lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(F)cc4)C3C2)nnc1C1CCCCC1
InChIKey: XUKSGYGUDPUQCB-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 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 443.64, ALogP 4.69, HBA 6, HBD 0, PSA 37.19, QED 0.46
Compound (SMILES): CCCCc1c(C)nc2nc(SCc3nc4c(c(=O)[nH]c(=O)n4CCCC)n3CC)nn2c1C
InChIKey: FTDVJTZJKKOHSY-UHFFFAOYSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Inhibition of GST-tagged human BRDT bromodomain1 using H4KAc 5/8/12/16 peptide as substrate incubated overnight by HTRF assay
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 484.63, ALogP 3.4, HBA 10, HBD 1, PSA 115.76, QED 0.34
Compound (SMILES): CCCCn1c(=O)[nH]c(=O)c2c1ncn2CC
InChIKey: MJFNWOLXWYRXQS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of GST-tagged human BRD4 bromodomain2 using H4KAc 5/8/12/16 peptide as substrate incubated overnight by HTRF assay
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 236.27, ALogP 0.71, HBA 5, HBD 1, PSA 72.68, QED 0.85
Compound (SMILES): CCn1cnc2c1c(=O)[nH]c(=O)n2Cc1ccc(Cl)cc1
InChIKey: ZUHFEYWVQFKDLX-UHFFFAOYSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Inhibition of GST-tagged human BRDT bromodomain1 using H4KAc 5/8/12/16 peptide as substrate incubated overnight by HTRF assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 304.74, ALogP 1.61, HBA 5, HBD 1, PSA 72.68, QED 0.8
Compound (SMILES): Nc1nc(-c2cc(C(=O)O)ccn2)cs1
InChIKey: FAOZNCYQMCTIBT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 221.24, ALogP 1.49, HBA 5, HBD 2, PSA 89.1, QED 0.8
Compound (SMILES): CN(CCc1cnn(-c2nccc3c(=O)[nH]cnc23)c1)Cc1ccc(F)cc1
InChIKey: NLGUSOLKPNWPKR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 13400 nM (pChEMBL 4.869999885559082)
Descriptors: MW 378.41, ALogP 2.32, HBA 6, HBD 1, PSA 79.7, QED 0.56
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(Cc5ccc(Cl)cc5)CC4)cn3)nccc12
InChIKey: MIHKHZZRKYZHJU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 448.96, ALogP 3.65, HBA 6, HBD 1, PSA 79.7, QED 0.49
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5ccc(Cl)cc5)CC4)cn3)nccc12
InChIKey: SQDIBEJSOSAPGF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 6740 nM (pChEMBL 5.170000076293945)
Descriptors: MW 434.93, ALogP 3.58, HBA 6, HBD 1, PSA 79.7, QED 0.52
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5cccs5)CC4)cn3)nccc12
InChIKey: XIVQRYFYMNIDET-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 406.52, ALogP 2.99, HBA 7, HBD 1, PSA 79.7, QED 0.55
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5cc(Cl)cc(Cl)c5)CC4)cn3)nccc12
InChIKey: RLRGPZGIQMEBLC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 469.38, ALogP 4.23, HBA 6, HBD 1, PSA 79.7, QED 0.47
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5cccc(Cl)c5)CC4)cn3)nccc12
InChIKey: LDSDVQOOEYCWQS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 12900 nM (pChEMBL 4.889999866485596)
Descriptors: MW 434.93, ALogP 3.58, HBA 6, HBD 1, PSA 79.7, QED 0.52
Compound (SMILES): O=C(O)c1ccncc1NCc1ccccc1
InChIKey: WQXQGYTXHBAVJS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q6B0I6
Assay: Inhibition of human KDM4D (11 to 341 residues) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 228.25, ALogP 2.39, HBA 3, HBD 2, PSA 62.22, QED 0.84
Compound (SMILES): O=C(O)c1ccncc1NCc1ccco1
InChIKey: ZNWWSWJQMFNZDV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q6B0I6
