lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)N[C@@H](C)C(=O)SN[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: WULNGTQLUMPOHE-QHLIUQDXSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in absence of albumin by CRE luciferase reporter gene assay
Measurement: EC50 = 0.027 nM (pChEMBL 10.569999694824219)
Descriptors: MW 3634.22
Compound (SMILES): Cc1cc(C)c(-c2cc(NC(=O)CSCC(=O)NCc3ccc(F)cc3)n(-c3ccccc3)n2)cc1C
InChIKey: WNBCWNUHZQIEPY-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-gp mediated multidrug resistance in human DU145-TxR cells overexpressing P-gp assessed as potentiation of paclitaxel-induced cytotoxicity by measuring paclitaxel IC50 at 5 uM after 48 hrs by MTT assay (Rvb = 2120 nM)
Measurement: IC50 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 516.64, ALogP 5.59, HBA 5, HBD 2, PSA 76.02, QED 0.3
Compound (SMILES): COc1ccccc1N1CCC2(CCN(CCCSc3nnc(-c4ccccc4)[nH]3)CC2)CC1
InChIKey: UNDYONYPTZDMOJ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [125I]IABN from recombinant human D2 long receptor stably expressed in HEK293 cell membranes measured after 60 mins by scintillation counting analysis
Measurement: Ki = 1162 nM (pChEMBL 5.929999828338623)
Descriptors: MW 477.68, ALogP 5.35, HBA 6, HBD 1, PSA 57.28, QED 0.35
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)C[C@@H](C(F)F)SC(N)=N1
InChIKey: YCQCOERWQMZZQJ-UGSOOPFHSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin)
Measurement: IC50 = 6.23 nM (pChEMBL 8.210000038146973)
Descriptors: MW 443.43, ALogP 3.47, HBA 7, HBD 2, PSA 102.49, QED 0.66
Compound (SMILES): Cc1c(C#Cc2cnc3cnc(-c4ccc(N)cc4)cn23)cccc1C(=O)Nc1cc(CN2CCN(C)CC2)cc(-c2ccccc2)c1
InChIKey: ZNNDCLZKVULOKL-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of recombinant human His-tagged TrkB catalytic domain (526 to 838 residues) expressed in baculovirus expression system using tyr 01 as substrate incubated for 1 hr by Z'-Lyte assay
Measurement: IC50 = 24.19 nM (pChEMBL 7.619999885559082)
Descriptors: MW 631.78, ALogP 6.35, HBA 7, HBD 2, PSA 91.79, QED 0.16
Compound (SMILES): CC(C)(CC(c1ccc(F)cc1)c1ccc(F)cc1)NC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12
InChIKey: PBWAFYKWWMLLGW-VWLOTQADSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay
Measurement: EC50 = 0.08128 nM (pChEMBL 10.09000015258789)
Descriptors: MW 478.54, ALogP 5.14, HBA 4, HBD 4, PSA 85.35, QED 0.28
Compound (SMILES): CCc1ccc(Cc2cc3c(cc2F)CO[C@]32O[C@H](C)[C@@H](O)[C@H](O)[C@H]2O)s1
InChIKey: FEMMNKQITNDNJD-RDHZRAOUSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Inhibition of human full length SGLT1 expressed in NIH3T3 cells measured after 1 hr in presence of [14C]-methyl-alpha -D-glucopyranoside by scintillation counter method
Measurement: IC50 = 25900 nM (pChEMBL 4.590000152587891)
Descriptors: MW 394.46, ALogP 2.22, HBA 6, HBD 3, PSA 79.15, QED 0.74
Compound (SMILES): CC(=O)N1N=C(c2ccc(OS(N)(=O)=O)cc2)CC1c1ccc(Cl)cc1
InChIKey: RJZGMGAAMZVUBB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 393.85, ALogP 2.62, HBA 5, HBD 1, PSA 102.06, QED 0.86
Compound (SMILES): O=C(O)c1[nH]c(-c2cccc(Oc3ccccc3)c2)cc(=O)c1O
InChIKey: GDNXJTYOGINMBB-UHFFFAOYSA-N
Target: Polymerase acidic protein (SINGLE PROTEIN), Influenza A virus (A/Puerto Rico/8/1934(H1N1))
UniProt: P03433
Assay: Inhibition of Influenza A virus RNA-dependent RNA polymerase PA N-terminal endonuclease using [6-FAM]AATCGCAGGCAGCACTC[TAM] substrate and measured over 45 mins by fluorescence based assay
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 323.3, ALogP 3.24, HBA 4, HBD 3, PSA 99.62, QED 0.68
Compound (SMILES): O=C1N(c2ccccc2)CC2(CCN(CCc3ccccc3)CC2)OC12CC2
InChIKey: ZCMSPFVAMUOJIK-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHOK1 cells assessed as stimulation of cAMP accumulation incubated for 45 mins by HTRF assay
Measurement: EC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 376.5, ALogP 3.66, HBA 3, HBD 0, PSA 32.78, QED 0.82
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2c3c(ccnc13)C(=O)N2C
InChIKey: JRXOGGRRYJHKKK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of tetra-acetylated histone H4 peptide (1-21) from recombinant human N-terminal His-tagged BRD4 BD2 (349 to 460 residues) expressed in Escherichia coli incubated for 30 mins followed by further incubation with tetra-acetylated histone H4 peptide (1-21) for 30 mins by Alphascreen assay
Measurement: IC50 = 4599 nM (pChEMBL 5.340000152587891)
Descriptors: MW 369.4, ALogP 2.63, HBA 5, HBD 1, PSA 88.6, QED 0.76
Compound (SMILES): COC(=O)Nc1ccc2c(c1)NC(=O)CC/C=C/C[C@H](N1CC[C@H](c3cccc(Cl)c3)CC1=O)c1nc-2c[nH]1
