lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@@H](C)Cc1c(C)cc(O)cc1C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: ILKPOIXWHKKYRB-NJFSYGJFSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]diprenorphine from human MOR expressed in mouse NG108-15 cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 1232.54
Compound (SMILES): CO[C@]12CCC3(C[C@@H]1C(C)(C)O)[C@H]1Cc4ccc(O)c5c4[C@]3(CCN1CC1CC1)[C@@H]2O5
InChIKey: OIJXLIIMXHRJJH-BBMUJXPWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]HS665 from KOR in guinea pig brain membranes measured after 45 mins by scintillation counting method
Measurement: Ki = 1.589 nM (pChEMBL 8.800000190734863)
Descriptors: MW 425.57, ALogP 3.39, HBA 5, HBD 2, PSA 62.16, QED 0.77
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(F)cn2)C1
InChIKey: JTIFUJUJDWUQEV-LSDHHAIUSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Binding affinity to human CDK9/CyclinT assessed as equilibrium dissociation constant by surface plasmon resonance analysis
Measurement: Kd = 0.123 nM (pChEMBL 9.90999984741211)
Descriptors: MW 413.5, ALogP 3.3, HBA 5, HBD 2, PSA 88.91, QED 0.8
Compound (SMILES): CC(C)n1cc(C(=O)Nc2cc3cc(-c4cncn4C(C)C)ccc3cn2)cn1
InChIKey: SOKCEAXUEAIORP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 388.48, ALogP 4.71, HBA 6, HBD 1, PSA 77.63, QED 0.54
Compound (SMILES): C[C@@H](NC(=O)Cn1nc2ccccn2c1=O)c1ccc(Cl)c(F)c1
InChIKey: DYFLSCLFNKJKOS-SNVBAGLBSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 >= 100 nM (pChEMBL 7)
Descriptors: MW 348.76, ALogP 2.17, HBA 5, HBD 1, PSA 68.4, QED 0.79
Compound (SMILES): COc1cccc2c(N3CCN(c4ccccc4F)CC3)c(C#N)cnc12
InChIKey: IVIYDHTVCLPJQV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Positive allosteric modulation of rat mGlu7 expressed in HEK293 cells co- expressing GIRK assessed as potentiation of L-AP4-induced thallium flux incubated for 140 sec by FluoZin2-AM dye based fluorescence analysis
Measurement: EC50 = 879 nM (pChEMBL 6.059999942779541)
Descriptors: MW 362.41, ALogP 3.58, HBA 5, HBD 0, PSA 52.39, QED 0.71
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4C[C@@H](N(C)C)CC4=O)c(C=O)nc32)ncc1C#N
InChIKey: LWBSWJUHXCHFLP-FQEVSTJZSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q03142
Assay: Inhibition of FGFR4 in mouse BAF3 cells assessed as decrease in FGFR4 phosphorylation incubated for 40 mins
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 521.58, ALogP 1.83, HBA 9, HBD 1, PSA 140.99, QED 0.39
Compound (SMILES): COc1cc(S(=O)(=O)CC(=O)N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2S(=O)(=O)C(C)C)n1
InChIKey: UOIPIFGVZNDCCW-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK G1202R mutant (unknown origin) using peptide substrate incubated for 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 637.18, ALogP 3.36, HBA 11, HBD 2, PSA 150.9, QED 0.34
Compound (SMILES): Cc1ccc(-c2cncc3[nH]c(-c4n[nH]c5ccc(-c6cncc(N)c6)nc45)nc23)s1
InChIKey: FPZGXIIIMIQQHX-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 424.49, ALogP 4.58, HBA 7, HBD 3, PSA 122.05, QED 0.38
Compound (SMILES): CO[C@@]12CC[C@@H](NCC(=O)NCC(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: PCHRSAVZQDSMPF-APVKTYTCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U69,593 from kappa opioid receptor in guinea-pig brain membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 203 nM (pChEMBL 6.690000057220459)
Descriptors: MW 431.49, ALogP -0.01, HBA 7, HBD 4, PSA 120.36, QED 0.5
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2ncccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: YFKOUTGKKFPEOH-QGZVFWFLSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of MDR1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): CN(CCCCCCOc1cc(O)c2c(=O)c3ccccc3oc2c1)Cc1ccc(O)cc1
InChIKey: GNJJURBAYZCGRE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Mixed-type inhibition of equine serum BuChE using varying levels of butylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured for 180 secs by Ellman's method based Lineweaver-burk plot analysis
