lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ncc(-c2ccc3c(c2)COCC3)cc1NS(C)(=O)=O
InChIKey: VCAPFXXCRFAHSN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3KD (unknown origin) by HTRF assay
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 334.4, ALogP 2.2, HBA 5, HBD 1, PSA 77.52, QED 0.93
Compound (SMILES): CCn1nc(C)cc1C(=O)Nc1nc2cc(C(=O)O)cnc2n1CCCNC(=O)OC(C)(C)C
InChIKey: SSWKNXZVFJIXTL-UHFFFAOYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at STING in human THP1 cells assessed as stimulation of IRF3 pathway measured after 20 hrs by luciferase reporter gene assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 471.52, ALogP 2.82, HBA 9, HBD 3, PSA 153.26, QED 0.42
Compound (SMILES): NC(=O)c1ccc(C(=O)NC(C(=O)NO)c2ccc(-c3cc(F)c(F)c(F)c3)cc2)cc1
InChIKey: TXNPYVWHSYMGNU-UHFFFAOYSA-N
Target: Aminopeptidase N (SINGLE PROTEIN), Homo sapiens
UniProt: P15144
Assay: Inhibition of soluble human APN ectodomain stably expressed in HEK293 GnTI(-) cells using H-Leu-NHMec as substrate preincubated for 10 mins followed by substrate addition and measured for 1 hr by spectrofluorimetric method
Measurement: Ki = 82.1 nM (pChEMBL 7.090000152587891)
Descriptors: MW 443.38, ALogP 2.85, HBA 4, HBD 4, PSA 121.52, QED 0.27
Compound (SMILES): Cc1noc(C)c1S(=O)(=O)N1CCN(C(=O)c2cnn(-c3nn4cccc4c(=O)[nH]3)c2C)CC1
InChIKey: RTIWHDRLFVVGFQ-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of terbium-labeled SNAP-tagged human SPR in presence of sulfasalazine-labeled SNAP-tagged EGFP by homogenous TR-FRET assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 486.51, ALogP 0.27, HBA 10, HBD 1, PSA 151.7, QED 0.43
Compound (SMILES): COCCNCCC(=O)Nc1sc2c(c1-c1nc3cnccc3s1)CCNC2
InChIKey: IITGMICIVDIGOW-UHFFFAOYSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc assessed as reduction in c-Myc/Max/Ebox DNA complex formation using pre-formed complex of c-Myc and biotinylated DNA containing single Ebox-sequence followed by compound addition and further addition of his6-tagged c-Max and incubated for 2 hrs by AlphaScreen assay
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 417.56, ALogP 2.63, HBA 8, HBD 3, PSA 88.17, QED 0.49
Compound (SMILES): CN(C)CCCNC(=O)[C@H]1CC(=O)N(c2ccc(S(N)(=O)=O)cc2)[C@@H]1c1ccc(Cl)cc1
InChIKey: FKMBSEVMCQVMPX-PZJWPPBQSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 960.2 nM (pChEMBL 6.019999980926514)
Descriptors: MW 479, ALogP 2.15, HBA 5, HBD 2, PSA 112.81, QED 0.56
Compound (SMILES): CN1CCN(c2nc3ccc(F)cc3c(=O)n2-c2ccc(OC(F)(F)F)cc2)CC1
InChIKey: APUUNOKUBAGYKV-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Agonist activity at recombinant human TRPV4 expressed in HEK293 cells assessed as increase in intracellular calcium level after 30 mins by Fura-2 AM/Pluronic F-127 probe based fluorescence assay
Measurement: EC50 = 2060 nM (pChEMBL 5.690000057220459)
Descriptors: MW 422.38, ALogP 3.18, HBA 6, HBD 0, PSA 50.6, QED 0.61
Compound (SMILES): Nc1ncnc2c3c(n(-c4ccc(NC(=O)Cc5ccccc5)c(OC(F)(F)F)c4)c12)CCC3
InChIKey: LAPWFCDXPZWPEV-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Displacement of kinase tracer 236 from recombinant human His-tagged CSF1R cytoplasmic domain (538 to 910 residues) expressed in baculovirus-infected insect cells measured after 5 hrs by TR-FRET based LanthaScreen assay
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 467.45, ALogP 4.57, HBA 6, HBD 2, PSA 95.06, QED 0.45
Compound (SMILES): Cc1ccc(CN[C@H]2CC[C@H](CS(=O)(=O)N3CCC(NC(=O)c4cc(C5CC5)on4)CC3)CC2)nc1
InChIKey: AHBRFCMWFIUNQF-XUTJKUGGSA-N
Target: Histone-lysine N-methyltransferase SMYD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H7B4
Assay: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 515.68, ALogP 3.13, HBA 7, HBD 2, PSA 117.43, QED 0.53
Compound (SMILES): CC(C)(C)c1ccc(CN(Cc2ccnc(NCC(=O)O)c2)S(=O)(=O)c2cccnc2)cc1.Cl
InChIKey: JMGIXUOXUMCIKU-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at recombinant human EP2 receptor expressed in HEK293 cells assessed as induction of cAMP accumulation after 30 mins
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 468.58, ALogP 3.66, HBA 6, HBD 2, PSA 112.49, QED 0.49
Compound (SMILES): Fc1ccc2nc(-n3ccnn3)n(C3CC3)c2c1
InChIKey: WREQQPAOQUFRBG-UHFFFAOYSA-N
Target: Cytochrome P450 11B2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P19099
Assay: Inhibition of human recombinant CYP11B2 using deoxycorticosterone as substrate incubated for 90 mins by cell-based HPLC analysis
Measurement: IC50 = 1064 nM (pChEMBL 5.96999979019165)
Descriptors: MW 243.25, ALogP 2.09, HBA 5, HBD 0, PSA 48.53, QED 0.69
Compound (SMILES): Cn1cc(CC(=O)Nc2ccc(-n3c4c(c5ncnc(N)c53)CCC4)cc2)cn1