InChIKey: YMEHWISYYMKMFO-WOMRJYOTSA-N
Target: Coagulation factor VII (SINGLE PROTEIN), Homo sapiens
UniProt: P08709
Assay: Inhibition of activated human coagulation factor 7
Measurement: Ki = 4850 nM (pChEMBL 5.309999942779541)
Descriptors: MW 548.04, ALogP 6.03, HBA 5, HBD 3, PSA 116.42, QED 0.35
Compound (SMILES): O=C(NO)c1ccc(CN2c3ccccc3Sc3ccccc32)cc1
InChIKey: MKMZJKFJHZVYQT-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant N-terminal GST-tagged human HDAC6 expressed in baculovirus expression system using fluorogenic ZMAL as substrate incubated for 90 mins by fluorescence assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 348.43, ALogP 4.61, HBA 4, HBD 2, PSA 52.57, QED 0.54
Compound (SMILES): CC1=NC(c2cn(S(=O)(=O)c3cccs3)c3ccc(C)cc23)CN1
InChIKey: WKTZUHBCQBTTDQ-UHFFFAOYSA-N
Target: Kallikrein-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P49862
Assay: Inhibition of thermolysin activated recombinant human C-terminal 10-His tagged KLK7 (E23 to H252 residues) using MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence analysis
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 359.48, ALogP 3.31, HBA 6, HBD 1, PSA 63.46, QED 0.78
Compound (SMILES): C=CS(=O)(=O)N1CC(n2cc(-c3cc4cc(C)cc(OC)c4s3)c3c(N)ncnc32)C1
InChIKey: LOWUCVWGIWOXOG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant FGFR4 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 455.57, ALogP 3.54, HBA 8, HBD 1, PSA 103.34, QED 0.49
Compound (SMILES): Cc1c(C(O)CN2CCN(C(=O)Cc3ccc(-n4cnnn4)cc3)CC2)ccc2c1COC2=O
InChIKey: CAOIZQQGDHVYBO-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of ROMK (unknown origin) after 30 mins by 86Rb+ efflux assay
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 462.51, ALogP 1.06, HBA 9, HBD 1, PSA 113.68, QED 0.54
Compound (SMILES): CN1CCN(CCOc2cc3ncnc(Nc4c(Cl)ccc5c4OCO5)c3cc2OC2CCOCC2)CC1
InChIKey: XKSFRXVKOXYUJX-UHFFFAOYSA-N
Target: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99640
Assay: Displacement of (6-FAM)KI(pY)VV from PKMYT1 kinase domain (unknown origin) by fluorescence polarization binding assay
Measurement: Ki = 5248.07 nM (pChEMBL 5.28000020980835)
Descriptors: MW 542.04, ALogP 3.94, HBA 10, HBD 1, PSA 90.44, QED 0.45
Compound (SMILES): CN1CCN(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(O)cc3)cc2)CC1.Cl.Cl
InChIKey: ZTABGVCSNBOTNS-JZYARHMISA-N
Target: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
Assay: Binding affinity to ERRbeta (unknown origin) using fluorescein-conjugated coactivator PGC-1alpha incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 1980 nM (pChEMBL 5.699999809265137)
Descriptors: MW 428.58, ALogP 4.88, HBA 4, HBD 2, PSA 46.94, QED 0.53
Compound (SMILES): COc1cc(CCNc2nc(C#Cc3cccnc3)nc3c2ncn3[C@H]2[C@H](O)[C@H](O)[C@@H]3C[C@@H]32)ccc1O
InChIKey: KXXPXXBZSQVHKJ-LJWFOBJUSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I]I-AB-MECA from recombinant mouse A3AR expressed in HEK293 cell membranes measured after 60 mins by liquid scintillation counting method
Measurement: Ki = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 498.54, ALogP 1.9, HBA 10, HBD 4, PSA 138.44, QED 0.29
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1cccc2c(NC(=O)[C@H](Cc3ccccc3)NC(=O)c3ccccn3)cccc12
InChIKey: JZOBREFCPPFGFL-VWLOTQADSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of USP30 (unknown origin) using Ubiquitin-Rhodamine110-Glycine as substrate incubated for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 530.65, ALogP 4.29, HBA 5, HBD 3, PSA 117.26, QED 0.31
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@](C)(CCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)C(C)(C)S)[C@@H](C)O)C(C)(C)S
InChIKey: QHCXEJJWDKPICI-CJUXWKHVSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1642.89
Compound (SMILES): N#Cc1ccc(N2CCN(CCCCNC(=O)c3ccc(-c4ccsc4)cc3)CC2)cc1
InChIKey: YVBCMZPFSJOCJN-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of 2,3-dimethoxy-5-[125I]-iodo-N-[9-benzyl-9-azabicyclo[3.3.1]nonan-3beta-yl]benzamide from human dopamine D2L receptor expressed in HEK293 cells measured after 60 mins by gamma counting analysis
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 444.6, ALogP 4.62, HBA 5, HBD 1, PSA 59.37, QED 0.52
Compound (SMILES): COc1cc2c(cc1OC)CN(CCCOc1ccc(C(C)=O)c(O)c1)CC2
InChIKey: UGTOHDDXGFCAEE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butyrylthiocholine chloride as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 57900 nM (pChEMBL 4.239999771118164)
Descriptors: MW 385.46, ALogP 3.44, HBA 6, HBD 1, PSA 68.23, QED 0.55
Compound (SMILES): Nc1cc(C(F)(F)F)c(-c2nc(N3CCCCC3)c3c(n2)N2CCOC[C@H]2C3)cn1
