lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cccc2[nH]c(C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]3CCCNC3=O)C(=O)COC(=O)c3c(C(F)(F)F)cccc3C(F)(F)F)cc12
InChIKey: PKJWLVLOGHATRZ-NWVWQQAFSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CL protease incubated for 30 mins by FRET assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 726.67, ALogP 5.19, HBA 7, HBD 4, PSA 155.69, QED 0.14
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](CCC(=O)NC(C)(C)C)NC(=O)CCNC(=O)CCl)C(=O)NCc2ccc(C)cc2)cc1
InChIKey: LZTBDEHSOCWSHD-UIOOFZCWSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome subunit beta-5c (unknown origin) using Ac-WLA-AMC as substrate and measured after 30 mins
Measurement: IC50 = 347 nM (pChEMBL 6.460000038146973)
Descriptors: MW 630.19, ALogP 2.27, HBA 6, HBD 5, PSA 154.73, QED 0.18
Compound (SMILES): COC1=C(Br)[C@H](O)[C@@]2(C=C1Br)CC(C(=O)NCCc1cc(Br)c(OCCC(C(=O)[O-])[N+](C)(C)C)c(Br)c1)=NO2
InChIKey: ZKNRYKRVFBEUOU-CHATWSTOSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse BuChE using butyrylthiocholine as substrate preincubated with enzyme for 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 803.14, ALogP 2.89, HBA 8, HBD 2, PSA 129.51, QED 0.33
Compound (SMILES): COc1cc2c(cc1OC1CCCC1)C(=O)/C(=C/c1ccncc1)C2
InChIKey: XZBWXPSEZIYZDG-MHWRWJLKSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of PDE4D7 (unknown origin)
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 335.4, ALogP 4.23, HBA 4, HBD 0, PSA 48.42, QED 0.78
Compound (SMILES): CCCN1CCN(c2cccc(C3CCCCN3S(=O)(=O)c3cc(Cl)cc(Cl)c3)c2)CC1
InChIKey: AKFQMBJQZZAKNP-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H](+)-pentazocine from human sigma 1 receptor transfected in human HEK293T cells assessed as inhibition constant by radioligand competition binding assay
Measurement: Ki = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 496.5, ALogP 5.44, HBA 4, HBD 0, PSA 43.86, QED 0.53
Compound (SMILES): COc1cc2nc(NCCCN(C)C)nc(NCCCNc3ccccc3)c2cc1OC
InChIKey: PIBPGIZBVJIBSO-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a (unknown origin) assessed as reduction in substrate methylation using histone H3 and SAM as substrate measured after 15 to 60 mins by microfluidic capillary electrophoresis analysis
Measurement: Ki = 48300 nM (pChEMBL 4.320000171661377)
Descriptors: MW 438.58, ALogP 3.92, HBA 8, HBD 3, PSA 83.57, QED 0.35
Compound (SMILES): COc1cc2c(NCC(=O)O)ccnc2cc1OCCCN1CCCC1
InChIKey: ILYMMKKJPARSNU-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of GLP (unknown origin)
Measurement: IC50 = 15643 nM (pChEMBL 4.809999942779541)
Descriptors: MW 359.43, ALogP 2.6, HBA 6, HBD 2, PSA 83.92, QED 0.67
Compound (SMILES): CC(O)CSc1nc(NCc2ccc(-n3cccn3)cc2)c2n[nH]c(C(C)C)c2n1
InChIKey: WXFNPYZGKHGERJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/G1/S-specific cyclin-D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of GST-tagged CDK2/cyclin D1 (unknown origin) expressed in Sf9 cells using RPPTLSPIPHIPR peptide as substrate in presence of ATP and [gamma33-P] ATP by radioisotope filter binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 423.55, ALogP 3.75, HBA 8, HBD 3, PSA 104.54, QED 0.29
Compound (SMILES): Nc1nc(Nc2ccc(S(N)(=O)=O)cc2)nn1C(=O)Nc1ccc(-c2ccc(OCc3ccccc3)c(C(=O)O)c2)cc1
InChIKey: KMNBCUUTUMNJGS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Binding affinity to wild type JAK2 JH1 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as dissociation constant measured upto 30 mins in presence of tracer by competitive fluorescence polarization assay
Measurement: Kd = 5750 nM (pChEMBL 5.239999771118164)
Descriptors: MW 599.63, ALogP 4.28, HBA 10, HBD 5, PSA 204.55, QED 0.16
Compound (SMILES): [2H]c1c([2H])c([2H])c([C@@H]2C[C@@H](N3CCN(C([2H])([2H])[2H])C(C)(C)C3)c3cc(Cl)ccc32)c([2H])c1[2H]
InChIKey: BYPMJBXPNZMNQD-WHCYFCLHSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28564
Assay: Displacement of [125I]CYP from rat brain 5HT1B receptor measured after 120 mins by scintillation counting analysis
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 354.93, ALogP 4.94, HBA 2, HBD 0, PSA 6.48, QED 0.75
Compound (SMILES): C=CC(=O)Nc1cccc(C)c1Nc1cc2[nH]c(=O)c(-c3c(Cl)c(OC)cc(OC)c3Cl)cc2cn1
InChIKey: GWVFKOTWKHBCGN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) using Poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 525.39, ALogP 6.09, HBA 6, HBD 3, PSA 105.34, QED 0.25
Compound (SMILES): Nc1n[nH]c2cc(-c3cn([C@@H]4CN[C@H](C(=O)Nc5ccc(Cl)cc5Cl)C4)nn3)ccc12
InChIKey: RCMBBRKIGQGXGS-SJCJKPOMSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 3667.06 nM (pChEMBL 5.440000057220459)
