lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2ncccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: YFKOUTGKKFPEOH-QGZVFWFLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by manual patch clamp method
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): CN(CCCCCCOc1cc(O)c2c(=O)c3ccccc3oc2c1)Cc1ccc(O)cc1
InChIKey: GNJJURBAYZCGRE-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Mixed-type inhibition of electric eel AChE using varying levels of acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured for 180 secs by Ellman's method based Lineweaver-burk plot analysis
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 447.53, ALogP 5.43, HBA 6, HBD 2, PSA 83.14, QED 0.25
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4ccc5c(cnn5C)c4)cc3c2)cn1
InChIKey: ZUUIIFQSDQMWET-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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 382.43, ALogP 3.77, HBA 6, HBD 1, PSA 77.63, QED 0.52
Compound (SMILES): Cc1[nH]c(C(=O)Nc2ccc(C(=O)N[C@@H](C)C(=O)O)cc2OC2CCNCC2)c(Cl)c1Cl.Cl
InChIKey: AHULTIYRDXIPLD-MERQFXBCSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase using biotinylated oligonucleotide as substrate incubated for 30 mins in presence of ATP by fluorescence-based microplate reader assay
Measurement: IC50 = 9.9 nM (pChEMBL 8)
Descriptors: MW 483.35, ALogP 3.22, HBA 5, HBD 5, PSA 132.55, QED 0.41
Compound (SMILES): CNC(=O)CCCCC[C@H](NC(=O)Cn1ccc2cc(C#N)ccc21)c1ncc(-c2ccc(CN(C)C)cc2)o1
InChIKey: NXOLTHXMXKDRIS-SANMLTNESA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant his tagged HDAC3 expressed in baculovirus expression system using FLUOR DE LYS-SIRT1 as fluorogenic substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by spectrophotometer based analysis
Measurement: IC50 = 3360 nM (pChEMBL 5.46999979019165)
Descriptors: MW 540.67, ALogP 4.78, HBA 7, HBD 2, PSA 116.19, QED 0.24
Compound (SMILES): Cc1cc2ccnc(N[C@@H]3CCNC[C@H]3C(=O)NC3CCOCC3)c2[nH]c1=O
InChIKey: YJYLTSMMMZXXPP-HZPDHXFCSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Inhibition of ATAD2 (unknown origin) by TR-FRET assay
Measurement: IC50 > 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 385.47, ALogP 0.92, HBA 6, HBD 4, PSA 108.14, QED 0.62
Compound (SMILES): COCC(=O)NC[C@@H]1CNCCO[C@H]1c1ccc(Cl)c(F)c1.Cl
InChIKey: PFKJVWIMJKFOGW-JDOFTSHGSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of human DAT expressed in CHO-K1 cells assessed as inhibition of [3H]-dopamine reuptake measured after 60 mins by Microscintillation counting analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 330.79, ALogP 1.52, HBA 4, HBD 2, PSA 59.59, QED 0.86
Compound (SMILES): CCC(Nc1nnc(-c2ccc(OC)cc2)o1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: JDPHTOJNZVWWNV-QLCVBSLISA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFN-gamma/LPS induced human whole blood assessed as tryptophan/kynurenine level measured after 18 hrs by RapidFire mass spectrometry
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 460.55, ALogP 6.6, HBA 6, HBD 1, PSA 73.07, QED 0.34
Compound (SMILES): COc1ccc(-c2c3c(nn2C(C)C)CCNCC3)cc1
InChIKey: HFAGGJZWKFFGLM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor by competitive radioligand binding assay
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 285.39, ALogP 2.83, HBA 4, HBD 1, PSA 39.08, QED 0.94
Compound (SMILES): C[C@@](CO)(OC[C@H]1O[C@@H](n2ncc3c(NC4CCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O)P(=O)(O)O
InChIKey: DWPITEDBCBAYRP-DLOISVIMSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of CD73 in human NCI-H1568 cells assessed as reduction in AMP-induced ADO expression preincubated for 15 mins followed by AMP addition and measured after 1 hr by LC-MS/MS analysis
Measurement: EC50 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 507.87, ALogP 0.36, HBA 11, HBD 6, PSA 192.31, QED 0.21
Compound (SMILES): CNC(=O)c1cncc(-c2cnc(Cl)c(NS(=O)(=O)c3ccccc3)c2)c1
