lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1C(N)=N[C@](C)(c2cc(NC(=O)c3ccc(F)cn3)ccc2F)CS1(=O)=O
InChIKey: YHYKUSGACIYRML-KRWDZBQOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: HTRF FRET Assay: Inhibitor IC50s at purified human autoBACE-2 were determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light. Inhibitor compounds, prepared at 3x the desired final concentration in 1xBACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO were pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1xBACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30 C. The assay was initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 M for 4 M for autoBACE-2) prepared in 1xBACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30 C.
Measurement: Ki = 4.88 nM (pChEMBL 8.3100004196167)
Descriptors: MW 409.42, ALogP 1.42, HBA 6, HBD 2, PSA 117.75, QED 0.79
Compound (SMILES): O=C(O)COC[C@H]1CC[C@H](COC(=O)N(c2ccccc2)c2ccc(Cl)cc2)CC1
InChIKey: NPDKXVKJRHPDQT-IYARVYRRSA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P43253
Assay: Agonist activity at recombinant rat IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method
Measurement: EC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 431.92, ALogP 5.52, HBA 4, HBD 1, PSA 76.07, QED 0.59
Compound (SMILES): CC1(C)CN(C(=O)c2ccc(-c3cccc4nc(NC(=O)C5CC5)nn34)cc2)C1
InChIKey: MPYACSQFXVMWNO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: JAK2 Inhibition Assay: Recombinant human JAK2 (catalytic domain, amino acids 866-1154; catalog number PV4210) was purchased from Invitrogen. 0.0125 mU of JAK2 was incubated with 25 nM Ulight-JAK1(tyr1023) peptide (Perkin Elmer catalog number TRF0121) in kinase reaction buffer (41.66 mM HEPES pH7.0, 0.016% Triton X-100, 12.5 mM MgCl2, 3.33 mM DTT, 7.5M ATP) with or without 4L containing test compound or vehicle (DMSO, 1% final concentration), in a total volume of 20L, in a white 384 Luminotrac 200 plate (Greiner, catalog number 781075). After 60 min at room temperature, reactions were stopped by adding 20L/well of detection mixture (1x detection buffer (Perkin Elmer, catalog number CR97-100C), 0.5 nM Europium-anti-phosphotyrosine (PT66) (Perkin Elmer, catalog number AD0068), 10 mM EDTA). Readout is performed using the Envision with excitation at 320 nm and measuring emission at 615 nm (Perkin Elmer). Kinase activity was calculated by subtracting relative fluorescence units (RFU) obtained in the presence of a positive control inhibitor (10M staurosporine) from RFU obtained in the presence of vehicle. The ability of a test compound to inhibit this activity was determined as: Percentage inhibition=((RFU determined for sample with test compound present-RFU determined for sample with positive control inhibitor) divided by (RFU determined in the presence of vehicle-RFU determined for sample with positive control inhibitor))*100. Dose dilution series are prepared for compound enabling the testing of dose-response effects in the JAK2 assay and the calculation of the IC50 for the compound. Each compound is routinely tested at concentration of 20M followed by a 1/5 serial dilution, 8 points (20M-4M-800 nM-160 nM-32 nM-6.4 nM-1.28 nM-0.26 nM) in a final concentration of 1% DMSO. When potency of compound series increases, more dilutions are prepared and/or the top concentration are lowered (e.g. 5M, 1M). The data are expressed as the average IC50 from the assays standard error of the mean.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 389.46, ALogP 3.23, HBA 5, HBD 1, PSA 79.6, QED 0.74
Compound (SMILES): O=C(Nc1nc2cccc(-c3ccc(CN4CCS(=O)(=O)CC4)cc3)n2n1)C1CC1
InChIKey: RIJLVEAXPNLDTC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin)
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 425.51, ALogP 1.98, HBA 7, HBD 1, PSA 96.67, QED 0.67
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)nc2)CC1
InChIKey: UZWDCWONPYILKI-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using (YSPTSPS)2KK peptide as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 3112 nM (pChEMBL 5.510000228881836)
Descriptors: MW 506.61, ALogP 4.94, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): COC(=O)N[C@@H](C)CNc1nccc(-c2cn(C(C)C)nc2-c2cc(Cl)cc(NS(C)(=O)=O)c2F)n1
InChIKey: CMJCXYNUCSMDBY-ZDUSSCGKSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Compound was evaluated for inhibition of human ADRB1 in an in vitro assay measured by radioactivity method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 540.02, ALogP 3.91, HBA 9, HBD 3, PSA 140.13, QED 0.37
Compound (SMILES): CCCN(CCC)C(=O)C1=Cc2ccc(-c3ccc(C(=O)N4CCCC4)cc3)cc2N=C(N)C1
InChIKey: QSPOQCXMGPDIHI-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 (unknown origin)
