lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1CCC(c2nc(C(F)(F)F)ccc2CNC(=O)Nc2cccc3[nH]c(=O)ccc23)CC1
InChIKey: BEIHCSFDVGJNKP-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human TRPV1 expressed in HEK cells assessed as inhibition of 10 nM capsaicin-induced calcium uptake by FLIPR assay
Measurement: IC50 = 1.44 nM (pChEMBL 8.84000015258789)
Descriptors: MW 458.48, ALogP 5.56, HBA 3, HBD 3, PSA 86.88, QED 0.48
Compound (SMILES): CC1(C)OC(=O)N(c2ccc(F)c(C(F)(F)F)c2)C1=O
InChIKey: NQKYBRKGGMQTFM-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Inhibition of wild-type androgen receptor in human LAPC4 cells assessed as inhibition of DHT-induced luciferase activity measured after 24 hrs by luciferase reporter assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 291.2, ALogP 3.11, HBA 3, HBD 0, PSA 46.61, QED 0.75
Compound (SMILES): Cc1ccccc1OC[C@@H]1CCCN(C(=O)CCc2nc(-c3ccccn3)no2)C1
InChIKey: QLLWIUIKEVFMKW-GOSISDBHSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Displacement of [3H]-SB67404 from human orexin 1 receptor expressed in CHO cells incubated for 2 hrs by whole cell radioligand binding assay
Measurement: Ki = 15135.61 nM (pChEMBL 4.820000171661377)
Descriptors: MW 406.49, ALogP 3.69, HBA 6, HBD 0, PSA 81.35, QED 0.6
Compound (SMILES): COc1ccc(-n2c(CC(C)C)nc3c(c(=O)c4ccccc4n3C)c2=O)cc1Cl
InChIKey: MCZLVBATDDLDAC-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Positive allosteric modulator activity at human dopamine D5 receptor expressed in CHO-K1 cells assessed as potentiation of dopamine-induced beta-arrestin2 recruitment by measuring dopamine EC50 at 50 uM incubated for 90 mins by PathHunter assay (Rvb = 81.7 nM)
Measurement: EC50 = 57.7 nM (pChEMBL 7.239999771118164)
Descriptors: MW 423.9, ALogP 4.1, HBA 6, HBD 0, PSA 66.12, QED 0.46
Compound (SMILES): CN1CCC(COc2ccc(CN3CCCc4cccc(NC(=O)c5cc6sccc6n5C)c43)cc2)CC1
InChIKey: KQHUDUNXEMXDTN-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant LSD1 using fluorogenic ADHP based substrate preincubated for 30 mins followed by substrate addition measured after 10 mins by horseradish peroxidase coupled fluorescence assay
Measurement: IC50 = 53.49 nM (pChEMBL 7.269999980926514)
Descriptors: MW 528.72, ALogP 6.17, HBA 6, HBD 1, PSA 49.74, QED 0.31
Compound (SMILES): CC(=O)Nc1ccc2c(c1)c(=O)n(CCc1ccccc1)c1n[nH]c(=S)n21
InChIKey: WXOJSKLCQUJIFR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of biotin-Ahx-CETFDPPLHSpTAI-NH2 binding to recombinant human full-length HA-EGFP-tagged Plk1 PBD expressed in HEK293A cells preincubated for 30 mins followed by biotin-Ahx-CETFDPPLHSpTAI-NH2 addition and measured after 1 hr by 3,3',5,5'-tetramethylbenzidine substrate based ELISA
Measurement: IC50 = 2190 nM (pChEMBL 5.659999847412109)
Descriptors: MW 379.45, ALogP 2.91, HBA 6, HBD 2, PSA 84.19, QED 0.53
Compound (SMILES): CC(=O)Nc1cccc(OCCCN2CCC(c3noc4cc(F)ccc34)CC2)c1
InChIKey: NCNRXHBCJNHSAO-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding affinity to D2 receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 411.48, ALogP 4.57, HBA 5, HBD 1, PSA 67.6, QED 0.58
Compound (SMILES): C/C(=N\NC(N)=S)c1nnn(-c2ccc(F)cc2)c1C
InChIKey: BEPDFRPSNCPHCP-VIZOYTHASA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX1 by colorimetric analysis
Measurement: IC50 = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 292.34, ALogP 1.27, HBA 5, HBD 2, PSA 81.12, QED 0.51
Compound (SMILES): Nc1ncc(-c2cnn(C3CCNCC3)c2)cc1OC1CCCCC1
InChIKey: FMBMSNBLEDENFC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IVH8
Assay: Inhibition of GLK (unknown origin) by alphascreen assay
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 341.46, ALogP 3.16, HBA 6, HBD 2, PSA 77.99, QED 0.89
Compound (SMILES): COC1CCN(C(=O)N[C@H]2CC[C@H](c3ccc(-c4c[nH]c([C@@H]5CCCN5C(=O)[C@H](NC(=O)N5CC[C@@H](NC(=O)OCc6ccccc6)C5)c5ccccc5)n4)cc3)CC2)CC1
InChIKey: XICVZIZAXPSQGB-ZFRPBYHLSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of Hepatitis C virus 1a NS5A
Measurement: EC50 = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 831.03, ALogP 7.04, HBA 7, HBD 4, PSA 161.23, QED 0.13
Compound (SMILES): CCCCCCCCC[C@H](C)C(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: YHJBQVKMEHMNSJ-ARTPSBNFSA-N
Target: Medium/long-chain-fatty-acid--CoA/3-oxocholest-4-en-26-oate--CoA ligase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WQ51
Assay: Inhibition of Mycobacterium tuberculosis H37Rv FACL19 Spectra expressed in Escherichia coli BL21(DE3) cells assessed as cleavage of MEsG by spectroscopic analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 528.63, ALogP 1.18, HBA 12, HBD 4, PSA 191.78, QED 0.26
