lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccccc1N1CCN(CCC[C@H]2CCCN2S(=O)(=O)c2ccc(F)cc2)CC1
InChIKey: UXSHRVWFLXSVKK-NRFANRHFSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to human recombinant 5-HT1A expressed in CHO cells assessed as inhibition constant
Measurement: Ki = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 461.6, ALogP 3.59, HBA 5, HBD 0, PSA 53.09, QED 0.6
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)C/C=C(\F)[C@@H](N)Cc1ccc(O)cc1)C(=O)NC1CC1
InChIKey: GXSYRAHYTOZOPD-DQKXXYJSSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from human delta opioid receptor expressed in CHO cell membrane measured after 90 mins by liquid scintillation counting method
Measurement: Ki = 103.5 nM (pChEMBL 6.989999771118164)
Descriptors: MW 595.72, ALogP 2.16, HBA 6, HBD 6, PSA 162.65, QED 0.17
Compound (SMILES): C[C@H]1CCCN(c2ncc(Cl)c(Nc3ccc4c(c3)c3c(c(=O)n4C)OCC(F)(F)[C@H](C4CC4)N3)n2)C1
InChIKey: BBIACINZYUBHFF-FPTDNZKUSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Degradation of BCL6 in human OCI-Ly1 cells incubated for 2 hrs by MSD assay
Measurement: EC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 531.01, ALogP 5.18, HBA 8, HBD 2, PSA 84.31, QED 0.48
Compound (SMILES): COc1cc2nc3c(c(N4CCOCC4)c2cc1OC)CCCC3
InChIKey: XAPKYBVMPJHUOI-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of C-terminal 6His-tagged human recombinant BuChE (29 to 602 residues) using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 767 nM (pChEMBL 6.119999885559082)
Descriptors: MW 328.41, ALogP 2.97, HBA 5, HBD 0, PSA 43.82, QED 0.87
Compound (SMILES): COCCN1CCN(C(=O)CNC2CC2c2cc(F)cc(F)c2OCc2ccccc2)CC1
InChIKey: VJZGWPGLDBLBQW-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human LSD1 assessed as inhibitory constant using Histone H3(1-20)K4me2 peptide as substrate incubated for 10 mins followed by substrate addition by peroxidase-coupled reaction assay
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 459.54, ALogP 2.78, HBA 5, HBD 1, PSA 54.04, QED 0.59
Compound (SMILES): CC(=O)Nc1cc(-c2cc(F)c(OC[C@@H](N)CC(C)C)c(C(F)(F)F)c2)ccn1
InChIKey: XYXJLVVKIBEGES-HNNXBMFYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q3UHJ0
Assay: Displacement of 3H-LP-927443 from AAK1 in C57BL6 mouse brain homogenate assessed as inhibition constant incubated for 1 hr by liquid scintillation counter analysis
Measurement: Ki = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 413.42, ALogP 4.62, HBA 4, HBD 2, PSA 77.24, QED 0.65
Compound (SMILES): COc1ccc2c(c1)/C(=N/NC(=O)c1cc3cc(Br)ccc3o1)C(=O)N2
InChIKey: OOWQXKMJEAHJBX-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3 beta (unknown origin)
Measurement: IC50 = 40.13 nM (pChEMBL 7.400000095367432)
Descriptors: MW 414.22, ALogP 3.29, HBA 5, HBD 2, PSA 92.93, QED 0.64
Compound (SMILES): O=C(Nc1nccs1)C(c1ncn2c1CCC2)N1Cc2c(F)cc(C#Cc3ccc(CN4CCCCC4)cc3)cc2C1=O
InChIKey: HTJDDZPMJOPDOY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/C797S mutant (unknown origin) phosphorylation expressed in mouse BaF3 cells measured after 4 hrs by HTRF assay
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 594.72, ALogP 5.15, HBA 7, HBD 1, PSA 83.36, QED 0.31
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CC[C@H](NC(=O)[C@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: JQKDWSJGLLIFBM-MRVWCRGKSA-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 = 8070 nM (pChEMBL 5.090000152587891)
Descriptors: MW 403.43, ALogP 2.88, HBA 5, HBD 2, PSA 88.39, QED 0.8
Compound (SMILES): O=c1n(CCCCCCN2CCN(c3cccc4cccnc34)CC2)nc2ccccn12
InChIKey: XKFTZAKZMPILFS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-5-OH-DPAT from human full length 5-HT1AR expressed in HEK293 cells by radioligand binding assay
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 430.56, ALogP 3.43, HBA 7, HBD 0, PSA 58.67, QED 0.4