InChIKey: ZGIKRQIWUKJPFY-GFCCVEGCSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BPZ7
Assay: Inhibition of mTORC2 in human A2058 cells assessed as reduction in PKB phosphorylation at S473 residues incubated for 1 hr by Western blot analysis
Measurement: IC50 = 2075 nM (pChEMBL 5.679999828338623)
Descriptors: MW 420.44, ALogP 2.89, HBA 7, HBD 1, PSA 80.4, QED 0.8
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc3c(ccc4oc5cc(-c6cnc([C@@H]7CCCN7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]6)ccc5c(=O)c43)c2)[nH]1)C(C)C
InChIKey: DUOQYSIUCQOGJM-XAHXWSECSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A Y93H mutant in HCV genotype 1a assessed as decrease in viral replication
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 830.94, ALogP 6.97, HBA 10, HBD 4, PSA 204.85, QED 0.08
Compound (SMILES): Clc1ccccc1C1C=C(c2cccc3ccccc23)Nc2nncn21
InChIKey: YNNKNSLVTNNPJP-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel Ache using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by Ellman method
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 358.83, ALogP 5.14, HBA 4, HBD 1, PSA 42.74, QED 0.54
Compound (SMILES): O=C(Oc1cccc(N2CCS(=O)(=O)CC2)c1)N1CCC(O)(c2ccccc2)CC1
InChIKey: OLZGJBDEKZPDQO-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of rat recombinant His/GST-tagged FAAH expressed in Escherichia coli cells using AAMCA as substrate incubated for 15 mins followed by substrate addition and measured after every 20 mins for 4 hrs by fluorescence based assay
Measurement: IC50 = 78.1 nM (pChEMBL 7.110000133514404)
Descriptors: MW 430.53, ALogP 2.4, HBA 6, HBD 1, PSA 87.15, QED 0.8
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@](C)(NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)CCC/C=C/CCC[C@@](C)(C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: NAWDZLCHPHJGNY-SRAXFJQUSA-N
Target: Relaxin-3 receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSD7
Assay: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay
Measurement: EC50 = 5.248 nM (pChEMBL 8.279999732971191)
Descriptors: MW 2387.83
Compound (SMILES): O=C(CCCNc1c2c(nc3cc(Cl)ccc13)CCCC2)NC12CC3CC(F)(CC(C1)c1ccccc13)C2
InChIKey: TYMUTPUANLZRMT-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChE expressed in HEK293 cells using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by spectrophotometry analysis
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 532.1, ALogP 7.38, HBA 3, HBD 2, PSA 54.02, QED 0.33
Compound (SMILES): Cc1cccc(N2CCN(CCCCNC(=O)c3ccc(-c4ccsc4)cc3)CC2)c1
InChIKey: YSHFOVKURWTKBI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of 2,3-dimethoxy-5-[125I]-iodo-N-[9-benzyl-9-azabicyclo[3.3.1]nonan-3beta-yl]benzamide from human dopamine D2L receptor expressed in HEK293 cells measured after 60 mins by gamma counting analysis
Measurement: Ki = 16318 nM (pChEMBL 4.789999961853027)
Descriptors: MW 433.62, ALogP 5.06, HBA 4, HBD 1, PSA 35.58, QED 0.5
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)CN(C)Cc2ccccc2)CC1
InChIKey: YYKDCELXHDVJDL-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 337.47, ALogP 2.78, HBA 3, HBD 0, PSA 26.79, QED 0.84
Compound (SMILES): COc1ccccc1C1CCN(c2nc(C3(C)CCC3)nc3ccc(N(C)CCO)cc23)CC1
InChIKey: IYXHEPYZZHBMIL-UHFFFAOYSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: NTR1 Ca2+ Flux Dose Response: NTSR1 (NTR1) CHO cells are plated in 20 uL of assay media containing Ham's F12 supplemented with 10% fetal bovine serum and 0.4 mg/mL G418 at a concentration of 1.0×106 cells per mL into black, 384-well assay plates with clear bottoms using a Multidrop liquid handler. Assay plates are incubated at 37° C. in 5% CO2. The next day, the assay plates are aspirated to remove growth media and washed once with 20 uL of DPBS. The DPBS is then aspirated from the assay plate and replaced with 25 uL of Fluo-4 NW calcium dye prepared according to the manufacturer's recommendations then the plates are incubated for 1 hour at 37° C. Following the incubation in the presence of dye, the assay is run on a Molecular Devices FlexStation-III using 494 excitation and 516 emission wavelengths set to read for 90 seconds with the addition at 18 seconds of 5 uL of 6× final concentration of test compounds and peptide control diluted in assay media containing 0.1% BSA and no more than 9% DMSO to yield a maximum final DMSO concentration of 1.5%. Percent activation is calculated based on the maximum response minus the minimum value over the time course relative to the neurotensin 1 control peptide at 100 pM. EC50 values were calculated for those compounds tested in 8-point dose dependent response.