InChIKey: RBROLBBSQGEWBD-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Displacement of kinase tracer 236 from recombinant human His-tagged CSF1R cytoplasmic domain (538 to 910 residues) expressed in baculovirus-infected insect cells measured after 5 hrs by TR-FRET based LanthaScreen assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 387.45, ALogP 2.41, HBA 7, HBD 2, PSA 103.65, QED 0.56
Compound (SMILES): CC(OC(C)(C)C)[C@H](NC(=O)[C@H](Cc1ccccc1)N=[N+]=[N-])C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](C)C(=O)[C@@]1(C)CO1
InChIKey: ITRQYUFRZMXDMA-DXSRSINFSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of catalytic activity of constitutive proteasome 20s subunit beta5 in human Raji cells incubated for 1 hr by BODIPY(TMR)-NC-005-VS probe based competitive activity based protein profiling assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.72, ALogP 3.19, HBA 7, HBD 3, PSA 174.89, QED 0.12
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(N)=O)[C@@H](C)O
InChIKey: FOIBNGWWTFPCCR-UERHRRBTSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 binding to human interleukin-23 receptor incubated for 2 hrs by competitive binding ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1523.76
Compound (SMILES): CN(CC1CCCCC1)C(=O)c1ccc(NC(=O)c2ccc(-c3nc4cc(Cl)c(Cl)cc4[nH]3)cc2)c(C(=O)O)c1
InChIKey: UDZSXDKMXITQCB-UHFFFAOYSA-N
Target: Neurotrypsin (SINGLE PROTEIN), Homo sapiens
UniProt: P56730
Assay: Inhibition of human neurotrypsin
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 579.48, ALogP 7.14, HBA 4, HBD 3, PSA 115.39, QED 0.22
Compound (SMILES): COc1cc2nc(C)nc(N[C@H](C)c3cc(N)cc(C(F)(F)F)c3C)c2cc1[C@H]1CC[C@@H](C(=O)N(C)CCO)CC1
InChIKey: OLRAWTOSZGUDML-RLLQIKCJSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of GST-tagged SOS1 (564 to 1049 amino acids) (unknown origin) assessed as reduction SOS1/6xHis-Tev-tagged K-Ras G12D mutant (1 to 169 residues) interaction incubated for 30 mins by AlphaLISA method
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 573.66, ALogP 5.75, HBA 7, HBD 3, PSA 113.6, QED 0.29
Compound (SMILES): O=c1c(-c2ccc(OCCN3CCCCC3)cc2)coc2cc(OCCN3CCCC3)ccc12
InChIKey: LKWBRFHBJPNBMM-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Inhibition of human H3R expressed in methylhistamine-induced human H3-bla U2OS cells incubated for 30 mins by beta-lactamase complementation technology
Measurement: IC50 = 2070 nM (pChEMBL 5.679999828338623)
Descriptors: MW 462.59, ALogP 4.8, HBA 6, HBD 0, PSA 55.15, QED 0.46
Compound (SMILES): COC(=O)CS(=O)(=O)c1ccc(CNC(=O)c2cc3c(Cl)cc(C)cc3n2C)cc1
InChIKey: KPUHIUIDWCFOQD-UHFFFAOYSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of N-terminal HIS-tagged and TEV cleavage site containing full length PHGDH (unknown origin) expressed in Escherichia coli assessed as reduction in conversion of 3-Phosphoglycerate and NAD to 3-Phosphohydroxypyruvate and NADH using 250 uM NAD and 500 uM 3-PG incubated for 240 mins by fluorescence based assay
Measurement: IC50 = 3386 nM (pChEMBL 5.46999979019165)
Descriptors: MW 448.93, ALogP 3.02, HBA 6, HBD 1, PSA 94.47, QED 0.58
Compound (SMILES): CC(=O)N1CCN(c2ccc(CN3[C@@H](C)CC[C@H](c4ccc(Cl)cc4)S3(=O)=O)c(F)c2)CC1
InChIKey: NDILJNQRYYYGKG-BXKMTCNYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORc-LBD assessed as inhibition of SRC1 co-activator peptide recruitment by FRET assay
Measurement: EC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 494.03, ALogP 4.2, HBA 4, HBD 0, PSA 60.93, QED 0.64
Compound (SMILES): COc1cc(OC)c(-c2cn3ccc(N4CCN(c5cccc(F)n5)CC4)cc3n2)cc1Cl
InChIKey: WLARCIYCMOIZCQ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SUV39H2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H5I1
Assay: Inhibition of SUV39H2 (unknown origin) using H3 histone peptide substrate and [3H]-SAM incubated for 3 hrs by microbeta counting based assay
Measurement: IC50 = 98.8 nM (pChEMBL 7)
Descriptors: MW 467.93, ALogP 4.53, HBA 7, HBD 0, PSA 55.13, QED 0.4
Compound (SMILES): O=C(CCCCCn1cc(-c2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)nn1)NO
InChIKey: IKTSOHKYDYDWRP-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 542.62, ALogP 5.53, HBA 9, HBD 4, PSA 137.57, QED 0.08
Compound (SMILES): CCCN(CCC)C(=O)c1cc(C(=O)N[C@@H](Cc2ccccc2)[C@H](O)CNC(C)(C)c2cccc(OC)c2)cc(C(F)(F)F)c1
InChIKey: KTBBODWOBFLAOA-IOWSJCHKSA-N
Target: Plasmepsin 4 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q17SB2
Assay: Inhibition of Plasmodium falciparum plasmepsin 4 using DABCYL-Glu-Arg-Nle-Phe-Leu-Ser-Phe-Pro-EDANS as substrate preincubated for 30 mins followed by substrate addition and measured every min for 8 to 15 mins by FRET assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 627.75, ALogP 6.2, HBA 5, HBD 3, PSA 90.9, QED 0.19
Compound (SMILES): Cc1ccc(-c2cc(=O)c3c(ccc4ccccc43)o2)cc1
InChIKey: RCJBVSDMTQRCFC-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P80457
