lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccccc1CNC[C@H]1C[C@]1(F)c1ccccc1.Cl
InChIKey: XIYFCBBJYLALPD-CLRXKPRGSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at recombinant human unedited 5HT2C receptor isoform INI expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 789 nM (pChEMBL 6.099999904632568)
Descriptors: MW 285.36, ALogP 3.67, HBA 2, HBD 1, PSA 21.26, QED 0.87
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(Cl)c2)n1)[C@@H](CC)N(O)C=O
InChIKey: NPBCILDTXSXRMM-VEXUSMLFSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 634.09, ALogP 2.69, HBA 8, HBD 6, PSA 215.33, QED 0.05
Compound (SMILES): NC(=O)c1cccc2c1O/C(=C\c1ccc(C(=O)N3CCn4c(nnc4C4CC4)C3)cc1)C2=O
InChIKey: JJCAYWVTBMMQMQ-UNOMPAQXSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
Measurement: IC50 = 1.905 nM (pChEMBL 8.720000267028809)
Descriptors: MW 455.47, ALogP 2.53, HBA 7, HBD 1, PSA 120.41, QED 0.6
Compound (SMILES): O=C(NCc1ncccc1F)c1csc(CCN(CCc2nc3ccccc3[nH]2)CCc2nc3ccccc3[nH]2)n1
InChIKey: MHHORLBKGYNPFZ-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 568.68, ALogP 4.69, HBA 7, HBD 3, PSA 115.48, QED 0.2
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2cc3c4c(c2)OCc2cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)[C@@H](C)OC)[nH]5)cc(c2-4)OC3)[nH]1)C(C)C
InChIKey: WZEUKUCQPGSKAK-HDGYKJARSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A L31M mutant in HCV genotype 2a JFH1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 3.67 nM (pChEMBL 8.4399995803833)
Descriptors: MW 810.91, ALogP 5.39, HBA 11, HBD 4, PSA 202.33, QED 0.15
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: SZJWBGRSKSWDFV-CJRHXHJGSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.092 nM (pChEMBL 10.039999961853027)
Descriptors: MW 3878.35
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(Cc5ccc(OCCOCCOC)cc5)CC4)cc3)[nH]c2c1=O
InChIKey: GJCIASZFDKSPKP-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from recombinant human A3 adenosine receptor expressed in CHO cell membranes measured after 45 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 626.74, ALogP 2.04, HBA 10, HBD 2, PSA 151.85, QED 0.2
Compound (SMILES): Cc1ccc(Sc2nn([C@H]3C[C@H](O)[C@@H](COS(N)(=O)=O)O3)c3ncnc(N)c23)c(F)c1
InChIKey: GRYCCRMITKNCNZ-DMDPSCGWSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 470.51, ALogP 0.88, HBA 11, HBD 3, PSA 168.47, QED 0.47
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: PUUYZGUJCFFWLL-OMQKSHNASA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.062 nM (pChEMBL 10.210000038146973)
Descriptors: MW 3789.3
Compound (SMILES): CN1CCN(c2ccc(CCNC(=O)c3sc4nc(Cl)ccc4c3N)cc2)CC1
InChIKey: BKYXQYOKUBCGOW-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 429.98, ALogP 3.26, HBA 6, HBD 2, PSA 74.49, QED 0.61
Compound (SMILES): O=c1cc(NCCCN2CCN(c3nccc4ccc(F)cc34)CC2)c2c(o1)CCSC2
InChIKey: ZFSYWNWTEZXQAZ-UHFFFAOYSA-N
Target: DNA topoisomerase 4 subunit A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0C1U9
Assay: Inhibition of Staphylococcus aureus ATCC 29213 DNA topoisomerase 4 subunit ParC assessed as reduction in decatenation of kinetoplast DNA incubated for 30 mins by ethidium bromide staining based gel electrophoresis method
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 454.57, ALogP 3.74, HBA 7, HBD 1, PSA 61.61, QED 0.57
Compound (SMILES): CN(C)C(=O)c1ccc(N(Cc2ccc(Br)o2)C(=O)c2ccc(O)cc2O)cc1
InChIKey: CYJUFMHEEQFJAT-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15120
Assay: Inhibition of PDHK3 (unknown origin) by radiometric biochemical kinase assay