Compound (SMILES): CC(C)N1CCC[C@H](Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: HKSXMVBEMPZHJC-AWEZNQCLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 369.9, ALogP 4.56, HBA 4, HBD 2, PSA 56.84, QED 0.71
Compound (SMILES): CCCCCCCCCCCOc1ccccc1CCC(=O)O[C@H]1COCC[C@@H]1OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: FTEXYKVSENDFKC-RNXOBYDBSA-N
Target: Probable G-protein coupled receptor 34 (SINGLE PROTEIN), Mus musculus
UniProt: Q9R1K6
Assay: Agonist activity at mouse GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 587.65, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.1
Compound (SMILES): O=C(CN1CCN(CCCc2c[nH]c3ccc(F)cc23)CC1)N(c1ccccc1)C1CCCCC1
InChIKey: QFHZTAFMZCTOBW-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2 receptor expressed in HEK293 cells incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay
Measurement: Ki = 2161.35 nM (pChEMBL 5.670000076293945)
Descriptors: MW 476.64, ALogP 5.22, HBA 3, HBD 1, PSA 42.58, QED 0.48
Compound (SMILES): CCC(=O)N(CCN1CCC(Cc2ccc(C)cc2)CC1)c1ccc(OC)cc1
InChIKey: ZIPKXVUJNLWDTA-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pnetazocin from sigma1 receptor in guinea pig brain membrane incubated for 150 mins by liquid scintillation counting method
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 394.56, ALogP 4.7, HBA 3, HBD 0, PSA 32.78, QED 0.65
Compound (SMILES): C[C@]1(c2cc(/C=C(\F)c3ccc(C#N)cn3)ccc2F)N=C(N)S[C@@]2(C(=O)N3CCC3)C[C@H]21
InChIKey: HLXYTIWCONMVCO-GQRGEFGTSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: In Vitro Enzymatic BACE1 and BACE2 FRET (Fluorescence Resonance Energy Transfer) Assays: The cDNAs for both human recombinant BACE1 and 2 with C-terminal 6-His Tags were cloned into transient protein expression vectors, which were subsequently transfected into mammalian cell lines. These recombinant proteins were further purified using Ni-NTA affinity chromatography (Qiagen). The assay buffer used in these screens was 0.05M acetate, pH 4.5, 8% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.02 nM for BACE1 and 0.64 nM for BACE2) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 590 nm).
Measurement: IC50 = 1.36 nM (pChEMBL 8.869999885559082)
Descriptors: MW 465.53, ALogP 3.83, HBA 6, HBD 1, PSA 95.37, QED 0.74
Compound (SMILES): Cc1ccc(OC[C@H]2O[C@H](O[C@@H]3[C@@H](O)[C@H](O[C@H]4O[C@H](CN)[C@@H](O)[C@H](O)[C@H]4O)[C@@H](N)C[C@H]3N)[C@H](O)[C@@H](N)[C@@H]2O)cc1
InChIKey: LUEXEMVZTABOBD-MJOPLTPXSA-N
Target: Gap junction alpha-1 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P17302
Assay: Inhibition of human Cx43 expressed in Escherichia coli LB2003 cells in medium containing 8 mM K+ and 10 uM IPTG by measuring cell growth after 18 hrs by plate reader
Measurement: IC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 574.63, ALogP -4.9, HBA 15, HBD 10, PSA 271.61, QED 0.14
Compound (SMILES): Cc1c(Cc2ccc(-c3ccc(C(F)(F)F)cc3)cc2)c(=O)oc2cc(OCC(O)CN3CCC(C(N)=O)CC3)ccc12
InChIKey: ARKOWTJMRLDFRL-UHFFFAOYSA-N
Target: Envelope glycoprotein (SINGLE PROTEIN), Lake Victoria marburgvirus (strain Musoke-80) (MARV) (Marburg virus (strainKenya/Musoke/1980))
UniProt: P35253
Assay: Inhibition of envelope glycoprotein in HIV pseudotyped Marburgvirus infected in human A549 cells assessed as reduction in virus entry measured after 48 hrs by luciferase reporter gene assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 594.63, ALogP 5.32, HBA 6, HBD 2, PSA 106, QED 0.25
Compound (SMILES): NC(=O)[C@H]1CCCN1C(=O)c1ccc2nc(Nc3ccc(-c4nc(N5CCOCC5)nc(N5CCOCC5)n4)cc3)[nH]c2c1
InChIKey: CWWWLWINFJYDAB-XMMPIXPASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after 1 hr in presence of ATP by ADP-Glo reagent based assay
Measurement: IC50 = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 598.67, ALogP 1.92, HBA 11, HBD 3, PSA 167.72, QED 0.28
Compound (SMILES): CCCCCCCCCCCCNC(=O)CCCC
InChIKey: JWXQCDAQGRKRGO-UHFFFAOYSA-N
Target: Epoxide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07099
Assay: Inhibition of human mEH using CMNGC as substrate preincubated for 5 mins followed by substrate addition and measured at 30 secs interval for 10 mins by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 269.47, ALogP 5.21, HBA 1, HBD 1, PSA 29.1, QED 0.43
Compound (SMILES): CC(C)(CO)Cn1nc(-c2c[nH]c3ccccc23)c2c(N)ncnc21
InChIKey: CEWOYNHYISZPFC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase D1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15139
