lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Compound was evaluated for inhibition of human KDR in an in vitro cell free assay measured by time-resolved fluorescence resonance energy transfer method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CNc1nc(C#Cc2ccc(Br)s2)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(C(=O)OC)C[C@H]12
InChIKey: RJBNRAHSRNPIGX-AQPYCOETSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of [3H]mazindol binding to recombinant human SERT expressed in HEK293 cell membranes preincubated for 10 mins followed by radioligand addition measured after 90 mins by micro beta scintillation counting analysis
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 504.37, ALogP 1.55, HBA 10, HBD 3, PSA 122.39, QED 0.36
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIPK1 incubated for 40 min in presence of ATP by ADP-Glo luminescence kinase assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(Cl)s4)cc31)[C@H](O)[C@@H]2O
InChIKey: QCISRXOREXVJGP-NEWQXWLQSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Mus musculus
UniProt: Q61327
Assay: Inhibition of mouse DAT expressed in HEK293 cells assessed as reduction in [3H]-DA uptake
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 457.94, ALogP 1.62, HBA 8, HBD 4, PSA 112.3, QED 0.44
Compound (SMILES): CCCN(CCCCOc1ccc2c(/C=N/O)cnn2c1)[C@H]1CCc2c(O)cccc2C1
InChIKey: HBUKKEFQANLSNF-XLKFHUSGSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells assessed as induction of renilla luciferase 2-tagged beta-arrestin-1 recruitment after 15 mins by BRET assay
Measurement: EC50 = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 436.56, ALogP 4.28, HBA 7, HBD 2, PSA 82.59, QED 0.21
Compound (SMILES): O=C(NCC(=O)N1CCCC1)Nc1ccc2cnccc2c1
InChIKey: DMIDPTCQPIJYFE-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O60678
Assay: Binding affinity to ePL-tagged human PRMT3 methyltransferase domain (211 to 531 residues) expressed in HEK293 cells assessed as protein stabilization incubated for 6 hrs by chemiluminescence based InCELL Hunter assay
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 298.35, ALogP 1.98, HBA 3, HBD 2, PSA 74.33, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)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(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: SVUZBYDIXUMDGY-WVEXBLHFSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of biotinylated K-Ras G12D mutant (unknown origin) assessed as reduction in SOS1 (564 to 1049 residues)-mediated BODIPY-GDP-GTP exchange after 1 hr by TR-FRET assay
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 2561.06
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Displacement of [3H]CGP12177 from human recombinant beta1 adrenergic receptor expressed in HEK293 cell membranes after 90 mins by beta counting method
Measurement: Ki = 10232.93 nM (pChEMBL 4.989999771118164)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): CCOC(=O)c1cc2cc(OCCCCN3CCN(c4ccccc4OC)CC3)ccn2n1
InChIKey: HSTZLQFEUGWBDW-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human Dopamine D3 receptor expressed in HEK293T cell membranes coexpressing GalphaoA incubated for 30 mins measured after 75 mins by [35S]GTPgammaS binding assay
Measurement: EC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 452.56, ALogP 3.5, HBA 8, HBD 0, PSA 68.54, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: ADP-sugar pyrophosphatase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKK9
Assay: Antagonist activity at N-terminal his6-tagged human recombinant NUDT5 (1 to 208 residues) expressed in Escherichia coli Rosetta (DE3) expressed in HEK293 cells incubated for 2 hrs by nanoBRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: XTJBTJMEXZEGIF-XIKOKIGWSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 397.4, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.62
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR autophosphorylation at Tyr1068 residue in EGFR-amplified human A-431 cells preincubated with compound for 1 hrs followed by stimulation with human recombinant EGF and measured after 10 mins by HTRF-based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CCCN(CCCCOc1ccc2c(C=O)cnn2c1)[C@H]1CCc2c(O)cccc2C1
InChIKey: NWVXCTHMKYPUKK-NRFANRHFSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells assessed as induction of renilla luciferase 2-tagged beta-arrestin-2 recruitment after 15 mins by BRET assay