Compound (SMILES): Cc1nc(N)sc1-c1ccc(N/C(N)=N/C(=O)NCCCCCCNC(=O)/N=C(\N)Nc2ccc(-c3sc(N)nc3C)cc2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: DELOJSXVQMABAD-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H] mepyramine from human histamine H1 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RGS4 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 662.85, ALogP 4.85, HBA 8, HBD 8, PSA 236.84, QED 0.06
Compound (SMILES): C[C@@H]1CCCN(c2ncc(Cl)c(Nc3ccc4c(c3)c3c(c(=O)n4C)OCC(F)(F)[C@H](C4CC4)N3)n2)C1
InChIKey: BBIACINZYUBHFF-PEBXRYMYSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Degradation of BCL6 in human OCI-Ly1 cells incubated for 2 hrs by MSD assay
Measurement: EC50 = 32.6 nM (pChEMBL 7.489999771118164)
Descriptors: MW 531.01, ALogP 5.18, HBA 8, HBD 2, PSA 84.31, QED 0.48
Compound (SMILES): CNC(=O)[C@]1(C)CC[C@@H](Nc2ncc3c(Br)nn(-c4ccc(-c5nnc(C)s5)c(CCO)c4)c3n2)C1
InChIKey: WAYMNYVTTBCOHI-OYLFLEFRSA-N
Target: eIF-2-alpha kinase GCN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2K8
Assay: Inhibition of GCN2 in human SK-OV-3 cells assessed as reduction in phosphorylation of eIF2alpha by cellular assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 571.51, ALogP 3.66, HBA 10, HBD 3, PSA 130.74, QED 0.31
Compound (SMILES): C=CC(=O)Nc1ccc(-c2cn([C@@H]3CN[C@H](C(=O)Nc4ccc(Cl)c(C(F)(F)F)c4)C3)nn2)cn1
InChIKey: QDXRELOFIZDHGS-YOEHRIQHSA-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 = 139.64 nM (pChEMBL 6.860000133514404)
Descriptors: MW 505.89, ALogP 3.68, HBA 7, HBD 3, PSA 113.83, QED 0.44
Compound (SMILES): O=C1C(=O)N(CCc2ccccc2)c2ccc(F)cc21
InChIKey: FMQVEHDXVCRVTP-UHFFFAOYSA-N
Target: Parkinson disease protein 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99497
Assay: Inhibition of PARK7 (unknown origin) using DiFUMAc as substrate preincubated for 1 hrs followed by substrate addition and measured after 1 hrs by fluorescence plate reader analysis
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 269.27, ALogP 2.6, HBA 2, HBD 0, PSA 37.38, QED 0.8
Compound (SMILES): CCCCc1nc(C2CCN(CCc3c[nH]c4ccc(C#N)cc34)CC2)cn1-c1ccc(Oc2ccc(Cl)cc2)cc1
InChIKey: NSTCHFNFLIONCS-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 > 100 nM (pChEMBL 7)
Descriptors: MW 578.16, ALogP 8.44, HBA 5, HBD 1, PSA 69.87, QED 0.18
Compound (SMILES): Cn1c(=O)[nH]c(=O)c2c1nc(Sc1nc3ccccc3[nH]1)n2Cc1cnco1
InChIKey: AGMWNRMJABUMDS-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 = 1410 nM (pChEMBL 5.849999904632568)
Descriptors: MW 395.4, ALogP 1.49, HBA 9, HBD 2, PSA 127.39, QED 0.47
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)N[C@H]5CC[C@](O)(C(F)(F)F)CC5)c4n3)cc(NS(C)(=O)=O)c2C1=O
InChIKey: HGSPCVJTIYJJKQ-BMEKPBSDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using 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 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 635.67, ALogP 3.07, HBA 9, HBD 4, PSA 172.02, QED 0.31
Compound (SMILES): Cn1cc(S(N)(=O)=O)c2cc(NC(=O)c3cc(-c4ccc(Cl)cc4)nc4ccccc34)ccc21
InChIKey: AILQJRPKMBKQQX-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 = 29380 nM (pChEMBL 4.53000020980835)
Descriptors: MW 490.97, ALogP 4.95, HBA 5, HBD 2, PSA 107.08, QED 0.37
Compound (SMILES): COC1CN(c2cc(NC(=O)c3cccc(-c4cnn(C)c4)n3)c(C(F)(F)F)cn2)C1
InChIKey: KHTCIOWVELAJLF-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in human SH-SY5Y cells assessed as inhibition of tetracycline induced LRRK2 phosphorylation at Ser935 residue incubated for 90 mins by MSD assay
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 432.41, ALogP 2.98, HBA 7, HBD 1, PSA 85.17, QED 0.67
Compound (SMILES): Cc1cc(Oc2ccc(Cn3nc4ccc(Cl)cc4c3C(=O)NS(=O)(=O)c3ccc(NCc4ccco4)c([N+](=O)[O-])c3)cc2)cc(C)c1Cl
InChIKey: IMUMIQGNKAABEB-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of BCL-2 (unknown origin) by fluorescence polarization competition assay
Measurement: Ki = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 720.59, ALogP 8.03, HBA 10, HBD 2, PSA 158.6, QED 0.1
Compound (SMILES): COc1cc(N2CCN(CCCCCCCCCCCCNC(=O)CC34CC5CC(CC(C5)C3)C4)CC2)ccc1Nc1ncc2c(C)cc(=O)n(-c3cccc(NC(C)=O)c3)c2n1