Assay: Inhibition of recombinant FLAG-tagged PKD1 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 336.4, ALogP 2.58, HBA 6, HBD 3, PSA 105.64, QED 0.53
Compound (SMILES): CC(C)(O)c1cc(Nc2cc(Oc3cn(C4CC4)nc3-c3ccc(C#N)cc3)ccn2)ccn1
InChIKey: BMFDPTZPMFMHEN-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) measured after 120 mins of incubation by ADP-Glo kinase assay
Measurement: IC50 = 31.4 nM (pChEMBL 7.5)
Descriptors: MW 452.52, ALogP 5.31, HBA 8, HBD 2, PSA 108.88, QED 0.39
Compound (SMILES): CN1CCN(Cc2ccc(-c3cccc(C(=O)Nc4ccccc4CC(=O)O)c3)cc2)CC1
InChIKey: UTWXDNZWMQAUKL-UHFFFAOYSA-N
Target: Succinate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXA5
Assay: Antagonist activity at human SUCNR1 expressed in human CHEM1 cells incubated for 60 mins in presence of [35S]GTPgammaS by scintillation proximity assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 443.55, ALogP 3.98, HBA 4, HBD 2, PSA 72.88, QED 0.58
Compound (SMILES): COc1cc(NC(=O)CC/C(C)=C/Cc2c(O)c3c(c(C)c2OC)COC3=O)ccc1Cl
InChIKey: GFKRWPNMQSLPGF-WLRTZDKTSA-N
Target: Inosine-5'-monophosphate dehydrogenase (SINGLE PROTEIN), Cryptosporidium parvum
UniProt: Q8T6T2
Assay: Inhibition of Cryptosporidium parvum IMPDH expressed in Escherichia coli assessed as apparent inhibition constant using NAD as substrate by fluorescence assay
Measurement: Ki = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 459.93, ALogP 4.95, HBA 6, HBD 2, PSA 94.09, QED 0.43
Compound (SMILES): O=C(NCCCN1CCCC1)c1ccnc(-c2ccccc2N2CCN(CCc3c[nH]c4ccccc34)CC2)c1
InChIKey: ZRGMZIXVBWLLHA-UHFFFAOYSA-N
Target: N-lysine methyltransferase SMYD2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRG4
Assay: Inhibition of SMYD2 (unknown origin)
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 536.72, ALogP 4.81, HBA 5, HBD 2, PSA 67.5, QED 0.28
Compound (SMILES): Cc1nn(-c2ccccn2)c2c1C(=O)NCC(C)(C)C2Br
InChIKey: ITBMILFXWRILTC-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of human N-terminal GST-tagged CDK2 (1 to 298 residues)/Cyclin A (174 to 432 residues) expressed in Escherichia coli Turner (DE3) cells assessed as reduction in ADP formation using PKTPKKAKKL as substrate by resorufin dye based fluorescence assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 349.23, ALogP 2.78, HBA 4, HBD 1, PSA 59.81, QED 0.81
Compound (SMILES): Oc1ccc(Cc2nnc3sc(Nc4cccc(Cl)c4)nn23)cc1F
InChIKey: MDQXNVZAFBXRIJ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using poly Glu-Tyr as substrate preincubated for 10 mins followed by ATP addition by phosphoenolpyruvate/pyruvate kinase/lactate dehydrogenase coupled radiometric assay
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 375.82, ALogP 4.02, HBA 7, HBD 2, PSA 75.34, QED 0.56
Compound (SMILES): Cc1cc(Cl)cc(N2C=Nc3cc(C)c(-c4cncc(O)c4)cc3C2C(=O)N(C)C[C@@H]2CCCN2)c1
InChIKey: NXEOXXTUJXYHIV-LWAJAQLZSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at human SST2 expressed in CHO-K1 cells assessed as reduction in NKH477-induced intracellular cAMP accumulation
Measurement: EC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 504.03, ALogP 5.16, HBA 6, HBD 2, PSA 81.06, QED 0.5
Compound (SMILES): COc1ccc(NC(=O)CC2SCCNC2=O)cc1
InChIKey: NWPAXMXJJARHNG-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Binding affinity to full length biotinylated 6His/Avi-tagged/Tev-fused human MEK1 expressed in Escherichia coli in presence of AMP-PNP by SPR assay
Measurement: Kd = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 280.35, ALogP 1.26, HBA 4, HBD 2, PSA 67.43, QED 0.87
Compound (SMILES): FC(F)(F)c1cccc(-c2nc3nc(n2)Nc2cc(Cl)cc(c2)C/C=C\COCCN3)n1
InChIKey: VTOBJSPIZKGERB-UPHRSURJSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 462.86, ALogP 4.89, HBA 7, HBD 2, PSA 84.85, QED 0.5
Compound (SMILES): CCOc1ccc(-n2cnc(C(=O)O)c2)cc1C#N
InChIKey: OPXHIBWVKUOLAH-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P80457
Assay: Inhibition of bovine xanthine oxidase assessed as reduction in uric acid formation using xanthine as substrate incubated for 3 mins by microplate assay
Measurement: IC50 = 226.3 nM (pChEMBL 6.639999866485596)
Descriptors: MW 257.25, ALogP 1.84, HBA 5, HBD 1, PSA 88.14, QED 0.9
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](C)NC(=O)c2ccc(-c3ccc(C(C)=O)cc3)o2)C(=O)N[C@@H](CC(C)C)C(=O)C(=O)Nc2cc(OC)cc(OC)c2)cc1
InChIKey: RBQIVUPNAULZFJ-MSQADJIASA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of 20S immunoproteasome beta 5 chymotrypsin-like activity in human H226 cell using Suc-LLVY-AMC as substrate for 10 mins by fluorescence based assay