Assay: Inhibition of bovine milk xanthine oxidase using xanthine as substrate preincubated for 5 mins followed by substrate addition by UV-visible spectrophotometry
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 286.33, ALogP 4.92, HBA 2, HBD 0, PSA 30.21, QED 0.46
Compound (SMILES): Fc1ccc(-c2csc(-c3cn([C@H]4CN5CCC4CC5)nn3)c2)cn1
InChIKey: WOBDDEOMHCGDRB-INIZCTEOSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Displacement of [125I]-alpha-bungarotoxin from alpha7 nAChR in Wistar rat brain membrane incubated for 3 hrs by gamma counting analysis
Measurement: Ki = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 355.44, ALogP 3.47, HBA 6, HBD 0, PSA 46.84, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(C)=O)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C
InChIKey: USEVPSVMTBETHD-YZJIJPGJSA-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 suppression of TFPI-mediated inhibition of extrinsic tenase complex by measuring factor 10a activation using S-2222 substrate in presence of FVIIa, lipidated TF, phospholipid vesicles by micro-plate reader based assay
Measurement: EC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 3905.64
Compound (SMILES): Cc1nn2c(=O)cc(-c3ccc([N+](=O)[O-])cc3)[nH]c2c1-c1ccc(OC(F)(F)F)cc1
InChIKey: YCSYOKCCJHUTBM-UHFFFAOYSA-N
Target: PH and SEC7 domain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: A5PKW4
Assay: Inhibition of N-terminal His-tagged and N-terminal alpha-helix lacking Arf6 (14 to 175 residues) (unknown origin) expressed in Escherichia coli using 20 nM Arf6 in presence of ARNO (50 to 255 residues) incubated for 1 hr by fluorometric high throughput assay
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 430.34, ALogP 4.47, HBA 6, HBD 1, PSA 102.53, QED 0.38
Compound (SMILES): O=C(O)c1cc(C2CC2)cc(NS(=O)(=O)c2cc(Br)cc(Cl)c2O)c1O
InChIKey: RWFJMOHRSSMXSO-UHFFFAOYSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Displacement of FITC-labelled DEEEIDVVSVE from N-terminal SUMO-fused 6His-tagged WDR5 (unknown origin) (22 to 334 residues) expressed in Escherichia coli BL21(DE3) shaken for 2 mins and incubated for 60 mins by fluorescence polarization assay
Measurement: Kd = 207 nM (pChEMBL 6.679999828338623)
Descriptors: MW 462.7, ALogP 3.89, HBA 5, HBD 4, PSA 123.93, QED 0.5
Compound (SMILES): C=C1C(=O)OCC1C(O)c1cn(Cc2nc3ccccc3o2)c2ccc(Cl)cc12
InChIKey: BNPGJHSPCUEGCI-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant LSD1 (unknown origin) (catalytic domain 157 to 852 residues) expressed in Escherichia coli BL21 using H3K4me1 as substrate incubated for 1 hr by horse-radish peroxidase/amplex red-based fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.84, ALogP 4.25, HBA 6, HBD 1, PSA 77.49, QED 0.4
Compound (SMILES): Fc1ccc(-c2nc(C3CCNCC3)sc2-c2ccnc(NCc3ccncc3)n2)cc1
InChIKey: YWNZQAHWRLIRPK-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells by Q-patch clamp assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 446.56, ALogP 4.88, HBA 7, HBD 2, PSA 75.62, QED 0.44
Compound (SMILES): C=CC(=O)N1CCN(C(CC)c2ccc([C@H](C)Nc3nc(N)cc(N4C(=O)OCC4(C)C)n3)cc2)CC1
InChIKey: IRYXPSUOUWFUGU-YMXDCFFPSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Biochemical Assay: IDH1 mutant (R132H and R132C) and IDH2 mutant (R140Q and R172K) proteins containing N-terminal His-tag are expressed in E. coli and purified using nickel affinity chromatography by methods commonly used and well known to those skilled in the art. The enzyme assays are carried out in V-bottom 96 well polypropylene plates containing 100 mM Tris-HCl buffer, 1 mM DTT, 0.005% TRITON X-100, 120 mM NaCl. For IDH1 R132H, α-ketoglutarate, NADPH and MnCl2 are included at final concentrations of 300 μM, 2.5 μM and 300 μM respectively. For IDH1 R132C, α-ketoglutarate, NADPH and MnCl2 are included at final concentrations of 100 μM, 10 μM and 100 μM respectively. For IDH2 R172K, α-ketoglutarate, NADPH, and MnCl2 are included at final concentrations of 150 μM, 10 μM and 150 μM respectively. For IDH2 R140Q, α-ketoglutarate, NADPH, and MnCl2 are included at final concentrations of 300 μM, 10 μM, and 100 μM respectively. Final pH=7.0. Test compound, dissolved in DMSO stock, is diluted in the reaction mixture at a final DMSO concentration of 4%. Compounds are tested in dose-response format. The assay is started by addition of enzyme. Enzymes are used at the following final concentrations: IDH1 R132H, 2 nM; IDH1 R132C, 0.5 nM; IDH2 R172K, 1.2 nM; IDH2 R140Q, 1.2 nM and the assay is allowed to continue for the following times: 40 minutes for IDH-1R132C, 60 minutes for IDH-1HR132H and 50 minutes for the IDH-2172K and IDH-2R140Q enzymes. The reaction is quenched by adding ACN (50:50) containing d5-3HG as an internal standard for mass spectrometry analysis and quantitation of reaction product.