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 459.3, ALogP 4, HBA 5, HBD 2, PSA 94.22, QED 0.6
Compound (SMILES): CCCCN(c1nc2cc(CNC(=O)NC)ccc2o1)[C@H](C)c1ccc(-c2ccccc2-c2nnn[nH]2)cc1
InChIKey: KFWLXBQVZWESCT-LJQANCHMSA-N
Target: Chemerin-like receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: P97468
Assay: Inhibition of chemR23 expressed in mouse BA/F3 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 524.63, ALogP 5.47, HBA 7, HBD 3, PSA 124.86, QED 0.22
Compound (SMILES): O=CN(O)C[C@@H](CC1CCCC1)C(=O)NCNC(=O)c1cccc(-c2ccccc2)c1
InChIKey: VNEGSKMNJTWROA-JOCHJYFZSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 423.51, ALogP 3.2, HBA 4, HBD 3, PSA 98.74, QED 0.24
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cncnc1
InChIKey: YMHMMIRRHFVEGM-YBEGLDIGSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: FAAH Assay: All reagents were purchased from Sigma-Aldrich unless specified. Human and Rat Fatty Acid Amide Hydrolase (FAAH) genes used in assay have been described by Patricelli et al. (Biochemistry. 1998, 37(43), 15177-87). The transmembrane domain-deleted Fatty Acid Amide Hydrolase (FAAH) genes were cloned into pET15b (Novagen, #69661) (human FAAH)/pET 28a (Novagen, #69864-3) (rat FAAH gene) plasmids and expressed in E coli BL21 DE3. Chaperone protein groEL-groES in pGRO7 plasmid (Takara Bio Inc, Japan) was co-expressed with Fatty Acid Amide Hydrolase (FAAH) to improve solubility of the protein expressed in E coli. The protein was expressed and enriched as described in Mileni et al. (Proc Natl Acad Sci USA. 2008, 105(35),12820-4). Briefly, the bacterial cultures in Luria Broth (2 L) were induced with arabinose (2 mM) and Isopropyl (β-D-1-thiogalactopyranoside, IPTG (1 mM), for 20 h at room temperature. The cultures were centrifuged at 1200×g for 10 min and the cell pellet was resuspended in 100 mL buffer containing of 20 mM NaPi (pH 7.4), 100 mM NaCl, Benzonase (500u), Aprotinin (1 μg/mL) and Leupeptin (1 μg/mL). Cells were lyzed by sonication (Amp 20%, Pulse 15 s×15, on ice) and the cell debris removed by centrifugation at 5000×g for 20 min. The supernatant was enriched via ultracentrifugation at 100,000×g for 1 h and the cell pellet was resuspended in 16 mL buffer containing 20 mM NaPi (pH 7.8), 500 mM NaCl, 1% Triton X-100. The resuspended cell extract was subjected to ultra-centrifugation at 100,000×g for 1 h and the enriched supernatant was used in the in vitro assay. All protein extraction steps were carried out on ice or at 4° C.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 454.45, ALogP 5.44, HBA 5, HBD 1, PSA 77, QED 0.56
Compound (SMILES): N=C(N)NCCCC[C@H](N)C(=O)NCCCC[C@H](N)C(=O)N[C@@H](CCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: KROMCBSZKAWFOP-SXYSDOLCSA-N
Target: Neuropilin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14786
Assay: Inhibition of human biotinylated VEGF-A165 binding to recombinant human NRP1 receptor after 2 hrs by chemiluminescence analysis
Measurement: IC50 = 8912.51 nM (pChEMBL 5.050000190734863)
Descriptors: MW 669.83, ALogP -3.76, HBA 10, HBD 13, PSA 346.77, QED 0.03
Compound (SMILES): O=C(/C=C(\O)C(=O)O)/C=C/c1ccc(NC(=O)c2ccc3ccccc3c2)cc1
InChIKey: ZSFVWJGOTUAOPM-DWVIGKKNSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 8981 nM (pChEMBL 5.050000190734863)
Descriptors: MW 387.39, ALogP 4.2, HBA 4, HBD 3, PSA 103.7, QED 0.43
Compound (SMILES): Cc1ccccc1C(=O)N1C(=O)C[C@H]1C(=O)O