Assay: Inhibition of human KDM4D (11 to 341 residues) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 218.21, ALogP 1.98, HBA 4, HBD 2, PSA 75.36, QED 0.82
Compound (SMILES): Cc1ccc(CNc2cnccc2C(=O)O)s1
InChIKey: RFUZGPWCXINBNW-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Enzymatic Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 248.31, ALogP 2.76, HBA 4, HBD 2, PSA 62.22, QED 0.87
Compound (SMILES): Cc1ccsc1CNc1cnccc1C(=O)O
InChIKey: IDVBVEOFBRZZEI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of KDM4A (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 248.31, ALogP 2.76, HBA 4, HBD 2, PSA 62.22, QED 0.87
Compound (SMILES): O=C(O)c1cccnc1NCc1ccco1
InChIKey: IQHMQGUDRIPWGH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of full length human HALO-tagged KDM4C expressed in human U2OS cells assessed as level of H3K9Me3 demethylation incubated overnight by Hoechst 33342/HaloTag/ Alexa Fluor 647 staining-based image analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 218.21, ALogP 1.98, HBA 4, HBD 2, PSA 75.36, QED 0.82
Compound (SMILES): Cc1ccsc1CNc1ncccc1C(=O)O
InChIKey: GIDVSGXIJGUURN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4E (SINGLE PROTEIN), Homo sapiens
UniProt: B2RXH2
Assay: Inhibition of KDM4E (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 248.31, ALogP 2.76, HBA 4, HBD 2, PSA 62.22, QED 0.87
Compound (SMILES): CCCCCCCCNC(=O)Oc1cccc(-c2ccc(C(C)C(=O)O)cc2F)c1
InChIKey: UXTCVRSNFHPCCG-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of recombinant human COX2 assessed as production of PGF2-alpha preincubated with compound followed by the addition of 5 uM arachidonic acid as substrate by enzyme immunoassay
Measurement: IC50 = 28800 nM (pChEMBL 4.539999961853027)
Descriptors: MW 415.51, ALogP 6.13, HBA 3, HBD 2, PSA 75.63, QED 0.43
Compound (SMILES): CC(C)CNC(=O)Oc1cccc(-c2ccc(C(C)C(=O)O)cc2F)c1
InChIKey: QZDOJQZQXSELTJ-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: In Vitro Human FAAH Fluorescent Assay: Human recombinant FAAH was obtained from a HEK-293 FAAH-1 overexpressing stable cell line. Cells were grown in DMEM medium containing 10% FBS, 1% pen/strep, 1% glutamine and 500 μg/mL G418. To obtain membrane preparation cells were scraped off with cold phosphate-buffered saline (PBS) and collected by centrifugation (500×g, 10 minutes, 4° C.); the cell pellet was re-suspended in 20 mM Tris-HCl pH 7.4, 0.32 M sucrose, disrupted by sonication (10 pulses, 5 times) and centrifuged (800×g, 15 minutes, 4° C.); the collected supernatant was centrifuged at 105,000×g for 1 h at 4° C. and the pellet was re-suspended in PBS.The fluorescent assay to measure FAAH activity was performed in 96 wells black plates: 2.5 μg of human FAAH-1 membrane preparation were pre-incubated for 50 minutes at 37° C., in 180 μL of assay buffer (50 mM TrisHCl pH 7.4, 0.05% Fatty acid-free BSA) with 10 μL of inhibitor or 10 μL DMSO to measure FAAH total activity. The background (no activity) samples were prepared using 180 μL of assay buffer without human FAAH-1 and 10 μL of DMSO. The reaction was then started by the addition of 10 μL of substrate (AMC arachidonyl amide, N. 10005098, Cayman Chemical) dissolved in ethanol and used at a final concentration of 2 μM. The reaction was carried out for 30 minutes at 37° C. and fluorescence was measured with a Tecan Infinite M200 nanoquant plate reader (excitation wavelength 350 nm/emission wavelength 460 nm).
