lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C1NCc2nc(-c3c(F)cccc3F)cc(Nc3ccc(N4CCC(F)(F)CC4)cn3)c21
InChIKey: FTOZFPJBOXLHFW-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Tyk2 & JAK2 Caliper Assay: The caliper machine employs an off chip mobility shift assay to detect phosphorylated peptide substrates from kinase assays, using microfluidics technology. The assays are carried out at ATP concentration equivalent to the ATP Km, and at 1 mM ATP. Compounds are serially diluted in DMSO then further diluted in assay buffer (25 mM HEPES, pH 7.5, 0.01% Brij-35, 0.01% Triton, 0.5 mM EGTA). 5 ul of diluted compound was added into wells first, then 10 ul of enzyme mix was added into wells, followed by 10 uL of substrate mix (peptide and ATP in 10 mM MgCl2) to start reaction. Reaction was incubated at 28° C. for 25 min and then added 25 ul stop buffer (100 mM HEPES, 0.015% Brij-35, 50 mM EDTA), followed by reading with Caliper. JAK2 at 1 nM final concentration and TYK2 at 9.75 nM are from Carna, and substrates used are ATP at 20 and 16 uM, respectively. JAK2 assay uses peptide 22 and TYK2 uses peptide 30 (Caliper), each at 3 uM.
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 457.43, ALogP 4.64, HBA 5, HBD 2, PSA 70.15, QED 0.56
Compound (SMILES): CC(C)(O)c1cc(C(F)(F)F)ncc1-c1ccc(C2(C(=O)Nc3ccc(F)cc3)COC2)cc1
InChIKey: ICJRFPZBMMQAPU-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 8643 nM (pChEMBL 5.059999942779541)
Descriptors: MW 474.45, ALogP 5.04, HBA 4, HBD 2, PSA 71.45, QED 0.51
Compound (SMILES): Cc1nnc(C2CCN(c3ccc(Nc4nccc(-c5ccc(C(=O)NCC#N)cc5)n4)cc3)CC2)o1
InChIKey: YAPGULIZAFUFTB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Assay: NCEs were screened using in vitro JAK (1, 2 and 3) kinase assay on ADP Glo platform (Promega). Fixed amount of recombinant purified human JAK (25 ng of JAK1 and 10 ng of JAK2 and JAK3 per reaction, from Life Technologies Ltd) were incubated with increasing concentration of NCEs in 1× kinase reaction buffer (40 mM Tris-Cl, pH7.5, 20 mM MgCl2, 0.1 mg/ml BSA and 50 μM DTT). Enzymatic reaction was initiated by adding a substrate cocktail containing 50 μM of ATP (final concentration) and 5 μg for JAK1 and 2.5 μg for JAK2 and JAK3 of polyGln4Tyr1 (Signal Chem) in total 25 μl of reaction in 96 well plate. The reaction was incubated at room temperature for 1 hr.After 1 hr of incubation equal volume (25 μl per reaction) of ADP Glo was added and incubated at room temperature for 40 min.This was followed by addition of kinase detection reagent (50 μl per reaction) and incubation at room temperature for 30 min. Finally, plate was read for luminescence at an integration time of 500 millisecond per well.
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 494.56, ALogP 4.22, HBA 9, HBD 2, PSA 132.86, QED 0.36
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cc(C)c3cnc(Nc4ccc(N5CCN(CCCCCCCCNC(=O)CC67CC8CC(CC(C8)C6)C7)CC5)cc4OC)nc32)c1
InChIKey: BXAWAIYNEJHEJJ-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Induction of AKT3 degradation in human NCI-H1975 cells assessed as reduction in AKT3 protein level incubated for 24 hrs under serum free medium by Western blot analysis
Measurement: EC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 815.08, ALogP 8.15, HBA 10, HBD 3, PSA 133.72, QED 0.07
Compound (SMILES): CC(=O)c1cc(C(=O)Nc2cc(CO)cc(-c3cnn(C)c3)c2F)c2cc(O)ccn12
InChIKey: VLSSRXAUNKQKKE-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Inhibition of C-terminal biotinylated tetra-acetylated histone peptide H4 binding to His6-fused human CBP bromodomain (R1081 to G1197 residues) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 422.42, ALogP 3.13, HBA 7, HBD 3, PSA 108.86, QED 0.43
Compound (SMILES): O=C(NCCO)c1ccc2ccc(C(=O)c3ccccc3)c-2cc1
InChIKey: GKOFSDREONKYIS-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 319.36, ALogP 2.74, HBA 3, HBD 2, PSA 66.4, QED 0.71
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1cc(OC)ncc1C#N
InChIKey: AXDZSJQRHYIUDG-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Determination of the % Inhibition for FXIa: FXIa inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Sturzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human FXIa (Enzyme Research Laboratories) was incubated at 25° C. with the fluorogenic substrate Z-Gly-Pro-Arg-AFC and 40 μM of the test compound (or alternatively at various concentrations of the test compound in order to determine IC50). Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 498.54, ALogP 2.49, HBA 9, HBD 1, PSA 124.06, QED 0.36
Compound (SMILES): Cc1cc2ncccc2cc1Nc1ncc2c(n1)n(C1CCNCC1)c(=O)n2C