Measurement: EC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 460.62, ALogP 4.89, HBA 6, HBD 1, PSA 61.72, QED 0.54
Compound (SMILES): COc1cc2c(cc1OC)C(=O)C(Cc1cn(CC3CCN(Cc4ccccc4)CC3)nn1)C2
InChIKey: WAMFQMXOUNENQQ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured for 5 mins by Ellman's method
Measurement: IC50 = 4920 nM (pChEMBL 5.309999942779541)
Descriptors: MW 460.58, ALogP 3.81, HBA 7, HBD 0, PSA 69.48, QED 0.51
Compound (SMILES): CN(C)C1(Cc2ccccc2)CCN(c2cc(C(F)(F)F)ccc2CNC(=O)Nc2cccc3c2CC(O)CC3)CC1
InChIKey: ZHNPAVPMIUGHIS-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Displacement of [3H]RTX from recombinant human TRPV1 expressed in CHO cells incubated for 60 mins by liquid scintillation counter
Measurement: Ki = 0.95 nM (pChEMBL 9.020000457763672)
Descriptors: MW 580.7, ALogP 6.02, HBA 4, HBD 3, PSA 67.84, QED 0.32
Compound (SMILES): CC1(c2ccc(S(N)(=O)=O)cc2)NC(=O)N(CC(=O)c2cccc(C(F)(F)F)c2)C1=O
InChIKey: YRFNUNRYCVLHPX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1/ HEK293 cells at -80 mV holding potential by IonWorks patch-clamp assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 455.41, ALogP 2, HBA 5, HBD 2, PSA 126.64, QED 0.53
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: SZNIECFMYGPIDP-JAWNFBBLSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 whole cells incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 0.515 nM (pChEMBL 9.289999961853027)
Descriptors: MW 3674.13
Compound (SMILES): COc1ccc2c3c(cccc13)C(=O)N(CCCNCCS[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O)C2=O
InChIKey: CRSUKZHNUMRQBT-ILRYNQFESA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition of recombinant human OGA expressed in Escherichia coli BL21 (DE3) using varying levels of 4-Mu-GlcNAc as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by dixon plot analysis
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 547.63, ALogP 0.1, HBA 10, HBD 5, PSA 157.66, QED 0.19
Compound (SMILES): O=C(NCc1ccccc1)c1cn(CCCCc2cc3cc(Cc4ccccc4)[nH]c3nn2)nn1
InChIKey: DAQXMSYRIRRRNL-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of GAC (unknown origin)
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 465.56, ALogP 4.09, HBA 6, HBD 2, PSA 101.38, QED 0.3
Compound (SMILES): CCn1cnc(-c2ccc(OC)cc2)c1-c1ccc(/C=C/C(=O)NO)cc1
InChIKey: JRABOCDIAYUFQB-AWNIVKPZSA-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 Fluor-de-lys as substrate measured after 60 mins by fluorescence assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 363.42, ALogP 3.76, HBA 5, HBD 2, PSA 76.38, QED 0.4
Compound (SMILES): COc1ccc(Nc2ncc3c(n2)n(C2CCCCC2)c(=O)n3C)c(C)c1
InChIKey: TZBGTNVOICBCLO-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK in human A549 cells assessed as reduction in irradiation-induced autophosphorylation at S2056 residue preincubated for 1 hr followed by 8 Gy irradiation and measured after 1 hr by ELISA
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 367.45, ALogP 3.7, HBA 7, HBD 1, PSA 73.97, QED 0.76
Compound (SMILES): Fc1ccc(Cc2cc3c(nn2)CCNCC3)cc1
InChIKey: JFMGIQYZJAHLFQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at recombinant human 5-HT2C receptor transfected in CHOK1 cells assessed as calcium mobilization by FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 257.31, ALogP 1.89, HBA 3, HBD 1, PSA 37.81, QED 0.89
Compound (SMILES): CC(NC(=O)c1cnn(-c2ccccc2)c1)c1ccc(C(=O)N[C@@H](CCC2CCCCC2)C(N)=O)cc1
InChIKey: RYEFPWKRHLKVLM-GHZUAHJPSA-N
Target: Mitogen-activated protein kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15759
Assay: Inhibition of recombinant human His-tagged P38beta MAPK (1 to 364 residues) expressed in Escherichia coli incubated for 60 mins by [gamma-33P]ATP based scintillation counting method
Measurement: IC50 = 5050 nM (pChEMBL 5.300000190734863)
Descriptors: MW 501.63, ALogP 4.31, HBA 5, HBD 3, PSA 119.11, QED 0.38
Compound (SMILES): Fc1cccc(-c2cn([C@@H]3CN4CCC3CC4)nn2)c1
InChIKey: TZWVPYLQJDFQHL-OAHLLOKOSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Displacement of [3H]epibatidine from human alpha3beta4 nAChR transfected in HEK293 cell membranes after 120 mins by liquid scintillation counting
Measurement: Ki = 2.25 nM (pChEMBL 8.649999618530273)
Descriptors: MW 272.33, ALogP 2.35, HBA 4, HBD 0, PSA 33.95, QED 0.84
Compound (SMILES): Cn1cc(C(=O)NCc2ncccc2F)nc1CCNCc1nc2ccccc2[nH]1
InChIKey: QMHCBUQSQOLZLE-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 4913 nM (pChEMBL 5.309999942779541)
Descriptors: MW 407.45, ALogP 2.09, HBA 6, HBD 3, PSA 100.52, QED 0.39
Compound (SMILES): O=c1c2c(Cl)ccn2nc([C@@H]2CCCN2c2ncnc3[nH]cnc23)n1-c1ccccc1