Measurement: EC50 ~ 100 nM (pChEMBL 7)
Descriptors: MW 458.61, ALogP 5.01, HBA 4, HBD 1, PSA 79, QED 0.63
Compound (SMILES): COc1cnc(-n2cnc(C)n2)c2[nH]cc(C(=O)C(=O)N3CCN(C(=O)c4ccccc4)CC3)c12
InChIKey: QRPZBKAMSFHVRW-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human liver microsome CYP2C19 using mephenytoin as substrate incubated for 20 mins by LC-MS/MS analysis
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 473.49, ALogP 1.63, HBA 8, HBD 1, PSA 126.31, QED 0.34
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(OC)c2)nc1NC1CCOCC1
InChIKey: GYQYAJJFPNQOOW-UHFFFAOYSA-N
Target: Acyl-CoA dehydrogenase family member 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6JQN1
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 552.72, ALogP 2.7, HBA 10, HBD 3, PSA 121.11, QED 0.43
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H](C)NC1=O
InChIKey: HDHDTKMUACZDAA-PHNIDTBTSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK2936E cell membrane measured after 16-23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 13.18 nM (pChEMBL 7.880000114440918)
Descriptors: MW 1117.33
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc(OCCOC)cc3)ncc2F)c1
InChIKey: KXBDTLQSDKGAEB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human N-terminal GST-tagged JAK3 (781 to end residues) expressed in baculovirus infected Sf9 cells using poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 66.5 nM (pChEMBL 7.179999828338623)
Descriptors: MW 423.45, ALogP 4.25, HBA 7, HBD 3, PSA 97.4, QED 0.33
Compound (SMILES): CN1Cc2c(Cl)cc(Cl)cc2[C@H](c2cccc(S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)c2)C1.Cl.Cl
InChIKey: VFRAXTZDILCRKY-OWRGXFNZSA-N
Target: Sodium/hydrogen exchanger 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P48764
Assay: Inhibition of human NHE3-mediated sodium-dependant hydrogen ion antiport in Opossum kidney cells preincubated for 60 mins in NaCl-HEPES buffer followed by compound washout with NH4Cl-HEPES buffer containing BCECF-AM dye and subsequent washout with Na+ free HEPES buffer by fluorescence analysis
Measurement: IC50 = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 1145.07
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(OC)cc2)NC(=O)CCCSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: NSTRIRCPWQHTIA-DTRKZRJBSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human vasopressin V1a expressed in AVP-stimulated HEK293 cells after 5 hrs by firefly luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 988.18, ALogP -2.5, HBA 13, HBD 10, PSA 362.51, QED 0.07
Compound (SMILES): C[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]2CSSC[C@H](N)C(=O)N[C@H]3CSSC[C@H](NC1=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)CSSC[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC3=O)C(=O)N2
InChIKey: KXGCNMMJRFDFNR-WDRJZQOASA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Compound was evaluated for inhibition of human CHRM1 in an in vitro assay with cellular components measured by scintillation proximity assay
Measurement: AC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1526.77
Compound (SMILES): CCOC1O[C@H]([C@@H](COCc2ccccc2)OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1O
InChIKey: ULLNJSBQMBKOJH-VIVFLBMVSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Compound was evaluated for inhibition of human ACHE in an vitro cell free assay measured by absorbance method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 478.59, ALogP 4.5, HBA 6, HBD 1, PSA 66.38, QED 0.39
Compound (SMILES): CC=CC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccc(O)cc3)[C@H]2SC1
InChIKey: WDLWHQDACQUCJR-PBFPGSCMSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Binding affinity towards human ADRB2 in an in vitro assay with cellular components measured by radioactivity method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 389.43, ALogP 0.71, HBA 6, HBD 4, PSA 132.96, QED 0.55
Compound (SMILES): CN1CCN(C[C@@H](NC(=O)C[C@H]2CNC(=O)c3cc(-c4cccc(Cl)c4)cn32)C2CCCCC2)CC1
InChIKey: UKZRGBUTBINTPD-LOSJGSFVSA-N
Target: Activated CDC42 kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07912
Assay: Inhibition of ACK1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.1, ALogP 3.8, HBA 5, HBD 2, PSA 69.61, QED 0.59
Compound (SMILES): Fc1ccc(Oc2nccc3[nH]ccc23)cc1
InChIKey: ISIATOZGACZZRA-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 228.23, ALogP 3.49, HBA 2, HBD 1, PSA 37.91, QED 0.73
Compound (SMILES): COc1c(O)ccc2c(=O)c3c(O)cc4c(c3[nH]c12)C=CC(C)(C)O4
