lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: GPCRScan assay: inhibition of D4
Measurement: Ki = 5.495 nM (pChEMBL 8.260000228881836)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1cc(C(F)(F)F)ccc1-c1cc2cnn([C@@H](CC(C)C)c3ccc(C(=O)NCCC(=O)O)cc3)c2cc1C
InChIKey: GLNZNFHAEQNMBZ-MHZLTWQESA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using dextromethorphan as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 551.61, ALogP 7.18, HBA 4, HBD 2, PSA 84.22, QED 0.23
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Inhibition of Gal4-tagged FXR LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant human carbonic anhydrase 6 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): C[C@@H]1COCCN1c1nc(N2CCOC[C@@H]2C)nc2[nH]c(-c3cccc4[nH]ccc34)nc12
InChIKey: BYPBFDASESWSQG-CABCVRRESA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 1980 nM (pChEMBL 5.699999809265137)
Descriptors: MW 433.52, ALogP 2.95, HBA 7, HBD 2, PSA 95.19, QED 0.51
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: WXARPUMZGIXGKS-CZVJXMOHSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P32214
Assay: Displacement of [125I]-labeled rat amylin from rat amylin receptor expressed in BHK tkts13 cell membranes co-expressing RAMP3 incubated for 120 mins by scintillation proximity assay
Measurement: IC50 = 0.046 nM (pChEMBL 10.34000015258789)
Descriptors: MW 3716.21
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant human carbonic anhydrase 6 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Ca2+ assay (human TRAP1)
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): CC(C)c1cc(C(=O)N(C)c2ccc(NC(=O)CCCCCCC(=O)NO)cc2)c(O)cc1O
InChIKey: NRTQVEBKTMOYBI-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC7 (518 to 991 residues) expressed in baculovirus infected insect cells using Boc-K(Ac)-AMC as substrate after 90 mins by fluorimetry analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 471.55, ALogP 4.28, HBA 6, HBD 5, PSA 139.2, QED 0.19
Compound (SMILES): COc1ccc2c(c1)SC(=S)N1CCN=C21
InChIKey: BYIFHHTYFILUMK-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human C-terminal His-tagged N-terminal GST-tagged HDAC7 (518 to end residues) expressed in baculovirus infected Sf9 cells using Boc-Lys(TFA)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 250.35, ALogP 2.15, HBA 4, HBD 0, PSA 24.83, QED 0.71
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of TGFbetaR1 in anti-CD3/anti-CD28/IL-2/TGFbeta -stimulated human Treg cells assessed as downregulation of FOXP3 expression incubated for 5 days by flow cytometry analysis
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes
Measurement: IC50 = 21780 nM (pChEMBL 4.659999847412109)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): CC1=NC2(CCN(C)CC2)C(=O)N(c2c(C)cccc2C)C1=O
InChIKey: UOZGZTQNYJCRFH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]LSD from human 5-HT2B receptor expressed in HEK cells by radioligand binding assay
Measurement: Ki = 231 nM (pChEMBL 6.639999866485596)
Descriptors: MW 313.4, ALogP 2.1, HBA 4, HBD 0, PSA 52.98, QED 0.75
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(C(N)=O)cc3)CC2)nc2c1COC2
InChIKey: WIZBIQCUWVRTIO-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells at -80 mV holding potential by manual patch clamp assay
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 498.59, ALogP 3.96, HBA 8, HBD 2, PSA 126.39, QED 0.5
Compound (SMILES): CCN(C)C1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: JFKXPYCYZANQTG-JGKVKWKGSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 262.33, ALogP -1.15, HBA 7, HBD 3, PSA 85.52, QED 0.58
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(Cc2csc(-c4cccc(Cl)c4)n2)C3)n(C)c1=O
InChIKey: JFIAUWNUIUKPBJ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human A3 receptor expressed in CHO cell membrane by liquid scintillation counting method relative to control
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 442.93, ALogP 2.23, HBA 9, HBD 0, PSA 77.95, QED 0.49
Compound (SMILES): N#Cc1ccc2c(C(C[N+](=O)[O-])c3cccs3)c(-c3ccccc3)[nH]c2c1
