488.58, ALogP 4.59, HBA 7, HBD 0, PSA 50.08, QED 0.36
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 expressed in baculosomes preincubated for 10 mins followed by cofactor addition measured every minute for 10 mins using ethoxyresorufin as substrate by CYPEX assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4)C3C2)nnc1C1CCOCC1
InChIKey: BGRFOPBDZYUOMJ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol. 266: 79-85.
Measurement: Ki = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 427.62, ALogP 3.4, HBA 7, HBD 0, PSA 46.42, QED 0.5
Compound (SMILES): CCn1cc(-c2cccc(C(F)(F)F)c2)c2sc(C(=N)NC3CCS(=O)(=O)CC3)cc2c1=O
InChIKey: WRUWGLUCNBMGPS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPI1
Assay: Selectivity interaction (BROMOscan™ panel (DiscoverX)) EUB0000247b BRD7
Measurement: Kd = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 497.56, ALogP 4.26, HBA 6, HBD 2, PSA 92.02, QED 0.42
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Selectivity interaction (AlphaScreen) EUB0000323b BRD4
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3cccc4ccccc34)s2)n1
InChIKey: MENNDDDTIIZDDN-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of recombinant SIRT2 (unknown origin) deacetylase activity using Ac-RHKK(Ac)-MCA as substrate incubated for 60 mins in presence of NAD by fluorogenic assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 420.56, ALogP 5.02, HBA 6, HBD 1, PSA 67.77, QED 0.35
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4)C3C2)n1C
InChIKey: SBCYNHCFJBYRJY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 424.57, ALogP 3.47, HBA 8, HBD 0, PSA 63.22, QED 0.43
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4F)C3C2)n1C
InChIKey: YTXILLIRPDSLHZ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 510.56, ALogP 4.63, HBA 8, HBD 0, PSA 63.22, QED 0.26
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1cc[nH]c(=O)c1
InChIKey: CRAJXQNFXAOYDL-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Binding affinity to dopamine D4 receptor (unknown origin)
Measurement: Ki = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 504.58, ALogP 3.88, HBA 7, HBD 1, PSA 70.05, QED 0.39
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes after 120 mins by liquid scintillation counter method
Measurement: Ki = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4)C3C2)nnc1C1CCOCC1
InChIKey: BGRFOPBDZYUOMJ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 933 nM (pChEMBL 6.03000020980835)
Descriptors: MW 427.62, ALogP 3.4, HBA 7, HBD 0, PSA 46.42, QED 0.5
Compound (SMILES): CCn1cc(-c2cccc(C(F)(F)F)c2)c2sc(C(=N)NC3CCS(=O)(=O)CC3)cc2c1=O
InChIKey: WRUWGLUCNBMGPS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Selectivity interaction (NanoBRET assay (HEK293T cells)) EUB0000247b BRD9
Measurement: IC50 = 158.5 nM (pChEMBL 6.800000190734863)
Descriptors: MW 497.56, ALogP 4.26, HBA 6, HBD 2, PSA 92.02, QED 0.42
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Selectivity interaction (ITC) EUB0000323b BRD4
Measurement: Kd = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4)C3C2)n1C
InChIKey: SBCYNHCFJBYRJY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol. 266: 79-85.
Measurement: Ki = 4.17 nM (pChEMBL 8.380000114440918)
Descriptors: MW 424.57, ALogP 3.47, HBA 8, HBD 0, PSA 63.22, QED 0.43
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4F)C3C2)n1C
InChIKey: YTXILLIRPDSLHZ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 510.56, ALogP 4.63, HBA 8, HBD 0, PSA 63.22, QED 0.26
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes after 120 mins by liquid scintillation counter method
Measurement: Ki = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): CCn1cc(-c2cccc(C(F)(F)F)c2)c2sc(C(=N)NC3CCS(=O)(=O)CC3)cc2c1=O
InChIKey: WRUWGLUCNBMGPS-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Selectivity interaction (BROMOscan™ panel (DiscoverX)) EUB0000247b CECR2
Measurement: Kd = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 497.56, ALogP 4.26, HBA 6, HBD 2, PSA 92.02, QED 0.42
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Selectivity interaction (AlphaScreen) EUB0000323b BRPF1
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4)C3C2)n1C
InChIKey: SBCYNHCFJBYRJY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 424.57, ALogP 3.47, HBA 8, HBD 0, PSA 63.22, QED 0.43
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4F)C3C2)n1C
InChIKey: YTXILLIRPDSLHZ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 91.2 nM (pChEMBL 7.039999961853027)
Descriptors: MW 510.56, ALogP 4.63, HBA 8, HBD 0, PSA 63.22, QED 0.26
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes after 120 mins by liquid scintillation counter method
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): CCn1cc(-c2cccc(C(F)(F)F)c2)c2sc(C(=N)NC3CCS(=O)(=O)CC3)cc2c1=O
InChIKey: WRUWGLUCNBMGPS-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Selectivity interaction (BROMOscan™ panel (DiscoverX)) EUB0000247b CREBBP
Measurement: Kd = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 497.56, ALogP 4.26, HBA 6, HBD 2, PSA 92.02, QED 0.42
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain and PHD finger-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULD4
Assay: Selectivity interaction (ITC, single measurement) EUB0000323b BRPF3
Measurement: Kd = 2406 nM (pChEMBL 5.619999885559082)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): CCn1cc(-c2cccc(C(F)(F)F)c2)c2sc(C(=N)NC3CCS(=O)(=O)CC3)cc2c1=O
InChIKey: WRUWGLUCNBMGPS-UHFFFAOYSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Selectivity interaction (BROMOscan™ panel (DiscoverX)) EUB0000247b EP300
