lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1nn(C)cc1C(=O)Nc1cccc(-c2nncn2C(C)C)n1
InChIKey: XCGWZOOSJWALQR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 341.38, ALogP 1.92, HBA 8, HBD 1, PSA 99.75, QED 0.76
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3cccc([N+](=O)[O-])c3)CC2)cc1
InChIKey: KHRJNSMYBNDMTF-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human CA14 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 66.5 nM (pChEMBL 7.179999828338623)
Descriptors: MW 418.43, ALogP 0.84, HBA 6, HBD 1, PSA 143.92, QED 0.58
Compound (SMILES): CC(C)N(C(=O)c1cccc(C(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: CLEDVPXGVTYVTP-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Binding affinity to human HDAC8 pre-incubated for 10 mins before FITC-M344 addition and measured after 10 mins by fluorescence polarization assay
Measurement: IC50 = 62.5 nM (pChEMBL 7.199999809265137)
Descriptors: MW 366.34, ALogP 3.88, HBA 3, HBD 2, PSA 69.64, QED 0.64
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3cccc(Br)c3)CC2)cc1
InChIKey: ODJZGQFXLXQHJA-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human CA14 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 85.3 nM (pChEMBL 7.070000171661377)
Descriptors: MW 452.33, ALogP 1.69, HBA 4, HBD 1, PSA 100.78, QED 0.77
Compound (SMILES): CCN(CC)C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: OZWVOBLSVPGTGH-NSHDSACASA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 619.51, ALogP 4.33, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(SCC4CCOCC4)s3)C2)cc1
InChIKey: XPTUNGFRXJHQJG-HXUWFJFHSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 486.66, ALogP 4.5, HBA 7, HBD 2, PSA 83.56, QED 0.42
Compound (SMILES): CCN(c1ccc(C(=O)NO)cc1)S(=O)(=O)c1cccc(C(F)(F)F)c1
InChIKey: QDLQWVBUGGQYHL-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Binding affinity to human HDAC8 pre-incubated for 10 mins before FITC-M344 addition and measured after 10 mins by fluorescence polarization assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 388.37, ALogP 3.04, HBA 4, HBD 2, PSA 86.71, QED 0.61
Compound (SMILES): Cc1ccc(-c2ncnc(Nc3ccc(C(=N)N)cc3Cl)c2O)cc1
InChIKey: SNGWZJUYWHIFIM-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 353.81, ALogP 3.84, HBA 5, HBD 4, PSA 107.91, QED 0.42
Compound (SMILES): Cc1c(N2CCCC2)nc2ccc(Br)cc2c1C(=O)NC[C@H](CCC(=O)O)c1ccccc1Cl
InChIKey: YQOLEILXOBUDMU-KRWDZBQOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 10 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 544.88, ALogP 5.94, HBA 4, HBD 2, PSA 82.53, QED 0.37
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: GKYDUZGIMDOXEK-CVUOCSEZSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4R expressed in HEK293T cells co-expressing ARRB2 assessed as induction of beta-arrestin2 recruitment measured for 40 mins by D-luciferin based luminescence assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 951.1, ALogP -3.41, HBA 12, HBD 17, PSA 435.06, QED 0.02
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n(Cc5ccc(F)cc5OC)c(=O)c4c3)cc12
InChIKey: BASMYKLUFZUQTO-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 4a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 672.71, ALogP 5.88, HBA 8, HBD 1, PSA 123.74, QED 0.21
Compound (SMILES): CCC[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: CZPFBLHFGKUTTQ-TXVKUACNSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at full-length human RORgammat C278S mutant co-transfected with ROR response element by luciferase based reporter gene assay
Measurement: IC50 = 46.5 nM (pChEMBL 7.329999923706055)
Descriptors: MW 492.6, ALogP 6.49, HBA 5, HBD 0, PSA 79.53, QED 0.41
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3ccccc3F)CC2)cc1
InChIKey: NXIFLMUSIPVLEA-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human CA14 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 391.42, ALogP 1.07, HBA 4, HBD 1, PSA 100.78, QED 0.85
Compound (SMILES): COc1ccccc1SC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: HLUJXEXDDSDFKA-QATBIIFWSA-N
Target: Sphingosine-1-phosphate lyase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95470