Measurement: IC50 = 38.5 nM (pChEMBL 7.420000076293945)
Descriptors: MW 507.64, ALogP 3.75, HBA 8, HBD 2, PSA 116.92, QED 0.52
Compound (SMILES): Cc1cc(Cl)ccc1OCc1nnc(-c2ccccc2OC(F)(F)F)o1
InChIKey: FPRZJVFKRQOYHO-UHFFFAOYSA-N
Target: Anoctamin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5XXA6
Assay: Inhibition of YFP-fused ANO1 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 384.74, ALogP 5.18, HBA 5, HBD 0, PSA 57.38, QED 0.61
Compound (SMILES): CC1(C)Oc2cc(CC(=O)O)cc(O)c2[C@@H]2C[C@@H](O)CC[C@H]21
InChIKey: FBRJOSKSCYKYLF-QJPTWQEYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Displacement of [3H]CP55940 from CB1 receptor in rat brain membranes by scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 306.36, ALogP 2.43, HBA 4, HBD 3, PSA 86.99, QED 0.78
Compound (SMILES): Cc1c(C(=O)N2CCC3(CC2)CC(F)C3)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: CJMIWOKCRBBNHY-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of terbium-labeled SNAP-tagged human SPR in presence of sulfasalazine-labeled SNAP-tagged EGFP by homogenous TR-FRET assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 384.42, ALogP 1.87, HBA 6, HBD 1, PSA 88.29, QED 0.73
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)NCC(=O)O
InChIKey: HZLFZIQTWBACFC-UHFFFAOYSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of fibronectin binding to alpha5beta1 isolated from human K562 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 319.32, ALogP 0.72, HBA 4, HBD 3, PSA 115.81, QED 0.69
Compound (SMILES): O=C(O)CC1Cc2ccc(-c3cc(F)cc(OC(F)F)c3)cc2N1S(=O)(=O)c1cccc(C(F)(F)F)c1
InChIKey: UAFXMLYFRFORFY-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Agonist activity at APC-labeled biotinylated RORgammaT LBD (unknown origin) assessed as induction of biotinylated SRC-1 peptide recruitment incubated for 1 hr by dual FRET assay
Measurement: EC50 = 20.8 nM (pChEMBL 7.679999828338623)
Descriptors: MW 545.46, ALogP 5.71, HBA 4, HBD 1, PSA 83.91, QED 0.38
Compound (SMILES): COc1ccc(CCNC(=O)N2CCc3cc(OC)c(OC)cc3C2c2ccc(Br)cc2)cc1OC
InChIKey: FHTAIGCPDGQPDA-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8R455
Assay: Antagonist activity at recombinant rat TRPM8 expressed in HEK293 cells assessed as inhibition of icilin-induced intracellular calcium accumulation preincubated for 5 mins followed by icilin addition by Fluo-4-AM probe-based spectrofluorimetric assay
Measurement: IC50 = 48200 nM (pChEMBL 4.320000171661377)
Descriptors: MW 555.47, ALogP 5.38, HBA 5, HBD 1, PSA 69.26, QED 0.4
Compound (SMILES): CCCCCn1c(=O)oc2cc(C(=O)C34CC5CC(CC(C5)C3)C4)ccc21
InChIKey: AUCQYZKPNJCIOR-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55940 from human CB2 receptor expressed in CHO cell membranes after 1 hr by beta-counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 367.49, ALogP 5.18, HBA 4, HBD 0, PSA 52.21, QED 0.52
Compound (SMILES): CC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)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)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)NCCOCC(=O)N[C@H](CCCCN)C(N)=O)[C@@H](C)O
InChIKey: PLTVJUKENAQSOH-HOTOKBSCSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 binding to human interleukin-23 receptor incubated for 2 hrs by competitive binding ELISA
Measurement: IC50 = 3194 nM (pChEMBL 5.5)
Descriptors: MW 1840.13
Compound (SMILES): Cn1cnc(-c2nnc3n2CCN(C(=O)c2ccc(/C=C4\Oc5c(C(N)=O)cccc5C4=O)cc2)C3)c1
InChIKey: WUSATWKNDGXYRU-JAIQZWGSSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of human full-length N-terminal GST-tagged PARP1 expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 495.5, ALogP 2.05, HBA 9, HBD 1, PSA 138.23, QED 0.43
Compound (SMILES): COc1cc(OC)c(-c2cn3ccc(N4CCC(NC(=O)OC(C)(C)C)C4)cc3n2)cc1C#N
InChIKey: KMKJCFWBUMMGQM-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SUV39H2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H5I1
Assay: Inhibition of SUV39H2 (unknown origin) using H3 histone peptide substrate and [3H]-SAM incubated for 3 hrs by microbeta counting based assay
Measurement: IC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 463.54, ALogP 3.99, HBA 8, HBD 1, PSA 101.12, QED 0.61
Compound (SMILES): COc1c(NCCNc2nonc2/C(=N/O)Nc2ccc(F)c(Br)c2)c(=O)c1=O
InChIKey: CQJJCKORCPCRPO-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 expressed in Escherichia coli BL21 cells using L-tryptophan as substrate incubated for 30 mins by methylene blue dye based microplate reader analysis
Measurement: IC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 469.23, ALogP 1.35, HBA 10, HBD 4, PSA 150.97, QED 0.1
Compound (SMILES): COCCN(C)c1ccc2nc(C3(C)CC3)nc(N3CCC(c4ccccc4OC)CC3)c2c1
InChIKey: FNMIBFMZPJXUSK-UHFFFAOYSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Allosteric modulation of human GFP-fused PK-tagged Gq-coupled NTR1 expressed in CHOK1 cells assessed as induction of NT (8 to 13) peptide-mediated beta-arrestin recruitment measured after 90 mins by pathhunter assay
Measurement: EC50 = 2230 nM (pChEMBL 5.650000095367432)