InChIKey: BUAYUJMPGUYFPI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by electrophysiological assay based automated patch clamp method
Measurement: IC50 > 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 389.46, ALogP 2.65, HBA 8, HBD 2, PSA 89.66, QED 0.56
Compound (SMILES): O=C(NC1CCN(C(=O)C(F)(F)F)CC1)NC12CC3CC(Cl)(CC(C1)c1ccccc13)C2
InChIKey: LJRCVVXGTSHEFM-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human recombinant CYP2C19 using 3-cyano-7-ethoxycoumarin as a substrate preincubated for 5 mins followed by substrate addition by fluorescence plate reader analysis
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 469.94, ALogP 4.41, HBA 2, HBD 2, PSA 61.44, QED 0.63
Compound (SMILES): C#Cc1ccc2c(c1)C(c1ccccc1F)=NCC(=O)N2C
InChIKey: IRYAGFJMRZLHGE-UHFFFAOYSA-N
Target: GABA A receptor alpha-3/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P34903
Assay: Displacement of [3H]flunitrazepam from human recombinant alpha3beta2gamma2 GABAA receptor expressed in HEK cell membrane by competitive radioligand binding assay
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 292.31, ALogP 2.62, HBA 2, HBD 0, PSA 32.67, QED 0.74
Compound (SMILES): O=c1cc(C2CC2)[nH]c(=O)[nH]1
InChIKey: ABHXYFPEQCXJJJ-UHFFFAOYSA-N
Target: YTH domain-containing family protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BYJ9
Assay: Binding affinity to GST-tagged YTHDF1 m6A-reader domain (unknown origin) using RRACH-containing methylated oligoRNA incubated for 3 hrs by HTRF assay
Measurement: IC50 = 379000 nM (pChEMBL 3.4200000762939453)
Descriptors: MW 152.15, ALogP -0.06, HBA 2, HBD 2, PSA 65.72, QED 0.59
Compound (SMILES): O=C(O)c1ccc2noc(-c3ccc(Oc4ncc(Cl)cc4Cl)cc3)c2c1
InChIKey: BRJNOKMYWPQSOG-UHFFFAOYSA-N
Target: Inositol hexakisphosphate kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PC2
Assay: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay
Measurement: IC50 = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 401.21, ALogP 5.69, HBA 5, HBD 1, PSA 85.45, QED 0.47
Compound (SMILES): NS(=O)(=O)c1ccc(N/C=C/C(=O)c2ccc(F)cc2)cc1
InChIKey: JKAUEJKKIQTCJJ-MDZDMXLPSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 320.35, ALogP 2.28, HBA 4, HBD 2, PSA 89.26, QED 0.65
Compound (SMILES): O=C(Cc1ccccc1)N[C@@H](C[C@@H]1COc2c(Cl)cccc21)B(O)O
InChIKey: NVIDCSSIOTZCLS-CJNGLKHVSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human A549 cells using Suc-LLVY-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 6099 nM (pChEMBL 5.210000038146973)
Descriptors: MW 359.62
Compound (SMILES): O=C(NO)c1ccc(/C=N/NC(=O)c2cc(N3CCOCC3)nc(-c3cccc(O)c3)n2)cc1
InChIKey: QIXCKSONTDMMTH-ZVHZXABRSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 462.47, ALogP 1.57, HBA 9, HBD 4, PSA 149.27, QED 0.24
Compound (SMILES): CCn1c(=O)n(CCc2ccc(OC)cc2)c(=O)c2[nH]c(SSc3nc4c([nH]3)c(=O)n(CCc3ccc(OC)cc3)c(=O)n4CC)nc21
InChIKey: QSPDOXSSJZUJOC-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of human N-terminal His6 tagged SIRT1 (183-505-(GGGS)2-641-665 residues) expressed in Escherichia coli BL21 cells
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 690.81, ALogP 3.43, HBA 14, HBD 2, PSA 163.82, QED 0.17
Compound (SMILES): COc1cc(OC)c(NC(=O)Cn2c(=O)n(CC(=O)Nc3ccc(O)cc3)c(=O)c3ccccc32)cc1Cl
InChIKey: MQJIBWCCRRCRNJ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Displacement of [32P]S1P from human recombinant S1PR3 incubated for 60 mins by competitive binding assay based scintillation counter
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 538.94, ALogP 2.82, HBA 9, HBD 3, PSA 140.89, QED 0.29
Compound (SMILES): N#Cc1c(N)ncnc1N1CC(F)(F)C[C@H]1c1nc2cccc(Cl)c2c(=O)n1-c1ccccc1
InChIKey: DTDJOUMUGFQFTJ-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 479.88, ALogP 3.87, HBA 8, HBD 1, PSA 113.72, QED 0.47
Compound (SMILES): CCc1nc(NC(=O)NC(=O)C(C)(C)C)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: URZFDLKDKFIRGI-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of N-terminal GST-tagged PDGFRalpha (unknown origin) (550 to 1089 residues) measured by spectrophotometric analysis
Measurement: IC50 > 3300 nM (pChEMBL 5.480999946594238)
Descriptors: MW 422.49, ALogP 3.93, HBA 7, HBD 2, PSA 111.03, QED 0.64
Compound (SMILES): CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc3c(NC(=O)CN(C)C)n[nH]c3c2)ncc1Cl
InChIKey: FFMOPKLRQAOMEL-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK G1202R mutant (unknown origin) incubated for 1 hr and measured by mobility shift assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 543.05, ALogP 4.18, HBA 9, HBD 4, PSA 145, QED 0.24