Assay: Receptor [35S] GTPgammaS Binding Assays: (S1P1 GTPgammaS/S1P3 GTPgammaS): Compounds were loaded in a 384 Falcon v-bottom plate (0.5 l/well in a 11 point, 3-fold dilution). Membranes prepared from S1P1/CHO cells or EDG3-Gal5-bla HEK293T cells (EDG3 equivalent S1P3) were added to the compound plate (40 l/well, final protein 3 μg/well) with MULTIDROP®. [35S]GTP (1250 Ci/mmol, Perkin Elmer) was diluted in assay buffer: 20 mM HEPES, pH7.5, 10 mM MgCl2, 150 mM NaCl, 1 mM EGTA (ethylene glycol tetraacetic acid), 1 mM DTT (Dithiothreitol), 10 μM GDP, 0.1% fatty acid free BSA, and 10 μg/ml Saponin to 0.4 nM. 40 μl of the [35S] GTP solution was added to the compound plate with a final concentration of 0.2 nM. The reaction was kept at room temperature for 45 min. At the end of incubation, all the mixtures in the compound plate were transferred to Millipore 384-well FB filter plates via the VELOCITY11® Vprep liquid handler. The filter plate was washed with water 4 times by using the manifold Embla plate washer and dried at 60° C. for 45 min. MicroScint 20 scintillation fluid (30 μl) was added to each well for counting on the Packard TOPCOUNT®. EC50 is defined as the agonist concentration that corresponds to 50% of the Ymax (maximal response) obtained for each individual compound tested. The EC50 for Example 689 was determined to be 5.7 nM in the assay utilizing membranes prepared from S1P1/CHO cells. The EC50 for Example 689 was determined to be >2000 nM in the assay utilizing membranes prepared from EDG3-Gal5-bla HEK293T cells.A smaller value for GTPγS S1P1 EC50 value indicated greater activity for the compound in the GTPγS S1P1 binding assay. A larger value for the GTPγS S1P3 EC50 value indicated less activity in the GTPγS S1P3 binding assay. Example 689, which is the phosphate ester of Example 672, possessed activity as an agonist of S1P1 and is selective over S1P3. Example 697, which is the phosphate ester of Example 681, possessed activity as an agonist of S1P1 and is selective over S1P3. Thus the compounds of the present invention may be used in treating, preventing, or curing various S1P1 receptor-related conditions while reducing or minimizing the side effects due to S1P3 activity. The selectivity of the compounds of the present invention indicate their potential use in treating, preventing, or curing autoimmune and inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, lupus, psoriasis, or vascular diseases, while reducing or minimizing possible side effects due to S1P3 activity. Other potential uses of the compounds of the present invention include minimizing or reducing rejection of transplanted organs, while reducing or minimizing side effects due to S1P3 activity.
Measurement: EC50 < 10 nM (pChEMBL 8)
Descriptors: MW 477.56, ALogP 4.67, HBA 5, HBD 3, PSA 102.01, QED 0.38
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)CC2(CCCCC2)CNC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC1=O.O=C(O)C(F)(F)F
InChIKey: MSIIVKDPQBOVIB-JDCPXUKWSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Inhibition of fibrinogen binding to human platelet integrin alpha2b beta3 by ELISA based solid phase binding assay
Measurement: IC50 = 657 nM (pChEMBL 6.179999828338623)
Descriptors: MW 628.73, ALogP -0.99, HBA 7, HBD 9, PSA 244.7, QED 0.1
Compound (SMILES): COCCOc1ccccc1C1CCN(c2ccn3c(CC4CC4)nnc3c2Cl)CC1
InChIKey: PANKOZQZUGXYCW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human 5HT2A receptor expressed in HEK293 cells assessed as inhibition of 5HT-induced intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: IC50 = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 440.98, ALogP 4.74, HBA 6, HBD 0, PSA 51.89, QED 0.47
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: VZRCTKJCGGBKBW-NSHDSACASA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 649.52, ALogP 4.42, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n([C@H](COC)c5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: IWHVQSGPUREPKO-WJOKGBTCSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 4a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 686.74, ALogP 6.05, HBA 8, HBD 1, PSA 123.74, QED 0.2
Compound (SMILES): Cc1c(N2CCNCC2)nc2ccc(Br)cc2c1C(=O)NC[C@H](CCC(=O)O)c1ccccc1Cl
InChIKey: ZZSNHHKTFMLWFY-KRWDZBQOSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: GPCRScan assay: inhibition of Alpha2A
Measurement: Ki = 8468.01 nM (pChEMBL 5.070000171661377)
Descriptors: MW 559.89, ALogP 4.75, HBA 5, HBD 3, PSA 94.56, QED 0.37
Compound (SMILES): Cc1nccc2c1C(C)(C)Nc1cc(Br)ccc1-2
InChIKey: YBGLIPYAJPOYAD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding affinity to 5HT5A receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 303.2, ALogP 4.48, HBA 2, HBD 1, PSA 24.92, QED 0.78
Compound (SMILES): CN[C@@H](CCCNC(=N)N)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
InChIKey: AGBBPVCMSXHJNT-CMOCDZPBSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [3H]propionyl-pNPY from human Y5 receptor expressed in human HEC1B cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 619.77, ALogP -1.96, HBA 8, HBD 12, PSA 286.45, QED 0.04
Compound (SMILES): Cc1cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc(C)[n+]1CCCCCc1c[nH]cn1.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: APWOSIJGLAZRMM-UHFFFAOYSA-M
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Binding affinity to human recombinant NLuc/GPCR-fused H4R expressed in HEK293T cells measured after 30 mins by furimazine substrate based BRET assay