Measurement: EC50 = 13.4 nM (pChEMBL 7.869999885559082)
Descriptors: MW 421.54, ALogP 4.28, HBA 6, HBD 1, PSA 67.07, QED 0.39
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Compound was evaluated for inhibition of human PDE3A in an in vitro cell free assay measured by time-resolved fluorescence resonance energy transfer method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CNc1nc(C#Cc2ccc(Br)s2)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(C(=O)OC)C[C@H]12
InChIKey: RJBNRAHSRNPIGX-AQPYCOETSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]Mesulergine from human 5-HT2C receptor
Measurement: Ki = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 504.37, ALogP 1.55, HBA 10, HBD 3, PSA 122.39, QED 0.36
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Binding affinity to wild-type human partial length RIPK1 (M1 to K305 residues) expressed in bacterial expression system incubated for 1 hr under shaking condition by Kinomescan method
Measurement: Kd = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(Cl)s4)cc31)[C@H](O)[C@@H]2O
InChIKey: QCISRXOREXVJGP-NEWQXWLQSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of [125I]RTI-55 binding to recombinant human SERT expressed in HEK293 cell membranes preincubated for 10 mins followed by radioligand addition measured after 90 mins by micro beta scintillation counting analysis
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 457.94, ALogP 1.62, HBA 8, HBD 4, PSA 112.3, QED 0.44
Compound (SMILES): CCCN(CCCCOc1ccc2c(/C=N/O)cnn2c1)[C@H]1CCc2c(O)cccc2C1
InChIKey: HBUKKEFQANLSNF-XLKFHUSGSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells assessed as induction of renilla luciferase 2-tagged beta-arrestin-2 recruitment after 15 mins by BRET assay
Measurement: EC50 = 12.1 nM (pChEMBL 7.920000076293945)
Descriptors: MW 436.56, ALogP 4.28, HBA 7, HBD 2, PSA 82.59, QED 0.21
Compound (SMILES): O=C(NCC(=O)N1CCCC1)Nc1ccc2cnccc2c1
InChIKey: DMIDPTCQPIJYFE-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O60678
Assay: Binding affinity to ePL-tagged human PRMT3 methyltransferase domain (211 to 531 residues) expressed in human A549 cells assessed as protein stabilization incubated for 6 hrs by chemiluminescence based InCELL Hunter assay
Measurement: EC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 298.35, ALogP 1.98, HBA 3, HBD 2, PSA 74.33, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)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(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: SVUZBYDIXUMDGY-WVEXBLHFSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of biotinylated K-Ras G12D mutant (unknown origin) assessed as reduction in SOS1 (564 to 1049 residues)-mediated BODIPY-GDP-GTP exchange after 1 hr in presence of DTT by TR-FRET assay
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 2561.06
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [3H]CGP12177 from human recombinant beta2 adrenergic receptor expressed in HEK293 cell membranes after 90 mins by beta counting method
Measurement: Ki = 9549.93 nM (pChEMBL 5.019999980926514)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: The following describes a microfluidic, off-chip mobility shift kinase assay used to measure inherent potency of compounds against BTK enzyme. Compounds described by embodiments of the present invention were assayed using this protocol and the data from the same is recorded in Table 2 within the column labeled: Time Dependent BTK Enzyme Assay IC50. These IC50 values are reported in ranges wherein: A<100 nM, B<1 uM, and C>1 uM.2.5× stocks of full-length human BTK (08-080) from CarnaBio USA, Inc., Natick, Mass., 1.6×ATP and appropriate kinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM Hepes, pH 7.5, and 10 mM DTT.5 uL of enzyme buffer and 7.5 uL of ATP/kinKDR peptide substrate mix were added to Matrix (#115304) 384-well, sterile, polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 27 C. Following the incubation period, reactions were stopped by adding 60 uL stop buffer consisting of 100 mM Hepes, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (Caliper Life Sciences, Mountain View, Calif.), 5% DMSO. Stopped reactions were monitored at −2 PSI, −3000 V/−700 V in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was measured by off-chip mobility shift assay measuring the charge/mass difference between substrate and product resulting from peptide phosphorylation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel, Switzerland). Compounds described by embodiments of the present invention were assayed using this protocol and the data from the same is recorded in Table 2 within the column labeled: Time Dependent PBMC BTK Enzyme Assay IC50.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: XTJBTJMEXZEGIF-XIKOKIGWSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 = 4189 nM (pChEMBL 5.380000114440918)