InChIKey: IHWSJFBJORCEAK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta by ADP-Glo kinase assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 402.86, ALogP 2.96, HBA 5, HBD 2, PSA 101.05, QED 0.64
Compound (SMILES): C[C@]1(c2ccccc2)CN(C(=O)NCc2ccccc2)C[C@H]1c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: MUPBMBQMORRYNG-UKILVPOCSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat (unknown origin) expressed in Jurkat cells by reporter assay
Measurement: EC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 536.52, ALogP 6.27, HBA 2, HBD 2, PSA 52.57, QED 0.38
Compound (SMILES): CCCCc1cn(CC(O)(P(=O)([O-])O)P(=O)([O-])O)nn1.[Na+].[Na+]
InChIKey: WUQVDNQLHPYSKS-UHFFFAOYSA-L
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: Inhibition of GGPPS in human A549 cells assessed as reduction in cell growth incubated for 72 hrs by MTT assay
Measurement: IC50 = 22900 nM (pChEMBL 4.639999866485596)
Descriptors: MW 329.19, ALogP -0.38, HBA 6, HBD 5, PSA 166, QED 0.42
Compound (SMILES): Cc1ccc(C(=O)CSc2nnc(-c3ccc(S(N)(=O)=O)cc3)o2)cc1
InChIKey: XAVCGVMEWJZNQR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 201.1 nM (pChEMBL 6.699999809265137)
Descriptors: MW 389.46, ALogP 2.67, HBA 7, HBD 1, PSA 116.15, QED 0.51
Compound (SMILES): Nc1n[nH]c2cc(-c3ccc(=O)n(Cc4ccccc4F)c3)ccc12
InChIKey: DUHHTOOYELYHTE-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant CYP3A4 (unknown origin) using BFC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 334.35, ALogP 3.16, HBA 4, HBD 2, PSA 76.7, QED 0.6
Compound (SMILES): Cn1c(=O)c(OCc2ccc(C(=O)NO)cc2)c(C2CCCCC2)c2ccccc21
InChIKey: NNNACDVGTXZKNZ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using Fluor-de-Lys as substrate measured after 1 hr by fluorescence assay
Measurement: IC50 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 406.48, ALogP 4.28, HBA 5, HBD 2, PSA 80.56, QED 0.49
Compound (SMILES): Nc1ncnc2c1ncn2[C@H]1C[C@@H]2OP(=O)(S)OC[C@H]3O[C@@H](n4cnc5c(O)ncnc54)[C@H](F)[C@@H]3OP(=O)(S)OC[C@H]2O1
InChIKey: ZOHTYTWCUFTHSD-CBAZNMGYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of STING in human THP-1-Dual cells assessed as induction of type I IFNs by measuring stimulation of NF-kappaB pathway incubated for 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 9900 nM (pChEMBL 5)
Descriptors: MW 677.53, ALogP 2.37, HBA 18, HBD 4, PSA 222.97, QED 0.18
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(C(=O)CO)CC2
InChIKey: XPCGPXOUNZDGSJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 546.05, ALogP 3.68, HBA 9, HBD 3, PSA 133.75, QED 0.39
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1ccc(C(F)(F)F)cc1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: WZOZYFBDXFAVLI-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human butyrylcholinesterase in plasma using butyrylthiocholineiodide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured at 2 mins interval by Ellman's method
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 480.46, ALogP 5.69, HBA 4, HBD 0, PSA 40.8, QED 0.35
Compound (SMILES): CC(=O)Nc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(Cl)c(Cl)c3)CC2)c1
InChIKey: UCWSDAHSOCIBPK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation after 15 mins by Alphalisa assay
Measurement: EC50 = 0.5888 nM (pChEMBL 9.229999542236328)
Descriptors: MW 482.38, ALogP 4.56, HBA 4, HBD 2, PSA 70.67, QED 0.54
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2nnc(N)s2)nc2c1C[C@@H]1COCCN21
InChIKey: WZAQTKRFGGBJAQ-NXEZZACHSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of alexa fluor 647-labeled kinase tracer 314 binding to recombinant N-terminal GST-fused mTOR (1360 to 2549 residues) (unknown origin) by TR-FRET assay
Measurement: Ki = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 375.46, ALogP 0.56, HBA 10, HBD 1, PSA 102.52, QED 0.81
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)C(C)C