InChIKey: SOOCPBLZCOVDIQ-UHFFFAOYSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Induction of AKT2 degradation in human NCI-H1975 cells assessed as reduction in AKT2 protein level incubated for 24 hrs under serum free medium by Western blot analysis
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 859.17, ALogP 9.55, HBA 10, HBD 3, PSA 133.72, QED 0.07
Compound (SMILES): c1ccc2c(Cc3nncn3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: CHUTZBIFVIDRGL-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay
Measurement: EC50 = 401.9 nM (pChEMBL 6.400000095367432)
Descriptors: MW 306.37, ALogP 2.71, HBA 4, HBD 2, PSA 75.18, QED 0.57
Compound (SMILES): C#CCCCCN1C(=O)C2=C(SC[C@@H]3NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc4c[nH]c5ccccc45)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](Cc4cnc[nH]4)NC(=O)CNC(=O)[C@H](CCCC)NC(=O)[C@H](CS2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2c[nH]c4ccccc24)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC3=O)C1=O
InChIKey: HRTHPANNFOMYJE-LPRGXNBOSA-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 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 2230.59
Compound (SMILES): CCOC(=O)[C@@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)C(=O)c1c(-c2ccccc2)[nH]c2ccccc12
InChIKey: TXTXUJCZFZSISJ-RRPNLBNLSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of MDM2 (unknown origin) by ELISA
Measurement: IC50 = 11.65 nM (pChEMBL 7.929999828338623)
Descriptors: MW 553.66, ALogP 4.84, HBA 5, HBD 3, PSA 117.36, QED 0.13
Compound (SMILES): COc1cc2nc(NCCCN(C)C)nc(OC3CCN(Cc4ccccc4)CC3)c2cc1OC
InChIKey: GMIMRINGJXMLEA-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 479.63, ALogP 4.05, HBA 8, HBD 1, PSA 71.98, QED 0.41
Compound (SMILES): COc1cc(-c2ccn3nc(N)c(C(=O)NC4CC4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: XANZNPICXVINSW-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using 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 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 446.51, ALogP 2.63, HBA 7, HBD 2, PSA 114.85, QED 0.6
Compound (SMILES): CCOC(=O)c1cn(Cc2ccc(F)cc2)c2ccc(OCc3cccc4ccccc34)cc2c1=O
InChIKey: SWFYRRCYIDSQGP-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase catalytic activity incubated for 1 hrs in absence of LEDGF/p75 by HTRF assay
Measurement: IC50 = 41900 nM (pChEMBL 4.380000114440918)
Descriptors: MW 481.52, ALogP 6.1, HBA 5, HBD 0, PSA 57.53, QED 0.26
Compound (SMILES): N=C(N)NCCC[C@H](NCc1ccccn1)C(=O)NCc1ccc(CNCCCNC2CCCCC2)cc1
InChIKey: AMGQQWNQWHMPHG-MHZLTWQESA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Binding affinity to CXCR4 (unknown origin) expressed in CHO cells measured by 12G5 competitive binding method
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 522.74, ALogP 2.52, HBA 6, HBD 7, PSA 139.98, QED 0.1
Compound (SMILES): Cl.Nc1c(Cl)cc(C(CO)NC2CCCC2)cc1C(F)(F)F
InChIKey: FQQOLPPAGWDOAG-UHFFFAOYSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Agonist activity at beta1 adrenoceptor (unknown origin) expressed in HEK293 cells assessed as cAMP accumulation incubated for 60 mins by microplate reader analysis
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 322.76, ALogP 3.51, HBA 3, HBD 3, PSA 58.28, QED 0.74
Compound (SMILES): C=CC(=O)Nc1cccc(C)c1Nc1cc2c(cn1)cc(-c1c(Cl)c(OC)cc(OC)c1Cl)c(=O)n2CC
InChIKey: RNRSRGHTQPAPQD-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 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 553.45, ALogP 6.58, HBA 7, HBD 2, PSA 94.48, QED 0.24
Compound (SMILES): COc1ccc(C(=O)Nc2cccc([C@@]3(C)O[C@@H]4CO[C@H]5N4[C@@H]3O[C@]5(C)c3cccc(NC(=O)c4ccc(OC)cc4)c3)c2)cc1
InChIKey: CEFZLJAZLPOVTE-VNCSWJDHSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human OX2R expressed in CHO-K1 cells assessed as inhibition of orexin-A-induced increase in calcium mobilization preincubated for 15 mins followed orexin-A stimulation by Fura-2-AM dye based fluorescence assay
Measurement: Ki = 26.6 nM (pChEMBL 7.579999923706055)
Descriptors: MW 621.69, ALogP 5.71, HBA 8, HBD 2, PSA 107.59, QED 0.26
Compound (SMILES): COc1ccc(-c2ccc3[nH]c(=O)c4nnn(-c5ccc(N6CCNCC6)c(C(F)(F)F)c5)c4c3c2)cn1