Descriptors: MW 457.33, ALogP 3.25, HBA 7, HBD 4, PSA 126.54, QED 0.37
Compound (SMILES): O=C(NC1CCN(C(=O)C2CCOCC2)CC1)NC12CC3CC(Cl)(CC(C1)c1ccccc13)C2
InChIKey: FZXSDMYEPKMPLZ-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P34914
Assay: Inhibition of mouse sEH in using using Nonfluorescent Cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl] carbonate as substrate incubated for 5 mins
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 486.06, ALogP 4.28, HBA 3, HBD 2, PSA 70.67, QED 0.63
Compound (SMILES): FC(F)(F)c1cc(NCc2cccc3sccc23)c2cn[nH]c2c1
InChIKey: MAZDHTQQFZZMRB-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of N-terminal hexa-histidine tagged human IDO1 (12 to 403 residues) expressed in Escherichia coli Transetta (DE3) using L-tryptophan as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured after 30 to 60 mins by microplate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 347.37, ALogP 5.41, HBA 3, HBD 2, PSA 40.71, QED 0.52
Compound (SMILES): Cc1c(COc2ccc(CNCCCCCCC(=O)NO)c(OCc3cccc(C#N)c3)c2)cccc1-c1ccccc1
InChIKey: MWSWGNOJFLALFM-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using Boc-Lys-(acetyl)-AMC as substrate incubated for 0.5 hr and measured after 20 mins by fluorescence assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 577.73, ALogP 7.24, HBA 6, HBD 3, PSA 103.61, QED 0.07
Compound (SMILES): CCOc1nc(C(=O)NCC(=O)O)c(O)c2ccc(Oc3ccc(Oc4ccccc4)cc3)cc12
InChIKey: WUMKPFGSXLIWCG-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Agonist activity at human TR beta LBD (202 to 461 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as induction of N-terminal biotinylated coactivator SRC2-3 peptide recruitment by alphascreen assay
Measurement: EC50 = 17.8 nM (pChEMBL 7.75)
Descriptors: MW 474.47, ALogP 4.74, HBA 7, HBD 3, PSA 127.21, QED 0.32
Compound (SMILES): CC(F)(F)c1cc(-c2sc3cc(O)ccc3c2Oc2ccc(/C=C/C(=O)O)cc2)ccc1F
InChIKey: ILJHRHXDKVDOTK-NYYWCZLTSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha expressed in HEK293/Gal4 cells incubated for 24 hrs in presence of estradiol by luciferase reporter gene assay
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 470.47, ALogP 7.41, HBA 4, HBD 2, PSA 66.76, QED 0.29
Compound (SMILES): O=c1c2ccccc2nc2n1C(C1CN=Cc3[nH]c4ccccc4c31)CC2O
InChIKey: IBVMLZHBDCBNQN-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BuChE (unknown origin)
Measurement: IC50 = 9260 nM (pChEMBL 5.03000020980835)
Descriptors: MW 370.41, ALogP 3.07, HBA 5, HBD 2, PSA 83.27, QED 0.54
Compound (SMILES): COc1cc(OC)c(F)c(COc2cnc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)nc3)nc2)c1F
InChIKey: MYAWFSOGKJRLPC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of wild type N-terminal GST tagged FGFR3 (436 to 806 residues) (unknown origin) expressed in sf21 insect cells preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of ATP by off-chip mobility shift assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 555.63, ALogP 3.71, HBA 10, HBD 1, PSA 88.11, QED 0.42
Compound (SMILES): O=C1OC(c2ccccc2)(c2ccccn2)CC(O)=C1Sc1ccccc1Cl
InChIKey: HAKBTZJRYAPJAQ-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA (unknown origin)
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 409.89, ALogP 5.49, HBA 5, HBD 1, PSA 59.42, QED 0.58
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1cc(S(=O)(=O)F)ccc1OC)C(=O)N1CCC[C@H]1C(=O)N[C@@H]1CCc2c(F)cccc21
InChIKey: LXHMLZUEZVWXML-ZFIFVKQDSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Antagonist activity at N-terminal His-tagged XIAP-BIR3 domain (253 to 347 residues)(unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 635.69, ALogP 1.11, HBA 8, HBD 4, PSA 163.01, QED 0.27
Compound (SMILES): Cn1cc(S(N)(=O)=O)c2cc(NC(=O)c3cc(Cl)nc(Br)c3)ccc21
InChIKey: ILZSFWFTBWCREC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 by stopped flow CO2 assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 443.71, ALogP 2.89, HBA 5, HBD 2, PSA 107.08, QED 0.61
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)NC(=O)CCNC(=O)CCNC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC1=O
InChIKey: AVCYMJQSIAKJTE-MCCSDKBOSA-N
Target: TCF4-CTNNB1 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: P15884
Assay: Inhibition of FITC-labeled Tcf4 (unknown origin) / full length beta-catenin (1 to 781 residues) (unknown origin) protein-protein interaction measured after 1 hr by fluorescence polarization assay
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 1695.94
Compound (SMILES): C[C@H](c1cccc2ccccc12)N1CCC(C(=O)NCc2cc(F)cc(NC(=O)N3CCN(C)CC3)c2)CC1