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 359.4, ALogP 4.43, HBA 3, HBD 2, PSA 75.63, QED 0.8
Compound (SMILES): CCCCCCNC(=O)Oc1cccc(-c2ccc(C(C)C(=O)O)cc2F)c1
InChIKey: USQOVYLRWBOSQC-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: In Vitro Rat FAAH Radiometric Assay: Rat FAAH was prepared from male Sprague Dawley rat brains, homogenized in a potter in 20 mM of Tris HCl pH 7.4, 0.32 M sucrose.The radiometric assay used to measure FAAH activity was performed in eppendorf tubes: 50 μg of total rat brain homogenate were pre-incubated in 445.5 μL of assay buffer (50 mM Tris-HCl pH7.4, 0.05% Fatty acid-free bovine serum albumin (BSA)) with 4.5 μL of inhibitor (at appropriate concentration in DMSO) or DMSO alone (to measure FAAH total activity) for 10 minutes at 37° C. The blank (no activity control) was prepared using 445.5 μL of assay buffer and 4.5 μL of DMSO without the 50 μg of total rat brain homogenate.After 10 minutes of pre-incubation with test compounds, the reaction was started by adding of 50 μL of substrate and incubating for 30 min at 37° C. The substrate was prepared in assay buffer in order to achieve the final concentration of 1 μM arachidonoyl ethanolamide (Cayman Chemical N. 90050) and 0.6 nM anandamide [ethanolamine-1-3H](American Radiolabeled Chemicals Inc., ART. 0626, conc. 1 mCi/mL, S.A. 60 Ci/mmol). The reaction was stopped by adding cold 1:1 CHCl3/MeOH. After 10 minutes of centrifugation (845×g at 4° C.) 600 μL of aqueous phase were transferred into scintillation vials previously filled with 3 mL of scintillation fluid (Ultima Gold, Perkin Elmer Inc., Cat. 6013329). Radioactivity was measured by liquid scintillation counting (MicroBeta2 LumiJET Perkin Elmer Inc.).
Measurement: IC50 = 9.9 nM (pChEMBL 8)
Descriptors: MW 387.45, ALogP 5.35, HBA 3, HBD 2, PSA 75.63, QED 0.57
Compound (SMILES): CCCCCCNC(=O)Oc1cccc(-c2ccc(C(C)CO)cc2F)c1
InChIKey: WGAHHJUZFSFTHU-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: In Vitro Human FAAH Fluorescent Assay: Human recombinant FAAH was obtained from a HEK-293 FAAH-1 overexpressing stable cell line. Cells were grown in DMEM medium containing 10% FBS, 1% pen/strep, 1% glutamine and 500 μg/mL G418. To obtain membrane preparation cells were scraped off with cold phosphate-buffered saline (PBS) and collected by centrifugation (500×g, 10 minutes, 4° C.); the cell pellet was re-suspended in 20 mM Tris-HCl pH 7.4, 0.32 M sucrose, disrupted by sonication (10 pulses, 5 times) and centrifuged (800×g, 15 minutes, 4° C.); the collected supernatant was centrifuged at 105,000×g for 1 h at 4° C. and the pellet was re-suspended in PBS.The fluorescent assay to measure FAAH activity was performed in 96 wells black plates: 2.5 μg of human FAAH-1 membrane preparation were pre-incubated for 50 minutes at 37° C., in 180 μL of assay buffer (50 mM TrisHCl pH 7.4, 0.05% Fatty acid-free BSA) with 10 μL of inhibitor or 10 μL DMSO to measure FAAH total activity. The background (no activity) samples were prepared using 180 μL of assay buffer without human FAAH-1 and 10 μL of DMSO. The reaction was then started by the addition of 10 μL of substrate (AMC arachidonyl amide, N. 10005098, Cayman Chemical) dissolved in ethanol and used at a final concentration of 2 μM. The reaction was carried out for 30 minutes at 37° C. and fluorescence was measured with a Tecan Infinite M200 nanoquant plate reader (excitation wavelength 350 nm/emission wavelength 460 nm).