Compound (SMILES): CC(C)(C)c1ccc(-c2cn(-c3ccc(CN4CC(C(=O)[O-])C4)cc3)nn2)cc1.[Na+]
InChIKey: LSVQKOKEDVFVCV-UHFFFAOYSA-M
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 390.49, ALogP 3.75, HBA 5, HBD 1, PSA 71.25, QED 0.72
Compound (SMILES): Cl.Clc1ccc2[nH]c3c(c2c1)CCNC3c1cncnc1
InChIKey: MTOLIKLMRZKDQV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 284.75, ALogP 2.85, HBA 3, HBD 2, PSA 53.6, QED 0.72
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]2CSSC[C@H](NC(=O)[C@H](CCC(N)=O)NC2=O)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: SZCLBSHELXLOEC-OXOGCWQMSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells by Topcount beta counter analysis
Measurement: Ki = 97.72 nM (pChEMBL 7.010000228881836)
Descriptors: MW 2969.59
Compound (SMILES): Fc1ccc2c(Cc3nncn3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: IKILUYGGNRRSKR-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 717.3 nM (pChEMBL 6.139999866485596)
Descriptors: MW 324.36, ALogP 2.85, HBA 4, HBD 2, PSA 75.18, QED 0.57
Compound (SMILES): COc1cc(-c2cc3c(N[C@H]4CCN(C(=O)C5CCC5)C4)ncnc3s2)cnc1OC
InChIKey: XIPMIAQFOCCQEU-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate measured after 1 hr in presence of ATP by ADP-glo luminescence assay
Measurement: IC50 = 1365.5 nM (pChEMBL 5.869999885559082)
Descriptors: MW 439.54, ALogP 3.58, HBA 8, HBD 1, PSA 89.47, QED 0.63
Compound (SMILES): COC(=O)[C@@H]1CCCN1C(=O)[C@@H](Cc1ccc(O)cc1)N(C)C(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)N(C)C(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C
InChIKey: AKZOFLGCSPMBPS-YAQNKXQCSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) using Mca-Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Arg-Lys(Dnp)-Arg-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay
Measurement: IC50 = 775 nM (pChEMBL 6.110000133514404)
Descriptors: MW 1057.26
Compound (SMILES): COc1ccc(C2NCCc3c2[nH]c2ccc(F)cc32)c(OC)c1.Cl
InChIKey: UZUPBDVDHKDGQH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 159 nM (pChEMBL 6.800000190734863)
Descriptors: MW 326.37, ALogP 3.56, HBA 3, HBD 2, PSA 46.28, QED 0.77
Compound (SMILES): Cc1nc(-c2cnc(NC3CCCC3)[nH]c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: XUJIISUKTLKCLK-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of N-terminal GST-tagged PDGFRalpha (unknown origin) (550 to 1089 residues) measured by spectrophotometric analysis
Measurement: IC50 = 517 nM (pChEMBL 6.289999961853027)
Descriptors: MW 443.51, ALogP 4.08, HBA 8, HBD 2, PSA 110.61, QED 0.46
Compound (SMILES): c1cc(CNc2ncc(-c3ccncc3)c3nncn23)c2c(c1)OCC2
InChIKey: ADDFHWGEAOKELS-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate incubated for 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 344.38, ALogP 2.73, HBA 7, HBD 1, PSA 77.23, QED 0.61
Compound (SMILES): Cc1cc(Oc2ccc(Cn3nc4ccc(Cl)cc4c3C(=O)NS(=O)(=O)c3ccc([N+](=O)[O-])c(NCc4ccncc4)c3)cc2)cc(C)c1Cl
InChIKey: WQQYJBQVLMERIB-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of BCL-xL (unknown origin) by fluorescence polarization competition assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 731.62, ALogP 7.83, HBA 10, HBD 2, PSA 158.35, QED 0.1
Compound (SMILES): Cc1c(C#N)cccc1[C@@H](C)Nc1nnc(C)c2cnc(N3CCOCC3)cc12
InChIKey: ILPWEAHQRAWJIU-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of Labeled Tracer Ligand: Table 22: This Example illustrates that exemplary compounds of the present invention bind to SOS1 and prevent a labeled tracer ligand from occupying the S0S1 binding site. The ability of a compound of Formula (I) to bind to SOS1 was measured using a HTRF displacement assay. A recombinant human SOS1 polypeptide (corresponding to amino acids 560-1049, expressed in E. Coli with N-terminal His-TEV-AviTag-SOS1 (MW=59.4 kDa) and lanthanide labeled streptavidin (CisBio) was incubated with an exemplary compound of Formula (I) (in a DMSO stock solution) in buffer (25 mM HEPES pH 7.5, 25 mM NaCl, 1 mM DTT, 0.01% Brij 35, 0.02% BSA, 0.1% DMSO). After a 10-15 minute incubation at room temperature, a solution comprised of a custom-made Cy5 labelled tracer and MAb Anti-6HIS Tb cryptate Gold (Cisbio 61HI2TLA) in buffer was added to the solution containing the SOS1 polypeptide and exemplary compound of Formula (I). After a 1-hour incubation at room temperature, the HTRF signal was measured using Clairostar plate reader (BMG Labtech) according to the manufacturer's instructions. Excitation filter EX-TR was used, and emission 1 was detected at 650-610 nm and emission 2 detected at 620-610 nm. The HTRF ratio was calculated using the formula: [emission 1/emission 2]*10000.