InChIKey: RSPIDHXLVXDISW-VIFPVBQESA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Binding affinity to alpha4beta1 integrin receptor (unknown origin) incubated for 1 hr by scintillation proximity binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 233.22, ALogP 0.82, HBA 3, HBD 1, PSA 74.68, QED 0.61
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](C)NC1=O
InChIKey: ZDSIXCUNSXFSMQ-LBCAYJJCSA-N
Target: Integrin alpha-V/beta-8 (PROTEIN COMPLEX), Homo sapiens
UniProt: P26012
Assay: Inhibition of LAP binding to human integrin alphavbeta8 receptor after 1 hr by solid-phase binding assay
Measurement: IC50 = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 925.06, ALogP -2.93, HBA 11, HBD 11, PSA 343.52, QED 0.06
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc3c(c2)Oc2ccc4cc(-c5cnc([C@@H]6CCCN6C[C@@H](NC(=O)OC)C6CCOCC6)[nH]5)ccc4c2[C@H]3C)[nH]1)C1CCOCC1
InChIKey: XYYNLRWFHZDVKB-PWCZPXJNSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A L31V mutant in HCV genotype 1a assessed as decrease in viral replication
Measurement: EC50 = 0.03 nM (pChEMBL 10.520000457763672)
Descriptors: MW 901.08, ALogP 7.98, HBA 11, HBD 4, PSA 185.26, QED 0.1
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4CCN(C)CC4)cc3)c2C)cc(F)c1C(N)=O
InChIKey: ZOUWFECDLDOKNV-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) expressed in HEK293 cells transfected with CAGA-luciferase and Renilla luciferase reporter measured after 24 hrs by dual luciferase reporter assay
Measurement: IC50 = 4297 nM (pChEMBL 5.369999885559082)
Descriptors: MW 434.52, ALogP 3.72, HBA 5, HBD 1, PSA 71.69, QED 0.66
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CCCN3C(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CO)NC1=O)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N2
InChIKey: STJCUZOTQPIXIR-JWKNPDOPSA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of recombinant human matriptase using Boc-QAR-MCA as susbtrate measured every 60 secs for 10 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1672.87
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)NCCCCCn1cc(C(=O)c2cccc3ccccc23)c2ccccc21
InChIKey: XOXIGOYEWHFRCB-GORMCOKISA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Agonist activity at MOR in Wistar rat brain membranes in presence of naloxone after 60 mins by [35S]-GTPgammaS binding assay
Measurement: EC50 = 1473 nM (pChEMBL 5.829999923706055)
Descriptors: MW 852.01, ALogP 4.05, HBA 9, HBD 7, PSA 213.75, QED 0.04
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CCC(=O)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O
InChIKey: VQPWOMHPWMPGET-JTEMBWBYSA-N
Target: Envelope glycoprotein gp160 (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q6QLK5
Assay: Inhibition of HIV1 gp41-induced cell-cell fusion between viral envelope expressing human HL2/3 cells to CD4/CCR5 receptor expressing TZM-bl cells at 1:1 ratio of hCS6ERE to compound incubated for 6 hrs by luciferase reporter gene assay
Measurement: EC50 = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 3013.46
Compound (SMILES): Cc1ccc(-c2cnc3ccn(CC(=O)N(C)C)c3c2)s1
InChIKey: QLVPQOVZXHEIDR-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 299.4, ALogP 3.16, HBA 4, HBD 0, PSA 38.13, QED 0.74
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2ccccc2)c1
InChIKey: SCUKDJAKLMTQPY-OAQYLSRUSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 411.5, ALogP 3.2, HBA 4, HBD 3, PSA 98.74, QED 0.16
Compound (SMILES): O=C(CCCCCCn1cc(Nc2ncc(Cl)c(Nc3ccc(Cl)cc3)n2)cn1)NO