Measurement: IC50 = 31.7 nM (pChEMBL 7.5)
Descriptors: MW 754.84, ALogP 4.76, HBA 10, HBD 4, PSA 191.37, QED 0.08
Compound (SMILES): CCC(Nc1c(Cl)cnc2ccc(-c3cnc(C(C)(C)O)nc3)cc12)c1ccccc1F
InChIKey: SCELQBVHISIVJG-UHFFFAOYSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Displacement of fluorescent labeled probe from human recombinant His-tagged TNFalpha (77 to 233 residues) expressed in Escherichia coli preincubated for 1 hr followed by fluorogenic probe addition and measured after 3 hrs by HTRF assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 450.95, ALogP 6.27, HBA 5, HBD 2, PSA 70.93, QED 0.36
Compound (SMILES): Nc1nn2c(-c3ccc([N+](=O)[O-])cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: XEDPDGPVDPXHDH-GHVJWSGMSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 2122 nM (pChEMBL 5.670000076293945)
Descriptors: MW 438.43, ALogP 2.95, HBA 10, HBD 2, PSA 184.23, QED 0.27
Compound (SMILES): COc1cc(C(Nc2ccc(C)cn2)c2ccc3cccnc3c2O)cc(OC)c1O
InChIKey: MITSWHDEOSTHCR-UHFFFAOYSA-N
Target: Protein disulfide-isomerase (SINGLE PROTEIN), Homo sapiens
UniProt: P07237
Assay: Inhibition of recombinant human wild-type N-terminal His-tagged PDIA1 expressed in Escherichia coli strain BL21(DE3) using bovine insulin as substrate preincubated for 1 hr followed by substrate addition
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 417.47, ALogP 4.57, HBA 7, HBD 3, PSA 96.73, QED 0.42
Compound (SMILES): [2H][C@@H]1C[C@@H](OC[C@H]2[C@@H](NS(=O)(=O)N(C)C)C[C@@H](C)N2C(=O)OC)CC[C@@]1([2H])c1cccc(F)c1
InChIKey: VRCBPPQSWQSLSW-QQQLQBHZSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Agonist activity at human recombinant OX2R expressed in CHOK1 cells assessed as increase in intracellular Ca2+ mobilization by measuring IP3 production incubated for 2 hrs by IP-one detection reagent based fluorescence assay
Measurement: IC50 = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 471.6, ALogP 2.86, HBA 5, HBD 1, PSA 88.18, QED 0.66
Compound (SMILES): Cc1nc2ccc(-c3cnn(C4CC4)c3)nc2n1-c1ccc(N2CCOCC2)c(F)c1
InChIKey: MGFWXJBMHPOZGA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to DYRK1A (unknown origin)
Measurement: Kd = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 418.48, ALogP 3.9, HBA 7, HBD 0, PSA 61, QED 0.5
Compound (SMILES): CCCC/N=C(\C)c1c(O)c2ccccc2oc1=O
InChIKey: VXRKMHKOOUBXBJ-MHWRWJLKSA-N
Target: Myosin-2 (SINGLE PROTEIN), Bos taurus
UniProt: Q9BE41
Assay: Inhibition of actin-activated bovine heart muscle myosin 2 assessed as phosphate level incubated for 6 to 24 mins by spectrophotometric method
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 259.3, ALogP 3.11, HBA 4, HBD 1, PSA 62.8, QED 0.52
Compound (SMILES): CCCC[C@H](N)C(=O)N[C@@H]1C[C@H](C(=O)NO)N(S(=O)(=O)c2ccc(OC)cc2)C1
InChIKey: LUHMIRSYHUCEHG-UHOFOFEASA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of MMP2 (unknown origin) using Mca-Lys-Pro-Leu-GlyLeu-Dpa-Ala-Arg-NH2 as substrate by fluorometric assay
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 428.51, ALogP -0.03, HBA 7, HBD 4, PSA 151.06, QED 0.32
Compound (SMILES): Cc1cc2cc(NC(=O)c3cc(C(=O)NO)ccc3Cl)ccc2n(C)c1=O
InChIKey: QNBKPOQRRXZDRO-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using H2N-Arg-His-Lys(Ac)-Lys(Ac)-AMC as substrate after 90 mins by fluorescence based micro plate assay
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 385.81, ALogP 2.87, HBA 5, HBD 3, PSA 100.43, QED 0.48
Compound (SMILES): COc1cccc(Nc2ccc(Cl)c3c2cc(C(=O)NS(=O)(=O)c2ccccc2F)n3C)c1
InChIKey: STUQIFHRGQKHDL-UHFFFAOYSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human liver FBPase expressed in Escherichia coli BL21(DE3) using FBP as substrate in presence of PGI and G6PDH by spectrophotometric method
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 487.94, ALogP 4.84, HBA 6, HBD 2, PSA 89.43, QED 0.41
Compound (SMILES): Nc1nnc(-c2ccccc2O)cc1N1CCC[C@@H](O)C1
InChIKey: VUGYKDOKOLKKRA-SNVBAGLBSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Binding affinity to SMARCA4 (unknown origin) by ITC analysis
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 286.33, ALogP 1.39, HBA 6, HBD 3, PSA 95.5, QED 0.77
Compound (SMILES): CCCCCn1nc(C(=O)NC(C)(C)CO)cc1C1CCCCC1
InChIKey: UJWJTEIYWBCRRB-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressing CHO cells co-expressing Galpha16 by calcium mobilization assay