InChIKey: LKEDSHSHGNAQDA-APYQUMOISA-N
Target: Glucagon receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30082
Assay: Agonist activity at rat glucagon receptor expressed in HEK293 cells assessed as stimulation of cAMP accumulation by FRET assay
Measurement: EC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 6190.04
Compound (SMILES): CNc1nc2c(-c3ccnc(OC)c3)cnn2cc1OC
InChIKey: PJNMAIKMKRLUIV-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) using biotin-labelled KKKVLTQMGSPSIRCSpSVS substrate in presence of [gamma33P] ATP measured after 40 min
Measurement: IC50 = 710 nM (pChEMBL 6.150000095367432)
Descriptors: MW 285.31, ALogP 1.85, HBA 7, HBD 1, PSA 73.57, QED 0.79
Compound (SMILES): CCC1CCCN(c2nc3ccc(Br)cc3c(C(=O)NCC(CCC(=O)O)c3ccccc3Cl)c2C)C1
InChIKey: ZJUNBYODVQMUCZ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 10 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 586.96, ALogP 6.96, HBA 4, HBD 2, PSA 82.53, QED 0.28
Compound (SMILES): C=CC(=O)Nc1ccc(O[C@@H]2CCC[C@@H](Nc3ncc(SCc4ncc(C(C)(C)C)o4)s3)C2)c(C(F)(F)F)c1
InChIKey: UULNNXNBBBWXDG-SJLPKXTDSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 298 nM (pChEMBL 6.53000020980835)
Descriptors: MW 580.7, ALogP 7.67, HBA 8, HBD 2, PSA 89.28, QED 0.2
Compound (SMILES): Cc1cc(-c2ccc3ncc(-c4cnn(C)c4)n3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: SLLWDVCXHJGGIT-HNNXBMFYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 2380 nM (pChEMBL 5.619999885559082)
Descriptors: MW 412.5, ALogP 3.86, HBA 6, HBD 0, PSA 68.32, QED 0.51
Compound (SMILES): CN(C)C(=O)c1ccc(-c2cc(C(=O)N[C@@H]3CCc4ccccc43)no2)cc1O
InChIKey: IXWUILRSNIQHDM-QGZVFWFLSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Affinity Biochemical interaction (HTRF-based inhibition assay) EUB0000731a MLLT3
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 391.43, ALogP 3.17, HBA 5, HBD 2, PSA 95.67, QED 0.71
Compound (SMILES): Br.N=C(N)[Se]Cc1ccc(CN2C(=O)C(=O)c3cc(Cl)cc(Cl)c32)cc1
InChIKey: CCILORANKRCLJP-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, dimeric NADP-preferring (SINGLE PROTEIN), Homo sapiens
UniProt: P30838
Assay: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate
Measurement: IC50 = 327 nM (pChEMBL 6.489999771118164)
Descriptors: MW 441.18
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)C3CCC(=O)N3)[C@@H](C)O)CSSC[C@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)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](CC(C)C)C(=O)N[C@H](C(=O)O)CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)O)NC1=O
InChIKey: NAIHDUVGMVAQOH-IDFYMFIFSA-N
Target: Relaxin-3 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU9
Assay: Agonist activity at human RXFP4 expressed in CHO-K1 cells assessed as reduction in forskolin-induced cAMP production by pCRE beta-galactosidase reporter assay
Measurement: EC50 = 4.571 nM (pChEMBL 8.34000015258789)
Descriptors: MW 5058.9
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4C[C@@H](C)N[C@@H](C)C4)c(C=O)nc32)ncc1C#N
InChIKey: IKPPEZYAZCCZLQ-HDICACEKSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q03142
Assay: Inhibition of FGFR4 in mouse BAF3 cells assessed as decrease in FGFR4 phosphorylation incubated for 40 mins
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 507.6, ALogP 2.35, HBA 9, HBD 2, PSA 132.71, QED 0.41
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: DVAPMYJVUZJNDK-DNVCBOLYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 421.52, ALogP 1.1, HBA 8, HBD 2, PSA 117.42, QED 0.76
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OC1CCN(Cc2ccccc2)CC1
InChIKey: PRPWHGXEZKOGPD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholineiodide as substrate incubated for 10 mins by Ellman's method
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 491.62, ALogP 3.96, HBA 7, HBD 2, PSA 96.45, QED 0.5
Compound (SMILES): N[C@H]1CN[C@@](CCCCB(O)O)(C(=O)O)C1
InChIKey: SHQWTXRBVVLSOY-VXNVDRBHSA-N