InChIKey: RGHLRMNPUGUZEY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase RIO2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BVS4
Assay: Inhibition of N-terminal hexahistidine-SUMO-tagged human full length RIOK2 (residues 1 to 321) expressed in Escherichia coli BL21 (DE3) incubated for 30 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 521.5, ALogP 3.76, HBA 8, HBD 2, PSA 100.96, QED 0.37
Compound (SMILES): O=C(Nc1ccn(-c2cncc(F)c2)n1)C1(c2ccccc2)CC1
InChIKey: MGVVGJUNHTXTGR-UHFFFAOYSA-N
Target: Very long chain fatty acid elongase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BW60
Assay: Inhibition of ELOVL1 in human HEK2936E cells assessed as reduction of C26:0 LPC synthesis incubated for 48 hrs by cellular assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 322.34, ALogP 3.08, HBA 4, HBD 1, PSA 59.81, QED 0.8
Compound (SMILES): CCOc1cccnc1Oc1cncc(-c2ncc(C(=O)NC3(CO)CCOC3)cn2)c1
InChIKey: DFNKRIPGDXQUEM-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: Inhibition of human DGAT2 expressed in Sf9 insect cell membrane using [1-14C]decanoyl-CoA and 1,2-didecanoyl-sn-glycerol as substrates assessed as incorporation of [1-14C]decanoyl into triacylglycerol preincubated for 120 mins followed by substrate addition and measured after 40 mins by scintillation counting method
Measurement: IC50 = 29.5 nM (pChEMBL 7.53000020980835)
Descriptors: MW 437.46, ALogP 2.01, HBA 9, HBD 2, PSA 128.58, QED 0.54
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(C(=O)N(C)C)c(C)[nH]c3c2)ncc1Cl
InChIKey: NQJLJKFROUEMTA-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ceritinib-resistant ALK L1196M mutant (1058 to 1620 residues) cytoplasmic domain expressed in baculovirus infected Sf21 cells incubated for 1 hrs in the presence of ATP by mobility shift assay
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 477.96, ALogP 4.47, HBA 6, HBD 4, PSA 115.04, QED 0.33
Compound (SMILES): O=C(Nc1ccc(F)cc1)c1cc2cccnc2n(CCCCF)c1=O
InChIKey: HLXDVVAGNXDIJA-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-WIN55212-2 from human CB2 receptor transfected in CHO cells membrane incubated for 90 mins
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 357.36, ALogP 3.54, HBA 4, HBD 1, PSA 63.99, QED 0.69
Compound (SMILES): O=C(CNCc1ccccc1)Nc1ccc(-c2nc(-c3ccnc(Nc4ccc(OC(F)(F)F)cc4)c3)no2)cc1
InChIKey: NFSPTCJOLBERPO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured after 5 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 39200 nM (pChEMBL 4.409999847412109)
Descriptors: MW 560.54, ALogP 6.17, HBA 8, HBD 3, PSA 114.2, QED 0.19
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: MPISIZFSGAZROV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S triple mutant (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 601.18, ALogP 4.21, HBA 10, HBD 3, PSA 114.96, QED 0.33
Compound (SMILES): CCCN(CCCCOCCOCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)C)C[C@@H](C)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: LNVXIMZTYRLPDR-UYNIEJFQSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant HDAC5 (unknown origin) using Boc-Lys(TFA)-AMC as substrate by fluorescence based plate reader assay
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 987.16, ALogP 5.66, HBA 14, HBD 4, PSA 210.58, QED 0.06
Compound (SMILES): CCC[C@H](C)COc1ccc([C@H](Cn2cc(CO)nn2)NC(=O)[C@@H](C)c2ccccc2)cc1
InChIKey: JFKYLVWNOYDKGA-RLSLOFABSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay
Measurement: EC50 = 48.98 nM (pChEMBL 7.309999942779541)
Descriptors: MW 450.58, ALogP 4.25, HBA 6, HBD 2, PSA 89.27, QED 0.43
Compound (SMILES): CS(=O)(=O)c1cccc(Cc2nnc(Cc3c[nH]c4cc(F)ccc34)n2CCCc2c[nH]cn2)c1
InChIKey: UROWFMUIRALGKF-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay
Measurement: EC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 492.58, ALogP 3.84, HBA 6, HBD 2, PSA 109.32, QED 0.32
Compound (SMILES): NCCCNCCCCNc1ccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3c2ncn3C2CCCC2)cc1