InChIKey: ZGUISYSWQQIAHK-JOCHJYFZSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of full-length wild-type SARS-CoV-2 papain-like protease (1564 to 1878 residues) expressed in Escherichia coli BL21 (DE3) using HCC-RLRGG-NH(CH2)4NH-DABCYL probe as substrate by enzymatic assay
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 531.68, ALogP 4.85, HBA 4, HBD 2, PSA 67.92, QED 0.48
Compound (SMILES): CC[C@@H]1c2nnc(C)n2-c2cnc(Nc3ccc(C(=O)NC4CCN(C(=O)CCCCOc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cc3OC)nc2N1CC1CCCCC1
InChIKey: RXBBVTLHCZOFSY-IFDNYZKCSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin) by alpha-screen assay
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 916.05, ALogP 5.34, HBA 15, HBD 3, PSA 223.18, QED 0.1
Compound (SMILES): N[C@@H]1COCC12CCN(c1cnc3c(-c4cccc(Cl)c4Cl)n[nH]c3n1)CC2
InChIKey: SIKKESBUGBWVRF-CYBMUJFWSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of human SHP2 assessed as downregulation of PERK level in human KYSE520 cells incubated for 2 hrs by Alpha screen assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 419.32, ALogP 3.27, HBA 6, HBD 2, PSA 92.95, QED 0.66
Compound (SMILES): O=C(Nc1nc2cccc(C3CCC4(CC3)CCN(C(=O)[C@@H]3CC3(F)F)CC4)n2n1)C1CC1
InChIKey: IBRBLXZHXVFSPN-KRWDZBQOSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 457.53, ALogP 4, HBA 5, HBD 1, PSA 79.6, QED 0.75
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(=O)N6CCCC6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: IPACCWMKAAYXIF-KUWYHPFGSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Mus musculus
UniProt: Q61503
Assay: Inhibition of mouse CD73 assessed as reduction in inorganic phosphate release upon substrate hydrolysis using AMP/ATP as substrate incubated for 1 hr followed by substrate addition and measured after 2 hrs by malachite green reagent based colorimetric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 553.83, ALogP 8.33, HBA 3, HBD 1, PSA 66.84, QED 0.36
Compound (SMILES): CCN(CC)Cc1ccccc1CNC(=O)c1cc(F)cc(NC(=O)c2ccc(F)cc2)c1
InChIKey: DXQJWRPPQGWZNM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 0.61 nM (pChEMBL 9.210000038146973)
Descriptors: MW 451.52, ALogP 4.99, HBA 3, HBD 2, PSA 61.44, QED 0.48
Compound (SMILES): CCCN(CCC)C(=O)Cc1c(-c2ccc(O)cc2)nc2ccc(Cl)cn12
InChIKey: YAYRZKKNXOKHBG-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Inhibition of TSPO (unknown origin) in mouse MA-10 cells assessed as increase in steroid steroidogenesis
Measurement: EC50 = 6990 nM (pChEMBL 5.159999847412109)
Descriptors: MW 385.9, ALogP 4.55, HBA 4, HBD 1, PSA 57.84, QED 0.65
Compound (SMILES): CCCCOC(=O)NS(=O)(=O)c1ccc(CCC)cc1-c1ccc(Cn2c(CCC)nc3ccccc32)cc1
InChIKey: MAXUOXHCKMAXJN-UHFFFAOYSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Displacement of [125-I]-[Sar1Ile8]-angiotensin II from human AT2R expressed in HEK293 cell membrane assessed as inhibition constant by radioligand binding assay
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 547.72, ALogP 6.87, HBA 6, HBD 1, PSA 90.29, QED 0.2
Compound (SMILES): C[C@H]1CC[C@@H](c2nc3cccc(Cl)c3c(=O)n2N2CCOCC2)N1c1ncnc(N)c1C#N
InChIKey: VFPBXXMPSOABTC-GUYCJALGSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin)
Measurement: IC50 = 295 nM (pChEMBL 6.53000020980835)
Descriptors: MW 466.93, ALogP 1.99, HBA 10, HBD 1, PSA 126.19, QED 0.62
Compound (SMILES): C/C(=N/NC(=O)Nc1ccc(S(C)(=O)=O)cc1)c1ccc([N+](=O)[O-])cc1
InChIKey: ITGIQHUJMPASCZ-WQRHYEAKSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL using 4-nitrophenyl acetate as substrate preincubated for 5 mins followed by substrate addition by fluorescence based colorimetry assay
Measurement: IC50 = 1280 nM (pChEMBL 5.889999866485596)
Descriptors: MW 376.39, ALogP 2.54, HBA 6, HBD 2, PSA 130.77, QED 0.47
Compound (SMILES): O=C(O)c1ccc(C(=O)OCCCCCCCCCCCCNC(=O)[C@@H]2CN(C(=O)c3ccc(C(=O)N4C[C@@H](C(=O)N[C@H]5C[C@@H]5c5ccccc5)[C@H](C(=O)N[C@H]5C[C@@H]5c5ccccc5)C4)cc3)C[C@H]2C(=O)N[C@H]2C[C@@H]2c2ccccc2)cc1
InChIKey: CSQGOLOINYAVNO-KQQPGTQMSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9EPQ1
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 1125.38
Compound (SMILES): O=[N+]([O-])c1ccc2[nH]c(CNc3cc(C(F)(F)F)cc4[nH]ncc34)cc2c1
InChIKey: BNXKZRXFXQGJIN-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of N-terminal hexa-histidine tagged human IDO1 (12 to 403 residues) expressed in Escherichia coli Transetta (DE3) using L-tryptophan as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured after 30 to 60 mins by microplate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 375.31, ALogP 4.58, HBA 4, HBD 3, PSA 99.64, QED 0.36
Compound (SMILES): CCCCCC/C=C\CCCCCCCc1cccc(OC(C)(C)C(=O)O)c1