Target: Arginase-2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P78540
Assay: Inhibition of human Arg2 by TOGA assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 230.07
Compound (SMILES): O=C(Nc1ccc(OC(CO)CO)nc1)c1n[nH]c2ccc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: JRKXYICQDHOPTH-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 502.58, ALogP 2.99, HBA 8, HBD 4, PSA 136.49, QED 0.27
Compound (SMILES): Cc1cc(-c2ccn3nc(N)nc3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: IBRQJCOMQXDQQV-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant N-terminal His-tagged full-length human PI3K p120gamma expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 347.42, ALogP 3.04, HBA 5, HBD 1, PSA 76.52, QED 0.79
Compound (SMILES): C[C@@H](NS(=O)(=O)c1ccc(Cl)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: CBGCUWGGVHTBIM-ZACQAIPSSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells preincubated for 2 hrs followed by IFNgamma stimulation and measured after 18 hrs by
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 446.98, ALogP 5.67, HBA 3, HBD 1, PSA 59.06, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(C#Cc4ccc(Cl)s4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: ADWCKXIAWARNSR-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 408 nM (pChEMBL 6.389999866485596)
Descriptors: MW 653.18, ALogP 6.14, HBA 8, HBD 2, PSA 128.17, QED 0.19
Compound (SMILES): CO[C@]12CCC3(C[C@@H]1C(C)(C)O)[C@H]1Cc4ccc(O)c5c4[C@]3(CCN1C)[C@@H]2O5
InChIKey: URIIOJFHFRUBEG-LEBBCELKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]HS665 from KOR in guinea pig brain membranes measured after 45 mins by scintillation counting method
Measurement: Ki = 3.411 nM (pChEMBL 8.470000267028809)
Descriptors: MW 385.5, ALogP 2.61, HBA 5, HBD 2, PSA 62.16, QED 0.82
Compound (SMILES): COc1cccc(O)c1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: BUYXRPOASRGKHF-QFIPXVFZSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant full length FLAG-tagged HDAC3 expressed in HEK293F cells in using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 555.66, ALogP 5.47, HBA 7, HBD 4, PSA 129.23, QED 0.16
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCC(O)C1
InChIKey: USGWWFWAYIOOFO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 16595.87 nM (pChEMBL 4.78000020980835)
Descriptors: MW 274.36, ALogP 1.42, HBA 3, HBD 1, PSA 43.78, QED 0.91
Compound (SMILES): CC[C@H]1OC2(CCN(CCc3ccccc3)CC2)CN(C)C1=O
InChIKey: QKSGTKTUVCNJNZ-QGZVFWFLSA-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 = 505 nM (pChEMBL 6.300000190734863)
Descriptors: MW 316.45, ALogP 2.33, HBA 3, HBD 0, PSA 32.78, QED 0.85
Compound (SMILES): COCCCCC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: ZJPSQGKCYKMKSJ-VOQZNFBZSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at human recombinant C-terminal GFP-fused S1P1 expressed in CHO cells assessed as induction of receptor internalization incubated for 50 mins by fluorescence based confocal laser scanning microscopic analysis
Measurement: EC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 425.51, ALogP 4.07, HBA 4, HBD 3, PSA 102.01, QED 0.39
Compound (SMILES): CCCOc1ccc2c(c1[C@H]1C[C@@H]1CN)CCO2.Cl
InChIKey: UWVLPYSRFUDFMR-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 257.04 nM (pChEMBL 6.590000152587891)
Descriptors: MW 247.34, ALogP 2.47, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): CNC(=O)COCC(=O)NCCCCNC(=O)COCC(=O)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: ASENGHRUTMGCNR-YNWXFNELSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Antagonist activity at human mu opioid receptor expressed in CHO cells co- expressing Gqi5 assessed as decrease in DAMGO-induced intracellular calcium mobilization incubated for 15 mins followed by DAMGO addition by Fluo-AM dye based fluorescence assay
Measurement: IC50 = 254 nM (pChEMBL 6.590000152587891)
Descriptors: MW 657.77, ALogP -0.77, HBA 10, HBD 6, PSA 187.79, QED 0.12