Descriptors: MW 460.62, ALogP 5.16, HBA 6, HBD 0, PSA 50.72, QED 0.46
Compound (SMILES): N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H]1CSCc2ccccc2CSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccc(F)cc2)C(=O)NNC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)CNC1=O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: PYJOZFZUINVNAW-FTMHIQFLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human DOR expressed in CHO cell membranes assessed as reduction in SNC80-induced response incubated for 1 hr by [35S]-GTPgammaS coupling assay
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 1111.26
Compound (SMILES): Cc1nn(-c2ccccc2)nc1COc1cc(N)nc2[nH]nnc12
InChIKey: JBOLAMDGILAMOV-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 322.33, ALogP 1.4, HBA 8, HBD 2, PSA 120.42, QED 0.58
Compound (SMILES): CNCC1CCN(Cc2ncc(-c3ccc(Cl)c(NC(=O)c4coc(N)n4)c3)s2)CC1
InChIKey: FATVSEIPDOFFLV-UHFFFAOYSA-N
Target: Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (SINGLE PROTEIN), Homo sapiens
UniProt: P22234
Assay: Inhibition of wild type full length human PAICS using CAIR as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by ADP2 tracer-based fluorescence assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 460.99, ALogP 3.72, HBA 8, HBD 3, PSA 109.31, QED 0.49
Compound (SMILES): N#Cc1ccc(S(=O)(=O)[C@H]2CN(S(=O)(=O)c3ccc(Cl)cc3C#N)C[C@@]2(O)CO)cc1
InChIKey: ZMDZJAAMFDJBFF-RBUKOAKNSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Antagonist activity at human TRPV4 expressed in BHK/AC9 cells assessed as inhibition of GSK634775-induced calcium immobilization pre-incubated for 10 mins followed by agonist addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 481.94, ALogP 0.65, HBA 8, HBD 2, PSA 159.56, QED 0.63
Compound (SMILES): COc1cc(OC)c(-c2cn3ccc(N4CCN(Cc5ncccn5)CC4)cc3n2)cc1Cl
InChIKey: KYYICCVPTRJVBV-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SUV39H2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H5I1
Assay: Inhibition of SUV39H2 (unknown origin) using H3 histone peptide substrate and [3H]-SAM incubated for 3 hrs by microbeta counting based assay
Measurement: IC50 = 9.25 nM (pChEMBL 8.029999732971191)
Descriptors: MW 464.96, ALogP 3.78, HBA 8, HBD 0, PSA 68.02, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ccc2N(C)C)c1
InChIKey: HCUGVXANZBUVFP-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of CatL-activated recombinant human C-terminal His10-tagged cathepsin C (25 to 463 residues) expressed in mouse myeloma cells using Gly-Phe-AFC as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins
Measurement: IC50 = 1520 nM (pChEMBL 5.820000171661377)
Descriptors: MW 502.62, ALogP 4.57, HBA 8, HBD 2, PSA 82.2, QED 0.41
Compound (SMILES): CCn1c(C(O)(c2ccccc2)c2ccccc2)nc2ccc(C(=O)Nc3cc(OC)c(OC)c(OC)c3)cc21
InChIKey: YBZDUZJFRCDJFS-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of N-terminal 6x-histidine tagged human ACSS2 expressed in insect cells assessed as reduction in pyrophosphate production using CoA and ATP incubated for 30 mins by pyrophosphatase coupled enzymatic assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 537.62, ALogP 5.62, HBA 7, HBD 2, PSA 94.84, QED 0.25
Compound (SMILES): CC(C)(C)C1C(C(=O)c2cc(Cl)ccc2Cl)C(c2ccccc2)N(C(=O)c2ccccc2)C1C(=O)O
InChIKey: KLKBHHWVJKEWSK-UHFFFAOYSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Corrector activity at CFTR F508del mutant (unknown origin) expressed in CFBE41o- cells measured after 18 to 24 hrs by HRP based luminescence assay
Measurement: EC50 = 2720 nM (pChEMBL 5.570000171661377)
Descriptors: MW 524.44, ALogP 6.81, HBA 3, HBD 1, PSA 74.68, QED 0.37
Compound (SMILES): CCc1cc(Br)ccc1Nc1nc(-c2sc(C)nc2C)cs1
InChIKey: BZUIHDMPMIWGET-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human mu opioid receptor expressed in CHOK1 cells coexpressing Galpha15 assessed as increase in intracellular calcium flux in presence of mu opioid receptor antagonist naloxone and incubated for 1 hr measured for 90 secs at 1.5 sec interval by FLIPR assay
Measurement: EC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 394.36, ALogP 5.95, HBA 5, HBD 1, PSA 37.81, QED 0.59
Compound (SMILES): CC(C)NC(=O)c1cccc(C(O)(c2ccccc2)c2nc3ccc(Cl)cc3n2C)c1
InChIKey: QGQBIDRZOJTIHK-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of N-terminal 6x-histidine tagged human ACSS2 expressed in insect cells assessed as reduction in pyrophosphate production using CoA and ATP incubated for 30 mins by pyrophosphatase coupled enzymatic assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 433.94, ALogP 4.65, HBA 4, HBD 2, PSA 67.15, QED 0.48
Compound (SMILES): O=C(NCc1ncccc1F)c1csc(C2CN(CCc3nc4ccccc4[nH]3)C2)n1
InChIKey: FYBJPPIACCHUAL-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as induction of ferroportin internalization and degradation incubated overnight by FACS assay
Measurement: EC50 = 3946 nM (pChEMBL 5.400000095367432)
Descriptors: MW 436.52, ALogP 3.13, HBA 6, HBD 2, PSA 86.8, QED 0.46
Compound (SMILES): Br.COc1cc(OC)c(-c2cn3ccc(N(C)C)cc3n2)cc1Cl
