lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1(NCC(=O)NCc2ccc(/C=C/C(=O)NO)cc2)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: DADBALWTMMVAKC-MDZDMXLPSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant his-tagged human HDAC3 using Ac-LeuGlyLys (Ac) AMC substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 381 nM (pChEMBL 6.420000076293945)
Descriptors: MW 584.51, ALogP 3.82, HBA 8, HBD 5, PSA 145.5, QED 0.15
Compound (SMILES): N#Cc1ccc(Oc2ccc3c(ccc(=O)n3CCN3CCCCC3)c2)cc1
InChIKey: KEFLKWVDEZWQCI-UHFFFAOYSA-N
Target: Sodium channel protein type 2 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q99250
Assay: Inhibition of recombinant human Nav1.2 expressed in HEK293 cells incubated for 3 mins by FRET based membrane potential assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 373.46, ALogP 4.15, HBA 5, HBD 0, PSA 58.26, QED 0.67
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)cc(=O)n1-c1cccc(Cl)c1Cl
InChIKey: WYUIJDCKOPRFJO-HXPMCKFVSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Biochemical Assay: The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2, E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 423.34, ALogP 3.18, HBA 6, HBD 1, PSA 73.38, QED 0.8
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](NC(C)=O)CCSCc2cccc(c2)CSCC[C@H](C(N)=O)NC1=O
InChIKey: UKQXFLRWJYDSTM-QVKFSNMJSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: EC50 = 190.55 nM (pChEMBL 6.71999979019165)
Descriptors: MW 1347.68
Compound (SMILES): Cc1nc(N[C@H](C)c2cccc(C(F)F)c2F)c2cc3c(cc2n1)OCC[C@H]1CN(CC(F)(F)F)CCN31
InChIKey: LLWSSGBFYYSLTH-ZBFHGGJFSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes at 10 uM using dextromethorphan as substrate preincubated for 10 mins followed by NADPH addition by LC/MS analysis
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 539.52, ALogP 6.02, HBA 6, HBD 1, PSA 53.52, QED 0.4
Compound (SMILES): C[C@H](CCC(=O)N1CCC(Oc2ccc([B-](F)(F)F)cc2)CC1)[C@H]1CC[C@H]2C3[C@@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C.[K+]
InChIKey: AKFCAUGATVEMIM-XFANABPOSA-N
Target: Autotaxin (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64610
Assay: Inhibition of rat ATX by Michaelis-Menten analysis
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 618.61
Compound (SMILES): Cl.Oc1cc(Cl)ccc1C1NCCc2c1[nH]c1ccc(F)cc21
InChIKey: BWKIWBMSBZTJST-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 316.76, ALogP 3.9, HBA 2, HBD 3, PSA 48.05, QED 0.64
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(-c3ccsc3)cc2OC)[C@H]1NC(C)=O
InChIKey: GIKVGXQUXGICDM-ICDZXHCJSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes incubated for 10 mins in the presence of NADPH by high performance liquid chromatography-tandem mass spectrometry
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 486.63, ALogP 4.38, HBA 6, HBD 3, PSA 96.89, QED 0.44
Compound (SMILES): O=C(O)Cc1ccc(O)cc1Oc1c(Cl)cccc1Cl
InChIKey: MVLANBGUENPEMS-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Ile414Met mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 313.14, ALogP 4.12, HBA 3, HBD 2, PSA 66.76, QED 0.89
Compound (SMILES): NC1CCCCC1NC(=O)P(=O)(O)O
InChIKey: XHCXISPZIHYKQD-UHFFFAOYSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of recombinant human MMP-12 using peptide substrate by ELISA
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 222.18, ALogP 0.14, HBA 3, HBD 4, PSA 112.65, QED 0.5
Compound (SMILES): CN1CC[C@@H](Oc2ccc(Cl)c(-c3nc4c(o3)C(=O)c3ccccc3C4=O)c2)C1
InChIKey: CBCIEAZGJGQSMW-CYBMUJFWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 36 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P275
Assay: Inhibition of USP36 (unknown origin) using Ub-Rho measured after 0.5 to 3 hrs
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.84, ALogP 3.85, HBA 6, HBD 0, PSA 72.64, QED 0.51
Compound (SMILES): Cc1ccc(O)c(C)c1-n1c(N)c(C(N)=O)c2cc(Cl)cnc21
InChIKey: QDLIHXNMTGWVGE-UHFFFAOYSA-N
Target: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99640
Assay: Inhibition of PKMYT1 (unknown origin)
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 330.78, ALogP 2.68, HBA 5, HBD 3, PSA 107.16, QED 0.67
Compound (SMILES): NC(=O)[C@@H](Nc1ccc2c(c1)OCCn1cc(N3C(=O)OC[C@H]3C(F)F)nc1-2)C1CC1
InChIKey: YUSWHXYYRGYCHG-BBRMVZONSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Biochemical Inhibition Assay: The biochemical inhibition of four PI3K isoforms by the Formula I compounds of Table 1. In addition, two clinically tested PI3K compounds, taselisib and pictilisib are included as comparators. The representative compounds of the invention exhibit strong activity against PI3Kα, and exhibit significantly enhanced selectivity relative to the other isoforms PI3Kβ, PI3Kδ, and PI3Kγ when compared to taselisib (GDC-0032) and pictilisib (GDC-0941). In particular, the selectivity ratios in the second from the right column of Table 2A show that each Formula I compounds 101-107 has a PI3K alpha to delta selectivity ratio far higher than taselisib or pictilisib. In fact, both taselisib and pictilisib have stronger activity against PI3K delta than against PI3K alpha, i.e. their selectivity ratios are less than 1. The selectivity ratios of Formula I compound 101-107 range from 301-fold to 634-fold.