Compound (SMILES): COc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: ZBGMKBKMVOGMLL-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX2 from human adenosine receptor A2A expressed in HEK293 cell membranes incubated for 30 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 520.57, ALogP 6.03, HBA 8, HBD 1, PSA 99.25, QED 0.29
Compound (SMILES): Cn1ncc(-c2ccc3cnc(NC(=O)[C@H]4CC[C@H](CO)CC4)cc3c2)c1CN1CCCCC1
InChIKey: AFXZSFRQUZCOKK-MXVIHJGJSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: The screening assay for DYRK1A kinase activity : Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.00016 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The DYRK1A kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission.Briefly, recombinant DYRK1A kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control.After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).The Emission ratio (Em) was calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation was then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves were generated and inhibitory concentration (IC50) values were calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 461.61, ALogP 4.36, HBA 6, HBD 2, PSA 83.28, QED 0.57
Compound (SMILES): Cc1cccc(-c2nnc(N3CCN(c4ccccn4)CC3)o2)c1
InChIKey: BCPJRBVIGIXBMJ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 5240 nM (pChEMBL 5.28000020980835)
Descriptors: MW 321.38, ALogP 2.77, HBA 6, HBD 0, PSA 58.29, QED 0.74
Compound (SMILES): CC(C)(C)CC(=O)Nc1cncc(-c2cnc3[nH]nc(-c4cc5cnccc5[nH]4)c3c2)c1
InChIKey: QAXOQQJRXNFSDF-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 425.5, ALogP 4.94, HBA 5, HBD 3, PSA 112.24, QED 0.38
Compound (SMILES): Cc1cn(C[C@](C)(O)C(=O)Nc2ccc(C#N)c(C(F)(F)F)c2)nc1Cl
InChIKey: AGPODQJBJRELMH-HNNXBMFYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Affinity Assay: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone. The results of this assay are reported as Ki values (nM) in Table 1 in the column labeled wt AR Binding (Ki(left)). As discussed above and is apparent from Table 1, there is a poor correlation between AR-LBD affinity and SARD activity. E.g., see in vitro SARD activity for 1002, 1005, 1015, 1019, 1020, and 1022 despite no binding affinity for the LBD.
Measurement: Ki = 1346 nM (pChEMBL 5.869999885559082)
Descriptors: MW 386.76, ALogP 3.13, HBA 5, HBD 2, PSA 90.94, QED 0.84
Compound (SMILES): CC(C(=O)Nc1ccc(Cl)cc1)N1CCC2(CC1)COc1cc(C(F)(F)F)ccc12
InChIKey: RVOJERZGLLIIRZ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human SKOV3 cells
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 438.88, ALogP 5.11, HBA 3, HBD 1, PSA 41.57, QED 0.72
Compound (SMILES): COc1ccc2nc3c(c(NCCCCCCN(CC(=O)NCCc4c[nH]c5ccc(OC)cc45)C(=O)CCCC[C@@H]4CCSS4)c2c1)CCCC3
InChIKey: ZYKIOUVTAQGDKW-JGCGQSQUSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE in human erythrocyte hemo-lyzates pre-incubated for 5 mins before addition of acetylthiocholine iodide substrate by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 746.06, ALogP 8.49, HBA 8, HBD 3, PSA 108.58, QED 0.06
Compound (SMILES): CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2sc(CN3CCN(C(=O)C4CCC4)CC3=O)cc2n1
InChIKey: FANCMOGTFZXBFZ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin)
Measurement: IC50 = 165 nM (pChEMBL 6.78000020980835)
Descriptors: MW 559.7, ALogP 3.4, HBA 9, HBD 0, PSA 96.69, QED 0.36
Compound (SMILES): Cc1cc(-c2ccn3nc(N)c(-c4ccccn4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: SOTXCCDMWLOUTG-HNNXBMFYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 424.51, ALogP 4.1, HBA 6, HBD 1, PSA 89.41, QED 0.53
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4CC[C@@H](N(C)C)C4=O)c(C=O)nc32)ncc1C#N
InChIKey: IINODIWIEGKWRS-OAQYLSRUSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q03142
Assay: Inhibition of FGFR4 in mouse BAF3 cells assessed as decrease in FGFR4 phosphorylation incubated for 40 mins