Measurement: Ki = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 447.53, ALogP 5.43, HBA 6, HBD 2, PSA 83.14, QED 0.25
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)c4ccc5c(cnn5C)c4)cc3c2)cn1
InChIKey: ZUUIIFQSDQMWET-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 382.43, ALogP 3.77, HBA 6, HBD 1, PSA 77.63, QED 0.52
Compound (SMILES): CNC(=O)CCCCC[C@H](NC(=O)Cn1ccc2cc(C#N)ccc21)c1ncc(-c2ccc(CN(C)C)cc2)o1
InChIKey: NXOLTHXMXKDRIS-SANMLTNESA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant his tagged HDAC1 expressed in baculovirus expression system using FLUOR DE LYS-SIRT1 as fluorogenic substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by spectrophotometer based analysis
Measurement: IC50 = 13900 nM (pChEMBL 4.860000133514404)
Descriptors: MW 540.67, ALogP 4.78, HBA 7, HBD 2, PSA 116.19, QED 0.24
Compound (SMILES): CCC(Nc1nnc(-c2ccc(OC)cc2)o1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: JDPHTOJNZVWWNV-QLCVBSLISA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin) assessed as CYP450 induction
Measurement: EC50 = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 460.55, ALogP 6.6, HBA 6, HBD 1, PSA 73.07, QED 0.34
Compound (SMILES): COc1ccc(-c2c3c(nn2C(C)C)CCNCC3)cc1
InChIKey: HFAGGJZWKFFGLM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]-CT from rat 5-HT7 receptor expressed in HEK293 cells by competitive radioligand binding assay
Measurement: Ki = 18 nM (pChEMBL 7.75)
Descriptors: MW 285.39, ALogP 2.83, HBA 4, HBD 1, PSA 39.08, QED 0.94
Compound (SMILES): C[C@@](CO)(OC[C@H]1O[C@@H](n2ncc3c(NC4CCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O)P(=O)(O)O
InChIKey: DWPITEDBCBAYRP-DLOISVIMSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Mus musculus
UniProt: Q61503
Assay: Inhibition of CD73 in mouse EMT6 cells assessed as reduction in AMP-induced ADO expression preincubated for 15 mins followed by AMP addition and measured after 1 hr by LC-MS/MS analysis
Measurement: EC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 507.87, ALogP 0.36, HBA 11, HBD 6, PSA 192.31, QED 0.21
Compound (SMILES): CNC(=O)c1cncc(-c2cnc(Cl)c(NS(=O)(=O)c3ccccc3)c2)c1
InChIKey: IHWSJFBJORCEAK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human PI3Kgamma by ADP-Glo kinase assay
Measurement: IC50 = 324 nM (pChEMBL 6.489999771118164)
Descriptors: MW 402.86, ALogP 2.96, HBA 5, HBD 2, PSA 101.05, QED 0.64
Compound (SMILES): C[C@]1(c2ccccc2)CN(C(=O)NCc2ccccc2)C[C@H]1c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: MUPBMBQMORRYNG-UKILVPOCSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 441 nM (pChEMBL 6.360000133514404)
Descriptors: MW 536.52, ALogP 6.27, HBA 2, HBD 2, PSA 52.57, QED 0.38
Compound (SMILES): Cc1ccc(C(=O)CSc2nnc(-c3ccc(S(N)(=O)=O)cc3)o2)cc1
InChIKey: XAVCGVMEWJZNQR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 230.6 nM (pChEMBL 6.639999866485596)
Descriptors: MW 389.46, ALogP 2.67, HBA 7, HBD 1, PSA 116.15, QED 0.51
Compound (SMILES): Nc1n[nH]c2cc(-c3ccc(=O)n(Cc4ccccc4F)c3)ccc12
InChIKey: DUHHTOOYELYHTE-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant CYP1A2 (unknown origin) using CEC as substrate measured after 15 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 334.35, ALogP 3.16, HBA 4, HBD 2, PSA 76.7, QED 0.6
Compound (SMILES): Nc1ncnc2c1ncn2[C@H]1C[C@@H]2OP(=O)(S)OC[C@H]3O[C@@H](n4cnc5c(O)ncnc54)[C@H](F)[C@@H]3OP(=O)(S)OC[C@H]2O1
InChIKey: ZOHTYTWCUFTHSD-CBAZNMGYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of STING in human blood assessed as induction of type I IFNs incubated for 18 to 20 hrs by QUANTI-Blue assay
Measurement: EC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 677.53, ALogP 2.37, HBA 18, HBD 4, PSA 222.97, QED 0.18
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1ccc(C(F)(F)F)cc1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: WZOZYFBDXFAVLI-UHFFFAOYSA-M