Measurement: Kd = 79.5 nM (pChEMBL 7.099999904632568)
Descriptors: MW 415.61, ALogP 5.52, HBA 2, HBD 1, PSA 35.8, QED 0.27
Compound (SMILES): CC(C)CCNC1=CC(=O)c2ccccc2C1=O
InChIKey: JLOBMWCZCWALTQ-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes using isoform-specific probe substrates incubated for 15 to 30 mins by by LC-MS/MS analysis
Measurement: IC50 = 39300 nM (pChEMBL 4.409999847412109)
Descriptors: MW 243.31, ALogP 2.59, HBA 3, HBD 1, PSA 46.17, QED 0.88
Compound (SMILES): N#Cc1cnc2cc(OC[C@H](O)CO)c(NC(=O)CC3CSSC3)cc2c1Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
InChIKey: UVWRRZRGHPHHLL-HSZRJFAPSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Kinase assay: KINOMEscan is based on a competition binding assay that quantitatively measures the ability of a compound to compete with an immobilized, active-site directed ligand. The assay is performed by combining three components: DNA-tagged kinase; immobilized ligand; and a test compound. The ability of the test compound to compete with the immobilized ligand is measured via quantitative PCR of the DNA tag.For most assays, kinase-tagged T7 phage strains were prepared in an E. coli host derived from the BL21 strain. E. coli were grown to log-phase and infected with T7 phage and incubated with shaking at 32° C. until lysis. The lysates were centrifuged and filtered to remove cell debris. The remaining kinases were produced in HEK-293 cells and subsequently tagged with DNA for qPCR detection. Streptavidin-coated magnetic beads were treated with biotinylated small molecule ligands for 30 minutes at room temperature to generate affinity resins for kinase assays. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce nonspecific binding. Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). All reactions were performed in polystyrene 96-well plates in a final volume of 0.135 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 M non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 655.17, ALogP 6.29, HBA 10, HBD 4, PSA 136.73, QED 0.13
Compound (SMILES): N#Cc1ccnc(Oc2nn([C@H]3C[C@H](F)C3)c3ncnc(N)c23)c1
InChIKey: USPIAMGRHIPYDO-MGCOHNPYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate measured after 10 mins by LC-MS/MS analysis
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 325.31, ALogP 2.14, HBA 8, HBD 1, PSA 115.53, QED 0.78
Compound (SMILES): CC(=O)N1CCC(c2ccc(-c3cc(C(=O)O)cc4cc(-c5ccc(C(F)(F)F)cc5)ccc34)cc2)CC1
InChIKey: AFRXCTUPOJKNDG-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Binding affinity to D1 receptor (unknown origin)
Measurement: Ki = 1390 nM (pChEMBL 5.860000133514404)
Descriptors: MW 517.55, ALogP 7.62, HBA 2, HBD 1, PSA 57.61, QED 0.3
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(CC(C)(C)C(=O)O)o3)nc2CC2CCCCC2)c(C(F)F)c1F)C(F)(F)F
InChIKey: ZHSFCHXKHOJYIG-SFHVURJKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: RORgammat (full-length human) Reporter Assay A: Cells used in this assay were transiently co-transfected with three different plasmids, one expressing the GAL4-DNA binding domain (DBD)-RORγt fusion protein under control of a CMV promoter (NH2-Gal4-DBD:RORC¿COOH in pCMV-BD, Stratagene #211342), and two reporter plasmids¿the firefly luciferase reporter under control of a GAL4 promoter (pFR-Luc 2× GAL4) and Renilla luciferase reporter under control of CMV promoter (pRL-CMV, Promega #E2261). The full-length coding sequence was used for human RORγt, i.e., nucleotides 142-1635 of human RORγt, transcript variant 2, NCBI Accession: NM_001001523.1 (SEQ ID NO: 1). HEK293T cells were plated at 35000 per well in 96-well plate in medium of MEM with 8.6% FBS. After 18-22 hours incubation, the transfection was carried out by using a PEI solution with 170.5 ng total DNA/well (50 ng pCMV-BD-ROR plus 20 ng of pFR-Luc reporter and 0.5 ng of pRL-CMV reporter plus 100 ng Carrier DNA (Clontech #630440) for each well). 4-6 hours after transfection, cells were treated with compounds for overnight in the medium with final concentration of FBS 1.1% and DMSO 0.1%. After overnight (16 to 20 hours) incubation, media were removed and cells were lysed with 20 μL 1× Passive Lysis Buffer (Promega) for 10-15 minutes. Luminescence was measured using a BMG LUMIstar OPTIMA plate reader, after addition of 75 μL/well firefly luciferase buffer, followed by 75 μL/well Renilla luciferase buffer. To calculate the effect of compounds on RORγt activity, firefly values were normalized against values of DMSO only and values of reference compound at saturating concentration, then further normalized against Renilla signals. IC50s were generated by plotting final Renilla normalized data against compound concentration and percent inhibition was calculated against DMSO control.