InChIKey: QZZCBJMHOODNJW-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 using Ulight-CAGAGAIETDKEYYTVKD as substrate measured after 60 mins by LANCE assay
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 464.36, ALogP 4.92, HBA 8, HBD 4, PSA 116.99, QED 0.18
Compound (SMILES): O=C(CC(=O)Nc1ccc2c(c1)B(O)OC2)Nc1ccc2c(c1)B(O)OC2
InChIKey: IXTVZIHDEVZCRN-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as reduction in CO2 hydration preincubated for 15 mins to 2 hrs by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 158 nM (pChEMBL 6.800000190734863)
Descriptors: MW 365.95
Compound (SMILES): COc1cc(Nc2ccnc3cc(C#N)ccc23)cc(OC)c1OC
InChIKey: BLWQIEISIMYCHD-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Binding affinity to biotinylated human RIPK2 (1 to 310 residues) expressed in Escherichia coli incubated for 1.5 hrs by fluorescent tracer dependent TR-FRET based competitive ligand binding displacement assay
Measurement: Kd = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 335.36, ALogP 3.88, HBA 6, HBD 1, PSA 76.4, QED 0.76
Compound (SMILES): Cc1nc2ccc(-c3cc(N)nc(N)c3)nc2n1C[C@@H](C)Oc1ccccc1
InChIKey: PUGXENIKUPHCAF-CYBMUJFWSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 374.45, ALogP 3.43, HBA 7, HBD 2, PSA 104.87, QED 0.55
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@H](C)c3ccc(N4CC5CCC(C4)N5)c(C#N)c3)sc2n1
InChIKey: NSXWVLYZUZRLNB-YCMKEVRSSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 460.61, ALogP 3.53, HBA 7, HBD 3, PSA 107.07, QED 0.54
Compound (SMILES): CNC(=O)NC1CCN(Cc2cc3nc(-c4cccc5[nH]ccc45)nc(N4CCOCC4)c3s2)CC1
InChIKey: NHLSOFMOYDDMIY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 505.65, ALogP 3.57, HBA 7, HBD 3, PSA 98.41, QED 0.38
Compound (SMILES): Cl.O=C(N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1cccc2sccc12
InChIKey: WXAIGWJXXHEMHA-NWLBSPLSSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at recombinant mouse mu opioid receptor expressed in CHO cell membrane assessed as [35]-GTPgammaS binding incubated for 1.5 hrs by scintillation counting method
Measurement: EC50 = 0.32 nM (pChEMBL 9.489999771118164)
Descriptors: MW 502.64, ALogP 3.97, HBA 6, HBD 3, PSA 82.03, QED 0.5
Compound (SMILES): CCCC[C@H](N)C(=O)Nc1ccc(C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)OCc2ccccc2)cc1
InChIKey: YNBUILPSIRWOEF-XCZPVHLTSA-N
Target: Endoplasmic reticulum aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P179
Assay: Competitive inhibition of human recombinant ERAP2 expressed in baculovirus infected sf9 cells using R-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis
Measurement: Ki = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 526.64, ALogP 4.71, HBA 5, HBD 4, PSA 126.31, QED 0.2
Compound (SMILES): FC(CCN1CCc2ccccc2CC1)Cc1ccccc1
InChIKey: CXVLJOUFQITMLT-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Inhibition of DOR (unknown origin)
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 297.42, ALogP 4.06, HBA 1, HBD 0, PSA 3.24, QED 0.8
Compound (SMILES): CCOc1cc2c(=O)oc(-c3ccccc3OC)nc2cc1OC
InChIKey: MICLUGCMNGFNIQ-UHFFFAOYSA-N
Target: Kallikrein-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P49862
Assay: KLK7 Assay: Materials: Recombinant human KLK7, Substrate S-2586 (Chromogenics, cat. no. 820894) KLK7 activity was determined at 37° C. in 10 mM Na phosphate pH 7.2, 0.5 M NaCl, with final concentrations of 2.5 ug/ml (100 nM) of KLK7, 1.0 mM substrate, 5% DMSO in the presence of 0 uM, 0.1 uM, 0.5 uM, 1.0 uM and 5 uM of inhibitor, in 96 well plates by measuring absorbance at 405 nm in a plate reader (Spectramax).