InChIKey: CIMPQGIVIDVYGC-KTKRTIGZSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at human PPARgamma expressed in HEK293 cells by luciferase/beta-galactosidase reporter gene assay
Measurement: EC50 = 1780 nM (pChEMBL 5.75)
Descriptors: MW 388.59, ALogP 7.34, HBA 2, HBD 1, PSA 46.53, QED 0.24
Compound (SMILES): CN1CCC(c2nnn3c2CO[C@@H]2CN(Cc4ccc(F)cc4)C[C@H]23)CC1
InChIKey: RIDIKARLEUHSPK-IEBWSBKVSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-1,3-di-O-tolylguanidine from human sigma 2 receptor/TMEM97 transfected in sigma 1 receptor knockout HEK293 cell membranes assessed as inhibition constant measured after 120 mins by liquid scintillation counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 371.46, ALogP 2.18, HBA 6, HBD 0, PSA 46.42, QED 0.83
Compound (SMILES): C=C(C)C(=O)OCCOC(=O)C1=C(C)NC(=S)NC1c1ccc(C)cc1
InChIKey: FTAJWJXCJPVMBR-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis
Measurement: Ki = 30.63 nM (pChEMBL 7.510000228881836)
Descriptors: MW 374.46, ALogP 2.45, HBA 5, HBD 2, PSA 76.66, QED 0.34
Compound (SMILES): COc1cc(N(C)CCN(C)C)c(NC(=O)c2ccncc2OC)cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
InChIKey: JQDANLPONAOSDC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M mutant (unknown origin) by mobility shift assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 580.69, ALogP 5.04, HBA 10, HBD 2, PSA 109.67, QED 0.22
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(C)c1F
InChIKey: KORWPMHMESLCMI-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Determination of the IC50 for plasma kallikrein: Plasma kallikrein inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Sturzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human plasma kallikrein (Protogen) was incubated at 25° C. with the fluorogenic substrate H-DPro-Phe-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 475.52, ALogP 3.06, HBA 7, HBD 1, PSA 91.04, QED 0.4
Compound (SMILES): CNCCCc1cc(C)cc(N)n1
InChIKey: MOHLCKRYTZYOGZ-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Inhibition of human nNOS using L-arginine as substrate assessed as reduction in NO production in the presence of NADPH by NO-hemoglobin capture assay
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 179.27, ALogP 1.12, HBA 3, HBD 2, PSA 50.94, QED 0.68
Compound (SMILES): N#Cc1ccccc1N1CCN(CCCN2C(=O)CCc3ccccc32)CC1.O=C(O)C(=O)O
InChIKey: ORJULAMCAJKNIW-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3R receptor expressed in HEK293T cell membrane incubated for 1 hr by MicroBeta scintillation counting method
Measurement: Ki = 338.84 nM (pChEMBL 6.46999979019165)
Descriptors: MW 374.49, ALogP 3.05, HBA 4, HBD 0, PSA 50.58, QED 0.81
Compound (SMILES): CCN1CCN(C(=O)c2ccc3nc(-c4cc(CCc5cc(OC)cc(OC)c5)[nH]n4)[nH]c3c2)CC1
InChIKey: XGKDTJAGVPINNR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 residues) expressed in baculovirus expression system using IGF-1Rtide peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hrs in the presence of ATP by ADP-Glo reagent based luminescence assay
Measurement: IC50 = 1.93 nM (pChEMBL 8.710000038146973)
Descriptors: MW 488.59, ALogP 3.53, HBA 6, HBD 2, PSA 99.37, QED 0.39
Compound (SMILES): COc1ccc(C2(C(=O)N(C)[C@H](C)C(=O)Nc3cccc4[nH]ncc34)CCCC2)cc1
InChIKey: IAVXXMLYPUUEOX-MRXNPFEDSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of EP300 in human LK2 cells assessed as reduction in intracellular histone H3 acetylation at lysine 27 residue incubated for 3 hrs by chemiluminescence based ELISA
Measurement: IC50 = 5020 nM (pChEMBL 5.300000190734863)
Descriptors: MW 420.51, ALogP 3.87, HBA 4, HBD 2, PSA 87.32, QED 0.63
Compound (SMILES): O=C(O)COc1ccc(OCc2cccc(-c3ccc4ccsc4c3)c2)cc1F
InChIKey: NVQBNMPXOIMOQX-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at pBIND tagged human PPARdelta expressed in human HepG2 cells incubated for 18 hrs by dual luciferase reporter assay
Measurement: EC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 408.45, ALogP 5.75, HBA 4, HBD 1, PSA 55.76, QED 0.42
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H]2CSc3nnc(nn3)SC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)CNC1=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: ZKFHMXVIVJCDFY-KHKKPXNASA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK2936E cell membrane measured after 16 to 23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 10.96 nM (pChEMBL 7.960000038146973)
Descriptors: MW 2135.45
Compound (SMILES): O=C(NCCOCCOCCOCCO)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: NXKUPDRFMJFCSV-LLULLSGYSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9EPQ1