InChIKey: COUZVMMRGYONAQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of CDK5/p25 (unknown origin) assessed as inhibition of phosphate incorporation using histone 1 and [gamma-33P]ATP as substrate after 30 mins by scintillation counting analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 339.35, ALogP 3.29, HBA 5, HBD 3, PSA 91.78, QED 0.59
Compound (SMILES): c1ccc(-c2ccc3[nH]ncc3c2)cc1
InChIKey: JQHTYMOOIFVIJV-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 194.24, ALogP 3.23, HBA 1, HBD 1, PSA 28.68, QED 0.63
Compound (SMILES): FC(F)(F)c1ccccc1-c1ccc2[nH]ncc2c1
InChIKey: PJYBQLCOMOPZIT-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in CHOK1 cells assessed as inhibition of menthol-induced calcium flux incubated 10 mins prior to menthol addition by FLIPR assay relative to control
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 262.23, ALogP 4.25, HBA 1, HBD 1, PSA 28.68, QED 0.7
Compound (SMILES): COc1cc(-c2cn(CC(=O)Nc3cc(C4CC4)nn3-c3ccccc3)nn2)ccc1-n1cnc(C)c1
InChIKey: FQGDIYVVDKJSNC-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of recombinant human TrkA expressed in DHFR deficient CHO cells assessed as inhibition of human beta-nerve growth factor-induced calcium influx by Fluo-4 AM dye based assay
Measurement: IC50 = 85.4 nM (pChEMBL 7.070000171661377)
Descriptors: MW 494.56, ALogP 4.15, HBA 9, HBD 1, PSA 104.68, QED 0.35
Compound (SMILES): O=C1NCCc2nc(OCc3cccc(F)c3)ccc21
InChIKey: FMUAFDSEYCJYKD-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 8 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P70579
Assay: Positive allosteric modulator activity at rat mGlu8 receptor expressed in HEK293 cells assessed as glutamate-induced GIRK channel-mediated thallium flux treated 140s prior to glutamate challenge by fluorescence analysis
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 272.28, ALogP 2.09, HBA 3, HBD 1, PSA 51.22, QED 0.93
Compound (SMILES): N#Cc1cccc(Cn2cc(NC(=O)c3n[nH]c4c3CC(c3cn[nH]c3)CC4)cn2)c1
InChIKey: NRJLSFKZAQFLCT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of ITK in human Jurkat cells assessed as reduction in PLC-gamma phosphorylation after 30 mins
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 412.46, ALogP 2.77, HBA 6, HBD 3, PSA 128.07, QED 0.46
Compound (SMILES): COc1cc2ccnc(Oc3ccc(F)cc3)c2cc1OC
InChIKey: AHHGHXFTQVZBPO-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 299.3, ALogP 4.18, HBA 4, HBD 0, PSA 40.58, QED 0.72
Compound (SMILES): CC12Cc3[nH]nc(C(=O)Nc4cnn(Cc5ccccc5)c4)c3CC1C2
InChIKey: CZAHTSYZRWGJOH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 347.42, ALogP 3.03, HBA 4, HBD 2, PSA 75.6, QED 0.76
Compound (SMILES): CC(C)(C)CNC(=O)CC1CNC(=O)c2cc(-c3ccsc3)cn21
InChIKey: PNMQDIXULZYDDT-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of aurora kinase 1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.47, ALogP 3.05, HBA 4, HBD 2, PSA 63.13, QED 0.89
Compound (SMILES): Fc1ccc(Oc2ncnc3[nH]ccc23)cc1
InChIKey: OSVVWQSAPRHYFQ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 229.21, ALogP 2.89, HBA 3, HBD 1, PSA 50.8, QED 0.73
Compound (SMILES): O=C(N[C@H](CO)c1ccc(Cl)c(F)c1)N1CCc2cnc(NC3CCOCC3)nc2C1
InChIKey: OJRJASQFNLOAKZ-LJQANCHMSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 449.91, ALogP 2.66, HBA 6, HBD 3, PSA 99.61, QED 0.65
Compound (SMILES): Fc1ccc(Oc2nccc3[nH]ccc23)c(F)c1
InChIKey: RELPPOJGGXOECP-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 246.22, ALogP 3.63, HBA 2, HBD 1, PSA 37.91, QED 0.75
Compound (SMILES): FC(F)(F)c1ccccc1-c1cc2cn[nH]c2cc1Cl
InChIKey: BIWXFLAZRBTWMI-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in CHOK1 cells assessed as inhibition of menthol-induced calcium flux incubated 10 mins prior to menthol addition by FLIPR assay relative to control
Measurement: IC50 = 17100 nM (pChEMBL 4.769999980926514)
Descriptors: MW 296.68, ALogP 4.9, HBA 1, HBD 1, PSA 28.68, QED 0.68
Compound (SMILES): Cc1cc2[nH]ncc2cc1-c1ccccc1C(F)(F)F
InChIKey: NXFIEIXVSJMOQL-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NET8
Assay: Antagonist activity at human TRPV3 expressed in CHOK1 cells assessed as inhibition of 2-APB-induced calcium flux incubated 10 mins prior to 2-APB addition by FLIPR assay relative to control
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 276.26, ALogP 4.56, HBA 1, HBD 1, PSA 28.68, QED 0.69
Compound (SMILES): CC(C)(N)COc1ccc(Nc2ccc(CCNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)cc2)cc1
InChIKey: JRRKWFRTDFOWAB-SANMLTNESA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Inhibition of muscarinic acetylcholine receptor M2 (unknown origin)
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 502.62, ALogP 3.96, HBA 7, HBD 6, PSA 132.63, QED 0.17
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCN(Cc2ccccc2)[C@@H]2CCC[C@H](N3CCCC3)[C@H]21