Measurement: Ki = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 327.34, ALogP 3.27, HBA 6, HBD 0, PSA 70.79, QED 0.72
Compound (SMILES): CCc1ccc(C(=O)Nc2ccc(C(F)(F)F)cc2)cc1-c1cccc(-c2cnc3cnccn23)c1
InChIKey: KULCILVQAXSMEP-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of human recombinant His-tagged c-Kit cytoplasmic domain (544 to 976 residues) expressed in baculovirus expression system using Ser/Thr 6 peptide as substrate after 1 hr in presence of 300 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 3984 nM (pChEMBL 5.400000095367432)
Descriptors: MW 486.5, ALogP 6.9, HBA 4, HBD 1, PSA 59.29, QED 0.29
Compound (SMILES): Cc1c(-c2ccc(N3CCNCC3)cc2)cncc1-c1ccc2c(c1)CNC2=O
InChIKey: ZCLWKSOLVKDHKE-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) expressed in HEK293 cells transfected with CAGA-luciferase and Renilla luciferase reporter measured after 24 hrs by dual luciferase reporter assay
Measurement: IC50 = 4810 nM (pChEMBL 5.320000171661377)
Descriptors: MW 384.48, ALogP 3.38, HBA 4, HBD 2, PSA 57.26, QED 0.73
Compound (SMILES): C[C@H]1OC2(CCN(CCc3ccccc3F)CC2)CN(c2cnccc2C(F)(F)F)C1=O
InChIKey: INCPDVXLHDEOLM-MRXNPFEDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells assessed as reduction in channel current at -80 mV holding potential by whole cell patch clamp assay
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 451.46, ALogP 4.07, HBA 4, HBD 0, PSA 45.67, QED 0.66
Compound (SMILES): CN(CC(=O)N(Cc1ccc(C(C)(C)C)cc1)c1ccc(C(=O)NO)cc1)S(=O)(=O)c1ccc(F)cc1
InChIKey: LINKSTNVTLNRAZ-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in baculovirus infected Sf9 cells using FAM-RHKK-TFAc as substrate incubated for 17 hrs by electrophoretic mobility shift assay
Measurement: IC50 = 697 nM (pChEMBL 6.159999847412109)
Descriptors: MW 527.62, ALogP 4.1, HBA 5, HBD 2, PSA 107.02, QED 0.34
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]1F
InChIKey: CCXCDDWASROAJA-QYYRPYCUSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBL9
Assay: Agonist activity at human P2X2R/P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: IC50 = 5370.32 nM (pChEMBL 5.269999980926514)
Descriptors: MW 509.17, ALogP -0.65, HBA 13, HBD 6, PSA 258.9, QED 0.24
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(Cl)cc2)cc1C#Cc1cc(-c2cnn(C)c2)cnc1N
InChIKey: JZKQBPWOWAPASE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 (447 to 761 residues) expressed in baculovirus infected Sf21 insect cells using poly (Glu, Tyr)4:1 as substrate measured after 1 hr by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 441.92, ALogP 4.68, HBA 5, HBD 2, PSA 85.83, QED 0.45
Compound (SMILES): CN(C)c1ccc2c(c1)SC(=S)N1CCCN=C21
InChIKey: UUFSKZQZJPVOEO-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human N-terminal His6/SUMO-tagged/C-terminal SII-tagged HDAC4 expressed in Escherichia coli BL21 DE3 using Boc-Lys(TFA)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 277.42, ALogP 2.6, HBA 4, HBD 0, PSA 18.84, QED 0.73
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCOCCOCCNC(=O)CS(=O)(=O)O)c1nnc(C)n1-2
InChIKey: ITOTWAQMJPBHEG-NRFANRHFSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 in human MX1 cells assessed as decrease in cell proliferation after 3 days by Celltiter-Glo assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 653.18, ALogP 2.34, HBA 11, HBD 3, PSA 174.1, QED 0.17
Compound (SMILES): CCOc1ccc2cc(-c3nn(CC4CCN(C)CC4)c4ncnc(N)c34)ccc2n1
InChIKey: AWJAAKKEYXUCFY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase D1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15139
Assay: Inhibition of recombinant FLAG-tagged PKD1 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay
Measurement: IC50 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 417.52, ALogP 3.36, HBA 8, HBD 1, PSA 94.98, QED 0.53
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)c1cccc(/C=C/C(=O)NO)c1)B1O[C@@H]2[C@@H]3C[C@H](C[C@]2(C)O1)C3(C)C
InChIKey: WAKGJPYDEKJAKC-PAUPOJMRSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin) pre-incubated for 5 mins before fluorogenic substrate Boc-Lys (acetyl)-AMC or Boc-Lys (triflouroacetyl)-AMC addition and measured after 30 mins by fluorescence based assay