Measurement: Ki = 335 nM (pChEMBL 6.46999979019165)
Descriptors: MW 433.42, ALogP 2.21, HBA 7, HBD 2, PSA 111.71, QED 0.72
Compound (SMILES): O=C(N[C@@H]1CCCN(c2ncnc3[nH]ncc23)C1)[C@H](Nc1cc(F)cc(Cl)c1)C1CC1
InChIKey: IVUHUFVVODTZOQ-CRAIPNDOSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Binding affinity to human full length BMX (M1 to H675 residues ) expressed in bacterial expression system assessed dissociation constant by Kinomescan method
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 443.91, ALogP 3.12, HBA 6, HBD 3, PSA 98.83, QED 0.54
Compound (SMILES): COc1cc(Nc2nc(CN)cc3c(-c4ccccc4)n[nH]c23)cc(OC)c1OC
InChIKey: MUOWIESEBCJGBI-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Binding affinity to Nluc-A3R (unknown origin) expressed in HEK293 cells by nanoBRET assay
Measurement: Kd = 257.04 nM (pChEMBL 6.590000152587891)
Descriptors: MW 405.46, ALogP 3.85, HBA 7, HBD 3, PSA 107.31, QED 0.43
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCCN1CCN(c2ccc(Cl)cc2)CC1
InChIKey: YHFOLWJGPOSZDG-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at D4R (unknown origin) expressed in human HEK293T cells assessed as inhibition of dopamine-induced beta arrestin-2 recruitment pretreated for 10 mins followed by dopamine addition and measured after 2.5 mins by BRET assay
Measurement: IC50 = 10471.29 nM (pChEMBL 4.980000019073486)
Descriptors: MW 383.92, ALogP 3.83, HBA 3, HBD 0, PSA 26.79, QED 0.78
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCCN1CCN(c2ccccn2)CC1
InChIKey: XBLQWGDDRIRBTR-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Partial agonist activity at D4R (unknown origin) expressed in human HEK293T cells assessed as Gi protein activation measured after 2.5 mins by BRET assay
Measurement: EC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 350.47, ALogP 2.57, HBA 4, HBD 0, PSA 39.68, QED 0.83
Compound (SMILES): Cl.NC/C(=C\F)[C@H]1Cc2ccccc2O1
InChIKey: LERSIUPHHFRESY-CGQRBHBASA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition of rat SSAO
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 193.22, ALogP 1.8, HBA 2, HBD 1, PSA 35.25, QED 0.78
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NCc4ccc(O)c(OC)c4)nc(C#Cc4ccc(Cl)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: HEQOMIVWTXTFCQ-QSNYBYPBSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I] N6-4-amino-3-iodobenzyl adenosine 5-N-methyluronamide from mouse A3A receptor stably expressed in HEK293 cell membrane by radioligand inhibition assay
Measurement: Ki = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 581.05, ALogP 2.3, HBA 11, HBD 5, PSA 154.65, QED 0.22
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)N[C@H]5CC[C@@](C)(O)CC5)c4n3)cc(OC(F)(F)F)c2C1=O
InChIKey: SULSIRXENHFWFG-BMEKPBSDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 29300 nM (pChEMBL 4.53000020980835)
Descriptors: MW 572.59, ALogP 4.05, HBA 8, HBD 3, PSA 135.08, QED 0.41
Compound (SMILES): Fc1ccc2c(Cc3nnc(Cc4ccccc4)n3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: GYNFPVIKWHESNR-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST5 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 414.49, ALogP 4.44, HBA 4, HBD 2, PSA 75.18, QED 0.39
Compound (SMILES): CC(O)[C@H](NC(=O)N[C@@H](CC(N)=O)c1nnc([C@@H](N)CO)s1)C(=O)O
InChIKey: ZHZFEBZMBHOQIK-WHFCDURNSA-N
Target: V-type immunoglobulin domain-containing suppressor of T-cell activation (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H7M9
Assay: Inhibition of VISTA (unknown origin)
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 376.4, ALogP -2.42, HBA 9, HBD 7, PSA 213.78, QED 0.24
Compound (SMILES): Cc1nc(NC(=O)NC(=O)C2(C)CCOCC2)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: CIQLUWGXRPQJFF-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of N-terminal His-Glu-TEV-tagged MET (unknown origin) (1050 to 1360 residues) measured by spectrophotometric analysis
Measurement: IC50 > 3300 nM (pChEMBL 5.480999946594238)
Descriptors: MW 450.5, ALogP 3.44, HBA 8, HBD 2, PSA 120.26, QED 0.61
Compound (SMILES): CC(C)n1cc(-c2ccnc3[nH]c(C4CCN(CC(=O)N5CCCCC5)CC4)cc23)ccc1=O
InChIKey: GLYHKPNATCXTDU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using 5FAM-YSPTSPSYSPTSPSYSPTSPSKKKK-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 90 mins in the presence of ATP at Km concentration by plate reader analysis
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 461.61, ALogP 4.16, HBA 5, HBD 1, PSA 74.23, QED 0.62
Compound (SMILES): C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CCN1CCC(Oc2ccccc2Cc2ccccc2)CC1)C(=O)NCCC(=O)N[C@@H](CCCCNC(=O)COc1ccc(/C=C/C2=[N+]3C(=Cc4ccc(-c5cccs5)n4[B-]3(F)F)C=C2)cc1)C(N)=O
InChIKey: QUFCRYDWDBOHAG-WTRYCTIGSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Binding affinity to NLuc-tagged human H4R expressed in HEK293T cell homogenates using NanoGlo as substrate preincubated for 2 hrs followed by substrate addition measured after 5 min by NanoBRET saturation binding assay