Descriptors: MW 397.4, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.62
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of FLAG-tagged TEC autophosphorylation in HEK293 cells incubated for 2 hrs by MSD electrochemiluminescence immunoassay
Measurement: IC50 = 14.3 nM (pChEMBL 7.840000152587891)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CCCN(CCCCOc1ccc2c(C=O)cnn2c1)[C@H]1CCc2c(O)cccc2C1
InChIKey: NWVXCTHMKYPUKK-NRFANRHFSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at ARMS2-PK2 tagged D2S receptor (unknown origin) expressed in HEK293 cells assessed as induction of EA-tagged beta-arrestin-2 recruitment incubated for 5 hrs measured after 60 mins by PathHunter assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 421.54, ALogP 4.28, HBA 6, HBD 1, PSA 67.07, QED 0.39
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Binding affinity towards human DRD3 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of RIPK1 (unknown origin) in presence of ATP by kinaseProfiler assay
Measurement: IC50 = 107.4 nM (pChEMBL 6.96999979019165)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(Cl)s4)cc31)[C@H](O)[C@@H]2O
InChIKey: QCISRXOREXVJGP-NEWQXWLQSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of [3H]mazindol binding to recombinant human SERT expressed in HEK293 cell membranes preincubated for 10 mins followed by radioligand addition measured after 90 mins by micro beta scintillation counting analysis
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 457.94, ALogP 1.62, HBA 8, HBD 4, PSA 112.3, QED 0.44
Compound (SMILES): CCCN(CCCCOc1ccc2c(/C=N/O)cnn2c1)[C@H]1CCc2c(O)cccc2C1
InChIKey: HBUKKEFQANLSNF-XLKFHUSGSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at ARMS2-PK2 tagged D2S receptor (unknown origin) expressed in HEK293 cells assessed as induction of EA-tagged beta-arrestin-2 recruitment incubated for 5 hrs measured after 60 mins by PathHunter assay
Measurement: EC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 436.56, ALogP 4.28, HBA 7, HBD 2, PSA 82.59, QED 0.21
Compound (SMILES): O=C(NCC(=O)N1CCCC1)Nc1ccc2cnccc2c1
InChIKey: DMIDPTCQPIJYFE-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O60678
Assay: Inhibition of wild type Flag-tagged human PRMT3 catalytic activity transfected in HEK293 cells assessed as reduction in H4R3me2a level incubated for 24 hrs by Western blot analysis
Measurement: IC50 = 225 nM (pChEMBL 6.650000095367432)
Descriptors: MW 298.35, ALogP 1.98, HBA 3, HBD 2, PSA 74.33, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)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(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: SVUZBYDIXUMDGY-WVEXBLHFSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Binding affinity to KRAS G12D mutant (unknown origin) assessed as dissociation constant by isothermal titration calorimetry
Measurement: Kd = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 2561.06
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma1 receptor in Hartley guinea pig brain cortex after 120 mins by scintillation counting method
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: The following describes a microfluidic, off-chip mobility shift kinase assay used to measure inherent potency of compounds against BTK enzyme. Compounds described by embodiments of the present invention were assayed using this protocol and the data from the same is recorded in Table 2 within the column labeled: Time Dependent BTK Enzyme Assay IC50. These IC50 values are reported in ranges wherein: A<100 nM, B<1 uM, and C>1 uM.2.5× stocks of full-length human BTK (08-080) from CarnaBio USA, Inc., Natick, Mass., 1.6×ATP and appropriate kinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM Hepes, pH 7.5, and 10 mM DTT.5 uL of enzyme buffer and 7.5 uL of ATP/kinKDR