Measurement: IC50 = 11100 nM (pChEMBL 4.960000038146973)
Descriptors: MW 511.43
Compound (SMILES): Cc1c(Cl)cc(C(C)Nc2ncnc3[nH]cnc23)c(-c2cccc(F)c2)c1C#N
InChIKey: IEXWGFFVZUJNEK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: TAM Kinase Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl (see Axl autophosphorylation assay above), or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu¿W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 406.85, ALogP 5.17, HBA 5, HBD 2, PSA 90.28, QED 0.49
Compound (SMILES): CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)NC(CCP(=O)(O)O)P(=O)(O)O)cc1
InChIKey: IYHDGYOJXJQQRF-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of HDAC9 (unknown origin)
Measurement: IC50 = 7840 nM (pChEMBL 5.110000133514404)
Descriptors: MW 526.39, ALogP 0.02, HBA 10, HBD 7, PSA 251, QED 0.18
Compound (SMILES): N[C@@]1(C(=O)O)CN(Cc2ccccc2)C[C@@H]1CCCB(O)O
InChIKey: RFGFRNXITMSLTI-ZFWWWQNUSA-N
Target: Arginase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05089
Assay: Inhibition Assay: Inhibition of arginase I (ARG I) and arginase II (ARG II) by Formula I or Formula II compounds is followed spectrophotometrically at 530 nm. The compound to be tested was dissolved in DMSO at an initial concentration 50-fold greater than its final concentration in the cuvette. 10 μl of the stock solution was diluted in 90 μl of the assay buffer that comprises 0.1M sodium phosphate buffer containing 130 mM NaCl, pH 7.4, to which is added ovalbumin (OVA) at a concentration of 1 mg/ml. Solutions of arginase I and II were prepared in 100 mM sodium phosphate buffer, pH 7.4 containing 1 mg/ml of OVA to give an arginase stock solution at a final concentration of 100 ng/ml.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 306.17
Compound (SMILES): O=C(CC1CC1)Nc1nc2ccc(Sc3nnc4ccc(-c5ccc(F)cc5)nn34)cc2s1
InChIKey: PYWIIDVJVPEJLN-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of phosphorylated MET Y1230H mutant (unknown origin) pre-incubated for 30 mins before biotinylated poly(glutamate-alanine-tyrosine) peptide addition and measured after 5 mins by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.56, ALogP 5.43, HBA 8, HBD 1, PSA 85.07, QED 0.35
Compound (SMILES): COc1ccccc1C1CCN(c2nc(C3(F)CC3)nc3ccc(N(C)CCO)cc23)CC1
InChIKey: BLWXTJQMEBQCIZ-UHFFFAOYSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: NTR1 Ca2+ Flux Dose Response: NTSR1 (NTR1) CHO cells are plated in 20 uL of assay media containing Ham's F12 supplemented with 10% fetal bovine serum and 0.4 mg/mL G418 at a concentration of 1.0×106 cells per mL into black, 384-well assay plates with clear bottoms using a Multidrop liquid handler. Assay plates are incubated at 37° C. in 5% CO2. The next day, the assay plates are aspirated to remove growth media and washed once with 20 uL of DPBS. The DPBS is then aspirated from the assay plate and replaced with 25 uL of Fluo-4 NW calcium dye prepared according to the manufacturer's recommendations then the plates are incubated for 1 hour at 37° C. Following the incubation in the presence of dye, the assay is run on a Molecular Devices FlexStation-III using 494 excitation and 516 emission wavelengths set to read for 90 seconds with the addition at 18 seconds of 5 uL of 6× final concentration of test compounds and peptide control diluted in assay media containing 0.1% BSA and no more than 9% DMSO to yield a maximum final DMSO concentration of 1.5%. Percent activation is calculated based on the maximum response minus the minimum value over the time course relative to the neurotensin 1 control peptide at 100 pM. EC50 values were calculated for those compounds tested in 8-point dose dependent response.
Measurement: EC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 450.56, ALogP 4.41, HBA 6, HBD 1, PSA 61.72, QED 0.58
Compound (SMILES): CC(C)(C)CNc1nccc(N2CCN(C(=N)N)CC2)n1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: DVONFQOOYIDACY-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of 5 nM [3H-pyrilamine from human H1R expressed in Sf9 cell membranes co-expressing RGS4 by competition binding assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 291.4, ALogP 0.95, HBA 5, HBD 3, PSA 94.16, QED 0.57