Measurement: Ki = 1.78 nM (pChEMBL 8.75)
Descriptors: MW 388.48, ALogP 3.52, HBA 7, HBD 1, PSA 86.96, QED 0.73
Compound (SMILES): Cc1nc([C@@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4cc(F)c(F)c(F)c4)nn3)[C@H]2O)n(-c2ccc(Cl)c(Cl)c2)n1
InChIKey: RMQLNSGIQUYFMI-WHCFWRGISA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Biological Assay: The Gal-3 assays were performed in 384 white Opti plates in three replicates at room temperature with gentle shaking at 250-300 rpmFrom the original stocks, 2.525× working stock concentrations of His-tagged recombinant human Gal-3 (hGal-3) and that of B-ASF were prepared. From the working stock, 20 μl of hGal-3 (15 nM) and 20 μl B-ASF (15 nM) were added to the plates. In Negative Control, only hGal-3 was added. A concentration range of 50× working stocks were prepared for the compounds in 100% DMSO. Aliquots of 1 uL of the compounds were added to the wells and pre-incubated with 20 μl hGal-3 per well for 30 minutes Then 20 μl B-ASF wereadded and incubated for another 1 hour. To detect the signal, 5 μL (final conc. of 1.0 nM) terbium labelled Anti-His antibody was added and incubated for 30 min followed by adding 5 μL (final conc. of 20 nM) Streptavidin d2 and incubation for another 1 hour. The assay signal was detected using HTRF screen protocol (Excitation wavelength=340 nm, emission wavelength=615 nm/665 nm) on Envision 2104 Multilabel Reader. Data analysed using Toolset and Curve Master. Results are reported in the experimental section (IC50 in μM).
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 571.34, ALogP 2.95, HBA 10, HBD 3, PSA 131.34, QED 0.31
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(N)=O)C(C)C
InChIKey: DZZXXJLXJQWTGY-WFXMLNOXSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of human recombinant MMP-1 (Phe20 to Asn469 residue) using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 658.1, ALogP 1.14, HBA 7, HBD 6, PSA 213.86, QED 0.15
Compound (SMILES): C=CC(=O)N[C@H]1CCCC[C@H]1Nc1n[nH]c2ccc(O[C@H](C)c3c(Cl)cncc3Cl)cc12
InChIKey: RJGCYKPVGXIOBM-CAYVGHNUSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown orgin) using Tyr 04 peptide as substrate incubated for 1 hr in presence of 5 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.39, ALogP 5.43, HBA 5, HBD 3, PSA 91.93, QED 0.4
Compound (SMILES): CCCCCCCCC[C@@]1(CO)NC[C@H](O)[C@H]1O
InChIKey: QUUYIUNMVCBKPD-MJBXVCDLSA-N
Target: Lysosomal alpha-glucosidase (SINGLE PROTEIN), Homo sapiens
UniProt: P10253
Assay: Inhibition of human lysosomal alpha glucosidase assessed as release of p-nitrophenol using p-nitrophenyl glycoside as substrate by spectrometric assay
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 259.39, ALogP 1.18, HBA 4, HBD 4, PSA 72.72, QED 0.47
Compound (SMILES): Cc1nc2cnc3ccc(-c4cc(Cl)c(O)c(Cl)c4)cc3c2n1[C@@H]1CCCN(C)C1
InChIKey: YFEGRGXPXAYBGQ-MRXNPFEDSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Kinase/Tyr 6 peptide as substrate incubated for 1 hrs in presence of ATP by fluorescence microplate reader analysis
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 441.36, ALogP 5.84, HBA 5, HBD 1, PSA 54.18, QED 0.42
Compound (SMILES): CCCC[Si](C)(C)c1cc(O)c2c(c1)OC(C)(C)c1ccc(CO)cc1-2
InChIKey: HHQQLOULHKYQJV-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at recombinant human CB1 receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin stimulation and measured after 15 mins by HTRF assay
Measurement: EC50 = 213.8 nM (pChEMBL 6.670000076293945)
Descriptors: MW 370.57
Compound (SMILES): Cc1cc(Oc2ccc(Cn3nc4ccc(Cl)cc4c3C(=O)NS(=O)(=O)c3ccc([N+](=O)[O-])c(NCc4ccn(C)n4)c3)cc2)cc(C)c1Cl
InChIKey: FKNJZFOOBQMIPB-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of BCL-xL (unknown origin) by fluorescence polarization competition assay
Measurement: Ki = 7410 nM (pChEMBL 5.130000114440918)
Descriptors: MW 734.62, ALogP 7.17, HBA 11, HBD 2, PSA 163.28, QED 0.1
Compound (SMILES): CCCCCCN1CCN(CCC(=O)Nc2nc3c(C)cccc3s2)CC1
InChIKey: OMCHHLIXQNKLTG-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membrane measured after 120 mins by scintillation counting method
Measurement: Ki = 238 nM (pChEMBL 6.619999885559082)
Descriptors: MW 388.58, ALogP 4.13, HBA 5, HBD 1, PSA 48.47, QED 0.66