Measurement: Kd < 1000 nM (pChEMBL 6)
Descriptors: MW 1259.3
Compound (SMILES): Clc1cccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: VKOTYLIRWRFADJ-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST5 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 430.94, ALogP 4.95, HBA 4, HBD 2, PSA 75.18, QED 0.37
Compound (SMILES): Nc1nc2c(ncn2[C@H]2O[C@H]3COP(=O)(O)O[C@H]4[C@@H](O)[C@@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: XRILCFTWUCUKJR-FLQQXUEZSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at STING in human 293T hSTING-R232 Cells incubated for 48 hrs by QUANTI-blue assay
Measurement: EC50 = 7230 nM (pChEMBL 5.139999866485596)
Descriptors: MW 674.42, ALogP -2.34, HBA 20, HBD 7, PSA 329.65, QED 0.11
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(-c3ccsc3)cc2Cl)[C@H]1NC(C)=O
InChIKey: ZBODECNZYYNPIT-RBZQAINGSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes incubated for 10 mins in the presence of NADPH by high performance liquid chromatography-tandem mass spectrometry
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 491.05, ALogP 5.02, HBA 5, HBD 3, PSA 87.66, QED 0.43
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4ccccc4Cl)ncnc32)[C@H](O)[C@@H]1O
InChIKey: TXRYRWFBJHQBFA-WHRBDNGYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 52.48 nM (pChEMBL 7.28000020980835)
Descriptors: MW 461.91, ALogP 1.5, HBA 10, HBD 4, PSA 134.78, QED 0.43
Compound (SMILES): COc1ccc(C(=O)O[C@@H]2[C@H](OC(=O)c3ccc(OC)cc3)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O[C@H]2n2cnc3c(N)ncnc32)cc1
InChIKey: RKFOOQRRMNOARS-UMCMBGNQSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Agonist activity at human P2X7R expressing HEK293 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 > 100000 nM (pChEMBL 4)
Descriptors: MW 775.45, ALogP 2.12, HBA 18, HBD 5, PSA 309.73, QED 0.09
Compound (SMILES): Cc1nc(NC(=O)NC(=O)Cc2ccc(F)cc2)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: HYTINAIANCXBTN-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of N-terminal His-Glu-TEV-tagged MET (unknown origin) (1050 to 1360 residues) measured by spectrophotometric analysis
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 460.47, ALogP 4.01, HBA 7, HBD 2, PSA 111.03, QED 0.45
Compound (SMILES): Cc1nc(N)oc1CCCN/C(N)=N/C(=O)NCc1ccccc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: CHVSQMVJWYLHBP-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 330.39, ALogP 1.31, HBA 4, HBD 4, PSA 131.56, QED 0.36
Compound (SMILES): Cn1c(=O)c(/C=C/c2ccccn2)nc2ccccc21
InChIKey: QRDWMCYHLUVDDX-MDZDMXLPSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 263.3, ALogP 2.5, HBA 4, HBD 0, PSA 47.78, QED 0.71
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CC[C@@H](NC(=O)[C@@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: JQKDWSJGLLIFBM-YUTCNCBUSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes incubated in presence NADPH by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 403.43, ALogP 2.88, HBA 5, HBD 2, PSA 88.39, QED 0.8
Compound (SMILES): O=C(NC1CN(Cc2cnn(Cc3ccccc3)c2)C1)c1cn(C2CC2)nn1
InChIKey: SGVKMHGESLELKH-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-36 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q96L73
Assay: Inhibition of NSD1 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 377.45, ALogP 1.47, HBA 7, HBD 1, PSA 80.87, QED 0.67
Compound (SMILES): COc1cc2c(Oc3ccc(Nc4nn(C)cc4C(=O)NC4CCCCC4)cc3F)ccnc2cc1OCCCN1CCOCC1
InChIKey: QBRQTJMZEYORSP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Binding affinity to FLT1 (unknown origin) assessed as dissociation constant by competition binding assay
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 632.74, ALogP 5.82, HBA 10, HBD 2, PSA 112, QED 0.19
Compound (SMILES): CC(C)n1cc(-c2ccnc3[nH]c(C4CCN(CC(=O)N(C)C)CC4)cc23)ccc1=O
InChIKey: HUUCUGRZFSMNOH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using 5FAM-YSPTSPSYSPTSPSYSPTSPSKKKK-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 90 mins in the presence of ATP at Km concentration by plate reader analysis
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 421.55, ALogP 3.24, HBA 5, HBD 1, PSA 74.23, QED 0.69
Compound (SMILES): COc1ccc(Cc2nnc(Cc3c[nH]c4ccc(OC)cc34)n2CCCc2c[nH]cn2)cc1
InChIKey: HYZDNKBSAADONB-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST5 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 456.55, ALogP 4.31, HBA 6, HBD 2, PSA 93.64, QED 0.33
Compound (SMILES): Oc1ccc(Oc2ccccc2Cl)c(Cc2nnn[nH]2)c1
InChIKey: DYKHACGUKFLZOC-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Glu355Gln mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 302.72, ALogP 2.94, HBA 5, HBD 2, PSA 83.92, QED 0.77
Compound (SMILES): CCNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)C/C=C(\F)[C@@H](N)Cc1ccc(O)cc1