Measurement: IC50 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 373.47, ALogP 5.26, HBA 3, HBD 2, PSA 58.56, QED 0.59
Compound (SMILES): CCCCC(NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCCNC(=O)CC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)C(C)(CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)C(CCCC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(C)=O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc2cnc[nH]2)C(=O)N1)C(=O)N[C@@H](CCC(=O)O)C(=O)NC(C)(CC(C)C)C(=O)N[C@H](C(N)=O)[C@@H](C)CC
InChIKey: YDQPYNOCHUULRC-KXFTWVOUSA-N
Target: Corticotropin-releasing factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P34998
Assay: Displacement of [125ITyr0-Glu1,Nle17]-PS-Svg in human CRF-R1 expressed in COS-M6 cells after 90 mins by gamma counting assay
Measurement: Ki = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 3962.67
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4OCc4ccccc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: XSVRBMOJKPAIJX-NKYRPOHVSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells assessed as kinetic dissociation constant by NanoBRET competition binding assay
Measurement: Kd = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 441.49, ALogP 0.99, HBA 10, HBD 4, PSA 134.78, QED 0.42
Compound (SMILES): Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(CN4CCOCC4)cc3)nc3c2cnn3C(C)C)c(=O)[nH]1
InChIKey: WGDUEUOSWFHQIH-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 41.8 nM (pChEMBL 7.380000114440918)
Descriptors: MW 514.63, ALogP 3.75, HBA 7, HBD 2, PSA 105.14, QED 0.39
Compound (SMILES): O=c1[nH]cnc2cnccc12
InChIKey: QMOPAFMMLWUTKI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of KDM5C (unknown origin) using biotin-H3K4me3 as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by alphascreen assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 147.14, ALogP 0.32, HBA 3, HBD 1, PSA 58.64, QED 0.58
Compound (SMILES): O=C(N[C@H]1CNC1=O)OCCCCC1CCCCC1
InChIKey: FNLUJRBWJBUJTC-LBPRGKRZSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition of human NAAA
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 268.36, ALogP 1.96, HBA 3, HBD 2, PSA 67.43, QED 0.57
Compound (SMILES): CCCOc1ccn2c(C(C)=O)cc(-c3cccc(OC)c3)c2c1
InChIKey: QQBGNWWJANJWNY-UHFFFAOYSA-N
Target: Bromodomain adjacent to zinc finger domain protein 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIF8
Assay: Affinity Phenotypic Cellular interaction (FRAP assay (displacement of BAZ2A/B from chromatin in SAHA-treated human U2OS cells, transfected with GFP-BAZ2A fusion construct)) EUB0000267b BAZ2B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 323.39, ALogP 4.61, HBA 4, HBD 0, PSA 39.94, QED 0.62
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: Binding affinity to partial length human BRD9 by BROMOscan assay
Measurement: Kd = 1.995 nM (pChEMBL 8.699999809265137)
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: Alphascreen assay. Binding to BRD1A (domain start/stop: E556-A688) by alphascreen assay
Measurement: IC50 = 1679 nM (pChEMBL 5.78000020980835)
Descriptors: MW 440.32, ALogP 2.76, HBA 6, HBD 1, PSA 82.33, QED 0.68
Compound (SMILES): COc1ccc(Oc2cc3c(cc2NS(=O)(=O)c2ccc(OC)c(OC)c2)n(C)c(=O)n3C)cc1
InChIKey: KNVIUMWNYXDULF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95696
Assay: Binding affinity to BRPF2 BRD1 (unknown origin) by isothermal titration calorimetry
Measurement: Kd = 1130 nM (pChEMBL 5.949999809265137)
Descriptors: MW 499.55, ALogP 3.5, HBA 9, HBD 1, PSA 110.02, QED 0.4
Compound (SMILES): CCOc1ccc(C(C)=O)cc1NC(=O)c1cccc(C(=O)O)c1
InChIKey: GFOBMGVVDGTGAJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Competitive binding affinity to human BRD2 bromodomain 2 expressed in T7 phage-infected Escherichia coli BL21(DE3) cells incubated for 1 hr by bromoscan assay