Measurement: EC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 335.49, ALogP 3.62, HBA 4, HBD 2, PSA 67.15, QED 0.71
Compound (SMILES): Nc1nc2sc(CCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)s3)cc2c(=O)[nH]1
InChIKey: VCNJYHGDMDELAI-LBPRGKRZSA-N
Target: Reduced folate transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P41440
Assay: Inhibition of human RFC expressed in Chinese Hamster MTXRII-OuaR2-4 R2 cells assessed as reduction in cell proliferation after 96 hrs by CellTiter-blue assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 464.53, ALogP 1.85, HBA 8, HBD 5, PSA 175.47, QED 0.3
Compound (SMILES): Cc1nnc2n1-c1ccc(-c3cnn(C)c3)cc1N(c1ccc(Cl)cc1)CC2
InChIKey: YKWIZXQJCBCRME-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His/FLAG-tagged BRD4 BD1 (unknown origin) using histone H4-TetraAcetylated-biotin peptide as substrate incubated for 20 mins by AlphaLISA assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 390.88, ALogP 4.32, HBA 6, HBD 0, PSA 51.77, QED 0.51
Compound (SMILES): COc1ccc(O)c(/C=N/Nc2nc(-c3ccc(S(C)(=O)=O)cc3)cs2)c1
InChIKey: WIYQKOSNHXVUKK-VXLYETTFSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of COX-1 (unknown origin) using arachidonic acid as substrate measured after 10 mins by fluorometric based multimode microplate reader
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 403.49, ALogP 3.37, HBA 8, HBD 2, PSA 100.88, QED 0.48
Compound (SMILES): O=C(Nc1ccc(C(F)(F)F)c(F)c1)NC1CCN(C(=O)C2CCCOC2)CC1
InChIKey: FACVJGCBIANJAJ-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki = 2.66 nM (pChEMBL 8.569999694824219)
Descriptors: MW 417.4, ALogP 3.38, HBA 3, HBD 2, PSA 70.67, QED 0.74
Compound (SMILES): COc1cc(OC)cc(Sc2c[nH]c3cc(Cl)ccc23)c1
InChIKey: OFWGAWFWBIHHSW-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 incubated for 60 mins in presence of L-tryptophan by HPLC analysis
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 319.81, ALogP 4.99, HBA 3, HBD 1, PSA 34.25, QED 0.74
Compound (SMILES): O=C(Nc1ccon1)NC12CC3CC(CC(C3)O1)C2
InChIKey: XKPVBTRISIICIM-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of recombinant human soluble epoxide hydrolase using CMNPC as substrate preincubated for 5 mins followed by substrate addition and measured at 30 secs interval for 10 mins by fluorescence assay
Measurement: IC50 = 911 nM (pChEMBL 6.039999961853027)
Descriptors: MW 263.3, ALogP 2.1, HBA 4, HBD 2, PSA 76.39, QED 0.86
Compound (SMILES): CCc1cc(C(=O)N2CS(=O)(=O)c3ccccc32)cc(C#N)c1O
InChIKey: JVXASWJRFPUFOH-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: Inhibition of URAT1 in human RPTEC assessed as inhibition of [14C]uric acid uptake preincubated for 15 mins followed by [14C]uric acid addition and incubated under shaking condition for 2 hrs by scintillation counter method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 342.38, ALogP 2.22, HBA 5, HBD 1, PSA 98.47, QED 0.9
Compound (SMILES): CCOCc1cn(-c2ccc(NC(=O)Nc3cc(C(C)C)ccc3C)cc2)nn1
InChIKey: MEIPCKWDYRWVCC-UHFFFAOYSA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Inhibition of human DDX3X using dsRNA as substrate measured every 30 sec for 40 mins by FRET assay
Measurement: IC50 = 1510 nM (pChEMBL 5.820000171661377)
Descriptors: MW 393.49, ALogP 4.88, HBA 5, HBD 2, PSA 81.07, QED 0.6
Compound (SMILES): COc1c(C)n(-c2ccc(OC3CCN(C4CCC4)CC3)cc2)ccc1=O
InChIKey: RCRQZRXKYFJPOM-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Antagonist activity at human histamine H3 receptor expressed in HEK293 cells preincubated for 5 mins followed by forskolin-stimulation and measured after 5 hrs by CRE-driven luciferase reporter gene assay
Measurement: IC50 = 2.43 nM (pChEMBL 8.609999656677246)
Descriptors: MW 368.48, ALogP 3.55, HBA 5, HBD 0, PSA 43.7, QED 0.81
Compound (SMILES): N#C/N=C1/SCCN1Cc1ccc(-c2ccc(Br)cc2)o1
InChIKey: QBFDSWNEOHCEIR-OBGWFSINSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human U-937 cells derived PDE4B using [3H] cAMP as substrate measured after 30 mins
Measurement: IC50 = 52700 nM (pChEMBL 4.28000020980835)
Descriptors: MW 362.25, ALogP 4.09, HBA 4, HBD 0, PSA 52.53, QED 0.77
Compound (SMILES): CN1CCN(c2ccc(-c3ccn4c(-c5csc6nccnc56)cnc4c3)cc2)CC1
InChIKey: XFMZPAXBRSRGGU-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 426.55, ALogP 4.42, HBA 7, HBD 0, PSA 49.56, QED 0.43
Compound (SMILES): CCNc1ncc2c(n1)CCN(C(=O)c1cc(C(C)C)c(O)cc1O)C2
InChIKey: MUAUOQRPMMQITE-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from N-terminal HSP90alpha (unknown origin) after 30 mins by fluorescence polarization competitive binding assay