InChIKey: HBOPEEJOMPTPGH-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulation of human Gi/Go-coupled CB1 receptor expressed in CHOK1 cells assessed as increase in CP55940-induced inhibition of forskolin-stimulated cAMP production preincubated for 30 mins followed by CP55940 addition and measured after 30 to 60 mins by Hit-hunter assay
Measurement: EC50 = 181 nM (pChEMBL 6.739999771118164)
Descriptors: MW 373.44, ALogP 5.18, HBA 4, HBD 1, PSA 82.72, QED 0.39
Compound (SMILES): CCc1cccc(N2CCN(C[C@@H](O)CCNC(=O)c3cc4ccccc4[nH]3)CC2)c1Cl
InChIKey: OIRZLTZLOKARTG-FQEVSTJZSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5-HT1A receptor (unknown origin) assessed as stimulation of [35S]GTPgammaS binding
Measurement: EC50 = 2060 nM (pChEMBL 5.690000057220459)
Descriptors: MW 455, ALogP 3.69, HBA 4, HBD 3, PSA 71.6, QED 0.49
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Binding affinity to DNA-tagged recombinant BTK (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd = 0.63 nM (pChEMBL 9.199999809265137)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Mus musculus
UniProt: P97477
Assay: Caliper Kinase Assay: The analyses were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 μl of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 39840 nM (pChEMBL 4.400000095367432)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)CN)C(C)C)CSSC[C@H]2NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CSSC[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)[C@H]([C@@H](C)CC)NC2=O
InChIKey: IWNWXPRWSFWNMU-GYSAZADJSA-N
Target: Tissue-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00750
Assay: Inhibition of tPA (unknown origin) incubated for 30 mins measured for 7 mins by morrison plot analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 3471
Compound (SMILES): Cc1cccc(Cn2nc(C)c3c(NC(=O)c4csc5c(N)ncnc45)cccc32)n1
InChIKey: KZVIZFHCMVWFNT-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Inhibition of recombinant human N-terminal His6-tagged DDR2 (467 to end residues) expressed in baculovirus infected Sf21 insect cells using Axltide as substrate in presence of [gamma-33P]-ATP or [gamma-32P]-ATP
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 429.51, ALogP 3.94, HBA 8, HBD 2, PSA 111.61, QED 0.45
Compound (SMILES): Cl.NCc1ccc(-n2c(-c3cccnc3N)nc3ccc(-c4ccccc4)nc32)cc1
InChIKey: UAUMLXOVAOBIIT-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using bufuralol as substrate after 10 mins by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 392.47, ALogP 4.19, HBA 6, HBD 2, PSA 95.64, QED 0.48
Compound (SMILES): COc1cccc(-c2ccc(NC(=O)Nc3ccc(Cl)cc3)s2)c1
InChIKey: ONNBCDSUCDVCHG-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: P47746
Assay: Allosteric modulator activity at CB1 receptor in mouse cerebellar membranes assessed as suppression of 100 nM CP55,940-induced [35S]GTPgammaS binding incubated for 60 mins by scintillation counting method
Measurement: IC50 = 3019.95 nM (pChEMBL 5.519999980926514)
Descriptors: MW 358.85, ALogP 5.72, HBA 3, HBD 2, PSA 50.36, QED 0.63
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): C=CCCn1cc(-c2cc(C(=O)N3CCOCC3)c3ncn(C)c3c2)c2cc[nH]c2c1=O
InChIKey: CBGFEMSXMIJQKG-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Inhibition of recombinant His-tagged CECR2 (unknown origin) after 10 mins by TR-FRET assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 431.5, ALogP 2.93, HBA 6, HBD 1, PSA 85.15, QED 0.49
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-NXHRWCDGSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Enzyme Assay: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z′-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen Biochemical Kinase Profiling Service. The Z′-LYTE biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores one at each end that make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophore on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CCN1CCN(c2cc(Nc3ncc(-c4ccncc4)s3)nc(C)n2)CC1.Cl