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 682.71, ALogP 7.33, HBA 8, HBD 2, PSA 135.28, QED 0.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)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
InChIKey: JCRVCNMDDFQPJX-IRGGMKSGSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [3H]propionyl-pNPY from human Y5 receptor expressed in human HEC1B cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 803.97, ALogP -3.3, HBA 10, HBD 16, PSA 394.52, QED 0.02
Compound (SMILES): COc1c(OCCOCCOCCOc2ccc(C3CCN(c4ccn5c(CC6CC6)nnc5c4Cl)CC3)cc2)cccc1C(=O)C1CCN(CCc2ccc(F)cc2)CC1
InChIKey: SLBQKYUURZKYBP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human HT2A receptor expressed in HEK293 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 854.46, ALogP 8.5, HBA 11, HBD 0, PSA 99.89, QED 0.05
Compound (SMILES): CC(C)N(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: JVCQXJCACOCTST-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of C-terminal FLAG and His-tagged full length human HDAC1 expressed in baculovirus expression system using FAM-TSRHK(Ac)KL-NH2 substrate incubated for 17 hrs by EMSA method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 434.34, ALogP 4.9, HBA 3, HBD 2, PSA 69.64, QED 0.41
Compound (SMILES): CC(C)c1cc(-c2ccc3c(c2)[C@H](N)CO3)cc([C@@H]2CNc3cccc(CC(=O)O)c3O2)c1
InChIKey: HECONMODEBIAKY-RDGATRHJSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of PKL (unknown origin) using D-Leu-Pro-Arg*Rh110-D-Pro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 444.53, ALogP 5.04, HBA 5, HBD 3, PSA 93.81, QED 0.51
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(CN(CCc4ccc(S(N)(=O)=O)cc4)Cc4cn([C@H]5C[C@H](n6cc(C)c(=O)[nH]c6=O)O[C@@H]5CO)nn4)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: VSBFRYBQVSVEQT-RWJWSVIKSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 810.85, ALogP -1.88, HBA 19, HBD 5, PSA 293.46, QED 0.08
Compound (SMILES): CC1(C)O[C@H]2[C@H](O)CN(CCCCCCn3cc(CNc4ccc(S(N)(=O)=O)cc4)nn3)C[C@H]2O1
InChIKey: PNQLYJMCGFDUPZ-VSKRKVRLSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 508.65, ALogP 1.29, HBA 10, HBD 3, PSA 144.83, QED 0.38
Compound (SMILES): CCn1nnc2c(C)c([C@@H](CC(=O)O)c3ccc4c(c3)CN(C(=O)c3c(C)c(C)cc(C)c3C)CC4)ccc21
InChIKey: LOIDURPHCVSHLE-MHZLTWQESA-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 524.67, ALogP 5.8, HBA 5, HBD 1, PSA 88.32, QED 0.34
Compound (SMILES): CC1(C)C(/C=C/C=C/C=C2/N(CCCCCC(=O)NCc3cc(C(=O)NCCN4CCC(N5CCC(n6c(=O)[nH]c7ccccc76)CC5)CC4)cc(C(=O)NCCN4CCN(CCCCC5CCN(CC(=O)N6c7ccccc7NC(=O)c7ccccc76)CC5)CC4)c3)c3ccc(S(=O)(=O)[O-])cc3C2(C)C)=[N+](CCCCS(=O)(=O)O)c2ccccc21.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: DAWVVXBEXHVVPS-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Binding affinity to human muscarinic M2 receptor expressed in CHO-K9 cells incubated in dark at 22 degree C for 2 hrs by FACSCalibur flow cytometric saturation binding study
Measurement: Kd = 0.65 nM (pChEMBL 9.1899995803833)
Descriptors: MW 1688.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(N)=O
InChIKey: VHDRCZPPRIRVKL-JPRYDEJLSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [3H]propionyl-pNPY from human Y5 receptor expressed in human HEC1B cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 1047.24
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(CNC(=O)Nc4cccc(S(N)(=O)=O)c4)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: JDLXXAQKDPZINZ-GVDBMIGSSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 520.53, ALogP -1.07, HBA 11, HBD 5, PSA 216.32, QED 0.26
Compound (SMILES): CC(C)c1cc(COc2ccccc2CC(=O)O)cc(-c2ccc3c(c2)[C@H](N)CO3)c1
InChIKey: WQVBAYOMZJYFJK-HSZRJFAPSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition of human F9a using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 417.51, ALogP 5.08, HBA 4, HBD 2, PSA 81.78, QED 0.56
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)NC(CCCN)C(=O)NCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)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
InChIKey: VHYRYVARWWZDRT-QPBWNTKFSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [3H]propionyl-pNPY from human Y5 receptor expressed in human HEC1B cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 1161.38
Compound (SMILES): NC1=N[C@](CF)(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)CCC1(F)F
InChIKey: JAHKMCQBZQTJIC-QGZVFWFLSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.35, ALogP 3.12, HBA 6, HBD 2, PSA 102.49, QED 0.69