Measurement: IC50 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 356.43, ALogP 2.64, HBA 6, HBD 3, PSA 98.58, QED 0.78
Compound (SMILES): CO[C@@H]1C[C@@H]2C[C@H](O)CC[C@]2(C)[C@H]2CC[C@]3(C)[C@@H]([C@H](C)CCC(=O)O)CC[C@H]3[C@H]12
InChIKey: FXNFUBOXADYMRJ-IFJDUOSNSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at recombinant human TGR5 expressed in CHO cells assessed as increase in cAMP accumulation after 30 mins by TR-FRET assay
Measurement: EC50 = 76.8 nM (pChEMBL 7.119999885559082)
Descriptors: MW 406.61, ALogP 5.13, HBA 3, HBD 2, PSA 66.76, QED 0.66
Compound (SMILES): O=P(O)(O)CCOC[C@H]1O[C@@H](n2cnc3c(NCc4ccccc4)nc(Cl)nc32)[C@H](O)[C@@H]1O
InChIKey: AJRXCVVGNJCZJU-SCFUHWHPSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of human CD73 expressed in CHO cells incubated for 60 mins before addition of AMP and further incubated for 60 mins by colorimetric assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.85, ALogP 0.91, HBA 10, HBD 5, PSA 172.08, QED 0.16
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCN3CCOCC3)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: BZAZMGAUYLFJOA-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulation of gamma secretase in human SH-SY5Y cells overexpressing wild type APP751 assessed as inhibition of amyloid beta (35 to 42 residues) formation incubated for overnight by ELISA
Measurement: IC50 = 177 nM (pChEMBL 6.75)
Descriptors: MW 520.66, ALogP 3.86, HBA 11, HBD 1, PSA 95.15, QED 0.37
Compound (SMILES): CCC/N=C1\S/C(=C\c2ccc(O)c(Br)c2)C(=O)N1c1ccccc1C
InChIKey: MWQNJADYDLCFTQ-JLZFKDTQSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Immunomodulatory activity at human S1PR1 expressed in CHO-K1 EDG1 beta-arrestin cells assessed as stimulation of beta-arrestin recruitment incubated for 90 mins at 37 degC followed by incubated for 15 mins in room temperature by pathhunter beta-arrestin assay
Measurement: IC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 431.36, ALogP 5.35, HBA 4, HBD 1, PSA 52.9, QED 0.66
Compound (SMILES): Cc1ccc(-c2cncc3[nH]c(-c4n[nH]c5cnc(-c6cncc(NC(=O)C7CCC7)c6)cc45)nc23)s1
InChIKey: LZFXVYVCALQDMM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 506.6, ALogP 5.73, HBA 7, HBD 3, PSA 125.13, QED 0.27
Compound (SMILES): COC(C)c1c(NC(=O)Nc2cnc(-n3nccn3)c(Cl)c2)cnc2ccccc12
InChIKey: VBSJYBDVDGVNPC-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 423.86, ALogP 4.22, HBA 7, HBD 2, PSA 106.85, QED 0.5
Compound (SMILES): C#CCOc1ccc(-c2cc(-c3ccc(OCCN4CCOCC4)cc3)nc(N)n2)cc1
InChIKey: SZNDVDHYJXHIKM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine iodide as substrate incubated for 30 mins followed by substrate addition and measured for 20 mins by Ellman's method
Measurement: IC50 = 666 nM (pChEMBL 6.179999828338623)
Descriptors: MW 430.51, ALogP 3.12, HBA 7, HBD 1, PSA 82.73, QED 0.55
Compound (SMILES): COc1cccc(NC(=O)N2CCOc3ccc(-c4ccncc4C)cc3C2)c1
InChIKey: ZWGJSFORKCINJR-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 394 nM (pChEMBL 6.409999847412109)
Descriptors: MW 389.45, ALogP 4.49, HBA 4, HBD 1, PSA 63.69, QED 0.72
Compound (SMILES): O=C(/C=C/c1ccc(CNC(=O)c2ccc(-c3csc(N4N=C(c5ccccc5)/C(=N/Nc5nccs5)C4=O)n3)cc2)cc1)NO
InChIKey: XIYISHSKDXWNPA-LCYNSZJLSA-N
Target: Apoptosis regulator BAX (SINGLE PROTEIN), Homo sapiens
UniProt: Q07812
Assay: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay
Measurement: EC50 = 2218.1 nM (pChEMBL 5.650000095367432)
Descriptors: MW 648.73, ALogP 4.93, HBA 11, HBD 4, PSA 161.27, QED 0.09
Compound (SMILES): O=C(N[C@H]1CCOC[C@@H]1O)c1cc(Cc2ccc(-n3cccn3)cc2)ccn1
InChIKey: GEIWYSYEKRVIQX-ICSRJNTNSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Positive allosteric modulation of human muscarinic M1 receptor stably expressed in CHO cells assessed as increase in Ach-induced intracellular calcium level preincubated for 10 mins followed by addition of Ach at EC20 concentration by Fluo-8AM dye based FLIPR TETRA method
Measurement: EC50 > 9000 nM (pChEMBL 5.046000003814697)
Descriptors: MW 378.43, ALogP 1.74, HBA 6, HBD 2, PSA 89.27, QED 0.71
Compound (SMILES): CCNC(=O)c1cccc(CNC(=O)c2ccc3c(c2)COc2cnccc2-3)c1
InChIKey: YKJXZODWOQJHCQ-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity. Compounds were tested in dose-response format, and the inhibition of kinase activity was calculated at each concentration of compound. The inhibition data were fit using a curve-fitting program to determine the IC50; i.e., the concentration of compound required to inhibit 50% of kinase activity.