InChIKey: ILHMXWRSMGUCKC-HNNXBMFYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged recombinant full length human p110delta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate measured after 80 mins by transcreener fluorescence polarization assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 432.88, ALogP 3.15, HBA 8, HBD 1, PSA 97, QED 0.47
Compound (SMILES): CCN1C(=O)CC(SC[C@@H](NC(=O)[C@@H](NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]2CCCN2C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(C)=O)C(C)C)C(C)C)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(N)=O)C1=O
InChIKey: IFOKHSDFIANELJ-BOWUULGZSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 16.4 nM (pChEMBL 7.789999961853027)
Descriptors: MW 2487.92
Compound (SMILES): COc1ccc(N[C@@H]2[C@@H](O)[C@@H](Sc3ccc(Cl)c(Cl)c3)O[C@H](CO)[C@@H]2O)cc1
InChIKey: LZZVVBWVAFTDIA-ICBNADEASA-N
Target: Galectin-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P47929
Assay: Binding affinity at recombinant human Galectin 7 expressed in Escherichia coli BL21 incubated for 5 mins by fluorescence anisotropy assay
Measurement: Kd = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 446.35, ALogP 3.01, HBA 7, HBD 4, PSA 91.18, QED 0.54
Compound (SMILES): Cc1ccc(C(ON)c2ccc(Cl)cc2)c(O)c1.Cl
InChIKey: DOWISSRARHSYBN-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R0V5
Assay: Inhibition of mouse IDO2 expressed in human T-REx cells using L-tryptophan as substrate after 20 hrs
Measurement: IC50 = 8770 nM (pChEMBL 5.059999942779541)
Descriptors: MW 263.72, ALogP 3.33, HBA 3, HBD 2, PSA 55.48, QED 0.84
Compound (SMILES): Cc1c(-c2n[nH]c(=S)[nH]2)nnn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: KSQJIDABRGZHPW-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human carbonic anhydrase 4 assessed as reduction in CO2 hydration incubated for 1 hr by phenol red staining-based stopped flow assay
Measurement: Ki = 1004.7 nM (pChEMBL 6)
Descriptors: MW 337.39, ALogP 0.67, HBA 7, HBD 3, PSA 135.34, QED 0.6
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCN(Cc2ccc(F)cc2)[C@H]2CCC[C@H](N3CCCC3)[C@H]21
InChIKey: QNPXHBMZSULUKK-OHSXHVKISA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from DOR in Sprague-Dawley rat brain membranes after 120 mins by scintillation counting method
Measurement: Ki = 397 nM (pChEMBL 6.400000095367432)
Descriptors: MW 504.48, ALogP 5.4, HBA 3, HBD 0, PSA 26.79, QED 0.55
Compound (SMILES): Cc1cc(N)nc2cc(-c3ccccc3CN)ccc12.Cl.Cl
InChIKey: YWYOFTOARNUCCC-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Inhibition of human nNOS expressed in Escherichia coli expression system assessed as reduction in NO production in presence of L-arginine measured for 30 sec by hemoglobin capture assay
Measurement: Ki = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 263.34, ALogP 3.25, HBA 3, HBD 2, PSA 64.93, QED 0.75
Compound (SMILES): CC[C@H](NC)C(=O)N[C@@H]1C(=O)N2[C@@H](CC[C@@H]1CCN)CC[C@H]2C(=O)NC(c1ccccc1)c1ccccc1.Cl.Cl
InChIKey: BSEMCYIXFFZRTP-CASDQYAFSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Binding affinity to His-tagged recombinant human XIAP BIR3 domain (241 to 356 residues) expressed in Escherichia coli BL21 using AbuRPF-K(5-Fam)-NH2) (FITC-SMAC) incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 519.69, ALogP 2.49, HBA 5, HBD 4, PSA 116.56, QED 0.38
Compound (SMILES): COC1CCC(C[C@H](NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)[C@H](Cc2ccccc2)N=[N+]=[N-])C(C)C)C(=O)[C@@]2(C)CO2)CC1
InChIKey: HKZNHVNDIDNJLS-SHMQMBFDSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of 20S constitutive proteasome beta 2 trypsin-like activity (unknown origin) by cell based ABPP assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 689.86, ALogP 3.67, HBA 8, HBD 4, PSA 200.91, QED 0.08
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc2ccc(Cl)cc2)NC(=O)CCCSC[C@@H](C(=O)N2CCC[C@H]2C(=O)NCCCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: YHANVBIORRRJHA-VGNPQVDOSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: In Vitro V2 Receptor Assay: Agonist activity of compounds on the human V2 receptor (h V2R) was determined in a transcriptional reporter gene assay by transiently transfecting an h V2 receptor expression DNA into HEK-293 (human embryonic kidney 293 cell line) cells in concert with a reporter DNA containing intracellular calcium responsive promoter elements regulating expression of firefly luciferase. See Boss, V., Talpade, D. J., Murphy, T. J. J. Biol. Chem. 1996, May 3; 271(18), 10429-10432 for further guidance on this assay. Cells were exposed to serial dilutions of compounds diluted 10-fold per dose for 5 h, followed by lysis of cells, determination of luciferase activity, and determination of compound efficacies and EC50 values through non-linear regression. Desmopressin (dDAVP) was used as an internal control in each experiment.