peptide substrate mix were added to Matrix (#115304) 384-well, sterile, polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 27 C. Following the incubation period, reactions were stopped by adding 60 uL stop buffer consisting of 100 mM Hepes, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (Caliper Life Sciences, Mountain View, Calif.), 5% DMSO. Stopped reactions were monitored at −2 PSI, −3000 V/−700 V in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was measured by off-chip mobility shift assay measuring the charge/mass difference between substrate and product resulting from peptide phosphorylation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel, Switzerland). Compounds described by embodiments of the present invention were assayed using this protocol and the data from the same is recorded in Table 2 within the column labeled: Time Dependent PBMC BTK Enzyme Assay IC50.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: XTJBTJMEXZEGIF-XIKOKIGWSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 = 7990 nM (pChEMBL 5.099999904632568)
Descriptors: MW 397.4, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.62
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Ambit kinase assay
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Binding affinity towards human CHRM2 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIPK1 assessed as inhibition constant by ADP-Glo Kinase assay
Measurement: Ki = 1.66 nM (pChEMBL 8.779999732971191)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): O=C(NCC(=O)N1CCCC1)Nc1ccc2cnccc2c1
InChIKey: DMIDPTCQPIJYFE-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O60678
Assay: Inhibition of wild type Flag-tagged human PRMT3 catalytic activity transfected in HEK293 cells assessed as inhibition of exogenous GFP-tagged H4R3 asymmetric dimethylation incubated for 24 hrs by Western blot analysis
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 298.35, ALogP 1.98, HBA 3, HBD 2, PSA 74.33, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)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(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: SVUZBYDIXUMDGY-WVEXBLHFSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Binding affinity to KRAS G12D mutant (unknown origin) using FAM-labelled peptide as substrate in presence of Tween20 by fluorescence polarization assay
Measurement: Kd = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 2561.06
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN 35,428 from DAT in Sprague-Dawley rat striatum after 120 mins by scintillation counting method
Measurement: Ki = 446.68 nM (pChEMBL 6.349999904632568)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of cytoplasmic recombinant human full length His-tagged BMX expressed in baculovirus by Z'-LYTE assay
Measurement: IC50 = 37.9 nM (pChEMBL 7.420000076293945)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: XTJBTJMEXZEGIF-XIKOKIGWSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNA0
Assay: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs in the presence of 50% Lewis rat plasma by Alphascreen assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 397.4, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.62
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of BMX (unknown origin) incubated for 1 hrs by Z'-LYTE kinase assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Compound was evaluated for inhibition of human F2 in an in vitro cell free assay measured by fluorescence spectroscopy
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2',1'-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay
Measurement: Ki = 0.9772 nM (pChEMBL 9.010000228881836)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): O=C(NCC(=O)N1CCCC1)Nc1ccc2cnccc2c1
InChIKey: DMIDPTCQPIJYFE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Inhibition of [3H]LSD binding to 5-HT2B receptor (unknown origin)
Measurement: Ki > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 298.35, ALogP 1.98, HBA 3, HBD 2, PSA 74.33, QED 0.91
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]-citalopram from SERT in Sprague-Dawley rat midbrain after 60 mins by scintillation counting method
Measurement: Ki = 46.77 nM (pChEMBL 7.329999923706055)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of recombinant human cytoplasmic full length His-tagged TEC expressed in baculovirus by Z'-LYTE assay