InChIKey: JSWMYIDCXMVIHJ-ZWEKWIFMSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-deltorphin 2 from human delta-opioid receptor transfected in CHO-K1 cell by scintillation counting
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 486.49, ALogP 5.27, HBA 3, HBD 0, PSA 26.79, QED 0.58
Compound (SMILES): COC(=O)N1CCN(C(=O)Cc2ccc(Cl)c(Cl)c2)[C@H]2[C@H]1CCC[C@@H]2N1CCCC1
InChIKey: PAVYSOUZQLFNIW-QKNQBKEWSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-naloxone from human mu-opioid receptor transfected in CHO-K1 cell by scintillation counting
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 454.4, ALogP 3.83, HBA 4, HBD 0, PSA 53.09, QED 0.7
Compound (SMILES): COc1cc2[nH]ncc2cc1-c1ccccc1C(F)(F)F
InChIKey: PPHJNQDDPYIFET-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in CHOK1 cells assessed as inhibition of menthol-induced calcium flux incubated 10 mins prior to menthol addition by FLIPR assay relative to control
Measurement: IC50 = 10900 nM (pChEMBL 4.960000038146973)
Descriptors: MW 292.26, ALogP 4.26, HBA 2, HBD 1, PSA 37.91, QED 0.77
Compound (SMILES): FC(F)(F)c1ccccc1-c1cc2cn[nH]c2cc1OCC1CC1
InChIKey: BZTMKWCWKFEAKS-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in CHOK1 cells assessed as inhibition of menthol-induced calcium flux incubated 10 mins prior to menthol addition by FLIPR assay relative to control
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 332.33, ALogP 5.04, HBA 2, HBD 1, PSA 37.91, QED 0.73
Compound (SMILES): FC(F)(F)Oc1cc2[nH]ncc2cc1-c1ccccc1C(F)(F)F
InChIKey: XOQQYLAKAJMBHH-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in CHOK1 cells assessed as inhibition of menthol-induced calcium flux incubated 10 mins prior to menthol addition by FLIPR assay relative to control
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 346.23, ALogP 5.15, HBA 2, HBD 1, PSA 37.91, QED 0.65
Compound (SMILES): O=C(O)COC[C@H]1CC[C@H](COC(=O)N(c2ccccc2)c2ccc(Cl)cc2)CC1
InChIKey: NPDKXVKJRHPDQT-IYARVYRRSA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43119
Assay: Displacement of [3H]-iloprost from recombinant human IP receptor expressed in CHO-K1 cell membranes incubated for 1 hr by top count scintillation counting method
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 431.92, ALogP 5.52, HBA 4, HBD 1, PSA 76.07, QED 0.59
Compound (SMILES): CC1(C)CN(C(=O)c2ccc(-c3cccc4nc(NC(=O)C5CC5)nn34)cc2)C1
InChIKey: MPYACSQFXVMWNO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: JAK3 Inhibition Assay: Recombinant human JAK3 catalytic domain (amino acids 781-1124; catalog number PV3855) was purchased from Invitrogen. 0.025 mU of JAK3 was incubated with 2.5 ug polyGT substrate (Sigma catalog number Pb0275) in kinase reaction buffer (25 mM Tris pH 7.5, 0.5 mM EGTA, 0.5 mM Na3VO4, 5 mM b-glycerolphosphate, 0.01% Triton X-100, 1 uM non-radioactive ATP, 0.25 uCi 33P-gamma-ATP (GE Healthcare, catalog number AH9968) final concentrations) with or without 5 uL containing test compound or vehicle (DMSO, 1% final concentration), in a total volume of 25 uL, in a polypropylene 96-well plate (Greiner, V-bottom). After 105 min at 30° C., reactions were stopped by adding of 25 uL/well of 150 mM phosphoric acid. All of the terminated kinase reaction was transferred to prewashed (75 mM phosphoric acid) 96 well filter plates (Perkin Elmer catalog number 6005177) using a cell harvester (Perkin Elmer). Plates were washed 6 times with 300 uL per well of a 75 mM phosphoric acid solution and the bottom of the plates was sealed. 40 uL/well of Microscint-20 was added, the top of the plates was sealed and readout was performed using the Topcount (Perkin Elmer). Kinase activity was calculated by subtracting counts per minute (cpm) obtained in the presence of a positive control inhibitor (10 uM staurosporine) from cpm obtained in the presence of vehicle. The ability of a test compound to inhibit this activity was determined as: Percentage inhibition=((cpm determined for sample with test compound present-cpm determined for sample with positive control inhibitor) divided by (cpm determined in the presence of vehicle-cpm determined for sample with positive control inhibitor))*100. Dose dilution series were prepared for the compound enabling the testing of dose-response effects in the JAK3 assay and the calculation of the IC50 for the compound. Each compound was routinely tested at concentration of 20 uM followed by a 1/3 serial dilution, 8 points (20 uM-6.67 uM-2.22 uM-740 nM-247 nM-82 nM-27 nM-9 nM) in a final concentration of 1% DMSO. When potency of the compound series increased, more dilutions were prepared and/or the top concentration was lowered (e.g. 5 uM, 1 uM). The data are expressed as the average IC50 from the assays standard error of the mean.