InChIKey: JHYVRAUMOSIUCH-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SUV39H2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H5I1
Assay: Inhibition of SUV39H2 (unknown origin) using H3 histone peptide substrate and [3H]-SAM incubated for 3 hrs by microbeta counting based assay
Measurement: IC50 = 5.15 nM (pChEMBL 8.289999961853027)
Descriptors: MW 331.8, ALogP 3.74, HBA 5, HBD 0, PSA 39, QED 0.73
Compound (SMILES): O=C(c1cnn(-c2nc3c(c(=O)[nH]2)CCC3)c1)N1CCC(C2CC2)CC1
InChIKey: PYVQHUCGCGRFTP-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of terbium-labeled SNAP-tagged human SPR in presence of sulfasalazine-labeled SNAP-tagged EGFP by homogenous TR-FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 353.43, ALogP 1.71, HBA 5, HBD 1, PSA 83.88, QED 0.91
Compound (SMILES): COc1ccc2c(c1)c(-c1[nH]c(NC(=O)Cc3ccccc3)nc1C)cn2S(=O)(=O)c1ccccc1
InChIKey: RVATUCUFIHFGSE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from human 5HT2A receptor expressed in CHOK1 cells incubated for 1 hr by liquid scintillation counter method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 500.58, ALogP 4.77, HBA 6, HBD 2, PSA 106.08, QED 0.33
Compound (SMILES): Cc1ccc2nc(-c3ccc(Cl)cc3)cc(C(=O)OCc3ccccc3)c2c1
InChIKey: VGSCHZSSAKSCLU-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human recombinant N-terminal His-tagged DHODH (31 to 395 residues) expressed in Escherichia coli using DHO as substrate measured after 20 mins by DCPI dye-based assay
Measurement: IC50 = 7370 nM (pChEMBL 5.130000114440918)
Descriptors: MW 387.87, ALogP 6.22, HBA 3, HBD 0, PSA 39.19, QED 0.39
Compound (SMILES): Cc1ccc(C)n1-c1cc(C(=O)N/N=C/c2c(Cl)ncnc2Cl)ccc1C(=O)O
InChIKey: SNKGBXPGONRDQR-KTZMUZOWSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc assessed as reduction in c-Myc/Max/Ebox DNA complex formation using pre-formed complex of c-Myc and biotinylated DNA containing single Ebox-sequence followed by compound addition and further addition of his6-tagged c-Max and incubated for 2 hrs by AlphaScreen assay
Measurement: IC50 = 4880 nM (pChEMBL 5.309999942779541)
Descriptors: MW 432.27, ALogP 3.65, HBA 6, HBD 2, PSA 109.47, QED 0.36
Compound (SMILES): COc1ccc(/C=N/NC(=O)c2nn(-c3ccc(S(N)(=O)=O)cc3)c3nc(C)cc(=O)n23)cc1
InChIKey: VDZKJTZQIBBQIZ-FSJBWODESA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase-1 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 2381.9 nM (pChEMBL 5.619999885559082)
Descriptors: MW 481.49, ALogP 0.61, HBA 10, HBD 2, PSA 163.04, QED 0.3
Compound (SMILES): Cc1ccc(-n2nc(C(=O)N3CCN(C)CC3)nc2-c2ccc3c(c2)N(C2CCCC2)[C@H](C)C(=O)N3C)c(C)c1
InChIKey: XLDSWHQAEWXEHF-JOCHJYFZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Fluorescence Polarization Assay: Expression and purification of the BRD4(I) recognition domain: colonies of newly transformed plasmid DNA from E. coli BL21(DE3)-condon plus-RIL cells were cultivated in 50 mL of Terrific Broth medium containing 50 μg/mL kanamycin and 34 μg/mL chloramphenicol at 37° C. overnight (starting culture). The starting culture was then diluted 100-fold in 1 L of fresh TB medium and the cells were grown at 37° C. to an optical density of about 0.8 at  and then the temperature was lowered to 16° C. When the system was equilibrated at 16° C., the optical density at  was approximately 1.2, and protein expression was induced with 0.2 mmol of isopropyl-β-D-thiogalactopyranoside (IPTG) overnight at 16° C. Bacteria were harvested by centrifugation (4000×g, 20 minutes, 4° C.) and stored as a pellet at −80° C. The cells expressing His 6-tagged protein was resuspend in lysis buffer [50 mmol 4-hydroxyethylpiperazineethanesulfonic acid (HEPES), 25° C., pH 7.5, 500 mmol NaCl, 10 mmol imidazole, 5% glycerol and freshly added 0.5 mmol of tris(2-carboxyethyl)phosphine hydrochloride (TCEP) and 1 mmol of phenylmethanesulfonyl fluoride (PMSF)] and lysed at 4° C. using JN 3000PLUS high pressure homogenizer (JNBIO-Guangzhou, China). The lysate was clarified by centrifugation (12,000×g for 1 hour at 4° C.) and applied to a nickel-nitriloacetate agarose column. The column was washed once with 50 mL of wash buffer containing 30 mmol of imidazole. The protein was eluted using imidazole in an elution buffer in a stepwise elution (100-250 mmol imidazole in 50 mmol HEPES, 25° C., pH 7.5, 500 mmol NaCl, 5% glycerol). All fractions were collected and monitored by SDS-polyacrylamide gel electrophoresis (Bio-Rad Criterion TM Precast Gels, 4-12% Bis-Tris, 1.0 mm, from Bio-Rad, CA). After 1 mmol of dithiothreitol (DTT) was added, the eluted proteins were treated with tobacco plaque virus (TEV) protease overnight at 4° C. to remove the His6 tag. The protein was concentrated and further purified by size exclusion chromatography on a Superdex 75 16/60 HiLoad gel filtration column. The samples were monitored by SDS-polyacrylamide gel electrophoresis and concentrated to 8-10 mg/mL with gel filtration buffer, 10 mmol Hepes pH 7.5, 500 mM NaCl, 1 mmol DTT, and used for protein binding assays and crystallization.