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 521.58, ALogP 1.83, HBA 9, HBD 1, PSA 140.99, QED 0.39
Compound (SMILES): C=CC(=O)NCC1NC(=O)[C@@H](NC(C)=O)CCCCNC(=O)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@]2(C)CCC/C=C/CCC[C@@](C)(C(=O)N[C@@H](Cc3ccccc3)C(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC2=O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC1=O
InChIKey: RDEHKRNADKDMAL-JKKHURIASA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Covalent binding affinity to human Bcl2A1 by FBid based FP assay
Measurement: Ki = 46.7 nM (pChEMBL 7.329999923706055)
Descriptors: MW 1689.98
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)/C=C/c1nccs1
InChIKey: BHWDYFGTRWGKRI-JXMROGBWSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in human THP1 cells assessed as inhibition of IL-1beta release in presence of MSU
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 389.5, ALogP 3.24, HBA 5, HBD 2, PSA 88.16, QED 0.84
Compound (SMILES): O=C(N[C@@H](CCCCNC(=O)c1ccccc1C1CC1)c1ncc(-c2ccc3ccccc3c2)[nH]1)c1cncs1
InChIKey: DPTRGZNSYOSURO-MHZLTWQESA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant full length FLAG-tagged HDAC3 expressed in HEK293F cells in using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 549.7, ALogP 6.64, HBA 5, HBD 3, PSA 99.77, QED 0.16
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2c(c1)C(=C(C)C)C(=O)N2
InChIKey: CDERLIUJSXSXFH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of BRD2 BD1 (unknown origin) preincubated for 15 mins followed by peptide addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 358.42, ALogP 3.24, HBA 4, HBD 2, PSA 84.5, QED 0.82
Compound (SMILES): O=C(NO)c1ccc(Nc2ccnc3ccccc23)cc1
InChIKey: CRQRFXAGXWHWTJ-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC5 (656 to 1122 residues) expressed in baculovirus infected Sf9 insect cells using fluorogenic HDAC 2A substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 3370 nM (pChEMBL 5.46999979019165)
Descriptors: MW 279.3, ALogP 3.1, HBA 4, HBD 3, PSA 74.25, QED 0.51
Compound (SMILES): COc1cc(-c2cn([C@H]3CCc4ccccc4N(CC(F)(F)F)C3=O)nn2)ccc1-n1ccc(C)n1
InChIKey: LMWVEVSLAFDIRE-QFIPXVFZSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: GPCRScan assay: inhibition of Alpha1B
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 496.49, ALogP 4.53, HBA 7, HBD 0, PSA 78.07, QED 0.41
Compound (SMILES): O=C(NCC1(O)CCCC1)[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: BYPRNDXXUCKHDZ-VIICAESSSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in CD3/CD28-stimulated human whole blood assessed as suppression of IL17 incubated for 1 hr before CD3/CD28 stimulation for 20 hrs by AlphaLISA method
Measurement: EC50 = 87000 nM (pChEMBL 4.059999942779541)
Descriptors: MW 639.61, ALogP 6.18, HBA 4, HBD 2, PSA 83.47, QED 0.29
Compound (SMILES): OC/C=C/[C@H]1[C@@H]2CCC[C@@]1(c1cccc(O)c1)CCN2CCc1ccccc1
InChIKey: FTDOOEOFAZGQEK-ZADLEFMZSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHOK1 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by luminescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 377.53, ALogP 4.3, HBA 3, HBD 2, PSA 43.7, QED 0.74
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2cnccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: HESMLNQOTOVZRA-QGZVFWFLSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Binding affinity to SHP2 (unknown origin) by SPR analysis
Measurement: Kd = 0.92 nM (pChEMBL 9.039999961853027)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): Cn1cc(-c2ccccc2C(F)(F)F)c2cc(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)[nH]c2c1=O
InChIKey: QDEKZBBQXAWJKX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 571.3 nM (pChEMBL 6.239999771118164)
Descriptors: MW 559.55, ALogP 5.32, HBA 5, HBD 4, PSA 122.01, QED 0.21
Compound (SMILES): Cl.NC[C@@H]1C[C@H]1c1c(OCC2CC2)ccc2occc12