InChIKey: IWXVPEORISOBQZ-SAIGFBBZSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of PDGFRalpha (unknown origin)
Measurement: IC50 = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 534.76, ALogP 4.5, HBA 10, HBD 6, PSA 143.76, QED 0.16
Compound (SMILES): O=C1CCc2ccc(OCCCCN3CCN(C(=O)c4ccccn4)CC3)cc2N1
InChIKey: NKPZUJWHJYTWEE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor expressed in CHO-K1 cells measured after 1.5 hrs by Microbeta plate reader method
Measurement: Ki = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 408.5, ALogP 2.58, HBA 5, HBD 1, PSA 74.77, QED 0.71
Compound (SMILES): CN1CCC(N(Cc2ccc(F)cn2)C(=O)NCc2ccc(OCC(F)F)cc2)CC1
InChIKey: HHKZUYBSKLUYKA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Inverse agonist activity at 5-HT2A receptor (unknown origin) expressed in mouse NIH3T3 cells using o-nitrophenyl-D-galacto pyranoside incubated for 120 hrs
Measurement: IC50 = 6.01 nM (pChEMBL 8.220000267028809)
Descriptors: MW 436.48, ALogP 3.67, HBA 4, HBD 1, PSA 57.7, QED 0.69
Compound (SMILES): O=C(NCC#Cc1ccc(Nc2ncnc3c2ncn3[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc1)c1ccccc1
InChIKey: PLMNEORRSOTQPT-RKCWLVDCSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Agonist activity at human A1 receptor expressed in Flp-In-CHO cells assessed as stimulation of calcium mobilization by calcium mobilization assay
Measurement: EC50 = 74.13 nM (pChEMBL 7.130000114440918)
Descriptors: MW 500.52, ALogP 0.96, HBA 10, HBD 5, PSA 154.65, QED 0.24
Compound (SMILES): Cn1c(=O)[nH]c(=O)c2c1nc(Cc1nc3cc(NC(=O)CC[C@H](N)C(=O)O)ccc3[nH]1)n2Cc1ccccc1
InChIKey: YQQGCBNTUKQEBJ-INIZCTEOSA-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 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 530.55, ALogP 1.07, HBA 9, HBD 5, PSA 193.78, QED 0.19
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](O)[C@H](n5cc(-c6ccc(COc7cccc8ccccc78)cc6)c6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: DBFLURMMWIAUJW-DANBCEJISA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at human wild type full length STING expressed in 293T cells incubated for 7 hrs by luciferase/cell based assay
Measurement: EC50 = 2580 nM (pChEMBL 5.590000152587891)
Descriptors: MW 905.71, ALogP 2.66, HBA 20, HBD 7, PSA 325.99, QED 0.12
Compound (SMILES): CCOc1ccc2[nH]c(Cc3nc4c(c(=O)[nH]c(=O)n4CC)n3Cc3ccccc3)nc2c1
InChIKey: CPISMKNBAXDQEB-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWU9
Assay: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 444.5, ALogP 2.82, HBA 7, HBD 2, PSA 110.59, QED 0.4
Compound (SMILES): O=C(CS(=O)(=O)c1ccc(-c2ccccc2)cc1)NO
InChIKey: HYBHKZKKEGAPOP-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of MMP-2 (unknown origin)
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 291.33, ALogP 1.63, HBA 4, HBD 2, PSA 83.47, QED 0.66
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: JESVEDAOUMZINK-VYDIVQSQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 3115.69
Compound (SMILES): CCOc1nc(C(=O)NCC(=O)O)c(O)c2ccc(Oc3ccccc3)cc12
InChIKey: TXMLZQNXTUAMCS-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 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 382.37, ALogP 2.95, HBA 6, HBD 3, PSA 117.98, QED 0.57
Compound (SMILES): COc1cc(N2CCC3(CCN(C)CC3)CC2)c(C)cc1Nc1ncc(Cl)c(Nc2ccccc2P(C)(C)=O)n1
InChIKey: XQEYPEQDMUAORO-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK L1196M mutant (unknown origin) using biotinylated substrate incubated for 1 hr in the presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 583.12, ALogP 6.49, HBA 8, HBD 2, PSA 82.62, QED 0.31
Compound (SMILES): Brc1cccc(-c2nccc3c2[nH]c2ccccc23)c1
InChIKey: LJDAUNCFNFQWMR-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of TDO (unknown origin) assessed as reduction in N-formylkynurenine formation using L-tryptophan as substrate incubated for 75 mins by UV absorbance based analysis
Measurement: IC50 = 20290 nM (pChEMBL 4.690000057220459)
Descriptors: MW 323.19, ALogP 5.15, HBA 1, HBD 1, PSA 28.68, QED 0.52
Compound (SMILES): CCNNC(=O)c1coc(-c2ccc(Br)cc2)c1