InChIKey: SNLQNYOOKITUPG-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild type FLT3 ITD/D835Y double mutant (unknown origin) expressed in HEK293T cells assessed as decrease in FLT3 ITD/D835Y autophosphorylation at 0.1 to 1000 nM after 1 hr by Western blot analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 381.51, ALogP 3.19, HBA 8, HBD 1, PSA 70.07, QED 0.73
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: GPCRScan assay: inhibition of MOR
Measurement: Ki = 2781 nM (pChEMBL 5.559999942779541)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Inhibition of Gal4-tagged RXRalpha LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human carbonic anhydrase 7 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: WXARPUMZGIXGKS-CZVJXMOHSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled rat calcitonin from human calcitonin receptor expressed in BHK tkts13 cell membranes incubated for 1 hr by scintillation proximity assay
Measurement: IC50 = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 3716.21
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human carbonic anhydrase 7 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q6RI86
Assay: FLIPR Ca2+ assay (rat TRPA1)
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): CC(C)c1cc(C(=O)N(C)c2ccc(NC(=O)CCCCCCC(=O)NO)cc2)c(O)cc1O
InChIKey: NRTQVEBKTMOYBI-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant C-terminal His-fusion tagged and N-terminal Streptavidin2-tagged human HDAC8 (1 to 377 residues) expressed in insect cells using RHK-K(Ac)-AMC as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 422 nM (pChEMBL 6.380000114440918)
Descriptors: MW 471.55, ALogP 4.28, HBA 6, HBD 5, PSA 139.2, QED 0.19
Compound (SMILES): COc1ccc2c(c1)SC(=S)N1CCN=C21
InChIKey: BYIFHHTYFILUMK-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length N-terminal His6/SUMO-tagged HDAC8 expressed in Escherichia coli BL21 DE3 using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 250.35, ALogP 2.15, HBA 4, HBD 0, PSA 24.83, QED 0.71
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant CYP1A2 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): CC1=NC2(CCN(C)CC2)C(=O)N(c2c(C)cccc2C)C1=O
InChIKey: UOZGZTQNYJCRFH-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]Pentazocine from guinea pig sigma-1 receptor by radioligand binding assay
Measurement: Ki = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 313.4, ALogP 2.1, HBA 4, HBD 0, PSA 52.98, QED 0.75
Compound (SMILES): CCN(C)C1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: JFKXPYCYZANQTG-JGKVKWKGSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 262.33, ALogP -1.15, HBA 7, HBD 3, PSA 85.52, QED 0.58
Compound (SMILES): CCc1cccc(N2CCN(C[C@@H](O)CCNC(=O)c3cc4ccccc4[nH]3)CC2)c1Cl
InChIKey: OIRZLTZLOKARTG-FQEVSTJZSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Radioligand Binding Assay: Binding at dopamine D2-like receptors was determined using previously described methods. Membranes were prepared from HEK293 cells expressing human D2R, D3R or D4R, grown in a 50:50 mix of DMEM and Ham's F12 culture media, supplemented with 20 mM HEPES, 2 mM L-glutamine, 0.1 mM non-essential amino acids, 1× antibiotic/antimycotic, 10% heat-inactivated fetal bovine serum, and 200 μg/mL hygromycin (Life Technologies, Grand Island, N.Y.) and kept in an incubator at 37° C. and 5% CO2. Upon reaching 80-90% confluence, cells were harvested using pre-mixed Earle's Balanced Salt Solution (EBSS) with 5 μM EDTA (Life Technologies) and centrifuged at 3000 rpm for 10 min at 21° C. The supernatant was removed and the pellet was resuspended in 10 mL hypotonic lysis buffer (5 mM MgCl2.6H2O, 5 mM Tris, pH 7.4 at 4° C.) and centrifuged at 20,000 rpm for 30 min at 4° C. The pellet was then resuspended in fresh EBSS buffer made from 8.7 g/L Earle's Balanced Salts without phenol red (US Biological, Salem, Mass.), 2.2 g/L sodium bicarbonate, pH to 7.4. A Bradford protein assay (Bio-Rad, Hercules, Calif.) was used to determine the protein concentration and membranes were diluted to 500 μg/mL and stored in a −80° C. freezer for later use.