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 387.44, ALogP 3.32, HBA 4, HBD 2, PSA 80.32, QED 0.7
Compound (SMILES): COc1cc(OC)c2c(N3CCCCC3)nc(-c3cc(C)c(OCCCCC(=O)NO)c(C)c3)nc2c1
InChIKey: UBYFKEODBCEWTD-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human His-tagged HDAC6 expressed in baculovirus infected insect cells using Ac-Leu-Gly-Lys(Ac)-AMC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 508.62, ALogP 4.98, HBA 8, HBD 2, PSA 106.04, QED 0.22
Compound (SMILES): CNC(=O)c1cc(Oc2ccc(NC(=O)c3cccc(C(F)(F)F)c3)cc2)ccn1
InChIKey: WACDHHMEVMSODJ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) by caliper mobility shift assay
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 415.37, ALogP 4.5, HBA 4, HBD 2, PSA 80.32, QED 0.64
Compound (SMILES): CC1CN(c2nc(NCC(=O)O)c(C(=O)Nc3ccc4ccccc4c3)s2)CCN1C
InChIKey: MJZICDIVBHJTIX-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13526
Assay: Inhibition of N-terminal His tagged human Pin1 expressed in Escherichia coli BL21 (DE3) using Suc-Ala-Glu-Pro-Phe-4-nitroanilide as substrate preincubated with enzyme for 10 mins followed by substrate addition by UV-Vis spectrophotometer analysis
Measurement: IC50 = 37070 nM (pChEMBL 4.429999828338623)
Descriptors: MW 439.54, ALogP 3.19, HBA 7, HBD 3, PSA 97.8, QED 0.54
Compound (SMILES): COc1ccc2nc3c(c(NCCCCCCN(CC(=O)NCCc4c[nH]c5ccc(OC)cc45)C(=O)/C=C/c4ccc(O)c(OC)c4)c2c1)CCCC3
InChIKey: MFLCKOCRDJGDBD-CPNJWEJPSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE pre-incubated for 10 mins before addition of acetylthiocholine iodide substrate and further incubated for 15 mins by Ellman's method
Measurement: IC50 = 17.8 nM (pChEMBL 7.75)
Descriptors: MW 733.91, ALogP 7.2, HBA 8, HBD 4, PSA 138.04, QED 0.05
Compound (SMILES): C#CCN(C)C(=O)c1cc2cc(NC(C)=O)ccc2n1Cc1ccc(OC)cc1
InChIKey: KRPGWCHZBIGSMM-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Displacement of [3H]PK11195 from human TSPO A147T mutant expressed in HEK293 cells after 90 mins by scintillation counting method
Measurement: Ki = 2861.4 nM (pChEMBL 5.539999961853027)
Descriptors: MW 389.46, ALogP 3.36, HBA 4, HBD 1, PSA 63.57, QED 0.66
Compound (SMILES): O=C(N[C@H]1CCN(C2CC(F)(F)C2)C[C@@H]1C(=O)NC1(c2ncccn2)CC1)c1cc(-c2ccc(F)cc2F)on1
InChIKey: JMQQKOOATRBQER-ICSRJNTNSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs
Measurement: IC50 = 975 nM (pChEMBL 6.010000228881836)
Descriptors: MW 558.54, ALogP 3.43, HBA 7, HBD 2, PSA 113.25, QED 0.43
Compound (SMILES): COc1cccc(-c2cc(C(F)(F)F)n3nc(-c4cccs4)cc3n2)c1
InChIKey: HOTTTYVUXULYHX-UHFFFAOYSA-N
Target: Far upstream element-binding protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96AE4
Assay: Inhibition of 6xHis-tagged human FUBP1 expressed in HEK293T cells assessed as reduction in FUBP1 interaction with biotinylated NLC chip immobilized FUSE p21 oligonucleotide incubated for 21 hrs by SPR analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 375.38, ALogP 5.15, HBA 5, HBD 0, PSA 39.42, QED 0.5
Compound (SMILES): CSc1ncc2c(n1)N(C)CCN(c1cccc(-c3nnc(C)o3)c1)C2=O
InChIKey: OFOVPNFNRKXRFW-UHFFFAOYSA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 382.45, ALogP 2.65, HBA 8, HBD 0, PSA 88.25, QED 0.5
Compound (SMILES): COc1ccc(CC(=O)NC(=N)N[C@@H](C(=O)Nc2cc(S(N)(=O)=O)ccc2C)C(C)C)cc1OC.O=C(O)C(F)(F)F
InChIKey: MMYCXHMRQMBDSM-ZMBIFBSDSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human liver Cathepsin D preincubated for 10 mins followed by substrate addition and further incubated for 2 hrs in dark by fluorimetric analysis
Measurement: IC50 = 431 nM (pChEMBL 6.369999885559082)
Descriptors: MW 505.6, ALogP 1.51, HBA 7, HBD 5, PSA 172.7, QED 0.25
Compound (SMILES): O=C(N[C@@H]1CCCC[C@H]1O)c1cc(Cc2ccc(-c3cccnc3)cc2)c2cccn2n1
InChIKey: GQTBMPMAVUMHQO-RCZVLFRGSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Positive allosteric modulation of recombinant human muscarinic M1 receptor co-expressing pCRE-Luc reporter gene in CHO cells assessed as stimulation of luciferase activity in presence of acetylcholine substrate measured after 4 hrs by luciferase reporter gene assay
Measurement: EC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 426.52, ALogP 4.02, HBA 5, HBD 2, PSA 79.52, QED 0.51
Compound (SMILES): O=C([C@H]1CC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)CN1)N1CC[C@H](O)C1
InChIKey: DTNBKVWVJJDYHM-CKFHNAJUSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 474.49, ALogP 2.77, HBA 6, HBD 4, PSA 106.17, QED 0.46
Compound (SMILES): Cn1c(=O)oc2cc(NC(=O)CCCCN3CCN(Cc4ccccc4)CC3)ccc21
InChIKey: ZXBCEPJCYVDINZ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition and measured for 10 mins by Ellman's method