Measurement: Kd > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 327.34, ALogP 3.24, HBA 4, HBD 2, PSA 92.7, QED 0.79
Compound (SMILES): CCOc1ccc(C(C)=O)cc1NC(=O)c1cc(C(=O)O)cc(-c2ccoc2)c1
InChIKey: HEMBESATTQDKPY-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Competitive binding affinity to human BRD2 bromodomain 2 expressed in T7 phage-infected Escherichia coli BL21(DE3) cells incubated for 1 hr by bromoscan assay
Measurement: Kd = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 393.4, ALogP 4.5, HBA 5, HBD 2, PSA 105.84, QED 0.57
Compound (SMILES): CCOc1ccc(C(C)=O)cc1NC(=O)c1cc(COC)cc(C(=O)O)c1
InChIKey: GTJKBLFFCRMRAD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Competitive binding affinity to human BRD2 bromodomain 2 expressed in T7 phage-infected Escherichia coli BL21(DE3) cells incubated for 1 hr by bromoscan assay
Measurement: Kd > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 371.39, ALogP 3.38, HBA 5, HBD 2, PSA 101.93, QED 0.69
Compound (SMILES): O=c1[nH]c(Oc2ccc(Cl)c(O)c2)nc2cnccc12
InChIKey: OZMKCTFOIBLWOO-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H6Z9
Assay: Inhibition of full-length EGLN3 (unknown origin) expressed in Escherichia coli BL21(DE3) cells by HTRF assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 289.68, ALogP 2.47, HBA 5, HBD 2, PSA 88.1, QED 0.76
Compound (SMILES): CC(C)c1ccc(Oc2nc3cnccc3c(=O)[nH]2)cn1
InChIKey: PLQDLMAFBDRQSK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of human KDM5C transfected in U2OS cells assessed as inhibition of H3K9Me3 demethylation for 24 hrs
Measurement: IC50 = 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 282.3, ALogP 2.63, HBA 5, HBD 1, PSA 80.76, QED 0.8
Compound (SMILES): O=c1[nH]c(Oc2cnn(C3CCCC3)c2)nc2cnccc12
InChIKey: ARDXICZNEUJDDE-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H6Z9
Assay: Inhibition of full-length EGLN3 (unknown origin) expressed in Escherichia coli BL21(DE3) cells by HTRF assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 297.32, ALogP 2.42, HBA 6, HBD 1, PSA 85.69, QED 0.8
Compound (SMILES): O=c1[nH]c(Oc2cnn(CC3CCCCC3)c2)nc2cnccc12
InChIKey: IALMMJCSQDGXBB-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H6Z9
Assay: Inhibition of full-length EGLN3 (unknown origin) expressed in Escherichia coli BL21(DE3) cells by HTRF assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 325.37, ALogP 2.89, HBA 6, HBD 1, PSA 85.69, QED 0.8
Compound (SMILES): O=c1[nH]c(Oc2cnn(Cc3ccccc3)c2)nc2cnccc12
InChIKey: ZTYRLXUTLYBVHH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: Inhibition of KDM6B (unknown origin) by RFMS assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 319.32, ALogP 2.36, HBA 6, HBD 1, PSA 85.69, QED 0.62
Compound (SMILES): O=c1[nH]c(Oc2cnn(Cc3ccccc3)c2)nc2ncccc12
InChIKey: WUATWIOJLCSPRQ-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H6Z9
Assay: Inhibition of full-length EGLN3 (unknown origin) expressed in Escherichia coli BL21(DE3) cells by HTRF assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 319.32, ALogP 2.36, HBA 6, HBD 1, PSA 85.69, QED 0.62
Compound (SMILES): Cc1nc2c([N+](=O)[O-])c(Cl)c(Cl)cc2n1Cc1ccc(B2OC(=O)CN(C)CC(=O)O2)cc1
InChIKey: FUJZJWQLQGXDEK-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using testostrone as substrate preincubated for 10 mins followed by NADPH addition by LC/MS/MS analysis
Measurement: IC50 = 21940 nM (pChEMBL 4.659999847412109)
Descriptors: MW 491.1
Compound (SMILES): Cc1cc(C#N)ccc1N1CCN(S(=O)(=O)N[C@H](CCCNC(=O)OCc2ccccc2)C(=O)NO)CC1
InChIKey: FWILDXURZVZYSC-JOCHJYFZSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP-9 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate after 3 hrs by fluorometric assay
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