Measurement: IC50 = 408 nM (pChEMBL 6.389999866485596)
Descriptors: MW 389.46, ALogP 3.23, HBA 5, HBD 1, PSA 79.6, QED 0.74
Compound (SMILES): O=C(Nc1nc2cccc(-c3ccc(CN4CCS(=O)(=O)CC4)cc3)n2n1)C1CC1
InChIKey: RIJLVEAXPNLDTC-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 (unknown origin)
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 425.51, ALogP 1.98, HBA 7, HBD 1, PSA 96.67, QED 0.67
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)nc2)CC1
InChIKey: UZWDCWONPYILKI-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using (YSPTSPS)2KK peptide as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 506.61, ALogP 4.94, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): COC(=O)N[C@@H](C)CNc1nccc(-c2cn(C(C)C)nc2-c2cc(Cl)cc(NS(C)(=O)=O)c2F)n1
InChIKey: CMJCXYNUCSMDBY-ZDUSSCGKSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Binding affinity towards human ADRB2 in an in vitro assay with cellular components measured by radioactivity method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 540.02, ALogP 3.91, HBA 9, HBD 3, PSA 140.13, QED 0.37
Compound (SMILES): COc1cnc(-n2cnc(C)n2)c2[nH]cc(C(=O)C(=O)N3CCN(C(=O)c4ccccc4)CC3)c12
InChIKey: QRPZBKAMSFHVRW-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human liver microsome CYP2D6 using bufuralol as substrate incubated for 20 mins by LC-MS/MS analysis
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 473.49, ALogP 1.63, HBA 8, HBD 1, PSA 126.31, QED 0.34
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(OC)c2)nc1NC1CCOCC1
InChIKey: GYQYAJJFPNQOOW-UHFFFAOYSA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 552.72, ALogP 2.7, HBA 10, HBD 3, PSA 121.11, QED 0.43
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H](C)NC1=O
InChIKey: HDHDTKMUACZDAA-PHNIDTBTSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK2936E cell membrane measured after 16-23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 4.074 nM (pChEMBL 8.390000343322754)
Descriptors: MW 1117.33
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc(OCCOC)cc3)ncc2F)c1
InChIKey: KXBDTLQSDKGAEB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Omnia Assay Protocol for Potency Assessment Against BTK: Briefly, 10× stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM 3-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λem485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to 30 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (minutes) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response, Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 423.45, ALogP 4.25, HBA 7, HBD 3, PSA 97.4, QED 0.33
Compound (SMILES): CN1Cc2c(Cl)cc(Cl)cc2[C@H](c2cccc(S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)c2)C1.Cl.Cl
InChIKey: VFRAXTZDILCRKY-OWRGXFNZSA-N
Target: Nucleosome assembly protein 1-like 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99733
Assay: Inhibition of human Nap2B expressed in HEK293 cells assessed as inhibition of Pi uptake measured after 23 mins in presence of [33P]orthophosphoric acid by TopCount scintillation counting method
Measurement: IC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 1145.07
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(OC)cc2)NC(=O)CCCSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: NSTRIRCPWQHTIA-DTRKZRJBSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Agonist activity at recombinant human Gi/Go-coupled OTR expressed in CHOK1 cells assessed as induction of beta-arrestin recruitment measured after 90 mins in presence of 10% FBS by pathhunter assay
Measurement: EC50 = 2.99 nM (pChEMBL 8.520000457763672)
Descriptors: MW 988.18, ALogP -2.5, HBA 13, HBD 10, PSA 362.51, QED 0.07
Compound (SMILES): C[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]2CSSC[C@H](N)C(=O)N[C@H]3CSSC[C@H](NC1=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)CSSC[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC3=O)C(=O)N2
InChIKey: KXGCNMMJRFDFNR-WDRJZQOASA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Binding affinity towards human ADRA1A in an in vitro assay with cellular components (NIBR assay) measured by scintillation proximity assay