Compound (SMILES): FC(F)(F)Oc1cccc(Cc2nnc(CCc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: FNTJYGUEEBOGIQ-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 14.9 nM (pChEMBL 7.829999923706055)
Descriptors: MW 494.52, ALogP 5.39, HBA 5, HBD 2, PSA 84.41, QED 0.27
Compound (SMILES): O=C(NO)c1ccc(CN2CCN(Cc3ccccc3)CC2)cc1
InChIKey: YUDJFSRXZHYHCF-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human HDAC4 using fluorescent peptide Boc-Lys(trifluoroacetyl)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorogenic assay
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 325.41, ALogP 2.12, HBA 4, HBD 2, PSA 55.81, QED 0.65
Compound (SMILES): C[C@@H](C(=O)Nc1ccc(OC2CCN(C(=O)CCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)CC2)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: PLYOHMQINGIYDN-MXPGEODHSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to CRBN (unknown origin) assessed as dissociation constant by Biolayer Interferometry assay
Measurement: Kd = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 891.01, ALogP 6.23, HBA 11, HBD 3, PSA 185.57, QED 0.08
Compound (SMILES): Cc1cc(N)nc(C#CCN2CC(F)(F)C2)c1
InChIKey: OJUWVNWEQOIPOJ-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Inhibition of human iNOS using L-arginine as substrate assessed as reduction in NO production in the presence of NADPH by NO-hemoglobin capture assay
Measurement: Ki = 11089 nM (pChEMBL 4.960000038146973)
Descriptors: MW 237.25, ALogP 1.27, HBA 3, HBD 1, PSA 42.15, QED 0.75
Compound (SMILES): Nc1cc(C(F)(F)F)c(-c2cc(N3CCOCC3)nc(N3CCOCC3)c2)cn1
InChIKey: PYIZPPLCBSHXDH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to human N-terminal GST-tagged mTOR assessed as phosphorylated 4EBP1 by TR-FRET assay
Measurement: IC50 > 9100 nM (pChEMBL 5.040999889373779)
Descriptors: MW 409.41, ALogP 2.42, HBA 7, HBD 1, PSA 76.74, QED 0.83
Compound (SMILES): Cn1cncc1C#Cc1ccc2[nH]c3c(c2c1)-c1nc(N)ncc1CC3
InChIKey: MVGXKKGABQCPAD-UHFFFAOYSA-N
Target: 1-phosphatidylinositol 3-phosphate 5-kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2I7
Assay: Inhibition of PIKFYVE in HEK293 cells by NanoBRET assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 340.39, ALogP 2.44, HBA 5, HBD 2, PSA 85.41, QED 0.48
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CCCC3)ccc12
InChIKey: KIMPACVVSQUMHL-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP15 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N3
Assay: Inhibition of human N-terminal 6His-tagged PARP15 (460 to 656 residues) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 260.29, ALogP 1.79, HBA 3, HBD 2, PSA 74.95, QED 0.88
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1ncc(C)c(OC)c1C
InChIKey: GQIPLMKRGZCNHM-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Determination of the IC50 for KLK1: KLK1 inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Sturzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human KLK1 (Callbiochem) was incubated at 25° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 501.59, ALogP 3.24, HBA 8, HBD 1, PSA 100.27, QED 0.36
Compound (SMILES): CCn1c(=O)c2[nH]c(SSc3nc4c([nH]3)c(=O)n(CC)c(=O)n4CC)nc2n(CC)c1=O
InChIKey: IMFVZYLIKDQVRH-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of human N-terminal His6 tagged SIRT1 (183-505-(GGGS)2-641-665 residues) expressed in Escherichia coli BL21 cells
Measurement: IC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 478.56, ALogP 0.96, HBA 12, HBD 2, PSA 145.36, QED 0.37
Compound (SMILES): O=C(NO)c1ccc(CN(C2CC2)S(=O)(=O)c2cc(F)c(F)c(F)c2F)cc1
InChIKey: HYEWQOQZANKATO-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in insect Sf9 cells by EMSA analysis
Measurement: IC50 = 334 nM (pChEMBL 6.480000019073486)
Descriptors: MW 418.37, ALogP 2.72, HBA 4, HBD 2, PSA 86.71, QED 0.25
Compound (SMILES): CC(C)(C#N)C(=O)N1CC2(CCC(c3cccc4nc(NC(=O)C5CC5)nn34)CC2)C1
InChIKey: KPBHPWFZPIPDGP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 9669 nM (pChEMBL 5.010000228881836)
Descriptors: MW 420.52, ALogP 3.11, HBA 6, HBD 1, PSA 103.39, QED 0.82
Compound (SMILES): N[C@@H]1CCCC12CCN(c1cnc3c(-c4cccc(Cl)c4Cl)n[nH]c3n1)CC2
InChIKey: AKZKUGUQZMUCJC-CQSZACIVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 417.34, ALogP 4.42, HBA 5, HBD 2, PSA 83.72, QED 0.64
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(OC)c1OC
InChIKey: PSFFAYDLGJLXAU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) in absence of NADPH