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: MXRZJMKOFBANST-ZIUUJSQJSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ assessed as intracellular calcium mobilization measured for 43 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 869, ALogP -4.46, HBA 12, HBD 18, PSA 440.77, QED 0.02
Compound (SMILES): CCN(CC)C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: OZWVOBLSVPGTGH-NSHDSACASA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 619.51, ALogP 4.33, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): Cc1ccc(-c2ncnc(Nc3ccc(C(=N)N)cc3Cl)c2O)cc1
InChIKey: SNGWZJUYWHIFIM-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 353.81, ALogP 3.84, HBA 5, HBD 4, PSA 107.91, QED 0.42
Compound (SMILES): Cc1c(N2CCCC2)nc2ccc(Br)cc2c1C(=O)NC[C@H](CCC(=O)O)c1ccccc1Cl
InChIKey: YQOLEILXOBUDMU-KRWDZBQOSA-N
Target: Prostaglandin D2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q13258
Assay: Displacement of [3H]PGD2 from full-length recombinant human DP1 receptor expressed in Chem-1 cell membranes measured after 120 mins by scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 544.88, ALogP 5.94, HBA 4, HBD 2, PSA 82.53, QED 0.37
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: GKYDUZGIMDOXEK-CVUOCSEZSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ assessed as intracellular calcium mobilization measured for 43 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 951.1, ALogP -3.41, HBA 12, HBD 17, PSA 435.06, QED 0.02
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n(Cc5ccc(F)cc5OC)c(=O)c4c3)cc12
InChIKey: BASMYKLUFZUQTO-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase C316Y mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 672.71, ALogP 5.88, HBA 8, HBD 1, PSA 123.74, QED 0.21
Compound (SMILES): CCC[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: CZPFBLHFGKUTTQ-TXVKUACNSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at full-length human RORgammat C285S mutant co-transfected with ROR response element by luciferase based reporter gene assay
Measurement: IC50 = 28.1 nM (pChEMBL 7.550000190734863)
Descriptors: MW 492.6, ALogP 6.49, HBA 5, HBD 0, PSA 79.53, QED 0.41
Compound (SMILES): COc1ccccc1SC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: HLUJXEXDDSDFKA-QATBIIFWSA-N
Target: Sphingosine-1-phosphate lyase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95470
Assay: hS1P1 ERK Phosphorylation (S1P1 pERK): hS1P1/CHO cells were plated into BD Amine 384-well plates the day before the assay. On the day of the assay, growth medium was removed and replaced with serum-free medium (Ham's F-12 Invitrogen) and incubated for 2 hours. Test compounds pre-diluted in HBSS (Gibco)/20 mM HEPES (Gibco) were transferred to the cell plates and incubated for 7 minutes at 37° C. Cells were lysed in lysis buffer (Perkin Elmer) and phospho-ERK was measured using the SureFire pERK kit (Perkin Elmer) as described by the manufacturer. Data was plotted as percentage activation of the test compound relative to the efficacy of 10 μM S1P. The EC50 is defined as the concentration of test compound which produces 50% of the maximal response and was quantified using the 4 parameter logistic equation to fit the data.
Measurement: EC50 < 10 nM (pChEMBL 8)
Descriptors: MW 477.56, ALogP 4.67, HBA 5, HBD 3, PSA 102.01, QED 0.38
Compound (SMILES): COCCOc1ccccc1C1CCN(c2ccn3c(CC4CC4)nnc3c2Cl)CC1
InChIKey: PANKOZQZUGXYCW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A/Metabotropic glutamate receptor 2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q14416
Assay: Agonist activity at human 5HT2A/mGlu2 receptor expressed in HEK293 cells co-expressing Gqo5 assessed as increase in intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 440.98, ALogP 4.74, HBA 6, HBD 0, PSA 51.89, QED 0.47
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: VZRCTKJCGGBKBW-NSHDSACASA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 649.52, ALogP 4.42, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n([C@H](COC)c5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: IWHVQSGPUREPKO-WJOKGBTCSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase C316Y mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 686.74, ALogP 6.05, HBA 8, HBD 1, PSA 123.74, QED 0.2
Compound (SMILES): Cc1c(N2CCNCC2)nc2ccc(Br)cc2c1C(=O)NC[C@H](CCC(=O)O)c1ccccc1Cl