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 455, ALogP 3.69, HBA 4, HBD 3, PSA 71.6, QED 0.49
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Binding affinity to DNA-tagged recombinant BMX (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Caliper Kinase Assay: The analyses were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 μl of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 33810 nM (pChEMBL 4.46999979019165)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)CN)C(C)C)CSSC[C@H]2NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CSSC[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)[C@H]([C@@H](C)CC)NC2=O
InChIKey: IWNWXPRWSFWNMU-GYSAZADJSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of uPA (unknown origin) incubated for 30 mins measured for 7 mins by morrison plot analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 3471
Compound (SMILES): Cc1cccc(Cn2nc(C)c3c(NC(=O)c4csc5c(N)ncnc45)cccc32)n1
InChIKey: KZVIZFHCMVWFNT-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of recombinant human N-terminal GST-tagged c-RAF Y340D/Y341D double mutant (306 to 648 residues) expressed in baculovirus infected Sf21 insect cells using MEK1(K97R) as substrate in presence of [gamma-33P]-ATP or [gamma-32P]-ATP
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 429.51, ALogP 3.94, HBA 8, HBD 2, PSA 111.61, QED 0.45
Compound (SMILES): Cl.NCc1ccc(-n2c(-c3cccnc3N)nc3ccc(-c4ccccc4)nc32)cc1
InChIKey: UAUMLXOVAOBIIT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate after 10 mins by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 392.47, ALogP 4.19, HBA 6, HBD 2, PSA 95.64, QED 0.48
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Antagonist activity at C-terminal RLuc8-fused D1R (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay
Measurement: IC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-NXHRWCDGSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: GPCRScan assay: inhibition of MOR
Measurement: Ki = 2754.23 nM (pChEMBL 5.559999942779541)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Inhibition of Gal4-tagged ERalpha LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 18 nM (pChEMBL 7.75)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: WXARPUMZGIXGKS-CZVJXMOHSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Displacement of [125I]-labeled rat amylin from human amylin receptor expressed in BHK tkts13 whole cells co-expressing RAMP3 incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 1.067 nM (pChEMBL 8.970000267028809)
Descriptors: MW 3716.21
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1 nM (pChEMBL 9)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BLA8
Assay: FLIPR Ca2+ assay (mouse TRPA1)
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): CC(C)c1cc(C(=O)N(C)c2ccc(NC(=O)CCCCCCC(=O)NO)cc2)c(O)cc1O
InChIKey: NRTQVEBKTMOYBI-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of human HDAC9 using (Boc-Lys(trifluoroacetyl)-AMC) as substrate by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 471.55, ALogP 4.28, HBA 6, HBD 5, PSA 139.2, QED 0.19
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of recombinant CYP2C8 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 = 24190 nM (pChEMBL 4.619999885559082)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): CC1=NC2(CCN(C)CC2)C(=O)N(c2c(C)cccc2C)C1=O
InChIKey: UOZGZTQNYJCRFH-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma-2 receptor in rat PC12 cells by radioligand binding assay
Measurement: Ki = 696 nM (pChEMBL 6.159999847412109)
Descriptors: MW 313.4, ALogP 2.1, HBA 4, HBD 0, PSA 52.98, QED 0.75
Compound (SMILES): CCN(C)C1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: JFKXPYCYZANQTG-JGKVKWKGSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin) assessed as CYP3A4 induction
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 262.33, ALogP -1.15, HBA 7, HBD 3, PSA 85.52, QED 0.58