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 > 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 969.15, ALogP 3.24, HBA 10, HBD 5, PSA 204.94, QED 0.07
Compound (SMILES): Cl.O=C1Nc2ccc(F)cc2/C1=C1/Nc2ccccc2/C1=N\OCCS(=O)(=O)N1CCNCC1
InChIKey: IELKOWJXZGSUDD-WCFRLSLOSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysis
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 471.51, ALogP 1.57, HBA 7, HBD 3, PSA 112.13, QED 0.35
Compound (SMILES): CC1(N)CCN(c2cnc3c(-c4cccc(Cl)c4Cl)n[nH]c3n2)CC1
InChIKey: AMADCPJVPLUGQO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of human SHP2 assessed as downregulation of PERK level in human KYSE520 cells incubated for 2 hrs by Alpha screen assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 377.28, ALogP 3.64, HBA 5, HBD 2, PSA 83.72, QED 0.71
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1cccnc1C(F)(F)F
InChIKey: ULAOQOFMZICMAA-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibitory Activity In Vitro Assay: KLK1 inhibitory activity in vitro was determined using standard published methods. Human KLK1 (Callbiochem) was incubated at 25° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.5, ALogP 3.63, HBA 7, HBD 1, PSA 91.04, QED 0.37
Compound (SMILES): CCCc1nc(-c2ccc(Cn3c(CC)nc4c(C)cc(C)nc43)cc2)c(S(=O)(=O)NC(=O)OC)s1
InChIKey: NTPPXKUWVLDJKC-UHFFFAOYSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Displacement of 125I-[Sar1,Ile8]ANGII form recombinant human full length AT1 receptor expressed in HEK293 cells incubated for 120 mins by scintillation counting method
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 527.67, ALogP 4.78, HBA 9, HBD 1, PSA 116.07, QED 0.35
Compound (SMILES): COc1cc(F)ccc1-c1ccnc2[nH]c(C3CCC(NC(C)=O)C3)nc12
InChIKey: KPPLCUYUCVJBTH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 (unknown origin) using 5FAM-RRRFRPASPLRGPPK-COOH 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 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 368.41, ALogP 3.54, HBA 4, HBD 2, PSA 79.9, QED 0.74
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(CN5CCOCC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: AYMIOSAGFUFSMC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 residues) expressed in baculovirus expression system using IGF-1Rtide peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hrs in the presence of ATP by ADP-Glo reagent based luminescence assay
Measurement: IC50 = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 447.54, ALogP 3.59, HBA 6, HBD 2, PSA 88.29, QED 0.43
Compound (SMILES): O=C(CCCCCCn1c(C(=O)NC2C3CC4CC(C3)CC2C4)nc2ccccc21)NO
InChIKey: CNJSDBOFFPQBAC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorescence plate reader assay
Measurement: IC50 = 5.25 nM (pChEMBL 8.279999732971191)
Descriptors: MW 438.57, ALogP 4.05, HBA 5, HBD 3, PSA 96.25, QED 0.31
Compound (SMILES): C#CCN(C)CCCOc1cc(NCc2ccc(/C=C/C(=O)NO)cc2)ccc1Cl
InChIKey: JWIRZQYHZOIRPQ-FMIVXFBMSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human HDAC1 (379 to 382 residues) using RHKKAc-AMC fluorogenic peptide as substrate by fluorescence assay
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 427.93, ALogP 3.8, HBA 5, HBD 3, PSA 73.83, QED 0.17
Compound (SMILES): O=C(NCC1CC1)[C@@H]1CCCCOc2cccc(c2)C[C@H](N2CCCC2=O)C(=O)N[C@@H](CCc2ccccc2)C(=O)N1
InChIKey: QVCQIHDORLVVRW-AWCRTANDSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S immunoproteasome beta-5i subunit using Ac-ANW-AMC as substrate measured after 1.2 hrs in presence of SDS
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 574.72, ALogP 2.91, HBA 5, HBD 3, PSA 116.84, QED 0.47
Compound (SMILES): COc1cc([C@@H]2c3cc4c(cc3C[C@H]3COC(=O)[C@@H]32)OCO4)cc(OC)c1OC(=O)CC(=O)Nc1ccc(C(=O)Nc2ccccc2N)cc1
InChIKey: RUZISCYMEUSGBU-HEEDHUMYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human HDAC2 expressed in baculovirus infected Hi-5 insect cells using Ac-Lys-Tyr-Lys (epsilon-acetyl)-AMC as substrate incubated for 3 to 24 hrs by fluorescence based plate reader analysis
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 679.68, ALogP 4.68, HBA 11, HBD 3, PSA 173.74, QED 0.1
Compound (SMILES): COc1cc2nc(N3CCN(CCCCCC(=O)NO)CC3)nc(NC3CCN(Cc4ccccc4)CC3)c2cc1OC
InChIKey: VSEYIEDVOXUHFM-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 591.76, ALogP 3.91, HBA 10, HBD 3, PSA 115.32, QED 0.15
Compound (SMILES): C[C@@H]1CCCN1Cc1ccc(-c2cnc(N)c3c2CCN(C2CCC(O)CC2)C3=O)cc1F
InChIKey: QIGLCSOIUAUGES-PBPGXSGUSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of ALK2 (unknown origin)
Measurement: IC50 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 452.57, ALogP 3.76, HBA 5, HBD 2, PSA 82.69, QED 0.74
Compound (SMILES): COc1cc2ncnc3c2cc1OCCOCCOc1cc(Cl)ccc1N3