Measurement: IC50 = 37.9 nM (pChEMBL 7.420000076293945)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: XTJBTJMEXZEGIF-XIKOKIGWSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of human MMP2 using Mca-PQGL-(3-[2, 4-dinitrophenyl]-L-2, 3-diaminopropionyl)-AR-OH as substrate after 2 to 4 hrs by fluorescence assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 397.4, ALogP 2.38, HBA 3, HBD 3, PSA 87.3, QED 0.62
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) incubated for 1 hrs by Z'-LYTE kinase assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: Antagonist activity at human TBXA2R in an in vitro cell-based assay measured by fluorescence spectroscopy
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Binding affinity to RIPK1 (unknown origin)
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human SP/Myc epitope-tagged dopamine D4 receptor expressed in HEK293T cells assessed as inhibition of dopamine-induced RLuc8-fused Galphai1 activation preincubated for 15 mins followed by dopamine induction measured after 2 mins by BRET assay
Measurement: IC50 = 169.82 nM (pChEMBL 6.769999980926514)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of recombinant human cytoplasmic GST-tagged ERBB4 expressed in baculovirus by Z'-LYTE assay
Measurement: IC50 = 37.9 nM (pChEMBL 7.420000076293945)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Z'-LYTE Kinase Assay: The measurement of Btk enzyme inhibitory activity was performed using the following reagents: Z'-LYTE Kinase Assay Kit-Tyr 1 (containing Tyr 1 peptide, Thy 1 phospho-peptide, 5x kinase buffer, ATP, development reagent B, development buffer, and stop reagent), Tyr 1 peptide (Invitrogen), and Btk (Invitrogen) according to the instructions accompanying the kit.First 5 uL/well of either a solution prepared by diluting the test compound in dimethyl sulfoxide (DMSO) or DMSO alone was added to the wells of a 96-well assay plate together with 10 uL/well of substrate/enzyme mixture and allowed to react for 20 minutes at 30° C. The substrate/enzyme mixture solutions were prepared by dilution in kinase buffer (DL-dithiothreitol (DTT; 2.7 mM) and 1.33x kinase buffer) so that the final concentration of Tyr-1 peptide would be 4 uM, and the final concentration of Btk would be 5 nM. Next 5 uL/well of adenosine triphosphate was added (ATP; final concentration 36 uM).
Measurement: IC50 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Binding affinity towards human ADORA3 (agonistic activity) in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Binding affinity to RIP1 (unknown origin) assessed as dissociation constant by KINOMEscan assay
Measurement: Kd = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human SP/Myc epitope-tagged dopamine D4 receptor expressed in HEK293T cells assessed as inhibition of dopamine-induced mVenus-fused beta-arrestin2 recruitment preincubated for 15 mins followed by dopamine induction measured after 2 mins by BRET assay
Measurement: IC50 = 575.44 nM (pChEMBL 6.239999771118164)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human B cells assessed as reduction in anti-IgM/IL4-stimulated CD69 expression on B cells preincubated for 60 mins followed by anti-IgM antibody/IL4 stimulation and measured after 16 hrs by flow cytometry
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Z'-LYTE Kinase Assay: The measurement of Btk enzyme inhibitory activity was performed using the following reagents: Z'-LYTE Kinase Assay Kit-Tyr 1 (containing Tyr 1 peptide, Thy 1 phospho-peptide, 5x kinase buffer, ATP, development reagent B, development buffer, and stop reagent), Tyr 1 peptide (Invitrogen), and Btk (Invitrogen) according to the instructions accompanying the kit.First 5 uL/well of either a solution prepared by diluting the test compound in dimethyl sulfoxide (DMSO) or DMSO alone was added to the wells of a 96-well assay plate together with 10 uL/well of substrate/enzyme mixture and allowed to react for 20 minutes at 30° C. The substrate/enzyme mixture solutions were prepared by dilution in kinase buffer (DL-dithiothreitol (DTT; 2.7 mM) and 1.33x kinase buffer) so that the final concentration of Tyr-1 peptide would be 4 uM, and the final concentration of Btk would be 5 nM. Next 5 uL/well of adenosine triphosphate was added (ATP; final concentration 36 uM).