InChIKey: ZZSNHHKTFMLWFY-KRWDZBQOSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: GPCRScan assay: inhibition of Alpha2A
Measurement: Ki = 8511.38 nM (pChEMBL 5.070000171661377)
Descriptors: MW 559.89, ALogP 4.75, HBA 5, HBD 3, PSA 94.56, QED 0.37
Compound (SMILES): Cc1nccc2c1C(C)(C)Nc1cc(Br)ccc1-2
InChIKey: YBGLIPYAJPOYAD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Binding affinity to 5HT6 receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 303.2, ALogP 4.48, HBA 2, HBD 1, PSA 24.92, QED 0.78
Compound (SMILES): Cc1cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc(C)[n+]1CCCCCc1c[nH]cn1.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: APWOSIJGLAZRMM-UHFFFAOYSA-M
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Binding affinity to human recombinant NLuc/GPCR-fused H4R expressed in HEK293T cells measured after 30 mins by furimazine substrate based BRET assay
Measurement: Kd = 77.62 nM (pChEMBL 7.110000133514404)
Descriptors: MW 415.61, ALogP 5.52, HBA 2, HBD 1, PSA 35.8, QED 0.27
Compound (SMILES): CC(C)CCNC1=CC(=O)c2ccccc2C1=O
InChIKey: JLOBMWCZCWALTQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using isoform-specific probe substrates incubated for 15 to 30 mins by by LC-MS/MS analysis
Measurement: IC50 = 54100 nM (pChEMBL 4.269999980926514)
Descriptors: MW 243.31, ALogP 2.59, HBA 3, HBD 1, PSA 46.17, QED 0.88
Compound (SMILES): CC(=O)N1CCC(c2ccc(-c3cc(C(=O)O)cc4cc(-c5ccc(C(F)(F)F)cc5)ccc34)cc2)CC1
InChIKey: AFRXCTUPOJKNDG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1E (SINGLE PROTEIN), Homo sapiens
UniProt: P28566
Assay: Binding affinity to 5HT1E (unknown origin)
Measurement: Ki = 3910 nM (pChEMBL 5.409999847412109)
Descriptors: MW 517.55, ALogP 7.62, HBA 2, HBD 1, PSA 57.61, QED 0.3
Compound (SMILES): COc1c(OCCOCCOCCOc2ccc(C3CCN(c4ccn5c(CC6CC6)nnc5c4Cl)CC3)cc2)cccc1C(=O)C1CCN(CCc2ccc(F)cc2)CC1
InChIKey: SLBQKYUURZKYBP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human HT2A receptor expressed in HEK293 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 363.08 nM (pChEMBL 6.440000057220459)
Descriptors: MW 854.46, ALogP 8.5, HBA 11, HBD 0, PSA 99.89, QED 0.05
Compound (SMILES): CC(C)N(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: JVCQXJCACOCTST-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of C-terminal FLAG-tagged full length human HDAC2 expressed in baculovirus expression system using FAM-TSRHK(Ac)KL-NH2 substrate incubated for 17 hrs by EMSA method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 434.34, ALogP 4.9, HBA 3, HBD 2, PSA 69.64, QED 0.41
Compound (SMILES): CC(C)c1cc(-c2ccc3c(c2)[C@H](N)CO3)cc([C@@H]2CNc3cccc(CC(=O)O)c3O2)c1
InChIKey: HECONMODEBIAKY-RDGATRHJSA-N
Target: Tissue-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00750
Assay: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 444.53, ALogP 5.04, HBA 5, HBD 3, PSA 93.81, QED 0.51
Compound (SMILES): CC1(C)O[C@H]2[C@H](O)CN(CCCCCCn3cc(CNc4ccc(S(N)(=O)=O)cc4)nn3)C[C@H]2O1
InChIKey: PNQLYJMCGFDUPZ-VSKRKVRLSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 2980 nM (pChEMBL 5.53000020980835)
Descriptors: MW 508.65, ALogP 1.29, HBA 10, HBD 3, PSA 144.83, QED 0.38
Compound (SMILES): CCn1nnc2c(C)c([C@@H](CC(=O)O)c3ccc4c(c3)CN(C(=O)c3c(C)c(C)cc(C)c3C)CC4)ccc21
InChIKey: LOIDURPHCVSHLE-MHZLTWQESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.67, ALogP 5.8, HBA 5, HBD 1, PSA 88.32, QED 0.34
Compound (SMILES): CC(C)c1cc(COc2ccccc2CC(=O)O)cc(-c2ccc3c(c2)[C@H](N)CO3)c1
InChIKey: WQVBAYOMZJYFJK-HSZRJFAPSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human F10a using fluorescent peptide as substrate by florescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 417.51, ALogP 5.08, HBA 4, HBD 2, PSA 81.78, QED 0.56
Compound (SMILES): NC1=N[C@](CF)(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)CCC1(F)F
InChIKey: JAHKMCQBZQTJIC-QGZVFWFLSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.35, ALogP 3.12, HBA 6, HBD 2, PSA 102.49, QED 0.69
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: MXRZJMKOFBANST-ZIUUJSQJSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ assessed as intracellular calcium mobilization measured for 43 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 869, ALogP -4.46, HBA 12, HBD 18, PSA 440.77, QED 0.02
Compound (SMILES): CCN(CC)C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: OZWVOBLSVPGTGH-NSHDSACASA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 619.51, ALogP 4.33, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): Cc1c(N2CCCC2)nc2ccc(Br)cc2c1C(=O)NC[C@H](CCC(=O)O)c1ccccc1Cl