Measurement: IC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 541.7, ALogP 4.05, HBA 7, HBD 0, PSA 77.81, QED 0.5
Compound (SMILES): CCOP(=O)(OCC)C1(c2ccccc2)N=CC2C(=O)N(CCc3ccc(F)cc3)C(=O)C21
InChIKey: ZERIGJALQBIPQT-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 = 2238.72 nM (pChEMBL 5.650000095367432)
Descriptors: MW 472.45, ALogP 4.17, HBA 6, HBD 0, PSA 85.27, QED 0.4
Compound (SMILES): Cc1cncc(C(=O)n2c(-c3cn(-c4ccccc4)nc3-c3ccc(C(F)(F)F)cc3)nc3ccccc32)c1
InChIKey: QZMXAYFUSIDBCA-UHFFFAOYSA-N
Target: 3-oxoacyl-[acyl-carrier-protein] synthase 3 (SINGLE PROTEIN), Escherichia coli
UniProt: C3TDZ2
Assay: Inhibition of Escherichia coli FabH in presence of radiolabelled substrates and acetyl-coA by enzyme coupled FabD/FabH assay system
Measurement: IC50 = 22890 nM (pChEMBL 4.639999866485596)
Descriptors: MW 523.52, ALogP 6.97, HBA 6, HBD 0, PSA 65.6, QED 0.25
Compound (SMILES): CN1CCOc2c1cnn1c(-c3cccc(NCC4CCNCC4)c3)nnc21
InChIKey: OIHASQTWQZRYHF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of His tagged human recombinant PIM1 using PIM tide (ARKRRRHPSGPPTA) as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 379.47, ALogP 2.03, HBA 8, HBD 2, PSA 79.61, QED 0.72
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)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)C(C)(C)C)C(C)C
InChIKey: GPTMSLDFSKIYNH-DCDCRCPPSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 7.36 nM (pChEMBL 8.130000114440918)
Descriptors: MW 2417.8
Compound (SMILES): COc1ncc(-c2ccc3ncnc(NCCN4CCCCC4)c3c2)cc1[N+](=O)[O-]
InChIKey: IRVWQBGEHKMMGH-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) assessed as reduction in ATP depletion using lipid substrate after 40 mins by Kinase-Glo luminescent assay
Measurement: IC50 = 3175 nM (pChEMBL 5.5)
Descriptors: MW 408.46, ALogP 3.51, HBA 8, HBD 1, PSA 106.31, QED 0.47
Compound (SMILES): COc1ccc(-c2nc(NC(=O)C3CCN(Cc4ccccc4C#N)CC3)sc2-c2ccc(OC)cc2)cc1
InChIKey: FMOLUPOSSFZALR-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTCI as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by Ellman assay
Measurement: IC50 = 3580 nM (pChEMBL 5.449999809265137)
Descriptors: MW 538.67, ALogP 6.22, HBA 7, HBD 1, PSA 87.48, QED 0.29
Compound (SMILES): CNc1ncnc(Nc2[nH]c3c(-c4ccccc4)c(-c4ccccc4)nn3c(=O)c2-c2ccc(OC)cc2)n1
InChIKey: BYSOZLPJBPNBRC-UHFFFAOYSA-N
Target: S-adenosylmethionine synthase isoform type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31153
Assay: Inhibition of recombinant His6-tagged MAT2A (unknown origin) expressed in SF9 insect cells using L-Met as substrate preincubated for 60 mins followed by substrate and ATP addition and measured after 60 mins by spectrophotometric analysis
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 516.57, ALogP 5, HBA 9, HBD 3, PSA 122.12, QED 0.27
Compound (SMILES): CN(c1cccc(-c2ccc3c(NC(=O)C4CC4)n[nH]c3c2)c1)S(C)(=O)=O
InChIKey: XMMNMFOLOBSNMO-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of AAK1 (unknown origin) using Fos-Nfluc, Cfluc-kinase and rabbit reticulate lysate system after 1 hr by split luciferase assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 384.46, ALogP 2.97, HBA 4, HBD 2, PSA 95.16, QED 0.71
Compound (SMILES): CC(=O)Nc1cncc(-c2cc(C(=O)c3c(Cl)cccc3Cl)c[nH]2)c1
InChIKey: BLUGZEWNYPNWEF-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Inhibition of human DOTL1 (2 to 416 residues)-mediated methylation of nucleosome preincubated for 30 mins followed by addition of S-[methyl-3H-] adenosyl-L-methionine and nucleosome measured after 180 mins by scintillation proximity assay
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 374.23, ALogP 4.57, HBA 3, HBD 2, PSA 74.85, QED 0.66
Compound (SMILES): CN[C@H]1CC[C@H](CS(=O)(=O)N2CCC(NC(=O)c3cc(C4CC4)on3)CC2)CC1
InChIKey: XHQSCCOKDDGBND-KOMQPUFPSA-N
Target: Histone-lysine N-methyltransferase SMYD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H7B4
Assay: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 424.57, ALogP 1.85, HBA 6, HBD 2, PSA 104.54, QED 0.69
Compound (SMILES): CC(=O)Nc1sc2c(c1-c1nc3ccccc3s1)CCNC2C
InChIKey: FRURHNMAXCCCIB-UHFFFAOYSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc assessed as reduction in c-Myc/Max/Ebox DNA complex formation using pre-formed complex of c-Myc and biotinylated DNA containing single Ebox-sequence followed by compound addition and further addition of his6-tagged c-Max and incubated for 2 hrs by AlphaScreen assay
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 343.48, ALogP 4.19, HBA 5, HBD 2, PSA 54.02, QED 0.73
Compound (SMILES): Cc1nc2cc(C)c3c(N)c(C(=O)N[C@H]4CCc5ccccc54)sc3n2n1
InChIKey: OPFRWAYTYJICGP-AWEZNQCLSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulation of human M4 AchR expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 377.47, ALogP 3.56, HBA 6, HBD 2, PSA 85.31, QED 0.56
Compound (SMILES): CCCCc1ccc(OCC(=O)N(CC(=O)Nc2ccnnc2)C(C)C)cc1
InChIKey: ZFUGTCXOROLCPU-UHFFFAOYSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of 20S immunoproteasome LMP7 (unknown origin) using Ac-ANW-AMC as substrate preincubated for 15 mins followed by substrate addition by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.48, ALogP 3.07, HBA 5, HBD 1, PSA 84.42, QED 0.68
Compound (SMILES): Cc1c(N2CCN(Cc3ccon3)CC2)c(=O)n(C[C@H](N)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
InChIKey: QHROKEFOYNPNBZ-VWLOTQADSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity against human GnRH receptor expressed in HEK293 cells co-transfected with pGL4-NFAT promoter AP1-luc assessed as inhibition of 20 nM GnRH-induced NFAT activation pre-incubated for 1 hr before GnRH stimulation and measured after 6 hrs by luciferase reporter gene assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 586.59, ALogP 3.53, HBA 9, HBD 1, PSA 102.53, QED 0.32