Measurement: EC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 958.56, ALogP 0.12, HBA 10, HBD 10, PSA 299.9, QED 0.07
Compound (SMILES): Clc1ccc(-n2ccc(C(c3ccc(Cl)cc3Cl)n3ccnc3)c2)cc1
InChIKey: WYGZUDPMZOMYKX-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 in presence of NADPH by luciferase reporter gene assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 402.71, ALogP 6.27, HBA 3, HBD 0, PSA 22.75, QED 0.39
Compound (SMILES): COc1cc(Nc2nc(NC3CCOCC3)c(C(C)C)nc2C(N)=O)ccc1N1CCN(C)CC1.O=C(O)/C=C/C(=O)O
InChIKey: UXZXBEXWMWRJJG-WLHGVMLRSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of GST-tagged human ROS cytoplasmic domain (1883 to 2347 amino acids) expressed in baculovirus expression system pre-incubated before peptide substrate and ATP addition and measured after 30 mins
Measurement: IC50 = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 483.62, ALogP 2.79, HBA 9, HBD 3, PSA 117.87, QED 0.52
Compound (SMILES): N#Cc1cccc(-c2cc(NC(=O)C3(F)CCCN(C#N)C3)on2)c1
InChIKey: AXIFCCZGQFOIJY-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: USP30 Biochemical IC50 Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 339.33, ALogP 2.44, HBA 6, HBD 1, PSA 105.95, QED 0.86
Compound (SMILES): COc1ccccc1N1CCC(c2nc3c(c(=O)[nH]2)CCCC3)CC1
InChIKey: FJXCYPYLCGQHDG-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of recombinant human N-terminal TEV cleavage site-fused/FLAG-poly his-tagged TNKS2 SAM-PARP domain (613 to 1166 residues) expressed in Escherichia coli assessed as reduction in auto-PARylation preincubated for 10 mins followed by biotinylated-NAD+ addition and measured after 45 mins by ELISA
Measurement: IC50 = 6417 nM (pChEMBL 5.190000057220459)
Descriptors: MW 339.44, ALogP 3.04, HBA 4, HBD 1, PSA 58.22, QED 0.93
Compound (SMILES): Nc1ncc(-c2nc3c(c(N4CCOCC4)n2)CCN(C(=O)c2cc(Cc4n[nH]c(=O)c5ccccc45)ccc2F)C3)cn1
InChIKey: CRTCKATZPLYUCW-UHFFFAOYSA-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 by ADP-glo plus luminescence assay
Measurement: IC50 = 4.786 nM (pChEMBL 8.319999694824219)
Descriptors: MW 593.62, ALogP 2.52, HBA 10, HBD 2, PSA 156.11, QED 0.31
Compound (SMILES): CN(C)c1ccc(C(=O)Nc2cccc(NC(=O)COc3ccc4c(=O)ccoc4c3)c2)cc1
InChIKey: WVGDUQVQWLHVEA-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of recombinant human ROCK2 (11 to 552 residues) using KEAKEKRQEQIAKR as substrate incubated for 40 mins in presence of [gamma-33P]ATP and 10 uM ATP by radiometric scintillation counting analysis
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 457.49, ALogP 4.13, HBA 6, HBD 2, PSA 100.88, QED 0.43
Compound (SMILES): Cc1noc(C)c1-c1nc2sc3c(c2c(=O)[nH]1)CCN(CCCCCC(=O)Nc1ccccc1N)C3
InChIKey: IRIBRSPWFARBPX-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using biotinylated histone H3 KAc peptide (1 to 21 residues) as substrate by HTRF assay
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 506.63, ALogP 4.4, HBA 8, HBD 3, PSA 130.14, QED 0.24
Compound (SMILES): O=c1cc(-c2cccc(Cl)c2)sc2c1ccc1ccccc12
InChIKey: LBZBOWMAEGALTF-UHFFFAOYSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of human recombinant CYP1A1 using 7-ethoxyresorufin as substrate in presence of glucose-6-phosphate, glucose-6-phosphate dehydrogenase and NADPH-generating system incubated for 15 mins by fluorometry
Measurement: IC50 = 13.6 nM (pChEMBL 7.869999885559082)
Descriptors: MW 322.82, ALogP 5.74, HBA 2, HBD 0, PSA 17.07, QED 0.41
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)NC(C)(C)c2cn(Cc3ccc(Br)cc3)nn2)C[C@H](N)[C@H]1NC(C)=O
InChIKey: BNLICTDYHDAMBF-WMTXJRDZSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus (A/Memphis/1/1971(H3N2))
UniProt: P03471
Assay: Inhibition of Influenza A virus (A/Chicken/Hebei/LZF/2014(H5N2)) Neuraminidase N2 preincubated for 10 mins followed by MUNANA substrate addition and measured after 40 mins by fluorescence method
Measurement: IC50 = 4050 nM (pChEMBL 5.389999866485596)
Descriptors: MW 561.53, ALogP 3.18, HBA 7, HBD 3, PSA 124.16, QED 0.41
Compound (SMILES): CC(C)Cc1ccc(C(C)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CC(C)C)B(O)O)cc1
InChIKey: IDMLBBZTOALOPY-MTSQGGNFSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325)
UniProt: Q2G036
Assay: Inhibition of ClpP in methicillin-resistant Staphylococcus aureus ATCC 33591 assessed as reduction in bacteria-induced hemolysis of sheep erythrocytes by measuring hemoglobin release incubated for 15 mins