InChIKey: MGPYPYFNRVZVRY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) Del19 mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.82, ALogP 3.82, HBA 7, HBD 1, PSA 74.73, QED 0.68
Compound (SMILES): NC(=O)N1CCN(c2cccc(Cl)c2)CC1
InChIKey: DDHRRRBBKQJRMS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from 5-HT2AR (unknown origin) expressed in CHO-K1 cells by radioligand binding assay
Measurement: Ki = 32360 nM (pChEMBL 4.489999771118164)
Descriptors: MW 239.71, ALogP 1.54, HBA 2, HBD 1, PSA 49.57, QED 0.81
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CCCNS(=O)(=O)c1ccc(Oc2ccccc2)cc1)C(=O)N(C)[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(N)=O
InChIKey: IGOVNBYALNSOHR-QZCIJFHVSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of recombinant human MMP12 using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition by fluroscence based assay
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 972.13, ALogP 0.24, HBA 12, HBD 8, PSA 335.9, QED 0.06
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(-c3cccs3)cc2OC)[C@H]1NC(C)=O
InChIKey: AEQWUSSTTYLLFR-QQKQFIJSSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of Influenza A virus A/California/04/2009 (H1N1) Neuraminidase H274Y mutant using MUNANA as substrate preincubated for 10 mins followed by substrate addition and measured after 40 mins by fluorescence based microplate reader method
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 486.63, ALogP 4.38, HBA 6, HBD 3, PSA 96.89, QED 0.44
Compound (SMILES): COc1cc(Oc2c(-c3ccc(F)cc3CC(F)(F)F)sc3c2ccc2[nH]ncc23)ccc1NC1CN(CCCF)C1
InChIKey: JJPMYVJPFFROOP-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha expressed in HEK293/Gal4 cells incubated for 24 hrs in presence of estradiol by luciferase reporter gene assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 602.63, ALogP 7.95, HBA 6, HBD 2, PSA 62.41, QED 0.16
Compound (SMILES): O=c1nc2n(c3c1CN(Cc1ccccc1)CC3)CCN2Cc1ccc(F)c(Br)c1
InChIKey: MXNHOWULPTWEIK-UHFFFAOYSA-N
Target: ATP-dependent Clp protease proteolytic subunit, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16740
Assay: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay
Measurement: EC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 469.36, ALogP 3.72, HBA 5, HBD 0, PSA 41.37, QED 0.58
Compound (SMILES): O=C([O-])C1CN(Cc2ccc(C3=NOC(c4ccc(CCl)cc4)C3)cc2)C1.[Na+]
InChIKey: MWTHRZOLWLIACZ-UHFFFAOYSA-M
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at S1P1 receptor (unknown origin) expressed in PathHunter HEK 293 EDG1 Total GPCR Internalization cells assessed as receptor internalization incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 384.86, ALogP 3.81, HBA 4, HBD 1, PSA 62.13, QED 0.77
Compound (SMILES): COc1ccc2sc(C(=O)N(C)Cc3cc(F)cc(F)c3)cc2c1
InChIKey: FLWYCOJREJRWLJ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human recombinant GST-tagged Clk2 expressed in Baculovirus expression system using GRSRSRSRSRSRSRSR peptide as substrate in presence of ATP
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 347.39, ALogP 4.46, HBA 3, HBD 0, PSA 29.54, QED 0.7
Compound (SMILES): Cc1cnc(N2CCN(Cc3ccc4c(c3)[nH]c(=O)c3ccccc34)CC2)n1C
InChIKey: FLTKNCUXYGRLOI-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human recombinant N-terminal Avi-6His-TEV tagged PARP2 full length expressed in pFastBac expression system incubated for 4 hrs by fluorescence anisotropy binding assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 387.49, ALogP 3.05, HBA 5, HBD 1, PSA 57.16, QED 0.55
Compound (SMILES): CCOC(=O)c1cn(Cc2ccc(F)cc2)c2ccc(OCc3ccc(Cl)c(Cl)c3)cc2c1=O
InChIKey: YPIMBEHFAZBCTI-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase associated RNA-dependent DNA polymerase activity using poly(A)-oligo(dT) as template/primer incubated for 30 mins by multilabel counter plate reader analysis
Measurement: IC50 = 24100 nM (pChEMBL 4.619999885559082)
Descriptors: MW 500.35, ALogP 6.25, HBA 5, HBD 0, PSA 57.53, QED 0.28
Compound (SMILES): CC(CN1CCCC2CCCNC21)OCC(=O)N1Nc2cc(O)ccc2C2COc3cc(O)ccc3C21
InChIKey: DIKAQBJCHZVUSN-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at ERbeta (unknown origin)
Measurement: IC50 = 67.14 nM (pChEMBL 7.170000076293945)
Descriptors: MW 508.62, ALogP 3.31, HBA 8, HBD 4, PSA 106.53, QED 0.49
Compound (SMILES): COc1cccc(N2CCN(CCCN3C(=O)CCc4ccccc43)CC2)c1.O=C(O)C(=O)O
InChIKey: OQMDUZOTERVWTI-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3R receptor expressed in HEK293T cell membrane incubated for 1 hr by MicroBeta scintillation counting method
Measurement: Ki = 1548.82 nM (pChEMBL 5.809999942779541)