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1ccc(C(F)(F)F)cc1C
InChIKey: VKBATIPCCNTGIO-XNFLFYSQSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 818.8, ALogP 5.34, HBA 10, HBD 5, PSA 230.88, QED 0.04
Compound (SMILES): CO[C@@H]1[C@H](N(C)CCOCCOCCOCCNC(=O)CCC2=[N+]3C(=Cc4c(C)cc(C)n4[B-]3(F)F)C=C2)C[C@H]2O[C@]1(C)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: OSVUGUHRKMMBSE-INMRTLOZSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Binding affinity to recombinant N-terminal His-FLAG-GST-tagged TYK2 (unknown origin) (871 to 1187 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay
Measurement: Kd = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 915.85
Compound (SMILES): CN1CCOc2c1cnn1c(-c3ccc4cccc(NCC5(F)CCNCC5)c4n3)nnc21
InChIKey: HVQKSMUBAKDZPC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of PIM1 in human NCI-H1299 cells assessed as reduction in BAD phosphorylation at Ser-112 residue incubated for 4 hrs by ELISA
Measurement: EC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 448.51, ALogP 2.67, HBA 9, HBD 2, PSA 92.5, QED 0.49
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)NCP(=O)(O)O)c(OCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: RGWOWRVQVVNBOO-TZIWHRDSSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 610.6, ALogP 2.84, HBA 8, HBD 6, PSA 207.74, QED 0.04
Compound (SMILES): CN1CCN(C(=O)C(C)(C)c2ccc(C(=O)Nc3cn4cc(-c5cc(C(C)(C)C)cc(C(C)(C)C)c5)ccc4n3)cc2)CC1
InChIKey: BNTGVINQADRYBE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: NanoBRET (SGC Frankfurt) (DYRK1A)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 593.82, ALogP 6.9, HBA 5, HBD 1, PSA 69.95, QED 0.27
Compound (SMILES): CC(=O)N(C)C1CCN(Cc2cc3nc(-c4cccc5[nH]ncc45)nc(N4CCOCC4)c3s2)C1
InChIKey: XHGCCQVPDOWTLY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 491.62, ALogP 3.12, HBA 8, HBD 1, PSA 90.48, QED 0.46
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CCCCCCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: GHLFIGVGFVELAS-CWANVFDFSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of [3H]propionyl-pNPY from human NPY Y2 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ after 90 mins by liquid scintillation counting
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 1505.79
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)c(-c4ccccc4C)c3)sc2n1
InChIKey: GHPLYLNJSKZRFR-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 485.66, ALogP 4.54, HBA 6, HBD 3, PSA 83.28, QED 0.37
Compound (SMILES): Cc1cc(N)nc2cc(-c3ccc(OCc4cccnc4)c(CN)c3)ccc12
InChIKey: RSZQDXJFSPTWRD-UHFFFAOYSA-N
Target: Nitric oxide synthase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P29474
Assay: Inhibition of human eNOS expressed in Escherichia coli expression system assessed as reduction in NO production in presence of L-arginine measured for 30 sec by hemoglobin capture assay
Measurement: Ki = 7730 nM (pChEMBL 5.110000133514404)
Descriptors: MW 370.46, ALogP 4.23, HBA 5, HBD 2, PSA 87.05, QED 0.55
Compound (SMILES): CCN(CC)c1ccc([C@H]2C[C@@]3(C)[C@@H](CC[C@@]3(O)C#CC(C)(C)C)[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]32)cc1
InChIKey: HYTRMSLXHBYETF-KMSLUKAPSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Antagonist activity at human progesterone receptor expressed in CHO-K1 cells harboring firefly luciferase gene after 20 hrs by One-Glo luciferase reporter gene assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 501.76, ALogP 7.15, HBA 3, HBD 1, PSA 40.54, QED 0.45
Compound (SMILES): NCCCC[C@H](N)C(=O)O.O=C(Nc1ccc(Cl)cc1)c1ccc(NC(=O)c2ccc(-c3nc4cc(Cl)c(Cl)cc4[nH]3)cc2)c(C(=O)O)c1
InChIKey: OOCKZTOPBQREBQ-ZSCHJXSPSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of human plasmin assessed as reduction in liberation of free para-nitroanilide using S-2288 substrate incubated for 20 to 30 mins
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 579.83, ALogP 7.39, HBA 4, HBD 4, PSA 124.18, QED 0.17
Compound (SMILES): Cc1cn(-c2cc(NC(=O)c3ccc4c(c3)C[C@H](N(C)c3cncnc3)C4)cc(C34CC5CC(CC(C5)C3)C4)c2)cn1