InChIKey: FWDJGOHQYSBTRO-GUOSAUPISA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P32300
Assay: Agonist activity at FLAG-tagged mouse delta opioid receptor expressed in human HEK293 cells assessed as inhibition of forskolin stimulated cAMP production preincubated for 20 mins followed by forskolin stimulation and measured after 15 mins by GloSensor assay
Measurement: IC50 = 66.2 nM (pChEMBL 7.179999828338623)
Descriptors: MW 583.71, ALogP 2.02, HBA 6, HBD 6, PSA 162.65, QED 0.18
Compound (SMILES): CC1(NCC(=O)NCc2ccc(/C=C/C(=O)NO)cc2)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: DADBALWTMMVAKC-MDZDMXLPSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant his-tagged human HDAC8 using Boc-Lys (TFA)-AMC substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 584.51, ALogP 3.82, HBA 8, HBD 5, PSA 145.5, QED 0.15
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)cc(=O)n1-c1cccc(Cl)c1Cl
InChIKey: WYUIJDCKOPRFJO-HXPMCKFVSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Biochemical Assay: The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2, E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.34, ALogP 3.18, HBA 6, HBD 1, PSA 73.38, QED 0.8
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](NC(C)=O)CCSCc2cccc(c2)CSCC[C@H](C(N)=O)NC1=O
InChIKey: UKQXFLRWJYDSTM-QVKFSNMJSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Agonist activity at human MC5R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: IC50 = 16595.87 nM (pChEMBL 4.78000020980835)
Descriptors: MW 1347.68
Compound (SMILES): Cc1nc(N[C@H](C)c2cccc(C(F)F)c2F)c2cc3c(cc2n1)OCC[C@H]1CN(CC(F)(F)F)CCN31
InChIKey: LLWSSGBFYYSLTH-ZBFHGGJFSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Time-dependent inhibition of CYP2C9 (unknown origin) at 2 ul pre-incubated for 30 mins in presence or absence of NADPH incubated for 10 mins by LC/MS analysis
Measurement: IC50 = 14600 nM (pChEMBL 4.840000152587891)
Descriptors: MW 539.52, ALogP 6.02, HBA 6, HBD 1, PSA 53.52, QED 0.4
Compound (SMILES): C[C@H](CCC(=O)N1CCC(Oc2ccc([B-](F)(F)F)cc2)CC1)[C@H]1CC[C@H]2C3[C@@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C.[K+]
InChIKey: AKFCAUGATVEMIM-XFANABPOSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of LPA-mediated ATX activation in human BJeH cells assessed as AKT phosphorylation level incubated for 30 mins by Western blot analysis
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 618.61
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(-c3ccsc3)cc2OC)[C@H]1NC(C)=O
InChIKey: GIKVGXQUXGICDM-ICDZXHCJSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes incubated for 10 mins in the presence of NADPH by high performance liquid chromatography-tandem mass spectrometry
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 486.63, ALogP 4.38, HBA 6, HBD 3, PSA 96.89, QED 0.44
Compound (SMILES): O=C(O)Cc1ccc(O)cc1Oc1c(Cl)cccc1Cl
InChIKey: MVLANBGUENPEMS-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Ile464His mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 313.14, ALogP 4.12, HBA 3, HBD 2, PSA 66.76, QED 0.89
Compound (SMILES): NC1CCCCC1NC(=O)P(=O)(O)O
InChIKey: XHCXISPZIHYKQD-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP-13 using peptide substrate by ELISA
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 222.18, ALogP 0.14, HBA 3, HBD 4, PSA 112.65, QED 0.5
Compound (SMILES): CN1CC[C@@H](Oc2ccc(Cl)c(-c3nc4c(o3)C(=O)c3ccccc3C4=O)c2)C1
InChIKey: CBCIEAZGJGQSMW-CYBMUJFWSA-N
Target: Ataxin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P54252
Assay: Inhibition of Ataxin-3 (unknown origin) using Ub-Rho measured after 0.5 to 3 hrs
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.84, ALogP 3.85, HBA 6, HBD 0, PSA 72.64, QED 0.51
Compound (SMILES): NC(=O)[C@@H](Nc1ccc2c(c1)OCCn1cc(N3C(=O)OC[C@H]3C(F)F)nc1-2)C1CC1
InChIKey: YUSWHXYYRGYCHG-BBRMVZONSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Biochemical Inhibition Assay: The biochemical inhibition of four PI3K isoforms by the Formula I compounds of Table 1. In addition, two clinically tested PI3K compounds, taselisib and pictilisib are included as comparators. The representative compounds of the invention exhibit strong activity against PI3Kα, and exhibit significantly enhanced selectivity relative to the other isoforms PI3Kβ, PI3Kδ, and PI3Kγ when compared to taselisib (GDC-0032) and pictilisib (GDC-0941). In particular, the selectivity ratios in the second from the right column of Table 2A show that each Formula I compounds 101-107 has a PI3K alpha to delta selectivity ratio far higher than taselisib or pictilisib. In fact, both taselisib and pictilisib have stronger activity against PI3K delta than against PI3K alpha, i.e. their selectivity ratios are less than 1. The selectivity ratios of Formula I compound 101-107 range from 301-fold to 634-fold.