Descriptors: MW 379.5, ALogP 3.19, HBA 4, HBD 0, PSA 36.02, QED 0.77
Compound (SMILES): CN(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)C[C@H]1C[C@@H](c2ccc3c(N)ncnn23)[C@H](O)[C@@H]1O
InChIKey: RFGUNGMQLCSOBC-YSFUMNCJSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Inhibition of human DOT1L by hotspot PMT activity assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 509.66, ALogP 2.58, HBA 8, HBD 5, PSA 141.04, QED 0.29
Compound (SMILES): CCc1nc(C2CCN(CCCCc3c[nH]c4ccc(C#N)cc34)CC2)cn1-c1ccc(Oc2ccc(Cl)cc2)cc1
InChIKey: UNGCJSVLAMOZAY-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) expressed in human HEK293 cells
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 578.16, ALogP 8.44, HBA 5, HBD 1, PSA 69.87, QED 0.17
Compound (SMILES): COc1ccc(-c2cn3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cc3n2)c(OCCCN2CCCC2)c1
InChIKey: YEAISOQWERLVTR-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 expressed in HEK-blue hTLR7 cells assessed as inhibition of CL264-induced NFkappaB activation preincubated with compound for 1 hrs followed by CL264 addition and measured next day by SEAP-based spectrophotometry assay
Measurement: IC50 = 2950 nM (pChEMBL 5.53000020980835)
Descriptors: MW 535.69, ALogP 4.93, HBA 8, HBD 0, PSA 71.78, QED 0.38
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nc(OC)ccc1F
InChIKey: KQSCQCAZZHSOOR-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibitory Activity In Vitro Assay : Plasma kallikrein inhibitory activity in vitro was determined using standard published methods. Human plasma kallikrein (Protogen) was incubated at 25° C. with the fluorogenic substrate H-DPro-Phe-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 = 831 nM (pChEMBL 6.079999923706055)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): Cc1nc(Nc2cccc(N3CCCC3=O)n2)sc1-c1cc2c(c(S(=O)(=O)NC3COC3)c1)C(=O)N([C@@H](C)C(F)(F)F)C2
InChIKey: NHOGIGRHHZKFTF-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Enzymatic Activity Assay : The activity of recombinant human PI3Kγ ((aa144-1102)-6His) and PI3Kα, β, δ (6-His(p110-p85α)) was determined by measuring the ADP level after phosphorylation of DiC8-PIP2 using a commercially available ADP-Glo kit from Promega. The assay was carried out in white low volume 384 well plates in a final volume of 14 μl at R.T. The assay conditions contained the following: 50 mM Tris buffer pH 7.4, 2.1 mM DTT, 3 mM MgCl2, 0.05% CHAPS, 20 μM ATP, 80 μM DiC8-PIP2 and 1.2 nM PI3Kα, β, γ or 0.6 nM PI3Kδ. Potential inhibitors were made up in DMSO and then diluted in the assay to give a final concentration of not exceeding 1% (v/v) DMSO. A 10-point half-log dilution series of the inhibitors (highest concentration typically 0.1 μM for δ or γ and 33 μM for a or 1) was tested and the pIC50 determined using a 4-parameter logistic equation in a non-linear curve fitting routine. Routinely, inhibitors were pre-incubated with 3 μl of enzyme for 15 min prior to the addition of 2 μl substrate mixture for a further 60 min enzyme reaction. The phosphorylation was stopped with the addition of 3 μl ADP-Glo reagent (stop solution) followed by a 40 min incubation. Prior to detection 6 μl of ADP-Glo Kinase Detection Reagent was added and the plates were read in a micro plate reader using a Luminescence filter. All additions were followed by a short centrifugation step.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 636.68, ALogP 3.97, HBA 9, HBD 2, PSA 133.83, QED 0.38
Compound (SMILES): CCC[C@H]1N(C(=O)c2cnccc2C)CCC[C@@]1(Oc1csc(C(F)(F)F)c1)C(=O)N1CCN(c2ccccc2OCCO)CC1
InChIKey: CETNYWGGMLYJIH-NSJVFKKDSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using testosterone as substrate pretreated with NADPH
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 660.76, ALogP 5.41, HBA 8, HBD 1, PSA 95.44, QED 0.31
Compound (SMILES): CCNNC(=O)c1ccc(CN2c3ccccc3Sc3cccnc32)cc1
InChIKey: QBFBUPPMGQDWQW-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant HDAC2 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 376.49, ALogP 4.14, HBA 5, HBD 2, PSA 57.26, QED 0.66
Compound (SMILES): OC[C@@]1(c2ccc(F)cc2)NC[C@@H](O)[C@@H]1O
InChIKey: PPOXPJWNJJAFEN-VWYCJHECSA-N
Target: Sucrase-isomaltase, intestinal (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23739
Assay: Inhibition of rat intestinal sucrase assessed as release of p-nitrophenol using p-nitrophenyl glycoside as substrate by spectrometric assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 227.24, ALogP -0.66, HBA 4, HBD 4, PSA 72.72, QED 0.54
Compound (SMILES): CC(=O)Nc1cc(-c2cc(F)c(OC[C@@H](N)CC(C)C)c(Cl)c2)ccn1