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.43, ALogP 3.73, HBA 9, HBD 3, PSA 123.53, QED 0.41
Compound (SMILES): CCCCN(Cc1ccc(C(=O)NNCC)cc1)C(=O)Nc1ccccc1
InChIKey: SMSQNJXFQKRJOS-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant HDAC3 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 = 191 nM (pChEMBL 6.71999979019165)
Descriptors: MW 368.48, ALogP 3.78, HBA 3, HBD 3, PSA 73.47, QED 0.59
Compound (SMILES): COc1ccc2nc(-c3ccccc3)cc(C(=O)Nc3ccc4c(c3)c(S(N)(=O)=O)cn4C)c2c1
InChIKey: YTFKSJGHUQOYOQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 by stopped flow CO2 assay
Measurement: Ki = 45000 nM (pChEMBL 4.349999904632568)
Descriptors: MW 486.55, ALogP 4.3, HBA 6, HBD 2, PSA 116.31, QED 0.38
Compound (SMILES): Cc1nn(-c2ccc(C#N)c(Cl)c2)c(C)c1Oc1ccc(C(=O)NC(C)(C)C)cn1
InChIKey: NCUHRUDZAOKECU-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at wild-type Androgen receptor (unknown origin) expressed in African green monkey COS-7 cells measured as gene transcription level
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 423.9, ALogP 4.73, HBA 6, HBD 1, PSA 92.83, QED 0.65
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(-c5ccc(C(=O)N6CCOCC6)cc5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: USBWBRLHRGYCPG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal GST-tagged FGFR3 (436 to 806 residues) expressed in baculovirus expression system using IGF-1Rtide peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hrs in the presence of ATP by ADP-Glo reagent based luminescence assay
Measurement: IC50 = 46.78 nM (pChEMBL 7.329999923706055)
Descriptors: MW 537.62, ALogP 4.89, HBA 6, HBD 2, PSA 105.36, QED 0.29
Compound (SMILES): CC(C)Oc1ccc(C2CC(c3ccc(CN4CCC(C(=O)[O-])CC4)cc3)=NO2)cc1Cl.[Na+]
InChIKey: KUXQZKAGCJJXDZ-UHFFFAOYSA-M
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.97, ALogP 5.29, HBA 5, HBD 1, PSA 71.36, QED 0.61
Compound (SMILES): N#Cc1ccc2c(c1)C[C@H](CO)N[C@@H]2c1cc(F)cc(Cl)c1
InChIKey: UOCQJHUNCIRIPU-NVXWUHKLSA-N
Target: Transient receptor potential cation channel subfamily M member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TD43
Assay: Agonist activity at human TRPM4 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit by measuring membrane potential by FLIPR assay
Measurement: EC50 = 11481.54 nM (pChEMBL 4.940000057220459)
Descriptors: MW 316.76, ALogP 2.95, HBA 3, HBD 2, PSA 56.05, QED 0.9
Compound (SMILES): CC(C)(C)NCC(=O)N1CCc2cc(NCc3ccc(F)cc3)ccc21
InChIKey: LEFPDFZTPWRJEV-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of human recombinant sEH assessed as reduction in 6-methoxynaphthaldehyde formation using PHOME as substrate preincubated for 1 min followed by substrate addition and measured after 60 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 355.46, ALogP 3.72, HBA 3, HBD 2, PSA 44.37, QED 0.86
Compound (SMILES): O=C(NO)c1cccc(CN(C2CC2)S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)c1
InChIKey: QPBAKYKWDPVPBO-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in insect Sf9 cells by EMSA analysis
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 436.36, ALogP 2.85, HBA 4, HBD 2, PSA 86.71, QED 0.24
Compound (SMILES): Fc1c(-c2cccc3cccc(Cl)c23)ncc2c(N3CC4CCC(C3)N4)nc(OCC34CCCN3CCC4)nc12
InChIKey: FAKQXUSMRNQDHM-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: KRas G12D Binding Assay: Table 2: The ability of a compound to bind to KRAS G12D was measured using a TR-FRET displacement assay. Biotinylated GDP-loaded recombinant human KRAS G12D (corresponding to amino acids 1:169, produced at Array BioPharma) was incubated with a custom-made Cy5 labelled tracer, europium labelled streptavidin and compound (2% DMSO final) in buffer (50 mM HEPES [pH 7.5], 5mM MgCl2, 0.005% Tween-20 & 1 mM DTT). After a 60 minute incubation at 22° C., the reaction was measured using a PerkinElmer EnVision multimode plate reader via TR-FRET dual wavelength detection, and the percent of control (POC) calculated using a ratiometric emission factor. 100 POC is determined using no test compound and 0 POC is determined using a concentration of control compound that completely inhibits binding of the tracer to KRAS. The POC values were fit to a 4-parameter logistic curve and the IC50 value was determined as the concentration where the curve crosses 50 POC.