Compound (SMILES): CCc1cccc(N2CCN(C[C@@H](O)CCNC(=O)c3cc4ccccc4[nH]3)CC2)c1Cl
InChIKey: OIRZLTZLOKARTG-FQEVSTJZSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Radioligand Binding Assay: Binding at dopamine D2-like receptors was determined using previously described methods. Membranes were prepared from HEK293 cells expressing human D2R, D3R or D4R, grown in a 50:50 mix of DMEM and Ham's F12 culture media, supplemented with 20 mM HEPES, 2 mM L-glutamine, 0.1 mM non-essential amino acids, 1× antibiotic/antimycotic, 10% heat-inactivated fetal bovine serum, and 200 μg/mL hygromycin (Life Technologies, Grand Island, N.Y.) and kept in an incubator at 37° C. and 5% CO2. Upon reaching 80-90% confluence, cells were harvested using pre-mixed Earle's Balanced Salt Solution (EBSS) with 5 μM EDTA (Life Technologies) and centrifuged at 3000 rpm for 10 min at 21° C. The supernatant was removed and the pellet was resuspended in 10 mL hypotonic lysis buffer (5 mM MgCl2.6H2O, 5 mM Tris, pH 7.4 at 4° C.) and centrifuged at 20,000 rpm for 30 min at 4° C. The pellet was then resuspended in fresh EBSS buffer made from 8.7 g/L Earle's Balanced Salts without phenol red (US Biological, Salem, Mass.), 2.2 g/L sodium bicarbonate, pH to 7.4. A Bradford protein assay (Bio-Rad, Hercules, Calif.) was used to determine the protein concentration and membranes were diluted to 500 μg/mL and stored in a −80° C. freezer for later use.
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 455, ALogP 3.69, HBA 4, HBD 3, PSA 71.6, QED 0.49
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Binding affinity to DNA-tagged recombinant TEC (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Caliper Kinase Assay: The analyses were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 μl of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 19170 nM (pChEMBL 4.71999979019165)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): Cc1cccc(Cn2nc(C)c3c(NC(=O)c4csc5c(N)ncnc45)cccc32)n1
InChIKey: KZVIZFHCMVWFNT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of recombinant human N-terminal GST-tagged FGFR1 (456 to 765 residues) expressed in baculovirus infected Sf21 insect cells using IGF-IRtide (12-527) as substrate in presence of [gamma-33P]-ATP or [gamma-32P]-ATP
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 429.51, ALogP 3.94, HBA 8, HBD 2, PSA 111.61, QED 0.45
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Antagonist activity at C-terminal RLuc8-fused D1R (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay
Measurement: IC50 = 232.4 nM (pChEMBL 6.630000114440918)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human carbonic anhydrase 13 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-NXHRWCDGSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: GPCRScan assay: inhibition of KOR
Measurement: Ki = 2784.5 nM (pChEMBL 5.550000190734863)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Inhibition of Gal4-tagged PPARgamma LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: WXARPUMZGIXGKS-CZVJXMOHSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 whole cells incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 1.527 nM (pChEMBL 8.819999694824219)
Descriptors: MW 3716.21
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: ANK_REP_REGION domain-containing protein (SINGLE PROTEIN), Cavia porcellus
UniProt: H0VJD1
Assay: FLIPR Ca2+ assay (guinea pig TRPA1)
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): CC(C)c1cc(C(=O)N(C)c2ccc(NC(=O)CCCCCCC(=O)NO)cc2)c(O)cc1O
InChIKey: NRTQVEBKTMOYBI-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of human HDAC10 using fluorescent-labelled p53 residues 379 to 382 (RHKKAc) peptide as substrate by fluorescence assay
Measurement: IC50 = 2670 nM (pChEMBL 5.570000171661377)
Descriptors: MW 471.55, ALogP 4.28, HBA 6, HBD 5, PSA 139.2, QED 0.19