Measurement: Ki = 37.7 nM (pChEMBL 7.420000076293945)
Descriptors: MW 433.42, ALogP 2.21, HBA 7, HBD 2, PSA 111.71, QED 0.72
Compound (SMILES): COc1cc(Nc2nc(CN)cc3c(-c4ccccc4)n[nH]c23)cc(OC)c1OC
InChIKey: MUOWIESEBCJGBI-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Binding affinity to Nluc-A1R (unknown origin) expressed in HEK293 cells by nanoBRET assay
Measurement: Kd = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 405.46, ALogP 3.85, HBA 7, HBD 3, PSA 107.31, QED 0.43
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCCN1CCN(c2ccc(Cl)cc2)CC1
InChIKey: YHFOLWJGPOSZDG-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]7-OH-DPAT from human D4.4 receptor expressed in HEK293T cell membrane incubated for 1.5 hrs by MicroBeta scintillation counting method
Measurement: Ki = 1.479 nM (pChEMBL 8.829999923706055)
Descriptors: MW 383.92, ALogP 3.83, HBA 3, HBD 0, PSA 26.79, QED 0.78
Compound (SMILES): Cl.NC/C(=C\F)[C@H]1Cc2ccccc2O1
InChIKey: LERSIUPHHFRESY-CGQRBHBASA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Mus musculus
UniProt: Q8BW75
Assay: Inhibition of mouse muscle MAO-B
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 193.22, ALogP 1.8, HBA 2, HBD 1, PSA 35.25, QED 0.78
Compound (SMILES): Fc1ccc2c(Cc3nnc(Cc4ccccc4)n3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: GYNFPVIKWHESNR-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Activity Assays: Measurement of forskolin stimulated inhibition of cAMP was performed via time-resolved fluorescence resonance energy transfer (TR-FRET) LANCE assay (AD0262, PerkinElmer Life Science, Inc., Boston Mass.). Recombinant Chinese hamster ovary (CHO-K1) cells expressing human somatostatin SSTR4 cells (ES-524-CF, PerkinElmer Life Science, Inc., Boston Mass.) were thawed (37° C.), resuspended in 10 mL Hanks' balanced salt solution no phenol red (HBSS, Invitrogen, Carlsbad Calif.), and then centrifuged (150×g, 5 minutes). Cellular pellet resuspended in stimulation buffer containing HBSS 1×, HEPES 5 mM, Protease free BSA 0.1% (PerkinElmer), and 3-Isobutyl-1-methylxanthine 0.5 mM (pH 7.4) and seeded in 96-well plates at 4000 cells/well. LANCE cAMP assay was performed per manufacture instruction with assessment of respective compound, somatostatin-28 (Sigma-Aldrich Co., St. Louis, Mo.) as control agonist, against 5 μM forskolin, performed in triplicate across concentration curve. Fluorescence signal was measured at 20 hours (excitation 340 nm and emission 665 nm, 400-μs delay) via TR-FRET (FLUOSTAR Omega-F, BMG Labtech, Inc., Cary, N.C.). Data was calculated via GraphPad PRISM-5 software.