Measurement: Kd = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 497.56, ALogP 4.26, HBA 6, HBD 2, PSA 92.02, QED 0.42
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 BD1 (unknown origin) incubated for 60 mins by alphascreen competitive assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-spiperone from human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by liquid scintillation counter method
Measurement: Ki = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Transcription intermediary factor 1-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15164
Assay: Inhibition of TRIM24 (unknown origin) incubated for 60 mins by alphascreen competitive assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 BD1 (unknown origin) assessed as dissociation constant at 14 uM by Isothermal titration calorimetry
Measurement: Kd = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1ccc(=O)n(C)c1
InChIKey: STIWHEMFVTWALB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium Assay at hD2 recombinant receptor. CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 562 nM (pChEMBL 6.25)
Descriptors: MW 518.61, ALogP 3.89, HBA 8, HBD 0, PSA 59.19, QED 0.35
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95696
Assay: Affinity Biochemical interaction: (AlphaScreen) EUB0000323b BRD1
Measurement: IC50 = 1199 nM (pChEMBL 5.920000076293945)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95696
Assay: Affinity Biochemical interaction: (ITC) EUB0000323b BRD1
Measurement: Kd = 505 nM (pChEMBL 6.300000190734863)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Affinity Biochemical interaction: (AlphaScreen) EUB0000323b BRPF1
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Affinity Biochemical interaction: (ITC) EUB0000323b BRPF1
Measurement: Kd = 101 nM (pChEMBL 7)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): COc1cc2c(cc1NS(=O)(=O)c1ccc(Br)cc1C)n(C)c(=O)n2C
InChIKey: YUNQZQREIHWDQT-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Affinity On-target Cellular interaction: (NanoBRET assay, U2OS cells) EUB0000323b BRPF1
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): O=C(O)c1cn(C2CC2)c2cc(N3CCN(C(=O)c4cc([N+](=O)[O-])ccc4O)CC3)c(F)cc2c1=O
InChIKey: JDQJAAYTODKRBI-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human PI3K p110alpha/p85alpha by fluorescence-based immunoassay
Measurement: IC50 = 591 nM (pChEMBL 6.230000019073486)
Descriptors: MW 496.45, ALogP 2.75, HBA 8, HBD 2, PSA 146.22, QED 0.41
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4cc(Cl)ccc4O)CC3)cc21
InChIKey: VNSGCPMEMQJEKJ-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human PI3K p110alpha/p85alpha by fluorescence-based immunoassay
Measurement: IC50 = 712 nM (pChEMBL 6.150000095367432)
Descriptors: MW 473.89, ALogP 3.18, HBA 6, HBD 2, PSA 103.08, QED 0.6
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4c(C)cccc4O)CC3)cc21
InChIKey: DJXXWZURDKMNHY-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human PI3K p110alpha/p85alpha by fluorescence-based immunoassay
Measurement: IC50 = 914 nM (pChEMBL 6.039999961853027)
Descriptors: MW 453.47, ALogP 2.84, HBA 6, HBD 2, PSA 103.08, QED 0.63
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4cc(Br)ccc4O)CC3)cc21
InChIKey: HZQOQUAYXWXADG-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human PI3K p110alpha/p85alpha by fluorescence-based immunoassay
Measurement: IC50 = 695 nM (pChEMBL 6.159999847412109)
Descriptors: MW 518.34, ALogP 3.29, HBA 6, HBD 2, PSA 103.08, QED 0.55
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4cc(OC)ccc4O)CC3)cc21
InChIKey: RHZXZKXHSCHVHO-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of human PI3K p110alpha/p85alpha by fluorescence-based immunoassay
Measurement: IC50 = 698 nM (pChEMBL 6.159999847412109)
Descriptors: MW 469.47, ALogP 2.54, HBA 7, HBD 2, PSA 112.31, QED 0.59
Compound (SMILES): O=C(O)c1cn(C2CC2)c2cc(N3CCN(C(=O)c4cc([N+](=O)[O-])ccc4O)CC3)c(F)cc2c1=O
InChIKey: JDQJAAYTODKRBI-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta/Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3K p110beta/p85beta by fluorescence-based immunoassay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 496.45, ALogP 2.75, HBA 8, HBD 2, PSA 146.22, QED 0.41
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4cc(Cl)ccc4O)CC3)cc21
InChIKey: VNSGCPMEMQJEKJ-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta/Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3K p110beta/p85beta by fluorescence-based immunoassay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 473.89, ALogP 3.18, HBA 6, HBD 2, PSA 103.08, QED 0.6
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4c(C)cccc4O)CC3)cc21
InChIKey: DJXXWZURDKMNHY-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta/Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3K p110beta/p85beta by fluorescence-based immunoassay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 453.47, ALogP 2.84, HBA 6, HBD 2, PSA 103.08, QED 0.63
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4cc(Br)ccc4O)CC3)cc21
InChIKey: HZQOQUAYXWXADG-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta/Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3K p110beta/p85beta by fluorescence-based immunoassay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518.34, ALogP 3.29, HBA 6, HBD 2, PSA 103.08, QED 0.55
Compound (SMILES): CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=O)c4cc(OC)ccc4O)CC3)cc21
InChIKey: RHZXZKXHSCHVHO-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta/Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3K p110beta/p85beta by fluorescence-based immunoassay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 469.47, ALogP 2.54, HBA 7, HBD 2, PSA 112.31, QED 0.59