Measurement: EC50 = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 482.43
Compound (SMILES): C#CCN(Cc1ccc(F)cc1)c1ccc(NC(=O)OC(C)(C)C)c(NC(=O)OCC)c1
InChIKey: PHUNLNCZCLKHCM-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily KQT member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR82
Assay: Agonist activity at human KCNQ5 expressed in CHOK1 cells by whole cell patch clamp assay
Measurement: EC50 = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 441.5, ALogP 5.38, HBA 5, HBD 2, PSA 79.9, QED 0.56
Compound (SMILES): C#CCCCCNC(=O)NC(=N)NCCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ISUNFZYCVPJAPJ-LWRYEOACSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [3H]UR-MK300 from human NTS1R expressed in human HT-29 cells incubated for 2 hrs by scintillation counting method
Measurement: Ki = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 954.19, ALogP 0.3, HBA 11, HBD 14, PSA 345.18, QED 0.02
Compound (SMILES): O=C(NC12CC3CC(CC(C3)C1)C2)c1cn(CCN2CCOCC2)c2ncccc12
InChIKey: WRLFCJPUKWVRIM-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2-receptor expressed in CHO-K1 cells coexpressing G-alpha16 by Fluo-4-AM dye based calcium mobilization assay
Measurement: EC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 408.55, ALogP 3.07, HBA 5, HBD 1, PSA 59.39, QED 0.83
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: MITUTMSAQPEDAN-ITFIQBDBSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1620.81
Compound (SMILES): COc1ccc(CN2CCN(C(=O)c3cc4cc(Cl)ccc4n3Cc3ccc(F)cc3)CC2)cc1
InChIKey: XVHVZESNKQODLO-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 using arachidonic acid as substrate incubated for 5 mins by fluorescence-based assay
Measurement: IC50 = 23.21 nM (pChEMBL 7.630000114440918)
Descriptors: MW 491.99, ALogP 5.45, HBA 4, HBD 0, PSA 37.71, QED 0.36
Compound (SMILES): CCOP(=O)(OCC)C1(c2ccccc2)N=CC2C(=O)N(c3cccc([N+](=O)[O-])c3)C(=O)C21
InChIKey: CONRLYITUPHTMN-UHFFFAOYSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: Displacement of [3H]RX821002 from alpha2-AR in human brain frontal cortex incubated for 30 mins by liquid scintillation spectrometry
Measurement: Ki = 0.06607 nM (pChEMBL 10.180000305175781)
Descriptors: MW 471.41, ALogP 3.9, HBA 8, HBD 0, PSA 128.41, QED 0.25
Compound (SMILES): CN1CCC(NC(=O)c2ccncc2Nc2cc(-c3ccc4sc(N)nc4c3)c3nccnc3c2)C1
InChIKey: CBNLPDNEBAAKJY-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3 in human HCT116 cell lysates assessed as reduction in glycolytic-flux induced fructose-2,6-bisphosphate formation using fructose-6-phosphate as substrate treated with cells prior to glucose stimulation followed by PFK1 and substrate addition and measured at 0.5 mins interval for 45 mins
Measurement: IC50 = 6950 nM (pChEMBL 5.159999847412109)
Descriptors: MW 496.6, ALogP 4.06, HBA 9, HBD 3, PSA 121.95, QED 0.33
Compound (SMILES): O=c1cc(CC(O)CCN2CCN(c3nccc4ccc(F)cc34)CC2)c2ccccc2o1
InChIKey: MELNHVXWRBLZRI-UHFFFAOYSA-N
Target: DNA gyrase subunit A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P20831
Assay: Inhibition of Staphylococcus aureus ATCC 29213 DNA gyrase A assessed as reduction in enzyme-mediated supercoiling of relaxed pBR322 DNA by ethidium bromide staining based gel electrophoresis method
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 447.51, ALogP 3.6, HBA 6, HBD 1, PSA 69.81, QED 0.46
Compound (SMILES): COCCn1c(=O)n(C2CCOCC2)c2nc(-c3cnc4ccc(C#N)cn34)ncc21
InChIKey: MYKYDAQNRIXEBK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human N-terminal His-tagged JAK2 (826 to 1132 residues) expressed in baculovirus expression system using PolyGT-Biotin as substrate measured after 3 to 20 hrs by HTRF assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 419.45, ALogP 1.78, HBA 10, HBD 0, PSA 112.26, QED 0.48
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(C)c2)nc1N[C@H]1CC[C@](C)(O)CC1.O=C(O)/C=C/C(=O)O
InChIKey: CFWAEFQSQDLLPB-NWZJXHGHSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of GST-tagged human ROS cytoplasmic domain (1883 to 2347 amino acids) expressed in baculovirus expression system pre-incubated before peptide substrate and ATP addition and measured after 30 mins
Measurement: IC50 = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 564.78, ALogP 3.51, HBA 9, HBD 4, PSA 122.88, QED 0.38
Compound (SMILES): CN(C)CCc1cccc(C2CCN(CCc3cnn(-c4nccc5c(=O)[nH]cnc45)c3)CC2)c1