InChIKey: HMLRTUGCQZRYDU-STEACBGWSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 512.86 nM (pChEMBL 6.289999961853027)
Descriptors: MW 257.33, ALogP 3.28, HBA 3, HBD 1, PSA 48.39, QED 0.89
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CC[C@@]2(O)c1cn(-c2cccc(O)c2)nn1
InChIKey: CNCYPHLGQIATRW-YWBWYGPRSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at full length human ERalpha receptor assessed as inhibition of estradiol-induced activation incubated for 22 to 24 hrs by cell based luciferase reporter gene assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 431.54, ALogP 4.42, HBA 6, HBD 3, PSA 91.4, QED 0.56
Compound (SMILES): O=C(Nc1ccc(C(=O)N2CCCC2)nc1)c1n[nH]c2ccc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: YMHZSOUUPALNKM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (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 509.61, ALogP 4.49, HBA 6, HBD 2, PSA 107.11, QED 0.4
Compound (SMILES): O=C(Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(N6CCCCC6)cncc5[nH]4)c3c2)c1)C1CCC1
InChIKey: SLNKJVHWGSQBGB-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 492.59, ALogP 5.29, HBA 6, HBD 3, PSA 115.48, QED 0.31
Compound (SMILES): COC[C@@H](C)Oc1ccc2c(c1)Cc1cccc(-c3cc(=O)cc(N4CCOCC4)o3)c1S2
InChIKey: SYVQAQHCFMTBNA-QGZVFWFLSA-N
Target: Phosphatidylinositol 3-kinase catalytic subunit type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NEB9
Assay: Binding affinity to human Vps34 expressed in mammalian expression system
Measurement: Kd = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 465.57, ALogP 4.61, HBA 7, HBD 0, PSA 61.14, QED 0.41
Compound (SMILES): Cc1ncc(-c2ccc3[nH]nc(-c4nc5c(-c6cccc(F)c6)cccc5[nH]4)c3n2)n1C
InChIKey: RZMYKXZTSOCFDR-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 423.46, ALogP 5.02, HBA 5, HBD 2, PSA 88.07, QED 0.42
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CC(F)C2)c2cc(-c3ccc(C(F)(F)F)s3)cnc21
InChIKey: DOCHLUJBYYUVPG-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, NMDA 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13224
Assay: Standard cell-based calcium flux assay: NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2, 0.5 mM MgCl2 (standard assay) or 1.5 mM MgCl2 (HTS assay), 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl (standard assay) or 150 mM (HTS assay), 4 mM KCl (standard assay) or 3 mM (HTS assay), 2 mM CaCl2, 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to EC40 (standard assay) is used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 414.38, ALogP 2.66, HBA 6, HBD 0, PSA 60.13, QED 0.62
Compound (SMILES): COC(=O)N1CC[C@](CO)(Nc2nc(N3CCOCC3)nc(-c3cnc(N)nc3)c2F)C1
InChIKey: RTAAXWKPLMSXJJ-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal Myr signal and C-terminal Flag-tagged PI3K p110alpha expressed in rat Rat1 cells
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 448.46, ALogP 0.11, HBA 11, HBD 3, PSA 151.85, QED 0.57
Compound (SMILES): CCc1cc(-c2ccc3c(c2)-c2nnc(Nc4cccc(C(F)(F)F)c4)n2CCO3)ccn1
InChIKey: BKGOKPQNNKWLHW-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human liver microsomes CYP3A4 using testosterone as substrate by MUX-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 451.45, ALogP 5.72, HBA 6, HBD 1, PSA 64.86, QED 0.43
Compound (SMILES): CC1(C)OC(=O)c2ccc(Nc3ncc(C(=O)O)c(N[C@H](CO)c4ccccc4)n3)cc21
InChIKey: NTTPVLDIJOHTEV-GOSISDBHSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IVH8
Assay: Inhibition of GLK (unknown origin)
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 434.45, ALogP 3.47, HBA 8, HBD 4, PSA 133.67, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4cc(CC)ccn4)cc3)c2c1
InChIKey: VYZQSAKXLMEDCB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged EGFR (668 to 1210 residues) expressed in baculovirus expression system using Tyr 04 peptide as substrate preincubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 958 nM (pChEMBL 6.019999980926514)