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: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of recombinant human MMP-14 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate after 3 hrs by fluorometric assay
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 411.51, ALogP 0.11, HBA 7, HBD 2, PSA 116.98, QED 0.53
Compound (SMILES): CN1C(=O)c2c(nn(Cc3ccc(-c4ccccc4)cc3)c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12
InChIKey: DNWPSPOTOOQJAD-RPBOFIJWSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Inhibition of recombinant full lenght human PDE8A using fluorescent labeled cAMP as substrate after 15 mins by IMAP assay
Measurement: Ki = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 488.6, ALogP 5.52, HBA 6, HBD 1, PSA 65.76, QED 0.4
Compound (SMILES): CN1C(=O)c2c(nn(Cc3ccc(C(F)(F)F)nc3)c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12
InChIKey: HLJDFQMSWCGSIM-SJORKVTESA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Inhibition of recombinant full lenght human PDE8A using fluorescent labeled cAMP as substrate after 15 mins by IMAP assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 481.48, ALogP 4.27, HBA 7, HBD 1, PSA 78.65, QED 0.6
Compound (SMILES): CN1C(=O)c2c(nn(Cc3ccc(C(F)(F)F)cc3)c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12
InChIKey: OUNXNLRJDVSZSN-MOPGFXCFSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Inhibition of recombinant full lenght human PDE8A using fluorescent labeled cAMP as substrate after 15 mins by IMAP assay
Measurement: Ki = 54000 nM (pChEMBL 4.269999980926514)
Descriptors: MW 480.49, ALogP 4.88, HBA 6, HBD 1, PSA 65.76, QED 0.58
Compound (SMILES): COC(=O)[C@H](C)[C@@H]1N=C(c2ccc(Cl)cc2)c2cc(OC)ccc2-n2c(C)nnc21
InChIKey: FENXDXHDXYVGRJ-BLVKFPJESA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to BRD2 bromodomain 1 L110A mutant (unknown origin) expressed in competent Escherichia coli DH5-alpha cells by isothermal titration calorimetry
Measurement: Kd = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 424.89, ALogP 3.94, HBA 7, HBD 0, PSA 78.6, QED 0.59
Compound (SMILES): CN1C(=O)c2c(nn(Cc3ccc(-c4ccccn4)cc3)c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12
InChIKey: RJKWLGFYXTZMOU-RPWUZVMVSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Inhibition of recombinant full lenght human PDE8A using fluorescent labeled cAMP as substrate after 15 mins by IMAP assay
Measurement: Ki = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 489.58, ALogP 4.92, HBA 7, HBD 1, PSA 78.65, QED 0.43
Compound (SMILES): CN1C(=O)c2c(nn(Cc3ccc(-c4cccc(F)n4)cc3)c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12.O=P(O)(O)O
InChIKey: ZPIAAFIYOPWWJL-RFPXDPOKSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Inhibition of recombinant full lenght human PDE8A using fluorescent labeled cAMP as substrate after 15 mins by IMAP assay
Measurement: Ki = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 507.57, ALogP 5.06, HBA 7, HBD 1, PSA 78.65, QED 0.38
Compound (SMILES): CC(=O)NCCCCn1c2c(c3ccccc31)C(=O)NCC2
InChIKey: RYVLOOXFFIFQEN-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to BRD3 BD1 (unknown origin) by fluorescence anisotropy competition binding assay
Measurement: Ki = 17200 nM (pChEMBL 4.760000228881836)
Descriptors: MW 299.37, ALogP 1.84, HBA 3, HBD 2, PSA 63.13, QED 0.83
Compound (SMILES): CCOc1ccc2cc(-c3nn(C4CCCCC4)c(N)c3C(N)=O)ccc2n1
InChIKey: ONQFGFIAOHMNST-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Inhibition Assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). For description of the methods and assays, see WO 2011/094628, incorporated by reference herein. Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 379.46, ALogP 3.68, HBA 6, HBD 2, PSA 109.05, QED 0.7
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3cccc4ccccc34)s2)n1