InChIKey: VQBICUVJQVNKBH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: O94953
Assay: Inhibition of full length human KDM4B assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 1 uM 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 15 mins by AlphaScreen assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 471.61, ALogP 3.03, HBA 7, HBD 1, PSA 82.94, QED 0.43
Compound (SMILES): CC1CCN(c2nc3ccccc3[nH]2)CC1
InChIKey: PUHHTJJRHYUBDJ-UHFFFAOYSA-N
Target: Short transient receptor potential channel 5 (SINGLE PROTEIN), Mus musculus
UniProt: Q9QX29
Assay: Inhibition of mouse TRPC5 expressed in HEK293 cells co-expressing mu-opioid receptor assessed as reduction in DAMGO-induced membrane potential by FMP-2 dye based assay
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 215.3, ALogP 2.8, HBA 2, HBD 1, PSA 31.92, QED 0.79
Compound (SMILES): COc1nnc2ccc(N3CCC(c4ccc(N5CCC(N6CCN(C)C(=O)[C@H]6C)CC5)cc4)CC3)nn12
InChIKey: YBLYKYGYRRDASU-HXUWFJFHSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa647-labeled JQ1 derivative from wild type BRD4 bromodomain 1 (44 to 460 residues) N140A mutant (unknown origin) incubated for 1 hr by fluorescence polarization assay
Measurement: Ki = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 518.67, ALogP 2.65, HBA 9, HBD 0, PSA 82.34, QED 0.51
Compound (SMILES): O=C(O)c1cc2cc(-c3ccccc3)ccc2cc1O
InChIKey: NNSQHMPMHZAEPG-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; Grin1/Grin2b (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P35439
Assay: Negative allosteric modulation of rat GluN1/GluN2B expressed in Xenopus laevis oocytes assessed as inhibition of L-glutamate/glycine-induced current response at holding potential -60 mV by two-electrode voltage clamp method
Measurement: IC50 = 97800 nM (pChEMBL 4.010000228881836)
Descriptors: MW 264.28, ALogP 3.91, HBA 2, HBD 2, PSA 57.53, QED 0.74
Compound (SMILES): Cc1cc(-c2ccc(CC(=O)Nc3ccc(-c4cnccn4)cn3)cn2)ccn1
InChIKey: HKNLCIOYTMDVDE-UHFFFAOYSA-N
Target: Protein Wnt-3a (SINGLE PROTEIN), Homo sapiens
UniProt: P56704
Assay: Wnt-Luc Reporter Assay: Human embryonic kidney 293 cells (obtained from American Type Culture Collection, ATCC, Manassas, Va.) are cultured in DMEM medium (Gibco/Invitrogen, Carlsbad, Calif.) supplemented with 10% FBS (Gibco/Invitrogen, Carlsbad, Calif.), 50 unit/mL penicillin and 50 μg/mL of streptomycin (Gibco/Invitrogen, Carlsbad, Calif.) at 37° C. with 5% CO2 in air atmosphere. 293 cells in a 10 cm dish are co-transfected with 8 μg of STF-reporter plasmid containing a luciferase gene driven by Wnt-responsive elements and 2 μg of pcDNA3.1-Neo (Gibco/Invitrogen, Carlsbad, Calif.) with 30 μL of FuGENE6 (Roche Diagnostics, Indianapolis, Ind.) following the manufacturer's protocol. Stable cell lines (293 Wnt-Luc) were selected with 400 μg/mL of G418 (Gibco/Invitrogen, Carlsbad, Calif.). The 293 Wnt-Luc cells and L-cell Wnt3a cells (obtained from American Type Culture Collection, ATCC, Manassas, Va.) are trypsinized and co-cultured into a 384-well plate with DMEM medium supplemented with 2% FBS, and treated with different concentrations of a compound of the invention. After 24 hours, the firefly luciferase activities are assayed with the Bright-Glo Luciferase Assay System (Promega, Madison, Wis.). The IC50 is measured when the effect of the compound reduces the luminescence signal by 50%.
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 382.43, ALogP 3.49, HBA 6, HBD 1, PSA 93.55, QED 0.57
Compound (SMILES): c1ccc([C@H]([C@@H](c2ccccn2)N2CCCCC2)N2CCCCC2)nc1
InChIKey: QLTBRUVLRLFPSE-FGZHOGPDSA-N
Target: Potassium voltage-gated channel subfamily E member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15382
Assay: Inhibition of IKs (unknown origin)
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 350.51, ALogP 4.23, HBA 4, HBD 0, PSA 32.26, QED 0.81
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(NC(=O)c3ccc(C(F)(F)F)cc3)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: WFXNDEBDLFCINR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type human N-terminal GST-tagged EGFR (695 to end residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate after 60 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 108.7 nM (pChEMBL 6.960000038146973)
Descriptors: MW 557.58, ALogP 4.62, HBA 8, HBD 3, PSA 111.72, QED 0.29