Measurement: EC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 414.49, ALogP 4.44, HBA 4, HBD 2, PSA 75.18, QED 0.39
Compound (SMILES): CC(C)n1cc(-c2ccnc3[nH]c(C4CCN(CC(=O)N5CCCCC5)CC4)cc23)ccc1=O
InChIKey: GLYHKPNATCXTDU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 90 mins in the presence of ATP at Km concentration by plate reader analysis
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 461.61, ALogP 4.16, HBA 5, HBD 1, PSA 74.23, QED 0.62
Compound (SMILES): Nc1nc2c(ncn2[C@H]2O[C@H]3COP(=O)(O)O[C@H]4[C@@H](O)[C@@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: XRILCFTWUCUKJR-FLQQXUEZSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Mus musculus
UniProt: Q3TBT3
Assay: Agonist activity at STING in mouse 293T Cells incubated for 48 hrs by QUANTI-blue assay
Measurement: EC50 = 7010 nM (pChEMBL 5.150000095367432)
Descriptors: MW 674.42, ALogP -2.34, HBA 20, HBD 7, PSA 329.65, QED 0.11
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(-c3ccsc3)cc2Cl)[C@H]1NC(C)=O
InChIKey: ZBODECNZYYNPIT-RBZQAINGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes incubated for 10 mins in the presence of NADPH by high performance liquid chromatography-tandem mass spectrometry
Measurement: IC50 = 72500 nM (pChEMBL 4.139999866485596)
Descriptors: MW 491.05, ALogP 5.02, HBA 5, HBD 3, PSA 87.66, QED 0.43
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4ccccc4Cl)ncnc32)[C@H](O)[C@@H]1O
InChIKey: TXRYRWFBJHQBFA-WHRBDNGYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Inhibition of CA200645 binding to NanoLuc-fused human adenosine A1 receptor expressed in HEK293 cells assessed as kinetic dissociation constant by NanoBRET competition binding assay
Measurement: Kd = 45.71 nM (pChEMBL 7.340000152587891)
Descriptors: MW 461.91, ALogP 1.5, HBA 10, HBD 4, PSA 134.78, QED 0.43
Compound (SMILES): COc1ccc(C(=O)O[C@@H]2[C@H](OC(=O)c3ccc(OC)cc3)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O[C@H]2n2cnc3c(N)ncnc32)cc1
InChIKey: RKFOOQRRMNOARS-UMCMBGNQSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Agonist activity at human P2X7R expressed in HEK293 cells assessed as reduction in YO-PRO-1 iodide dye uptake preincubated for 30 mins followed by YO-PRO-1 iodide addition and measured after 2 hrs by fluorescence based multimode plate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 775.45, ALogP 2.12, HBA 18, HBD 5, PSA 309.73, QED 0.09
Compound (SMILES): Cc1nc(N)oc1CCCN/C(N)=N/C(=O)NCc1ccccc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: CHVSQMVJWYLHBP-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]-histamine from human histamine H4 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 330.39, ALogP 1.31, HBA 4, HBD 4, PSA 131.56, QED 0.36
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CC[C@@H](NC(=O)[C@@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: JQKDWSJGLLIFBM-YUTCNCBUSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes incubated in presence NADPH by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 403.43, ALogP 2.88, HBA 5, HBD 2, PSA 88.39, QED 0.8
Compound (SMILES): O=C(NC1CN(Cc2cnn(Cc3ccccc3)c2)C1)c1cn(C2CC2)nn1
InChIKey: SGVKMHGESLELKH-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase PRDM9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQV7
Assay: Inhibition of PRDM9 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 377.45, ALogP 1.47, HBA 7, HBD 1, PSA 80.87, QED 0.67
Compound (SMILES): COc1cc2c(Oc3ccc(Nc4nn(C)cc4C(=O)NC4CCCCC4)cc3F)ccnc2cc1OCCCN1CCOCC1
InChIKey: QBRQTJMZEYORSP-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Binding affinity to FLT3 (unknown origin) assessed as dissociation constant by competition binding assay
Measurement: Kd = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 632.74, ALogP 5.82, HBA 10, HBD 2, PSA 112, QED 0.19
Compound (SMILES): CC(C)n1cc(-c2ccnc3[nH]c(C4CCN(CC(=O)N(C)C)CC4)cc23)ccc1=O
InChIKey: HUUCUGRZFSMNOH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 90 mins in the presence of ATP at Km concentration by plate reader analysis
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 421.55, ALogP 3.24, HBA 5, HBD 1, PSA 74.23, QED 0.69
Compound (SMILES): COc1ccc(Cc2nnc(Cc3c[nH]c4ccc(OC)cc34)n2CCCc2c[nH]cn2)cc1
InChIKey: HYZDNKBSAADONB-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Activity Assays: Measurement of forskolin stimulated inhibition of cAMP was performed via time-resolved fluorescence resonance energy transfer (TR-FRET) LANCE assay (AD0262, PerkinElmer Life Science, Inc., Boston Mass.). Recombinant Chinese hamster ovary (CHO-K1) cells expressing human somatostatin SSTR4 cells (ES-524-CF, PerkinElmer Life Science, Inc., Boston Mass.) were thawed (37° C.), resuspended in 10 mL Hanks' balanced salt solution no phenol red (HBSS, Invitrogen, Carlsbad Calif.), and then centrifuged (150×g, 5 minutes). Cellular pellet resuspended in stimulation buffer containing HBSS 1×, HEPES 5 mM, Protease free BSA 0.1% (PerkinElmer), and 3-Isobutyl-1-methylxanthine 0.5 mM (pH 7.4) and seeded in 96-well plates at 4000 cells/well. LANCE cAMP assay was performed per manufacture instruction with assessment of respective compound, somatostatin-28 (Sigma-Aldrich Co., St. Louis, Mo.) as control agonist, against 5 μM forskolin, performed in triplicate across concentration curve. Fluorescence signal was measured at 20 hours (excitation 340 nm and emission 665 nm, 400-μs delay) via TR-FRET (FLUOSTAR Omega-F, BMG Labtech, Inc., Cary, N.C.). Data was calculated via GraphPad PRISM-5 software.