Measurement: AC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1526.77
Compound (SMILES): CCOC1O[C@H]([C@@H](COCc2ccccc2)OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1O
InChIKey: ULLNJSBQMBKOJH-VIVFLBMVSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding affinity towards human SLC6A2 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 478.59, ALogP 4.5, HBA 6, HBD 1, PSA 66.38, QED 0.39
Compound (SMILES): CC=CC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccc(O)cc3)[C@H]2SC1
InChIKey: WDLWHQDACQUCJR-PBFPGSCMSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding affinity towards human SLC6A3 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 389.43, ALogP 0.71, HBA 6, HBD 4, PSA 132.96, QED 0.55
Compound (SMILES): CN1CCN(C[C@@H](NC(=O)C[C@H]2CNC(=O)c3cc(-c4cccc(Cl)c4)cn32)C2CCCCC2)CC1
InChIKey: UKZRGBUTBINTPD-LOSJGSFVSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.1, ALogP 3.8, HBA 5, HBD 2, PSA 69.61, QED 0.59
Compound (SMILES): Fc1ccc(Oc2nccc3[nH]ccc23)cc1
InChIKey: ISIATOZGACZZRA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 228.23, ALogP 3.49, HBA 2, HBD 1, PSA 37.91, QED 0.73
Compound (SMILES): COc1c(O)ccc2c(=O)c3c(O)cc4c(c3[nH]c12)C=CC(C)(C)O4
InChIKey: COUZVMMRGYONAQ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T (unknown origin)
Measurement: IC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 339.35, ALogP 3.29, HBA 5, HBD 3, PSA 91.78, QED 0.59
Compound (SMILES): c1ccc(-c2ccc3[nH]ncc3c2)cc1
InChIKey: JQHTYMOOIFVIJV-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 168.9 nM (pChEMBL 6.769999980926514)
Descriptors: MW 194.24, ALogP 3.23, HBA 1, HBD 1, PSA 28.68, QED 0.63
Compound (SMILES): FC(F)(F)c1ccccc1-c1ccc2[nH]ncc2c1
InChIKey: PJYBQLCOMOPZIT-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: Antagonist activity at human TRPA1 expressed in CHO-TREX cells assessed as inhibition of allyl isothiocyanate-induced calcium flux incubated 10 mins prior to allyl isothiocyanate addition by FLIPR assay relative to control
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 262.23, ALogP 4.25, HBA 1, HBD 1, PSA 28.68, QED 0.7
Compound (SMILES): COc1cc(-c2cn(CC(=O)Nc3cc(C4CC4)nn3-c3ccccc3)nn2)ccc1-n1cnc(C)c1
InChIKey: FQGDIYVVDKJSNC-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of recombinant human TrkB expressed in DHFR deficient CHO cells assessed as inhibition of human brain-derived neurotrophic factor-induced calcium influx by Fluo-4 AM dye based assay
Measurement: IC50 = 132.2 nM (pChEMBL 6.880000114440918)
Descriptors: MW 494.56, ALogP 4.15, HBA 9, HBD 1, PSA 104.68, QED 0.35
Compound (SMILES): O=C1NCCc2nc(OCc3cccc(F)c3)ccc21
InChIKey: FMUAFDSEYCJYKD-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 272.28, ALogP 2.09, HBA 3, HBD 1, PSA 51.22, QED 0.93
Compound (SMILES): COc1cc2ccnc(Oc3ccc(F)cc3)c2cc1OC
InChIKey: AHHGHXFTQVZBPO-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 299.3, ALogP 4.18, HBA 4, HBD 0, PSA 40.58, QED 0.72
Compound (SMILES): CC(C)(C)CNC(=O)CC1CNC(=O)c2cc(-c3ccsc3)cn21
InChIKey: PNMQDIXULZYDDT-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of aurora kinase 2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.47, ALogP 3.05, HBA 4, HBD 2, PSA 63.13, QED 0.89
Compound (SMILES): Fc1ccc(Oc2ncnc3[nH]ccc23)cc1
InChIKey: OSVVWQSAPRHYFQ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 229.21, ALogP 2.89, HBA 3, HBD 1, PSA 50.8, QED 0.73
Compound (SMILES): O=C(N[C@H](CO)c1ccc(Cl)c(F)c1)N1CCc2cnc(NC3CCOCC3)nc2C1
InChIKey: OJRJASQFNLOAKZ-LJQANCHMSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Binding affinity to His-tagged recombinant human full length CDK2/Cyclin A after 60 mins by TR- FRET method
Measurement: Kd = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 449.91, ALogP 2.66, HBA 6, HBD 3, PSA 99.61, QED 0.65
Compound (SMILES): Fc1ccc(Oc2nccc3[nH]ccc23)c(F)c1
InChIKey: RELPPOJGGXOECP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS/competitive screening assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 246.22, ALogP 3.63, HBA 2, HBD 1, PSA 37.91, QED 0.75
Compound (SMILES): Cc1cc2[nH]ncc2cc1-c1ccccc1C(F)(F)F