InChIKey: YQOLEILXOBUDMU-KRWDZBQOSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Displacement of [3H]prostaglandin E2 from full-length recombinant human EP4 receptor expressed in HEK293 cell membranes measured after 120 mins by scintillation counting method
Measurement: IC50 > 9400 nM (pChEMBL 5.0269999504089355)
Descriptors: MW 544.88, ALogP 5.94, HBA 4, HBD 2, PSA 82.53, QED 0.37
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: GKYDUZGIMDOXEK-CVUOCSEZSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ assessed as intracellular calcium mobilization measured for 43 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 951.1, ALogP -3.41, HBA 12, HBD 17, PSA 435.06, QED 0.02
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n(Cc5ccc(F)cc5OC)c(=O)c4c3)cc12
InChIKey: BASMYKLUFZUQTO-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase S365A mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 177 nM (pChEMBL 6.75)
Descriptors: MW 672.71, ALogP 5.88, HBA 8, HBD 1, PSA 123.74, QED 0.21
Compound (SMILES): CCC[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: CZPFBLHFGKUTTQ-TXVKUACNSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at full-length human RORgammat C345S mutant co-transfected with ROR response element by luciferase based reporter gene assay
Measurement: IC50 = 37.4 nM (pChEMBL 7.429999828338623)
Descriptors: MW 492.6, ALogP 6.49, HBA 5, HBD 0, PSA 79.53, QED 0.41
Compound (SMILES): COCCOc1ccccc1C1CCN(c2ccn3c(CC4CC4)nnc3c2Cl)CC1
InChIKey: PANKOZQZUGXYCW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A/Metabotropic glutamate receptor 2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q14416
Assay: Agonist activity at human 5HT2A/mGlu2 receptor expressed in HEK293 cells co-expressing Gqo5 assessed as increase in intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: EC50 = 120.23 nM (pChEMBL 6.920000076293945)
Descriptors: MW 440.98, ALogP 4.74, HBA 6, HBD 0, PSA 51.89, QED 0.47
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: VZRCTKJCGGBKBW-NSHDSACASA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 649.52, ALogP 4.42, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n([C@H](COC)c5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: IWHVQSGPUREPKO-WJOKGBTCSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase S365A mutant in HCV genotype 1a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 36.6 nM (pChEMBL 7.440000057220459)
Descriptors: MW 686.74, ALogP 6.05, HBA 8, HBD 1, PSA 123.74, QED 0.2
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3C[C@@H](O)C[C@@H]3CO)cc2Cl)cccc1-c1ccccc1
InChIKey: HICWZHAPGJYTOC-IHLOFXLRSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 >= 10 nM (pChEMBL 8)
Descriptors: MW 569.1, ALogP 6.27, HBA 6, HBD 2, PSA 85.95, QED 0.23
Compound (SMILES): Cl.Clc1ccc(OC[C@@H]2C[C@H]3C[C@H]3N2)cn1
InChIKey: VZIQKVIAFWXNFL-ANYFZDTESA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 224.69, ALogP 1.86, HBA 3, HBD 1, PSA 34.15, QED 0.8
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)F)ccc(C(F)(F)F)n3n2)ncn1
InChIKey: SBIKCUDPZRLNAC-IVWMJMPLSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 483.45, ALogP 3.82, HBA 8, HBD 1, PSA 80.47, QED 0.53
Compound (SMILES): C[C@@H]1CN(c2nc(-c3cnn(C)c3)ncc2C#N)CCN1C(=O)C1CC1
InChIKey: RIECHNBHNSMPHW-GFCCVEGCSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged p110delta/untagged full-length p85alpha expressed in baculovirus infected Sf21 cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 351.41, ALogP 1.2, HBA 7, HBD 0, PSA 90.94, QED 0.83
Compound (SMILES): Cl.Clc1ccc(OC[C@@H]2CC[C@H]3C[C@H]3N2)cn1
InChIKey: QMNSKELMXWURIF-WUKJGCQFSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki = 20.5 nM (pChEMBL 7.690000057220459)
Descriptors: MW 238.72, ALogP 2.25, HBA 3, HBD 1, PSA 34.15, QED 0.82
Compound (SMILES): Cl.c1cncc(OC[C@]23C[C@H]2CCN3)c1
InChIKey: XIPZSVRUCKXKTQ-FOKYBFFNSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki = 241.9 nM (pChEMBL 6.619999885559082)
Descriptors: MW 190.25, ALogP 1.21, HBA 3, HBD 1, PSA 34.15, QED 0.78
Compound (SMILES): COc1ccc(-c2cnn3c(N)c(-c4ccccc4)c(OCCCN(C)C)nc23)cc1OC
InChIKey: ATYKMHIJRBRZOA-UHFFFAOYSA-N
Target: Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: P33176
Assay: Inhibition of KIF5B-RET (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 447.54, ALogP 3.99, HBA 8, HBD 1, PSA 87.14, QED 0.39