InChIKey: AKUJIVTZSHCXRK-HNNXBMFYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of full length human AAK1 expressed in HEK293F cells assessed as suppression of AP2 phosphorylation measured after 3 hrs by Western blot analysis based cellular assay
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 379.86, ALogP 4.25, HBA 4, HBD 2, PSA 77.24, QED 0.75
Compound (SMILES): Cc1c([C@@H](C)Nc2nnc(C)c3ccc(N4CCN(C)C(=O)C4)cc23)cccc1C(F)(F)F
InChIKey: FCHCXFHSLLVRGA-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of Labeled Tracer Ligand: Table 22: This Example illustrates that exemplary compounds of the present invention bind to SOS1 and prevent a labeled tracer ligand from occupying the S0S1 binding site. The ability of a compound of Formula (I) to bind to SOS1 was measured using a HTRF displacement assay. A recombinant human SOS1 polypeptide (corresponding to amino acids 560-1049, expressed in E. Coli with N-terminal His-TEV-AviTag-SOS1 (MW=59.4 kDa) and lanthanide labeled streptavidin (CisBio) was incubated with an exemplary compound of Formula (I) (in a DMSO stock solution) in buffer (25 mM HEPES pH 7.5, 25 mM NaCl, 1 mM DTT, 0.01% Brij 35, 0.02% BSA, 0.1% DMSO). After a 10-15 minute incubation at room temperature, a solution comprised of a custom-made Cy5 labelled tracer and MAb Anti-6HIS Tb cryptate Gold (Cisbio 61HI2TLA) in buffer was added to the solution containing the SOS1 polypeptide and exemplary compound of Formula (I). After a 1-hour incubation at room temperature, the HTRF signal was measured using Clairostar plate reader (BMG Labtech) according to the manufacturer's instructions. Excitation filter EX-TR was used, and emission 1 was detected at 650-610 nm and emission 2 detected at 620-610 nm. The HTRF ratio was calculated using the formula: [emission 1/emission 2]*10000.
Measurement: Ki = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 457.5, ALogP 4.72, HBA 5, HBD 1, PSA 61.36, QED 0.61
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)N(C1CCOCC1)CC(=O)N2C
InChIKey: MZQKKBHRPQCGSA-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha by Kinase-Glo assay
Measurement: IC50 = 187.1 nM (pChEMBL 6.730000019073486)
Descriptors: MW 394.44, ALogP 1.53, HBA 9, HBD 1, PSA 100.78, QED 0.71
Compound (SMILES): CC1(C)c2cc(OCCN3CCOCC3)ccc2C(=O)c2c1oc1cc(C#Cc3cc(OCCC4CC4)ccn3)ccc21
InChIKey: FLQOKVHRJKLLEM-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of KDR (unknown origin)
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 576.69, ALogP 5.99, HBA 7, HBD 0, PSA 74.03, QED 0.24
Compound (SMILES): O=C(NCCCNc1cc(-c2cn(-c3ccccc3)nc2-c2cccc(O)c2)ccn1)Nc1ccc(F)cc1
InChIKey: BCNMJLRKWYKBBZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3 (unknown origin)
Measurement: IC50 = 97.72 nM (pChEMBL 7.010000228881836)
Descriptors: MW 522.58, ALogP 6.07, HBA 6, HBD 4, PSA 104.1, QED 0.18
Compound (SMILES): Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(N4CCN(CCCCCCCC(=O)NO)CC4)nc3)cc3c2cnn3C(C)C)c(=O)[nH]1
InChIKey: GYQOOBXTZRTTLU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 30 mins by multimode microplate reader analysis
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 656.83, ALogP 4.88, HBA 9, HBD 4, PSA 148.48, QED 0.09
Compound (SMILES): CCc1cn(CCC#N)c(=O)c2sc(CN(CC)c3ccc(F)cc3)cc12
InChIKey: GDZUZOMECBQUNZ-UHFFFAOYSA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42262
Assay: Displacement of [3H]-HBT1 from His-tagged GluA2-AMPA (unknown origin) receptor expressed in CHO cells in presence of glutamate by scintillation proximity assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 383.49, ALogP 4.7, HBA 5, HBD 0, PSA 49.03, QED 0.59
Compound (SMILES): CCn1c(=O)[nH]c(=O)c2c1nc(Cc1nc3cc4c(cc3[nH]1)OCO4)n2Cc1ccccc1
InChIKey: DKITUBGXJSKLQY-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWU9
Assay: In Vitro Enzyme Activity Assay: These compounds according to the afore-mentioned examples were tested for tryptophan hydroxylase (TPH) inhibitory activity in a fluorescence-based in vitro assay, using recombinant human TPH1 (Swiss-Prot: P17752) and TPH2 (Swiss-Prot: Q8IWU9).The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, MA, USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).TPH1 and TPH2 inhibition was determined by measuring a compound dose response, using a serial dilution of a 5 mM DMSO stock solution. The potency of a given compound was calculated in GraphPad PRISM 6 software (San Diego, USA) with a Nonlinear Regression fit (log(inhibitor) vs. response-variable slope) using the relative fluorescence units (RFU) of the sample triplicates.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 444.45, ALogP 2.15, HBA 8, HBD 2, PSA 119.82, QED 0.43