Measurement: EC50 = 5.63 nM (pChEMBL 8.25)
Descriptors: MW 456.55, ALogP 4.31, HBA 6, HBD 2, PSA 93.64, QED 0.33
Compound (SMILES): Oc1ccc(Oc2ccccc2Cl)c(Cc2nnn[nH]2)c1
InChIKey: DYKHACGUKFLZOC-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Thr412Asn mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 302.72, ALogP 2.94, HBA 5, HBD 2, PSA 83.92, QED 0.77
Compound (SMILES): CCNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)C/C=C(\F)[C@@H](N)Cc1ccc(O)cc1
InChIKey: FWDJGOHQYSBTRO-GUOSAUPISA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human delta opioid receptor expressed in CHO cells co-expressing beta-arrestin2 assessed as beta-arrestin2 recruitment measured after 90 mins by PathHunter assay
Measurement: EC50 = 691.83 nM (pChEMBL 6.159999847412109)
Descriptors: MW 583.71, ALogP 2.02, HBA 6, HBD 6, PSA 162.65, QED 0.18
Compound (SMILES): CC1(NCC(=O)NCc2ccc(/C=C/C(=O)NO)cc2)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: DADBALWTMMVAKC-MDZDMXLPSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant N-terminal GST-tagged human HDAC5 expressed in HEK293 cells using Ac-LeuGlyLys (TFA)-AMC substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 3825 nM (pChEMBL 5.420000076293945)
Descriptors: MW 584.51, ALogP 3.82, HBA 8, HBD 5, PSA 145.5, QED 0.15
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)cc(=O)n1-c1cccc(Cl)c1Cl
InChIKey: WYUIJDCKOPRFJO-HXPMCKFVSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Biochemical Assay: The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2,E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 423.34, ALogP 3.18, HBA 6, HBD 1, PSA 73.38, QED 0.8
Compound (SMILES): Cc1nc(N[C@H](C)c2cccc(C(F)F)c2F)c2cc3c(cc2n1)OCC[C@H]1CN(CC(F)(F)F)CCN31
InChIKey: LLWSSGBFYYSLTH-ZBFHGGJFSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Time-dependent inhibition of CYP2C8 (unknown origin) at 2 ul pre-incubated for 30 mins in presence or absence of NADPH incubated for 10 mins by LC/MS analysis
Measurement: IC50 = 39100 nM (pChEMBL 4.409999847412109)
Descriptors: MW 539.52, ALogP 6.02, HBA 6, HBD 1, PSA 53.52, QED 0.4
Compound (SMILES): C[C@H](CCC(=O)N1CCC(Oc2ccc([B-](F)(F)F)cc2)CC1)[C@H]1CC[C@H]2C3[C@@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C.[K+]
InChIKey: AKFCAUGATVEMIM-XFANABPOSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of LPA-mediated ATX activation in human BJeH cells assessed as ERK phosphorylation level incubated for 30 mins by Western blot analysis
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 618.61
Compound (SMILES): O=C(O)Cc1ccc(O)cc1Oc1c(Cl)cccc1Cl
InChIKey: MVLANBGUENPEMS-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Phe467Met mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 313.14, ALogP 4.12, HBA 3, HBD 2, PSA 66.76, QED 0.89
Compound (SMILES): NC(=O)[C@@H](Nc1ccc2c(c1)OCCn1cc(N3C(=O)OC[C@H]3C(F)F)nc1-2)C1CC1
InChIKey: YUSWHXYYRGYCHG-BBRMVZONSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Inhibition Assay: The biochemical inhibition of four PI3K isoforms by the Formula I compounds of Table 1. In addition, two clinically tested PI3K compounds, taselisib and pictilisib are included as comparators. The representative compounds of the invention exhibit strong activity against PI3Kα, and exhibit significantly enhanced selectivity relative to the other isoforms PI3Kβ, PI3Kδ, and PI3Kγ when compared to taselisib (GDC-0032) and pictilisib (GDC-0941). In particular, the selectivity ratios in the second from the right column of Table 2A show that each Formula I compounds 101-107 has a PI3K alpha to delta selectivity ratio far higher than taselisib or pictilisib. In fact, both taselisib and pictilisib have stronger activity against PI3K delta than against PI3K alpha, i.e. their selectivity ratios are less than 1. The selectivity ratios of Formula I compound 101-107 range from 301-fold to 634-fold.