Measurement: IC50 = 21.1 nM (pChEMBL 7.679999828338623)
Descriptors: MW 559.09, ALogP 5.59, HBA 7, HBD 1, PSA 66.41, QED 0.34
Compound (SMILES): O=C(Nc1ccc(F)cc1)C1(c2ccc(-c3cnc(C(F)(F)F)cc3CO)cc2)COC1
InChIKey: KTZHBUHZJXHRMG-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 6302 nM (pChEMBL 5.199999809265137)
Descriptors: MW 446.4, ALogP 4.31, HBA 4, HBD 2, PSA 71.45, QED 0.57
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4cncc(OC)c4)c(C)c3c2)CC1
InChIKey: YMCRZNLISMOPNW-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonist activity at ODN2006 stimulated human TRL9 overexpressed in HEK293 cells assessed as inhibition of NF kappa B/Ap-1 activation preincubated with compound for 30 mins followed by ODN2006 stimulation measured after 22 hrs by SEAP reporter assay
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 378.52, ALogP 3.95, HBA 4, HBD 2, PSA 53.18, QED 0.68
Compound (SMILES): NC(=S)c1ccc(C(=O)OCCCCN2CCC(O)(c3ccc(Cl)cc3)CC2)cc1
InChIKey: IHAPRJBOWKJZEK-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]-DAMGO from Sprague-Dawley rat brain membrane mu opioid receptor incubated for 45 mins by liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 447, ALogP 3.89, HBA 5, HBD 2, PSA 75.79, QED 0.36
Compound (SMILES): CCCCN1CCN(CCC(=O)Nc2nc3c(C)cccc3s2)CC1
InChIKey: AXNBPJBIFWNNOJ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membrane measured after 120 mins by scintillation counting method
Measurement: Ki = 204 nM (pChEMBL 6.690000057220459)
Descriptors: MW 360.53, ALogP 3.35, HBA 5, HBD 1, PSA 48.47, QED 0.82
Compound (SMILES): Cc1nc(N)sc1-c1ccc(N/C(N)=N/C(=O)NCC(C)CCCc2ccccc2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RANHYVDDWVKRSF-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Ki = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 450.61, ALogP 4.8, HBA 4, HBD 4, PSA 118.42, QED 0.29
Compound (SMILES): Nc1nsc(-c2ccccc2)n1
InChIKey: WOZDQVLZCXNJPY-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Binding affinity to human wild type adenosine A2B receptor expressed in Expi293F cells assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 107700 nM (pChEMBL 3.9700000286102295)
Descriptors: MW 177.23, ALogP 1.79, HBA 4, HBD 1, PSA 51.8, QED 0.72
Compound (SMILES): CC(=O)Nc1cc(-c2ccc(OC[C@@H](N)CC(C)C)cc2)ccn1
InChIKey: NTUDYGKBBUSAQU-KRWDZBQOSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of full length human AAK1 expressed in HEK293F cells assessed as suppression of AP2 phosphorylation measured after 3 hrs by Western blot analysis based cellular assay
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 327.43, ALogP 3.46, HBA 4, HBD 2, PSA 77.24, QED 0.82
Compound (SMILES): O=C(NO)c1ccc(CN(C2CC2)S(=O)(=O)c2ccc(F)cc2)cc1
InChIKey: UVMTWKPGUFPPSP-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in insect Sf9 cells by EMSA analysis
Measurement: IC50 = 281 nM (pChEMBL 6.550000190734863)
Descriptors: MW 364.4, ALogP 2.3, HBA 4, HBD 2, PSA 86.71, QED 0.61
Compound (SMILES): CO[C@@H]1[C@H](O)CN(c2nccc(Nc3cc4c(C(C)C)ccc(N5C[C@H](CS(C)(=O)=O)[C@H]5C)c4cn3)n2)CC1(F)F
InChIKey: OXCAPCKBQKXXCL-JJMBJGOUSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGF stimulated EGFR L858R/T790M double mutant phosphorylation in human NCI-H1975 cells preincubated for 4 to 5 hrs followed by EGF stimulation for 10 mins by AlphaLISA method
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 590.7, ALogP 3.59, HBA 10, HBD 2, PSA 120.78, QED 0.4
Compound (SMILES): O=C(CCCCC/C=C\c1csc(Br)n1)NO
InChIKey: WLRUIAIHXAKVSH-XQRVVYSFSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length C-terminal FLAG-tagged human recombinant HDAC6 expressed inSf9 insect cells
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 319.22, ALogP 3.37, HBA 4, HBD 2, PSA 62.22, QED 0.46
Compound (SMILES): Cc1ccccc1N(C)C(=O)c1csc(-c2ccc(O)cc2)n1
InChIKey: MQCZVACSHKSREX-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Inhibition of human placental microsomal fraction 17beta-HS2 using [3H]-E2 as substrate in presence of NAD+ measured after 10 mins by HPLC method
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 324.41, ALogP 4.1, HBA 4, HBD 1, PSA 53.43, QED 0.79
Compound (SMILES): Nc1ncc(-c2ccc(CN3CCC(N4CCOCC4)CC3)cc2Cl)nc1C(=O)NC12CCC(O)(CC1)CC2
InChIKey: RIGIHWPKCOSNDD-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of wild type ALK2 (unknown origin) assessed as enzymatic activity by microfluidic mobility shift assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 555.12, ALogP 3.24, HBA 8, HBD 3, PSA 116.84, QED 0.5
Compound (SMILES): CC(C)NC(=O)c1cc(-c2ccccc2)[nH]n1
InChIKey: QXISDVIVHXPSKW-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Binding affinity to human wild type adenosine A2B receptor expressed in Expi293F cells assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 196000 nM (pChEMBL 3.7100000381469727)
Descriptors: MW 229.28, ALogP 2.21, HBA 2, HBD 2, PSA 57.78, QED 0.85