InChIKey: MENNDDDTIIZDDN-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of recombinant human His10-tagged Sirt3 (118 to 395 residues) expressed in Escherichia coli BL21(DE3) using Z-(Ac)Lys-AMC as substrate measured after 4 hrs by high-throughput fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 420.56, ALogP 5.02, HBA 6, HBD 1, PSA 67.77, QED 0.35
Compound (SMILES): CC1(c2nc(-c3ccccc3)c[nH]2)Cc2c([nH]c3ccccc23)C(C2CCOCC2)N1
InChIKey: VMVCWWJIBFEZGN-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Antagonist activity at human somatostatin receptor type 3 assessed as inhibition of cAMP levels
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 412.54, ALogP 5.09, HBA 3, HBD 3, PSA 65.73, QED 0.44
Compound (SMILES): CCCOc1cc(OCCCCN(C)C)cc(Oc2cc3c(cc2NS(=O)(=O)c2ccc(OC)c(OC)c2)n(C)c(=O)n3C)c1
InChIKey: HYQBRUSSCIAOOD-UHFFFAOYSA-N
Target: Bromodomain and PHD finger-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULD4
Assay: Binding affinity to recombinant human BRPF3 expressed in bacterial system by bromoscan assay
Measurement: Kd = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 642.78, ALogP 5, HBA 11, HBD 1, PSA 122.49, QED 0.17
Compound (SMILES): COc1ccc(N(C)c2nc(C)nc3ccccc23)cc1OCCCC(=O)NO
InChIKey: FWXZZFONXWYSEF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant HDAC3 (unknown origin) using AMC labeled AC-peptide as substrate incubated for 1 hr by fluorescence analysis
Measurement: IC50 = 439 nM (pChEMBL 6.360000133514404)
Descriptors: MW 396.45, ALogP 3.38, HBA 7, HBD 2, PSA 96.81, QED 0.34
Compound (SMILES): O=C(Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1)c1nnn(-c2ccc(F)cc2)c1C(F)(F)F
InChIKey: ULHLSSWDQFLSBL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using poly (Glu, Tyr) 4:1 as substrate after 30 mins by HTRF assay
Measurement: IC50 = 582.17 nM (pChEMBL 6.239999771118164)
Descriptors: MW 500.39, ALogP 5.49, HBA 6, HBD 2, PSA 97.72, QED 0.31
Compound (SMILES): O=C(O)c1ccnc(-c2cc(NC(=O)c3ccc(O)cc3)ccc2O)c1
InChIKey: MXKVATSZRALAIN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using ARTKQTARK(Me3)STGGKA peptide/100 uM alpha-ketoglutarate as substrate/cofactor incubated for 45 mins by MALDI assay
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 350.33, ALogP 3.11, HBA 5, HBD 4, PSA 119.75, QED 0.54
Compound (SMILES): Cc1cc(C(=O)Nc2ccc(O)c(-c3cc(C(=O)O)ccn3)c2)no1
InChIKey: SXVDKQLIPBWXCB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using biotinylated peptide/ 2 uM alpha-ketoglutarate as substrate/cofactor preincubated for 15 mins followed by substrate addition measured after 15 mins by alphascreen assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 339.31, ALogP 2.7, HBA 6, HBD 3, PSA 125.55, QED 0.62
Compound (SMILES): COc1cccc(CC(=O)Nc2ccc(O)c(-c3cc(C(=O)O)ccn3)c2)c1
InChIKey: QSWJSOQQNWMPME-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of KDM2A (unknown origin) expressed in Escherichia coli using Biotin H3 (28 to 48 residues) Me2 KDM2A Cognate Ligande/10 uM alpha-ketoglutarate as substrate/cofactor preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay
Measurement: IC50 = 89000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 378.38, ALogP 3.34, HBA 5, HBD 3, PSA 108.75, QED 0.57
Compound (SMILES): COCC(=O)Nc1ccc(O)c(-c2cc(C(=O)O)ccn2)c1
InChIKey: HHHINYOXTBYXCI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using ARTKQTARK(Me3)STGGKA peptide/100 uM alpha-ketoglutarate as substrate/cofactor incubated for 45 mins by MALDI assay
Measurement: IC50 = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 302.29, ALogP 1.74, HBA 5, HBD 3, PSA 108.75, QED 0.73
Compound (SMILES): CC(=O)Nc1ccc(O)c(-c2cc(C(=O)O)ccn2)c1
InChIKey: KWHVUGFDWSYWJF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using biotinylated peptide/ 2 uM alpha-ketoglutarate as substrate/cofactor preincubated for 15 mins followed by substrate addition measured after 15 mins by alphascreen assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 272.26, ALogP 2.11, HBA 4, HBD 3, PSA 99.52, QED 0.74