InChIKey: NXFIEIXVSJMOQL-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in CHOK1 cells assessed as inhibition of menthol-induced calcium flux incubated 10 mins prior to menthol addition by FLIPR assay relative to control
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 276.26, ALogP 4.56, HBA 1, HBD 1, PSA 28.68, QED 0.69
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCN(Cc2ccccc2)[C@@H]2CCC[C@H](N3CCCC3)[C@H]21
InChIKey: JSWMYIDCXMVIHJ-ZWEKWIFMSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-naloxone from human mu-opioid receptor transfected in CHO-K1 cell by scintillation counting
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 486.49, ALogP 5.27, HBA 3, HBD 0, PSA 26.79, QED 0.58
Compound (SMILES): COC(=O)N1CCN(C(=O)Cc2ccc(Cl)c(Cl)c2)[C@H]2[C@H]1CCC[C@@H]2N1CCCC1
InChIKey: PAVYSOUZQLFNIW-QKNQBKEWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]-U-69593 from kappa opioid receptor in guinea pig brain membrane after 120 mins by scintillation counting
Measurement: Ki = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 454.4, ALogP 3.83, HBA 4, HBD 0, PSA 53.09, QED 0.7
Compound (SMILES): CN1C(N)=N[C@](C)(c2cc(NC(=O)c3ccc(F)cn3)ccc2F)CS1(=O)=O
InChIKey: YHYKUSGACIYRML-KRWDZBQOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (1 to 454 residues) (unknown origin) using APP harboring Swedish Lys/Met mutant-derived peptide as substrate by FRET assay
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 409.42, ALogP 1.42, HBA 6, HBD 2, PSA 117.75, QED 0.79
Compound (SMILES): O=C(O)COC[C@H]1CC[C@H](COC(=O)N(c2ccccc2)c2ccc(Cl)cc2)CC1
InChIKey: NPDKXVKJRHPDQT-IYARVYRRSA-N
Target: Prostaglandin D2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q13258
Assay: Displacement of [3H]-PGD2 from recombinant human DP1 receptor
Measurement: Ki = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 431.92, ALogP 5.52, HBA 4, HBD 1, PSA 76.07, QED 0.59
Compound (SMILES): CC1(C)CN(C(=O)c2ccc(-c3cccc4nc(NC(=O)C5CC5)nn34)cc2)C1
InChIKey: MPYACSQFXVMWNO-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Inhibition Assay: Recombinant human TYK2 catalytic domain (amino acids 871-1187; catalog number 08-147) was purchased from Carna biosciences. 5 ng of TYK2 was incubated with 12.5 ug polyGT substrate (Sigma catalog number Pb0275) in kinase reaction buffer (25 mM Hepes pH 7.5, 100 mM NaCl, 0.2 mM Na3VO4, 0.1% NP-40, 0.1 uM non-radioactive ATP, 0.125 uCi 33P-gamma-ATP (GE Healthcare, catalog number AH9968) final concentrations) with or without 5 uL containing test compound or vehicle (DMSO, 1% final concentration), in a total volume of 25 uL, in a polypropylene 96-well plate (Greiner, V-bottom). After 90 min at 30° C., reactions were stopped by adding of 25 uL/well of 150 mM phosphoric acid. All of the terminated kinase reaction was transferred to prewashed (75 mM phosphoric acid) 96 well filter plates (Perkin Elmer catalog number 6005177) using a cell harvester (Perkin Elmer). Plates were washed 6 times with 300 uL per well of a 75 mM phosphoric acid solution and the bottom of the plates was sealed. 40 uL/well of Microscint-20 was added, the top of the plates was sealed and readout was performed using the Topcount (Perkin Elmer). Kinase activity was calculated by subtracting counts per minute (cpm) obtained in the presence of a positive control inhibitor (10 uM staurosporine) from cpm obtained in the presence of vehicle. The ability of a test compound to inhibit this activity was determined as: Percentage inhibition=((cpm determined for sample with test compound present-cpm determined for sample with positive control inhibitor) divided by (cpm determined in the presence of vehicle-cpm determined for sample with positive control inhibitor))*100. Dose dilution series were prepared for the compounds enabling the testing of dose-response effects in the TYK2 assay and the calculation of the IC50 for the compound. Each compound was routinely tested at concentration of 20 uM followed by a 1/3 serial dilution, 8 points (20 uM-6.67 uM-2.22 uM-740 nM-247 nM-82 nM-27 nM-9 nM) in a final concentration of 1% DMSO. When potency of compound series increased, more dilutions were prepared and/or the top concentration was lowered (e.g. 5 uM, 1 uM).