Compound (SMILES): CSc1ccc(CN(CCc2ccc(S(N)(=O)=O)cc2)C(=O)c2ccc(-c3cssc3=S)cc2)cc1
InChIKey: IKCSRQYZULOBDX-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 403.8 nM (pChEMBL 6.389999866485596)
Descriptors: MW 572.82, ALogP 6.46, HBA 7, HBD 1, PSA 80.47, QED 0.14
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)[nH]c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: UREZAFQRYNPCHA-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of N-terminal GST-tagged PDGFRalpha (unknown origin) (550 to 1089 residues) measured by spectrophotometric analysis
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 417.47, ALogP 3.55, HBA 8, HBD 2, PSA 110.61, QED 0.49
Compound (SMILES): Cc1cccc2sc(NC(=O)CCN3CCN(Cc4cc(F)ccc4F)CC3)nc12
InChIKey: KEEWNRZJJWZGPB-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membrane measured after 120 mins by scintillation counting method
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 430.52, ALogP 4.03, HBA 5, HBD 1, PSA 48.47, QED 0.64
Compound (SMILES): O=c1n(CCCCCCN2CCN(c3cccc(C(F)(F)F)c3)CC2)nc2ccccn12
InChIKey: HPCHKTZCFMXPGM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from 5-HT2AR (unknown origin) expressed in CHO-K1 cells by radioligand binding assay
Measurement: Ki = 291 nM (pChEMBL 6.539999961853027)
Descriptors: MW 447.51, ALogP 3.9, HBA 6, HBD 0, PSA 45.78, QED 0.49
Compound (SMILES): CN(C)S(=O)(=O)c1ccc(OCCNCC2COc3ccccc3O2)cc1.Cl
InChIKey: ZLVODBUBXKSGHQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant CA4 assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 392.48, ALogP 1.75, HBA 6, HBD 1, PSA 77.1, QED 0.69
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNC3C(C(N)=O)C(c4ccc(Oc5ccccc5)cc4)=NN32)CC1
InChIKey: PZWSKESWDIFAFK-MUKMJDFVSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of ITK (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 473.58, ALogP 2.71, HBA 6, HBD 2, PSA 100.26, QED 0.63
Compound (SMILES): O=C(NO)c1ccc(CCCN2CCN(C(c3ccccc3)c3ccccc3)CC2)cc1
InChIKey: SFMNWYGDIXMZNK-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human HDAC4 using fluorescent peptide Boc-Lys(trifluoroacetyl)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorogenic assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 429.56, ALogP 4.15, HBA 4, HBD 2, PSA 55.81, QED 0.42
Compound (SMILES): CC[N+](C)(CC)[C@H]1C[C@H]1Oc1ccc(/C=C/c2ccccc2)cc1.[I-]
InChIKey: XDAOTPVLMHRNED-NHIHCTNCSA-M
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Displacement of [3H]-epibatidine from human alpha4beta2 nAChR expressed in HEK293 cells membrane assessed as inhibition constant preincubated for 5 mins followed by overnight incubation with [3H]-epibatidine by gamma liquid scintilation counting analysis
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 322.47, ALogP 4.86, HBA 1, HBD 0, PSA 9.23, QED 0.52
Compound (SMILES): CC(C)(C)CNC(=S)Nc1ccc2c(c1)CCN2Cc1ccc(O)cc1
InChIKey: DAMNZJYASCYSJJ-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of human recombinant sEH assessed as reduction in 6-methoxynaphthaldehyde formation using PHOME as substrate preincubated for 1 min followed by substrate addition and measured after 60 mins by fluorescence based analysis
Measurement: IC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 369.53, ALogP 4.29, HBA 3, HBD 3, PSA 47.53, QED 0.7
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CCC4(CCN(C(=O)[C@@H]5CC5(F)F)CC4)C3)n2n1)C1CC1
InChIKey: QEDMOQUVDLNINX-HOTGVXAUSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 9391 nM (pChEMBL 5.03000020980835)
Descriptors: MW 443.5, ALogP 3.61, HBA 5, HBD 1, PSA 79.6, QED 0.78
Compound (SMILES): O=C(O)C1CN(Cc2ccc(C3=NOC(c4ccc(O)cc4)C3)cc2)C1
InChIKey: QRCYJPJDPYKBIR-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.39, ALogP 2.77, HBA 5, HBD 2, PSA 82.36, QED 0.86
Compound (SMILES): COc1ccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)cc1
InChIKey: NNWKRTWKYDLFJC-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 426.52, ALogP 4.31, HBA 5, HBD 2, PSA 84.41, QED 0.37
Compound (SMILES): NS(=O)(=O)c1cccc(NC(=O)c2cc(-c3cccc(C(F)(F)F)c3)nc3ccccc23)c1
InChIKey: LIDMFHVHDPNICD-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 64.6 nM (pChEMBL 7.190000057220459)
Descriptors: MW 471.46, ALogP 4.82, HBA 4, HBD 2, PSA 102.15, QED 0.45
Compound (SMILES): COc1ccccc1N1CCN(CC[C@@H](C(=O)N2CCCCCC2)c2ccccc2)CC1
InChIKey: JUAVWMUCGPXXJV-XMMPIXPASA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Binding affinity to 5-HT1D receptor (unknown origin) assessed as inhibition constant
Measurement: Ki = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 435.61, ALogP 4.39, HBA 4, HBD 0, PSA 36.02, QED 0.65
Compound (SMILES): CCCNNC(=O)c1ccc(CNC(C)=O)cc1
InChIKey: JVRNNDPMTJKBTF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3 using p53 (Ac-RHKK(Acetyl)-AMC) as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 249.31, ALogP 0.97, HBA 3, HBD 3, PSA 70.23, QED 0.52