Measurement: IC50 = 1057 nM (pChEMBL 5.980000019073486)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Binding affinity towards human HRH3 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2n[nH]c(Cc3ccccc3)n2)COc2ccccc21
InChIKey: LYPAFUINURXJSG-AWEZNQCLSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Binding affinity to RIP3 (unknown origin) assessed as dissociation constant by KINOMEscan assay
Measurement: Kd > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 377.4, ALogP 1.55, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Agonist activity at human SP/Myc epitope-tagged muscarinic M1 receptor expressed in HEK293T cells assessed as RLuc8-fused Galphaq activation after 2 mins by BRET assay
Measurement: EC50 = 186.21 nM (pChEMBL 6.730000019073486)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-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 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Z'-LYTE Kinase Assay: The measurement of Btk enzyme inhibitory activity was performed using the following reagents: Z'-LYTE Kinase Assay Kit-Tyr 1 (containing Tyr 1 peptide, Thy 1 phospho-peptide, 5x kinase buffer, ATP, development reagent B, development buffer, and stop reagent), Tyr 1 peptide (Invitrogen), and Btk (Invitrogen) according to the instructions accompanying the kit.First 5 uL/well of either a solution prepared by diluting the test compound in dimethyl sulfoxide (DMSO) or DMSO alone was added to the wells of a 96-well assay plate together with 10 uL/well of substrate/enzyme mixture and allowed to react for 20 minutes at 30° C. The substrate/enzyme mixture solutions were prepared by dilution in kinase buffer (DL-dithiothreitol (DTT; 2.7 mM) and 1.33x kinase buffer) so that the final concentration of Tyr-1 peptide would be 4 uM, and the final concentration of Btk would be 5 nM. Next 5 uL/well of adenosine triphosphate was added (ATP; final concentration 36 uM).
Measurement: IC50 = 1662 nM (pChEMBL 5.78000020980835)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human HTR2B in an in vitro cell-based assay (CRO assay) measured by time-resolved fluorescence resonance energy transfer method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human SP/Myc epitope-tagged muscarinic M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced RLuc8-fused Galphaq activation preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
Measurement: IC50 = 2630.27 nM (pChEMBL 5.579999923706055)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-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 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood-derived CD19+ B cells assessed as suppression of anti-IgM stimulated-CD69 expression preincubated for 1 hr followed by IgM stimulation for 18 hrs by FACS analysis
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding affinity towards human AR in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 = 11.9 nM (pChEMBL 7.920000076293945)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human SP/Myc epitope-tagged muscarinic M1 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced mVenus-fused beta-arrestin2 recruitment preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
Measurement: IC50 = 1202.26 nM (pChEMBL 5.920000076293945)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-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 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood derived-basophils assessed as suppression of IgE mediated-FcepsilonR ligation-stimulated CD63 expression
Measurement: IC50 = 312.3 nM (pChEMBL 6.5)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding affinity towards human PGR in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 = 285.2 nM (pChEMBL 6.539999961853027)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Agonist activity at human SP/Myc epitope-tagged muscarinic M4 receptor expressed in HEK293T cells assessed as RLuc8-fused Galphaq activation after 2 mins by BRET assay
Measurement: EC50 = 147.91 nM (pChEMBL 6.829999923706055)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Binding affinity to DNA-tagged recombinant ITK (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54
Compound (SMILES): CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: SEJLPXCPMNSRAM-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of full-length human recombinant BTK using FITC-Ahx-TSELKKVVALYDYMPMNAND-NH2 as substrate measured after 60 mins by caliper assay
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 454.49, ALogP 2.75, HBA 8, HBD 1, PSA 108.27, QED 0.48
Compound (SMILES): CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Compound was evaluated for inhibition of human PTGS1 in an in vitro cell free assay measured by time-resolved fluorescence resonance energy transfer method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 342.48, ALogP 4, HBA 3, HBD 1, PSA 54.37, QED 0.78
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCC(Cc2ccccc2)CC1
InChIKey: YCGXHEJETHPGPD-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Antagonist activity at human SP/Myc epitope-tagged muscarinic M4 receptor expressed in HEK293T cells assessed as inhibition of carbachol-induced RLuc8-fused Galphaq activation preincubated for 15 mins followed by carbachol induction measured after 2 mins by BRET assay
Measurement: IC50 = 8511.38 nM (pChEMBL 5.070000171661377)
Descriptors: MW 362.52, ALogP 4.31, HBA 2, HBD 0, PSA 23.55, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: QUIWHXQETADMGN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Binding affinity to DNA-tagged recombinant EGFR (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 429.52, ALogP 4.35, HBA 6, HBD 2, PSA 93.37, QED 0.54