InChIKey: HNSSFJBAQLSNOA-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 309.16, ALogP 2.96, HBA 3, HBD 2, PSA 54.27, QED 0.85
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)NCCCC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)COCCOCCNC(=O)c1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(=O)O)C(=O)NCCOCCOCC(=O)N[C@H]1CSCC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: RXLQPJAGXHHDMC-VMQDGMSWSA-N
Target: Albumin (SINGLE PROTEIN), Homo sapiens
UniProt: P02768
Assay: Binding affinity to human serum albumin by fluorescence polarization assay
Measurement: Kd = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 2781.11
Compound (SMILES): CCCCC[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2ccc(-c3ccccc3)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2[C@@H](c3ccccc3)CCN2CC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)CSSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC1=O
InChIKey: GMILEDVLYQQFCU-DZKKRDKRSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS in human ASPC1 cells harboring KRAS G12D mutant assessed as inhibition of ERK phosphorylation incubated for 2 hrs by AlphaScreen-based LDH membrane integrity assay
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 2114.58
Compound (SMILES): O=C(NCc1ccccc1C(=O)N[C@H](/C=C/S(=O)(=O)Oc1ccccc1)CCc1ccccc1)c1ccncc1
InChIKey: NRMMQFXZSPQQES-JUTYNXCLSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Irreversible inhibition of human Cathepsin L assessed as inhibition constant using Cbz-Phe-Arg-AMC as fluorogenic substrate by fluorometric assay
Measurement: Ki = 1150 nM (pChEMBL 5.940000057220459)
Descriptors: MW 555.66, ALogP 4.67, HBA 6, HBD 2, PSA 114.46, QED 0.25
Compound (SMILES): Cn1nc(C(=O)OCCCCNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)cc1COc1cccc([C@@H](NC(=O)O[C@H]2CN3CCC2CC3)c2ccccc2)c1
InChIKey: YWSIONULMMKTSJ-UZGNFBRWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 764.88, ALogP 4.72, HBA 12, HBD 5, PSA 180.27, QED 0.07
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)NCCCC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C(C)C)C(=O)O)C(=O)O
InChIKey: WVNFJUKQLUXMAI-UQKJNECSSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP1R expressed in frozen cells assessed as increase in cAMP production measured after 1 hr by HitHunter luminescence assay
Measurement: EC50 = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 3943.46
Compound (SMILES): COc1cc2ccn(C/C=C/C(=O)NCCCc3ccccc3)c(=O)c2cc1OC
InChIKey: NXLXBPDLHPZMCS-YRNVUSSQSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S constitutive proteosome beta5c subunit (unknown origin) assessed as substrate hydrolysis using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic substrate at 100 uM
Measurement: Ki = 10610 nM (pChEMBL 4.96999979019165)
Descriptors: MW 406.48, ALogP 3.32, HBA 5, HBD 1, PSA 69.56, QED 0.44
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCCN1CCN(c2ncccn2)CC1
InChIKey: CAWIYYLHESHZSB-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 = 2290.87 nM (pChEMBL 5.639999866485596)
Descriptors: MW 351.45, ALogP 1.97, HBA 5, HBD 0, PSA 52.57, QED 0.82
Compound (SMILES): Cn1ccnc1SCC1CCN(S(=O)(=O)c2ccc3ncccc3c2)CC1
InChIKey: XGGXPLTZWPQMAD-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Antagonist activity at human muscarinic M5 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by Fluo-4AM staining based fluorescence assay
Measurement: IC50 = 1380.38 nM (pChEMBL 5.860000133514404)
Descriptors: MW 402.55, ALogP 3.16, HBA 6, HBD 0, PSA 68.09, QED 0.61
Compound (SMILES): O=C(NC(=S)Nc1cc(Br)cc(C(F)(F)F)c1)c1ccc2c(c1)OCO2
InChIKey: PEIZZQHVKWDXRU-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity against human P2X7R stably transfected in human 1321N1 cells incubated for 30 mins by Fura-2 AM staining based calcium influx assay
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 447.23, ALogP 4.32, HBA 4, HBD 2, PSA 59.59, QED 0.67
Compound (SMILES): CN(c1ncnc2[nH]ccc12)N1CCCC(C(=O)NCC#N)C1
InChIKey: ZSDNEXABROUHAK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin)