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 433.42, ALogP 2.21, HBA 7, HBD 2, PSA 111.71, QED 0.72
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCCN1CCN(c2ccc(Cl)cc2)CC1
InChIKey: YHFOLWJGPOSZDG-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at D4R (unknown origin) expressed in human HEK293T cells assessed as beta arrestin-2 recruitment measured after 2.5 mins by BRET assay
Measurement: EC50 = 51.29 nM (pChEMBL 7.289999961853027)
Descriptors: MW 383.92, ALogP 3.83, HBA 3, HBD 0, PSA 26.79, QED 0.78
Compound (SMILES): Cl.NC/C(=C\F)[C@H]1Cc2ccccc2O1
InChIKey: LERSIUPHHFRESY-CGQRBHBASA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of recombinant human LOXL-2
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 193.22, ALogP 1.8, HBA 2, HBD 1, PSA 35.25, QED 0.78
Compound (SMILES): CC(C)n1cc(-c2ccnc3[nH]c(C4CCN(CC(=O)N5CCCCC5)CC4)cc23)ccc1=O
InChIKey: GLYHKPNATCXTDU-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of full length human GSK3beta in the presence of ATP at Km concentration
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 461.61, ALogP 4.16, HBA 5, HBD 1, PSA 74.23, QED 0.62
Compound (SMILES): Nc1nc2c(ncn2[C@H]2O[C@H]3COP(=O)(O)O[C@H]4[C@@H](O)[C@@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: XRILCFTWUCUKJR-FLQQXUEZSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Antagonist activity at STING (unknown origin) in L929 cells assessed as IFN-beta RNA level q-RTPCR analysis
Measurement: EC50 = 42.1 nM (pChEMBL 7.380000114440918)
Descriptors: MW 674.42, ALogP -2.34, HBA 20, HBD 7, PSA 329.65, QED 0.11
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4ccccc4Cl)ncnc32)[C@H](O)[C@@H]1O
InChIKey: TXRYRWFBJHQBFA-WHRBDNGYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells assessed as kinetic dissociation constant by NanoBRET competition binding assay
Measurement: Kd = 26.3 nM (pChEMBL 7.579999923706055)
Descriptors: MW 461.91, ALogP 1.5, HBA 10, HBD 4, PSA 134.78, QED 0.43
Compound (SMILES): COc1ccc(C(=O)O[C@@H]2[C@H](OC(=O)c3ccc(OC)cc3)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O[C@H]2n2cnc3c(N)ncnc32)cc1
InChIKey: RKFOOQRRMNOARS-UMCMBGNQSA-N
Target: P2X purinoceptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51575
Assay: Antagonist activity at human P2X1R 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 > 100000 nM (pChEMBL 4)
Descriptors: MW 775.45, ALogP 2.12, HBA 18, HBD 5, PSA 309.73, QED 0.09
Compound (SMILES): Cc1nc(N)oc1CCCN/C(N)=N/C(=O)NCc1ccccc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: CHVSQMVJWYLHBP-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]-histamine from human histamine H4 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 330.39, ALogP 1.31, HBA 4, HBD 4, PSA 131.56, QED 0.36
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CC[C@@H](NC(=O)[C@@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: JQKDWSJGLLIFBM-YUTCNCBUSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes incubated in presence NADPH by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 403.43, ALogP 2.88, HBA 5, HBD 2, PSA 88.39, QED 0.8
Compound (SMILES): O=C(NC1CN(Cc2cnn(Cc3ccccc3)c2)C1)c1cn(C2CC2)nn1
InChIKey: SGVKMHGESLELKH-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O60678
Assay: Inhibition of PRMT3 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 377.45, ALogP 1.47, HBA 7, HBD 1, PSA 80.87, QED 0.67
Compound (SMILES): COc1cc2c(Oc3ccc(Nc4nn(C)cc4C(=O)NC4CCCCC4)cc3F)ccnc2cc1OCCCN1CCOCC1
InChIKey: QBRQTJMZEYORSP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Binding affinity to FLT4 (unknown origin) assessed as dissociation constant by competition binding assay
Measurement: Kd = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 632.74, ALogP 5.82, HBA 10, HBD 2, PSA 112, QED 0.19
Compound (SMILES): CC(C)n1cc(-c2ccnc3[nH]c(C4CCN(CC(=O)N(C)C)CC4)cc23)ccc1=O
InChIKey: HUUCUGRZFSMNOH-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of full length human GSK3beta in the presence of ATP at Km concentration
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 421.55, ALogP 3.24, HBA 5, HBD 1, PSA 74.23, QED 0.69
Compound (SMILES): Oc1ccc(Oc2ccccc2Cl)c(Cc2nnn[nH]2)c1
InChIKey: DYKHACGUKFLZOC-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Ile414Met mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 302.72, ALogP 2.94, HBA 5, HBD 2, PSA 83.92, QED 0.77
Compound (SMILES): CCNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)C/C=C(\F)[C@@H](N)Cc1ccc(O)cc1
InChIKey: FWDJGOHQYSBTRO-GUOSAUPISA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human delta opioid receptor expressed in CHO cells co-expressing beta-arrestin2 assessed as beta-arrestin2 recruitment measured after 90 mins by PathHunter assay
Measurement: EC50 = 695 nM (pChEMBL 6.159999847412109)
Descriptors: MW 583.71, ALogP 2.02, HBA 6, HBD 6, PSA 162.65, QED 0.18
Compound (SMILES): CC1(NCC(=O)NCc2ccc(/C=C/C(=O)NO)cc2)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: DADBALWTMMVAKC-MDZDMXLPSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human HDAC7 using Ac-LeuGlyLys (TFA)-AMC substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 2680 nM (pChEMBL 5.570000171661377)
Descriptors: MW 584.51, ALogP 3.82, HBA 8, HBD 5, PSA 145.5, QED 0.15