Compound (SMILES): O=C(NCc1ncccc1F)c1cnc(CCNCCc2nc3ccccc3[nH]2)o1
InChIKey: IAAKEJBSOKSMGL-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as induction of ferroportin internalization and degradation incubated overnight by FACS assay
Measurement: EC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 408.44, ALogP 2.39, HBA 6, HBD 3, PSA 108.73, QED 0.37
Compound (SMILES): O=C(NCc1ccc(Cl)s1)c1ccc(NC(=O)c2cc3ccc(Cl)cc3s2)c(C(=O)O)c1
InChIKey: OIPIOICGQPNOCL-UHFFFAOYSA-N
Target: Neurotrypsin (SINGLE PROTEIN), Homo sapiens
UniProt: P56730
Assay: Inhibition of human neurotrypsin
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 505.4, ALogP 6.15, HBA 5, HBD 3, PSA 95.5, QED 0.29
Compound (SMILES): COc1c(C#N)ccc2[nH]c(-c3cn4c(n3)C(c3ccccc3Cl)CC(C)(O)C4)cc12
InChIKey: FVGUKPOYBXSMGS-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Inhibition of gamma secretase in human SKNBE2 cells expressing human APP695 assessed as increase in Abeta38 levels incubated for 18 hrs by sandwich ELISA
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 432.91, ALogP 4.85, HBA 5, HBD 2, PSA 86.86, QED 0.48
Compound (SMILES): O=C(NCCCCc1ccccc1)n1c(=O)oc2cc(N3CCOCC3)ccc21
InChIKey: CQJVVHKLKHJTSE-UHFFFAOYSA-N
Target: Acid ceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q13510
Assay: Inhibition of human acid ceramidase expressed in HEK293 cells using Rbm14-12 as substrate preincubated for 10 mins followed by substrate addition and measured after 3 hrs by fluorescence assay
Measurement: IC50 = 192 nM (pChEMBL 6.71999979019165)
Descriptors: MW 395.46, ALogP 3.01, HBA 6, HBD 1, PSA 76.71, QED 0.65
Compound (SMILES): CC(=O)NCCCC[C@H](NC(=O)C(C)(C)NC(=O)[C@H](Cc1cccc2ccccc12)NC(=O)[C@H](Cc1ccc(OCCN)cc1)NC(=O)[C@@H]1CSCC[C@H](NC(C)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCC(N)=O)C(=O)N1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O
InChIKey: GUFKDADBMGEWOW-FYFHZMENSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 binding to human interleukin-23 receptor incubated for 2 hrs by competitive binding ELISA
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1618.84
Compound (SMILES): COc1cc(S(N)(=O)=O)ccc1-c1noc(-c2ccccc2)n1
InChIKey: SGHGFZFSHPTXEN-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as reduction in CO2 hydration after 15 mins by phenol red staining-based stopped flow assay
Measurement: Ki = 459.3 nM (pChEMBL 6.340000152587891)
Descriptors: MW 331.35, ALogP 2.06, HBA 6, HBD 1, PSA 108.31, QED 0.78
Compound (SMILES): CC(C)(C)NC(=O)C(c1c(C(=O)O)[nH]c2cc(Cl)ccc12)N(C=O)Cc1ccc(OCCc2ccccc2)cc1
InChIKey: JVSRFYKFOWRYEA-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Displacement of 5'FAM-LTFEHYWAQLTS from human recombinant N-terminal domain of MDM2 (1 to 118 residues) expressed in Escherichia coli BL21 (DE3) cells measured after 15 mins by fluorescence polarization assay
Measurement: Ki = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 562.07, ALogP 5.76, HBA 4, HBD 3, PSA 111.73, QED 0.2
Compound (SMILES): O=C(NO)c1ncc(CS(=O)(=O)c2ccccc2)c(CO)c1O
InChIKey: FPUFEHAERIWFGW-UHFFFAOYSA-N
Target: Nonstructural protein 5 (SINGLE PROTEIN), Dengue virus
UniProt: V5TFZ2
Assay: Inhibition of recombinant N-terminal His6-tagged DENV2 NGC NS5 RNA dependent RNA polymerase
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 338.34, ALogP 0.37, HBA 7, HBD 4, PSA 136.82, QED 0.46
Compound (SMILES): N=C(N)NCCCC(NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)CNC(=O)CN)c1ccc2ccccc2c1)C(N)=O
InChIKey: HBYGNPLLBYLDKB-VYCSYZTNSA-N
Target: Genome polyprotein (SINGLE PROTEIN), West Nile virus
UniProt: P06935
Assay: Inhibition of West Nile virus NS2B-NS3 protease preincubated for 10 mins followed by Np-KKR-pNA addition and measured every 5 secs for 2 mins by fluorescence method
Measurement: Ki = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 864.03, ALogP -3.02, HBA 12, HBD 14, PSA 386.33, QED 0.02
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc3[nH]ncc3c2)c2ncc(-c3ccccc3)cc21
InChIKey: XOHKHMXVNYJHEX-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of recombinant human ACC1 expressed in Sf9 cells using acetyl Co-A as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by RapidFire-Mass spectrometry
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 395.47, ALogP 5.41, HBA 4, HBD 2, PSA 75.6, QED 0.43
Compound (SMILES): CCN(Cc1cccnc1)C(=O)Cn1c2ccccc2c2ccccc21
InChIKey: NTRDQWAVLNQVTK-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Displacement of [3H]PK11195 from wild-type human TSPO expressed in HEK293 cell membranes after 90 mins by scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 343.43, ALogP 4.24, HBA 3, HBD 0, PSA 38.13, QED 0.54
Compound (SMILES): Cn1ncc(Br)c1-c1ccc(C(=O)N[C@@H]2CNCC[C@H]2c2ccc(F)c(F)c2)cn1
InChIKey: AWJKEZBLMFXELX-IFXJQAMLSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of human Akt1 expressed in Escherichia coli using STK Substrate 2-biotin as substrate incubated for 1 hr by HTRF assay
Measurement: IC50 = 269.8 nM (pChEMBL 6.570000171661377)
Descriptors: MW 476.33, ALogP 3.4, HBA 5, HBD 2, PSA 71.84, QED 0.61
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CO)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(OCCN)cc1)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@](C)(CCCCN)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: NDMRDFBXAMTBFK-HTHYHTMMSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 binding to human interleukin-23 receptor incubated for 2 hrs by competitive binding ELISA
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 1669.95