Measurement: IC50 = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 313.37, ALogP 0.66, HBA 6, HBD 2, PSA 100.94, QED 0.8
Compound (SMILES): C[C@H]1CN(Cc2ccc(/C=C/C(=O)NO)cc2)C[C@@H]1c1nc2c(cnn2C2CCOCC2)c(=O)[nH]1
InChIKey: ZRIDRENRJOMKEQ-XSKGNTKESA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 478.55, ALogP 2.23, HBA 8, HBD 3, PSA 125.37, QED 0.28
Compound (SMILES): COCCO[C@H]1CC[C@H](NC(=O)c2cc(-c3cncs3)nc3[nH]ccc23)CC1
InChIKey: JUVJFMVGYBBDKN-HDJSIYSDSA-N
Target: ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P56528
Assay: Inhibition of mouse his tagged CD38 using N6-etheno-NAD as substrate by fluorescence microplate reader assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 400.5, ALogP 3.39, HBA 6, HBD 2, PSA 89.13, QED 0.59
Compound (SMILES): CCn1ccnc1SCC1CCN(S(=O)(=O)c2ccc3c(c2)CCO3)CC1
InChIKey: GLDMGNCZSOFLHW-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Antagonist activity at human muscarinic M5 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by Fluo-4AM staining based fluorescence assay
Measurement: IC50 = 120.23 nM (pChEMBL 6.920000076293945)
Descriptors: MW 407.56, ALogP 3.03, HBA 6, HBD 0, PSA 64.43, QED 0.69
Compound (SMILES): C=CC(=O)Nc1cccc(OC)c1Nc1n[nH]c2ccc(O[C@H](C)c3c(Cl)cncc3Cl)cc12
InChIKey: UXDICIZXQDTXGA-CYBMUJFWSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown orgin) using Tyr 04 peptide as substrate incubated for 1 hr in presence of 25 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.37, ALogP 6.28, HBA 6, HBD 3, PSA 101.16, QED 0.25
Compound (SMILES): Cc1ccccc1NC(=O)c1ccc(NC(=O)N2CCN(C(=O)c3cc(Cc4n[nH]c(=O)c5ccccc45)ccc3F)CC2)cc1
InChIKey: ANAQCVXUMUTPJY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of TNKS1 (unknown origin) using biotin-NAD+ as substrate incubated for 1 hr in the presence of deoxy-oligonucleotide by ELISA analysis relative to control
Measurement: IC50 = 130.5 nM (pChEMBL 6.880000114440918)
Descriptors: MW 618.67, ALogP 5.2, HBA 5, HBD 3, PSA 127.5, QED 0.24
Compound (SMILES): CCOc1ccc(F)cc1NC(=O)c1ccccc1NS(=O)(=O)C1CC1
InChIKey: TXZPRVKJSAUJSV-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LB2
Assay: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay
Measurement: EC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 378.43, ALogP 3.38, HBA 4, HBD 2, PSA 84.5, QED 0.77
Compound (SMILES): CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCNC(=O)c3ccc(C(=O)NCCOCCOCCOCCNS(=O)(=O)c4cccc(C5CN(C)Cc6c(Cl)cc(Cl)cc65)c4)cc3)c2)C1
InChIKey: NMZATJZWHZOUID-UHFFFAOYSA-N
Target: Sodium/hydrogen exchanger 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P26433
Assay: Inhibition of rat NHE3 expressed in opossum kidney cells assessed as reduction in Na-HEPES buffer-mediated pH recovery in presence of NEH1 inhibitor ethyl isopropyl amiloride by BCECF-AM dye based fluorescence assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1223.14
Compound (SMILES): C[C@@H]1CCCN1Cc1ccc(-c2cnc(N)c3c2CCN(C2CCCCC2)C3=O)cc1
InChIKey: SMMLJZCTRMSMMI-GOSISDBHSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of ALK2 (unknown origin)
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 418.59, ALogP 4.65, HBA 4, HBD 1, PSA 62.46, QED 0.79
Compound (SMILES): CN(CC[C@H](N)C(=O)O)C[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H]1O
InChIKey: JISVTSUBJCPLSV-PVYXKRRNSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 Y641N mutant (unknown origin)
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 381.39, ALogP -2.24, HBA 11, HBD 5, PSA 185.87, QED 0.35
Compound (SMILES): C[C@@]12CC[C@H]3[C@H](CCC4=C/C(=N\OCC(=O)N[C@@H](CCC(=O)O)C(=O)O)CC[C@]43C)[C@@H]1CC[C@@H]2O
InChIKey: BKULYGKWNYMZML-REBOFDGXSA-N
Target: Hepatic sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q14973
Assay: Inhibition of human NTCP mediated TCA uptake in HEK293 cells overexpressing NTCP preincubated for 5 mins followed by substrate addition and measured after 10 mins using [3H] taurocholic acid as substrate by liquid scintillation counter analysis
Measurement: IC50 = 51000 nM (pChEMBL 4.289999961853027)