Compound (SMILES): Cc1nnc(-c2cncc(OC[C@@H]3C[C@H]4C[C@H]4N3)c2)o1.O=C(O)C(=O)O
InChIKey: DIQMNIIVZFCXKQ-ACCMUYOQSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki = 407.3 nM (pChEMBL 6.389999866485596)
Descriptors: MW 272.31, ALogP 1.57, HBA 6, HBD 1, PSA 73.07, QED 0.91
Compound (SMILES): CC(C)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cn2)ncc1Cl
InChIKey: SZRNZUUUCFGQSQ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: Inhibition of recombinant human full-length N-terminal His-tagged CDK6/cyclinD3 expressed in baculovirus infected Sf9 insect cells using histone H1 as substrate measured after 60 mins by ADP-glo assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 437.98, ALogP 4.89, HBA 7, HBD 2, PSA 69.21, QED 0.57
Compound (SMILES): C[C@@]12C[C@@H]1CC(COc1cccnc1Cl)N2.Cl
InChIKey: MPLPEYOALGZCSY-XPVGXOBFSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 238.72, ALogP 2.25, HBA 3, HBD 1, PSA 34.15, QED 0.82
Compound (SMILES): Cn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ncns2)cc1F
InChIKey: NCYAOGNZTIDLCT-ABAIWWIYSA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q07699
Assay: Inhibition of human NaV1.1/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 455.51, ALogP 3.46, HBA 8, HBD 1, PSA 99, QED 0.61
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@H](CSSC[C@H](NC(=O)CNC(=O)[C@@H](N)CC(=O)NCCCC[C@H](C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC3=O)C(=O)N2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC1=O
InChIKey: XRRBKIXHRVPVKY-RVDDLKEKSA-N
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UGM1
Assay: Antagonist activity at human alpha9alpha10 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response measured after 5 mins by two electrode voltage-clamp assay
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 1790.02
Compound (SMILES): COc1cc(C2=CC3=NOC[C@H](c4cc(F)c(F)c(F)c4)N3CCC2)ccc1-n1cnc(C)c1
InChIKey: QMLSYCXFYJARPA-JOCHJYFZSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma secretase in HEK293 cells transfected with human APP with Swedish and London familial AD mutation assessed as reduction in Abeta42 levels incubated for 5 hrs by sandwich immuno-assay
Measurement: IC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 468.48, ALogP 5.17, HBA 6, HBD 0, PSA 51.88, QED 0.5
Compound (SMILES): Cn1nccc1[C@H]1CCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)cc1F
InChIKey: GHOSFOBBUGQTRM-WBMJQRKESA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q07699
Assay: Inhibition of human NaV1.1/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 435.46, ALogP 3, HBA 7, HBD 1, PSA 99, QED 0.64
Compound (SMILES): Cc1cc(C[C@@H](NC(=O)N2CCC(c3cc4ccccc4[nH]c3=O)CC2)C(=O)N[C@@H](CC2CCNCC2)C(=O)N2CCN(c3ccncc3)CC2)cc2cn[nH]c12
InChIKey: WGSUOJIEVHEZAD-AMAPPZPBSA-N
Target: Calcitonin-gene-related peptide receptor, CALCRL/RAMP1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60894
Assay: Radioligand Binding Assay: Human CGRP receptors expressed (consisting of CRLR and RAMP1) in insect Sf21 cell membrane homogenates were re-suspended in the binding buffer (10 mM HEPES, pH 7.4, 5 mM MgCl2, 0.2% BSA) to a final assay concentration of 0.6 μg protein per well. Saturation isotherms were determined by the addition of various concentrations of 3H-telcagepant (Ho et al, The Lancet, 2008, 372, 2115) (in a total reaction volume of 250 μL) for 60 min at rt. At the end of the incubation, membranes were filtered onto a unifilter, a 96-well white microplate with bonded GF/B filter pre-incubated with 0.5% PEI, with a Tomtec cell harvester and washed 5 times with distilled water. Non-specific binding (NSB) was measured in the presence of 10 nM MK-3207 hydrochloride (CAS No. 957116-20-0). Radioactivity on the filter was counted (1 min) on a microbeta counter after addition of 50 μL of scintillation fluid. For inhibition experiments, membranes were incubated with 0.5 nM 3H-telcagepant and 10 concentrations of the inhibitory compound (0.001-10 μM). IC50 values were derived from the inhibition curve and the affinity constant (Ki) values were calculated using the Cheng-Prussoff equation (Cheng et al, Biochem. Pharmacol. 1973, 22, 3099-3108). The pKi values (where pKi=−log10 Ki) of certain compounds of the invention are tabulated below.
Measurement: Ki = 0.079 nM (pChEMBL 10.100000381469727)
Descriptors: MW 772.96, ALogP 3.83, HBA 8, HBD 5, PSA 171.45, QED 0.14