Measurement: IC50 = 30860 nM (pChEMBL 4.510000228881836)
Descriptors: MW 422.53, ALogP 3.06, HBA 6, HBD 1, PSA 70.72, QED 0.57
Compound (SMILES): CC(C)(CNC(=O)c1cn(-c2ccc(Cl)cc2)nc1-c1ccccc1)N1CCOCC1
InChIKey: PTOBDOLLYDMPSN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged KDM5B expressed in Sf9 insect cells using biotin-H3K4me as substrate by ALPHA
Measurement: IC50 = 540.9 nM (pChEMBL 6.269999980926514)
Descriptors: MW 438.96, ALogP 4.03, HBA 5, HBD 1, PSA 59.39, QED 0.63
Compound (SMILES): Cc1cc(NC2Cc3c(C)ccc(C)c3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: SSKKUEPOXJAQCQ-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of N-terminal His6-tagged human DHODH expressed in Escherichia coli BL21 using L-DHO as substrate and CoQ as co-substrate by DCIP dye based spectrophotometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 357.41, ALogP 3.74, HBA 5, HBD 1, PSA 55.11, QED 0.78
Compound (SMILES): CC(C)(C)c1cc(Oc2c(Cl)cc(NC(=O)c3noc(=O)[nH]3)cc2Cl)n[nH]c1=O
InChIKey: VYSXTPWRHFACHR-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay for Thyroid Hormone Receptor Agonist Screening: LanthaScreen TR-FRET Thyroid Receptor alpha Coactivator Assay kit (ThermoFisher) and LanthaScreen TR-FRET Thyroid Receptor beta Coactivator Assay kit (ThermoFisher) were used for agonist compound screening. Compounds in DMSO were diluted using ECHO Liquid Handler (Labcyte Inc.) into 384 plates in 10-point 3-fold series in duplicate (5 micro M final top concentration). Buffer C (ThermoFisher) was added to each well before the 4× mixture of fluorescein-SCR2-2 coactivator (200 nM final concentration), Terbium-labeled anti-GST antibody (2 nM final concentration), and TR alpha-LBD (0.4 nM final concentration) or TR beta-LBD (1.0 nM final concentration) was added. After 2 hour incubation at room temperature in dark, the TR-FRET signal was measured on an EnVision plate reader (PerkinElmer) with excitation at 340 nm and dual emission readout at 495 and 520 nm with the delay time of 100 micro second and the integration time of 200 micro second. The ratio of emission signal at 520 and at 495 was used to calculate EC50 using GraphPad Prism (GraphPad Software). In every batch of compound screening, T3 (L-3,3′,5-Triiodothyronine sodium salt, >95%) (Calbiochem) was used as reference compound. The EC50 of T3 measured were within 3-fold of the reference value provided by the assay kit manufacturer (ThermoFisher Scientific). The Z′ factors measured in every batch of screening using T3 as high percent effect (HPE) control and 0.5% DMSO as zero percent effect (ZPE) control were in the range of 0.5 to 0.8. Compounds' THR-beta selectivity values are derived from T3-selectivity normalized data.
Measurement: EC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 440.24, ALogP 3.1, HBA 7, HBD 3, PSA 142.97, QED 0.57
Compound (SMILES): Cc1ccc(N(CC(C)F)S(=O)(=O)c2ccc([N+](=O)[O-])cc2)cc1
InChIKey: QLKQWLWXRLTHCV-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 352.39, ALogP 3.46, HBA 4, HBD 0, PSA 80.52, QED 0.59
Compound (SMILES): Cl.Clc1ccc2[nH]c3c(c2c1)CCNC3c1ccccc1Cl
InChIKey: CZTKLVZDFSUICK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 317.22, ALogP 4.71, HBA 1, HBD 2, PSA 27.82, QED 0.67
Compound (SMILES): CCC(=O)c1ccc(-c2cn(-c3ccc(CCN4CCc5cc(OC)c(OCCOCCOCCOC)cc5C4)cc3)nn2)cc1NC(=O)c1ccc2ccccc2n1
InChIKey: CHAZSVOPUAINSR-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 in topotecan-cultured human MCF7 cells using Hoechst 33342 as substrate measured after 2 hrs by fluorescence assay
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 798.94, ALogP 7, HBA 12, HBD 1, PSA 139.16, QED 0.06
Compound (SMILES): O=C(CN1CCN(C(=O)c2ccccc2F)CC1)N1CCN(CCCc2c[nH]c3ccccc23)CC1
InChIKey: RZMJYTHUZCYCES-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human plasma AChE using acetylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition and measured after 10 mins by Ellman's method
Measurement: IC50 = 20200 nM (pChEMBL 4.699999809265137)
Descriptors: MW 491.61, ALogP 2.84, HBA 4, HBD 1, PSA 62.89, QED 0.55
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cc(N3CCCCC3)ccn2c1=O)c1ccc(OC(F)(F)F)cc1
InChIKey: NJEHMSSTZPPARW-HNNXBMFYSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 463.46, ALogP 3.26, HBA 7, HBD 1, PSA 80.87, QED 0.61
Compound (SMILES): O=P(O)(O)COCC[C@H]1O[C@@H](n2ncc3c(NCc4ccccc4Cl)nc(Cl)nc32)[C@H](O)[C@@H]1O
InChIKey: QHXUEAYQJHERGY-ATNYBXOESA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay
Measurement: IC50 = 1201 nM (pChEMBL 5.920000076293945)
Descriptors: MW 534.29, ALogP 1.91, HBA 10, HBD 5, PSA 172.08, QED 0.15