Descriptors: MW 490.6, ALogP 3.12, HBA 6, HBD 4, PSA 145.52, QED 0.38
Compound (SMILES): CCNNC(=O)c1ccc(CN2c3ccccc3Oc3ccccc32)cc1
InChIKey: VIEOKDIWSWZOQL-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 359.43, ALogP 4.38, HBA 4, HBD 2, PSA 53.6, QED 0.66
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CSCc2ccccc2CSC(C)(C)[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: YRPCDHHSQYGEDU-SIXPOYHZSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Displacement of [125I]NDP-alpha-MSH from human MC1R expressed in HEK293 cells by competitive binding assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 1135.43
Compound (SMILES): CC1(N)CCN(c2cc(=O)n(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: ARBJGNWDHYZZEL-UHFFFAOYSA-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 = 180 nM (pChEMBL 6.75)
Descriptors: MW 368.27, ALogP 2.44, HBA 6, HBD 2, PSA 90.17, QED 0.85
Compound (SMILES): CNNC(=O)c1ccc(CNC(=O)c2ccccc2)cc1
InChIKey: UUYIULJWMUPBSX-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (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 = 878 nM (pChEMBL 6.059999942779541)
Descriptors: MW 283.33, ALogP 1.48, HBA 3, HBD 3, PSA 70.23, QED 0.73
Compound (SMILES): O=C(Nc1cnc(CN2CCNCC2)nc1)c1cc(C(=O)c2c(Cl)ccc(Cl)c2F)c[nH]1
InChIKey: BTHFZZGILQJRRF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13164
Assay: Inhibition of ERK5 phosphorylation in human HeLa cells incubated for 1 hr by Western blot densitometry analysis
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 477.33, ALogP 3.14, HBA 6, HBD 3, PSA 103.01, QED 0.37
Compound (SMILES): O=C(NCCCCCCCCCCO)[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: XITLYMQUBWKORI-GIUVAWJUSA-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 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 949.21, ALogP 6.31, HBA 7, HBD 5, PSA 177.25, QED 0.06
Compound (SMILES): Cc1ccc(NC(=S)NC(=O)C23CC4CC(CC(C4)C2)C3)c(Br)c1
InChIKey: YTLBMCWFPSKSTC-UHFFFAOYSA-N
Target: P2X purinoceptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99571
Assay: Antagonist activity at human P2X4 receptor expressed in human 1321N1 cells assessed as reduction in intracellular Ca2+ influx incubated for 30 mins by Fura-2 AM based fluorescence assay
Measurement: IC50 = 1562 nM (pChEMBL 5.809999942779541)
Descriptors: MW 407.38, ALogP 4.79, HBA 2, HBD 2, PSA 41.13, QED 0.69
Compound (SMILES): Fc1cc(F)c(F)c(-c2ccc(NC[C@@H]3CC34CCN(CC3CCOCC3)CC4)nn2)c1
InChIKey: KRMYNVCNISSHTN-KRWDZBQOSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Inhibition of human muscarinic acetylcholine M4 receptor expressed in CHO cells co-expressing Gqi5 in the presence of acetylcholine at EC80 concentration by calcium mobilization assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 446.52, ALogP 4.5, HBA 5, HBD 1, PSA 50.28, QED 0.66
Compound (SMILES): CCCn1c(=O)c2[nH]c(-c3cccc(OS(=O)(=O)F)c3)nc2n(CCC)c1=O
InChIKey: RMEHELNLDXUWDI-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine A2B receptor expressed in CHO cell membrane preincubated for 4 hrs followed by [3H]PSB-603 addition and measured after 0.5 hrs by radioligand displacement assay
Measurement: Ki = 524.81 nM (pChEMBL 6.28000020980835)
Descriptors: MW 410.43, ALogP 1.97, HBA 8, HBD 1, PSA 116.05, QED 0.6
Compound (SMILES): Cc1cccc2c1OC[C@H]2C[C@H](NC(=O)Cc1ccccc1C#N)B(O)O
InChIKey: INMJTQBLTOORGH-AEFFLSMTSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human 20S proteasome beta5 subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 364.21
Compound (SMILES): COc1cc(N2CCN(CCCCCCCCCCCCNC(=O)CC34CC5CC(CC(C5)C3)C4)CC2)ccc1Nc1ncc2c(C)cc(=O)n(-c3cccc(NC(=O)C4CC4)c3)c2n1
InChIKey: KLSALARRZCZNDM-UHFFFAOYSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Induction of AKT2 degradation in human NCI-H1975 cells assessed as reduction in AKT2 protein level incubated for 24 hrs under serum free medium by Western blot analysis
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 885.21, ALogP 9.94, HBA 10, HBD 3, PSA 133.72, QED 0.07