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4)C3C2)n1C
InChIKey: SBCYNHCFJBYRJY-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 = 1000 nM (pChEMBL 6)
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)cc4)C3C2)n1C
InChIKey: GOLAHDQVVNCLCU-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 492.57, ALogP 4.49, HBA 8, HBD 0, PSA 63.22, QED 0.36
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4F)C3C2)n1C
InChIKey: YTXILLIRPDSLHZ-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 = 109.65 nM (pChEMBL 6.960000038146973)
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: 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 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 442.56, ALogP 3.61, HBA 8, HBD 0, PSA 63.22, QED 0.41
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4cccc(C#N)c4)C3C2)n1C
InChIKey: QCALWRVXYCHRSG-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 449.58, ALogP 3.34, HBA 9, HBD 0, PSA 87.01, QED 0.4
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1cnccn1
InChIKey: IYZBRQAAJGEDNI-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 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 489.57, ALogP 3.98, HBA 8, HBD 0, PSA 62.97, QED 0.37
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4C(F)(F)F)C3C2)nnc1-c1cnccn1
InChIKey: MGPBHFVVGJDFMY-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 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 489.57, ALogP 3.98, HBA 8, HBD 0, PSA 62.97, QED 0.37
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(F)cc4)C3C2)nnc1-c1cnccn1
InChIKey: OACVKINMDRORAI-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 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 439.56, ALogP 3.1, HBA 8, HBD 0, PSA 62.97, QED 0.41
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4cccc(F)c4)C3C2)nnc1-c1cnccn1
InChIKey: UDUUCGMSUBUXNS-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 = 263 nM (pChEMBL 6.579999923706055)
Descriptors: MW 439.56, ALogP 3.1, HBA 8, HBD 0, PSA 62.97, QED 0.41
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4OC(F)(F)F)C3C2)nnc1-c1cnccn1
InChIKey: ZXYDGAXWWXINKE-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 = 34.7 nM (pChEMBL 7.460000038146973)
Descriptors: MW 505.57, ALogP 3.86, HBA 9, HBD 0, PSA 72.2, QED 0.34
Compound (SMILES): CC(C)Oc1ccccc1N1CCC2CN(CCCSc3nnc(-c4cnccn4)n3C)CC21
InChIKey: QNDFBMWALLMDKL-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 479.65, ALogP 3.75, HBA 9, HBD 0, PSA 72.2, QED 0.34
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(F)cc4F)C3C2)nnc1-c1cnccn1
InChIKey: OMXJWXICMCUBRZ-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 457.55, ALogP 3.24, HBA 8, HBD 0, PSA 62.97, QED 0.4
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: Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000195c CREBBP
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 468.59, ALogP 4.22, HBA 6, HBD 0, PSA 60.47, QED 0.61
Compound (SMILES): CN(C)C(=O)c1ccc(Oc2nc(-c3cccc4[nH]ncc34)nc(N3CCOCC3)n2)cc1
InChIKey: HOLZLKJUQNXYRK-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.48, ALogP 2.75, HBA 8, HBD 1, PSA 109.36, QED 0.5
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4C(F)(F)F)C3C2)nnc1-c1cccnc1
InChIKey: UFUQIVBOXLXINJ-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 = 630.96 nM (pChEMBL 6.199999809265137)
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: 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 = 1737.8 nM (pChEMBL 5.760000228881836)
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 7-benzyloxyquinoline 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: 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 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 504.58, ALogP 3.29, HBA 8, HBD 0, PSA 59.19, QED 0.36