Measurement: IC50 = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 389.46, ALogP 3.23, HBA 5, HBD 1, PSA 79.6, QED 0.74
Compound (SMILES): O=C(Nc1nc2cccc(-c3ccc(CN4CCS(=O)(=O)CC4)cc3)n2n1)C1CC1
InChIKey: RIJLVEAXPNLDTC-UHFFFAOYSA-N
Target: JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK2/TYK2 in human whole blood assessed as inhibition of IL-23-induced STAT-3 phosphorylation preincubated for 45 mins followed by IL-23 addition measured after 15 mins by FACS analysis
Measurement: IC50 = 10123 nM (pChEMBL 5)
Descriptors: MW 425.51, ALogP 1.98, HBA 7, HBD 1, PSA 96.67, QED 0.67
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)nc2)CC1
InChIKey: UZWDCWONPYILKI-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide
Measurement: Ki = 3910 nM (pChEMBL 5.409999847412109)
Descriptors: MW 506.61, ALogP 4.94, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): COC(=O)N[C@@H](C)CNc1nccc(-c2cn(C(C)C)nc2-c2cc(Cl)cc(NS(C)(=O)=O)c2F)n1
InChIKey: CMJCXYNUCSMDBY-ZDUSSCGKSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding affinity towards human SLC6A3 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 540.02, ALogP 3.91, HBA 9, HBD 3, PSA 140.13, QED 0.37
Compound (SMILES): COc1cnc(-n2cnc(C)n2)c2[nH]cc(C(=O)C(=O)N3CCN(C(=O)c4ccccc4)CC3)c12
InChIKey: QRPZBKAMSFHVRW-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human liver microsome CYP3A4 using testosterone as substrate incubated for 20 mins by LC-MS/MS analysis
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 473.49, ALogP 1.63, HBA 8, HBD 1, PSA 126.31, QED 0.34
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(OC)c2)nc1NC1CCOCC1
InChIKey: GYQYAJJFPNQOOW-UHFFFAOYSA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 552.72, ALogP 2.7, HBA 10, HBD 3, PSA 121.11, QED 0.43
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H](C)NC1=O
InChIKey: HDHDTKMUACZDAA-PHNIDTBTSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC5R expressed in HEK2936E cell membrane measured after 16-23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: IC50 = 1905.46 nM (pChEMBL 5.71999979019165)
Descriptors: MW 1117.33
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc(OCCOC)cc3)ncc2F)c1
InChIKey: KXBDTLQSDKGAEB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Omnia Assay: Briefly, 10x stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λem485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to 30 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (minutes) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response, Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 423.45, ALogP 4.25, HBA 7, HBD 3, PSA 97.4, QED 0.33
Compound (SMILES): CN1Cc2c(Cl)cc(Cl)cc2[C@H](c2cccc(S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)c2)C1.Cl.Cl
InChIKey: VFRAXTZDILCRKY-OWRGXFNZSA-N
Target: Sodium/hydrogen exchanger 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P26433
Assay: Inhibition of rat NHE-3-mediated Na+ dependent H+ antiport expressed in opossum kidney cells in presence of NHE-1 antagonist EIPA by BCECF-AM dye based fluorescence assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 1145.07
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(OC)cc2)NC(=O)CCCSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: NSTRIRCPWQHTIA-DTRKZRJBSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Displacement of [3H]OT from recombinant human OTR expressed in HEK293 cell membranes measured after 1 hr
Measurement: Ki = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 988.18, ALogP -2.5, HBA 13, HBD 10, PSA 362.51, QED 0.07
Compound (SMILES): C[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]2CSSC[C@H](N)C(=O)N[C@H]3CSSC[C@H](NC1=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)CSSC[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC3=O)C(=O)N2
InChIKey: KXGCNMMJRFDFNR-WDRJZQOASA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding affinity towards human DRD2 in an in vitro assay with cellular components measured by membrane filtration, scintillation proximity assay
Measurement: AC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1526.77
Compound (SMILES): CCOC1O[C@H]([C@@H](COCc2ccccc2)OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1O
InChIKey: ULLNJSBQMBKOJH-VIVFLBMVSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding affinity towards human SLC6A4 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 478.59, ALogP 4.5, HBA 6, HBD 1, PSA 66.38, QED 0.39
Compound (SMILES): CC=CC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccc(O)cc3)[C@H]2SC1
InChIKey: WDLWHQDACQUCJR-PBFPGSCMSA-N
Target: Neuronal acetylcholine receptor subunit alpha-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P43681
Assay: Binding affinity towards human CHRNA4 in an in vitro assay with cellular components measured by scintillation proximity assay
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 389.43, ALogP 0.71, HBA 6, HBD 4, PSA 132.96, QED 0.55
Compound (SMILES): CN1CCN(C[C@@H](NC(=O)C[C@H]2CNC(=O)c3cc(-c4cccc(Cl)c4)cn32)C2CCCCC2)CC1
InChIKey: UKZRGBUTBINTPD-LOSJGSFVSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.1, ALogP 3.8, HBA 5, HBD 2, PSA 69.61, QED 0.59