InChIKey: MNVFIXUOTSLQOL-BSSUVSBPSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of His-tagged human TrkC expressed in baculovirus expression system using Tyr1 peptide as substrate after 1.5 hrs by FRET-based Z-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 558.73, ALogP 6.29, HBA 6, HBD 1, PSA 75.94, QED 0.3
Compound (SMILES): CC(C)NC[C@H](O)COc1ccccc1CCNC(=O)NCCc1ccccc1OC[C@@H](O)CNC(C)C
InChIKey: JMPQBBZKTCKZGR-UIOOFZCWSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [3H]DHA from beta2 adrenergic receptor (unknown origin) stably expressed in HEK293 cell membranes measured after 90 mins by scintillation counting analysis
Measurement: Ki = 3.467 nM (pChEMBL 8.460000038146973)
Descriptors: MW 530.71, ALogP 2.25, HBA 7, HBD 6, PSA 124.11, QED 0.17
Compound (SMILES): CN1C[C@H](Nc2nc3cc[nH]c3c(=O)n2C)C[C@H](c2ccc3c(c2)OCCO3)C1
InChIKey: PUFPGLSWMMJNSE-LSDHHAIUSA-N
Target: Histone acetyltransferase KAT2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q92831
Assay: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry
Measurement: Kd = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 395.46, ALogP 1.93, HBA 7, HBD 2, PSA 84.41, QED 0.71
Compound (SMILES): CCCCC[C@@H](O)c1nc(-c2ccccc2)n(-c2ccccc2)c1/C=C/[C@@H](O)[C@@H](O)CCCC(=O)OC
InChIKey: VGXMROVCMLMHKD-WWGRTLCBSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at ALX/FPR2 in human THP1 cells harboring NF-kB-Luc assessed as inhibition of LPS-induced NFkB signalling activation by measuring reduction in IL-1beta secretion pretreated for 30 mins followed by LPS stimulation for 24 hrs by electrochemiluminescence assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 506.64, ALogP 5.23, HBA 7, HBD 3, PSA 104.81, QED 0.2
Compound (SMILES): Nc1ccc(-c2nc(N3C4CCC3COC4)c3c(n2)N2CCOC[C@H]2C3)cn1
InChIKey: XGLUOINQAVYTEU-YMAMQOFZSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to wild-type human partial length mTOR (L1382 to W2549 residues) expressed in mammalian expression system by kinome scan assay
Measurement: Kd = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 380.45, ALogP 1.25, HBA 8, HBD 1, PSA 89.63, QED 0.83
Compound (SMILES): O=C(CCCN1CCCN(c2ccc(Cl)cn2)CC1)c1ccc(F)cc1
InChIKey: KVGNSDMVYWRLTG-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D2 receptor by liquid scintillation counting
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 375.88, ALogP 4.05, HBA 4, HBD 0, PSA 36.44, QED 0.71
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@@H]1CCN(S(C)(=O)=O)c2ccc(Cc3ccc4c(c3)OCCO4)cc21.O=C(O)C(F)(F)F
InChIKey: RVUPMXHYNDJBJE-ZDGKEXRSSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 1 hr
Measurement: EC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 565.69, ALogP 3.27, HBA 7, HBD 3, PSA 131.19, QED 0.4
Compound (SMILES): CCn1ncc(-c2nc3c(N[C@H]4CCN(C(=O)C5CCOCC5)C4)ncnc3n2C)c1C
InChIKey: WFVKABQFHLSPFH-INIZCTEOSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of PDE5 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 438.54, ALogP 1.99, HBA 9, HBD 1, PSA 102.99, QED 0.65
Compound (SMILES): CCCCc1ccc(C(=O)C2CCN(C(=O)c3cc(O)ccc3F)CC2)cc1
InChIKey: NCCCUONVHAETDD-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL using 4-NPA as substrate after 30 mins
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 383.46, ALogP 4.61, HBA 3, HBD 1, PSA 57.61, QED 0.74
Compound (SMILES): Cc1ccc(-c2nn(-c3ccccc3)cc2C(=O)NOCc2ccccc2F)cc1
InChIKey: HVEABAGWWBLXHR-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 401.44, ALogP 4.85, HBA 4, HBD 1, PSA 56.15, QED 0.47
Compound (SMILES): O=C(O)CSc1nc(Cl)cc(Nc2cccc3c2CCCC3)n1
InChIKey: BPCUCWYWVVQEIW-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Activation of human Gal4-fused PPARgamma LBD transfected in HEK293T after 14 to 16 hrs by dual-glo luciferase reporter gene assay
Measurement: EC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 349.84, ALogP 3.93, HBA 5, HBD 2, PSA 75.11, QED 0.48
Compound (SMILES): COc1ccccc1CNC[C@H]1C[C@]1(F)c1ccccc1.Cl
InChIKey: XIYFCBBJYLALPD-CLRXKPRGSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at recombinant human 5HT2B receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 363 nM (pChEMBL 6.440000057220459)
Descriptors: MW 285.36, ALogP 3.67, HBA 2, HBD 1, PSA 21.26, QED 0.87