Descriptors: MW 438.49, ALogP 5.36, HBA 5, HBD 2, PSA 93.21, QED 0.38
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2ccncc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: KCWOIBDNAYKHIF-QGZVFWFLSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Binding affinity to SHP2 (unknown origin) by SPR analysis
Measurement: Kd = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3ccc(NC(=O)C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: GBQZRFCGAJTKDG-UHFFFAOYSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1S7
Assay: Inhibition of Staphylococcus aureus DNA topoisomerase 4 using supercoiled pNO1 plasmid DNA as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 413.24, ALogP 3.52, HBA 5, HBD 4, PSA 124.18, QED 0.49
Compound (SMILES): Fc1ccc(CNC2CCN(Cc3ccccc3)C2)c(F)c1
InChIKey: GZGCQOBTRUVMOI-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE-1 by FRET assay
Measurement: IC50 = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 302.37, ALogP 3.33, HBA 2, HBD 1, PSA 15.27, QED 0.91
Compound (SMILES): C=CC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3c(F)c(OC)cc(OC)c3F)c(=O)n(C)c2n1
InChIKey: PSKWUEAQZZDBSQ-UONOGXRCSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant human wild type N-His tagged FGFR4 (460-802) using Y10-Sox as substrate in presence of 250 uM ATP by Omnia kinase method
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 487.46, ALogP 1.77, HBA 9, HBD 2, PSA 116.6, QED 0.48
Compound (SMILES): CC(C)(O)C#Cc1cnc(Nc2cnc(C#N)cn2)cc1NC[C@H]1CNCCO1
InChIKey: IDZXROKRAQBADP-MRXNPFEDSA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Caliper Assay: CHK1 kinase activity was measured in a microfluidic assay that monitors the separation of a phosphorylated product from its substrate. The assay was run on an EZ Reader II (Caliper Life Sciences Ltd, Runcorn, UK) using separation buffer (#760367 Caliper LS) containing CR-8 (500 nM, #760278, Caliper LS). An ECHO® 550 (Labcyte Inc) acoustic dispenser was used to generate duplicate 8 pt dilution curves directly into 384 polypropylene assay plates (Greiner Bio-One, Gloucestershire, UK). For each test compound a 50 μM stock concentration in 100% DMSO was used. The total amount of DMSO dispensed per well was 250 nL to give a final assay concentration of 2.5% DMSO and test compound concentrations in the range 0.5-1000 nM. To this assay plate, 6 μL CHK1 (2 nM final concentration, in-house protein preparation), 2 μL peptide 10 (5-FAM-KKKVSRSGLYRSPSMPENLNRPR COOH, 1.5 μM final concentration, #760354 Caliper LS) and 2 μL ATP (90 μM final concentration) all diluted in kinase buffer (HEPES 50 mM, NaN3 0.02%, BSA 0.01%, sodium orthovanadate 0.1 mM, DTT 1 mM, MgCl2 2 mM, Tween 20 0.1%) were added. The plate was sealed and centrifuged (1 minute, 1000 rpm) before incubation for one hour at room temperature. The reaction was stopped by the addition of separation buffer (90 μL). The plate was read on an EZ Reader II, using a 12-sipper chip (760137-0372R, Caliper LS) with instrument settings of 1.5 psi and 1750 ΔV. The percentage conversion of product from substrate was generated automatically and the percentage inhibition was calculated relative to blank wells (containing no enzyme and 2.5% DMSO) and total wells (containing all reagents and 2.5% DMSO).
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 393.45, ALogP 1.01, HBA 9, HBD 4, PSA 128.01, QED 0.55
Compound (SMILES): CCCCC(NC1=NS(=O)(=O)c2ccccc21)C(=O)NC[C@@H](NC(=O)C1CCCC(NC(=O)[C@H](CC(C)(C)C)n2cc(CC3CCCCC3)nn2)C1)C(=O)NC(CCCCNC(=O)CCCC[C@@H]1SCC2NC(=O)NC21)C(N)=O
InChIKey: SMUPWRYLYIGLBT-OUVFRTDVSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Binding affinity to N-terminal GST-tagged recombinant human PTP1B (1 to 321 residues) expressed in Escherichia coli assessed as dissociation constant and measured for 120 sec by biolayer interferometry
Measurement: Kd = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 1136.5