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Noncompetitive inhibition of human acetylcholinesterase assessed as affinity towards free enzyme using acetylthiocholine iodide as substrate measured by Ellman's method based Lineweaver-Burk plot analysis
Measurement: Ki = 0.456 nM (pChEMBL 9.34000015258789)
Descriptors: MW 480.46, ALogP 5.69, HBA 4, HBD 0, PSA 40.8, QED 0.35
Compound (SMILES): CC(=O)Nc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(Cl)c(Cl)c3)CC2)c1
InChIKey: UCWSDAHSOCIBPK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 0.06607 nM (pChEMBL 10.180000305175781)
Descriptors: MW 482.38, ALogP 4.56, HBA 4, HBD 2, PSA 70.67, QED 0.54
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)C(C)C
InChIKey: LKEDSHSHGNAQDA-APYQUMOISA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Displacement of GLP-1-red from human GLP-1R expressed in CHO-K1 cells by fluorescent competitive binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 6190.04
Compound (SMILES): Cc1cc(-c2ccc3ncc(-c4cnn(C)c4)n3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: SLLWDVCXHJGGIT-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 412.5, ALogP 3.86, HBA 6, HBD 0, PSA 68.32, QED 0.51
Compound (SMILES): CN(C)C(=O)c1ccc(-c2cc(C(=O)N[C@@H]3CCc4ccccc43)no2)cc1O
InChIKey: IXWUILRSNIQHDM-QGZVFWFLSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Selectivity interaction (BioLayer Interferometry assay (BLI)) EUB0000731a MLLT1
Measurement: Kd = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 391.43, ALogP 3.17, HBA 5, HBD 2, PSA 95.67, QED 0.71
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)C3CCC(=O)N3)[C@@H](C)O)CSSC[C@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)O)CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)O)NC1=O
InChIKey: NAIHDUVGMVAQOH-IDFYMFIFSA-N
Target: Relaxin-3 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU9
Assay: Agonist activity at human RXFP4 expressed in CHO-K1 cells assessed as reduction in forskolin-induced cAMP production by pCRE beta-galactosidase reporter assay
Measurement: EC50 = 4.57 nM (pChEMBL 8.34000015258789)
Descriptors: MW 5058.9
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4C[C@@H](C)N[C@@H](C)C4)c(C=O)nc32)ncc1C#N
InChIKey: IKPPEZYAZCCZLQ-HDICACEKSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant non-phosphorylated FGFR4 kinase domain (442 to 753) (unknown origin) expressed in Sf9 insect cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 peptide as substrate in presence of ATP measured after 60 mins by caliper microfluidic mobility shift assay
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 507.6, ALogP 2.35, HBA 9, HBD 2, PSA 132.71, QED 0.41
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: DVAPMYJVUZJNDK-DNVCBOLYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: CDK2/Cyclin E1 Mobility Shift Assay: The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (± inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 421.52, ALogP 1.1, HBA 8, HBD 2, PSA 117.42, QED 0.76
Compound (SMILES): N[C@H]1CN[C@@](CCCCB(O)O)(C(=O)O)C1
InChIKey: SHQWTXRBVVLSOY-VXNVDRBHSA-N
Target: Arginase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05089
Assay: Biological Activity of Examples 1 to 30: The inhibitory effects of Examples 1 to 30 on the activity of Human Arginase 1 and Arginase 2 activity were quantified by measuring the formation of the thiol group from thioarginine using recombinant Arginase 1 or Arginase 2 produced from E. coli. The thiol group was detected with Ellman's reagent, 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB). DTNB reacts with the thiol to give the mixed disulfide and 2-nitro-5-thiobenzoic acid (TNB) which is quantified by the absorbance of the anion (TNB2−) at 412 nm.The assays were run in clear 384 well plates (Greiner cat no: 781101). Various concentrations of Examples 1 to 30 in 300 nL DMSO were dispensed to assay plates using an Echo acoustic dispenser immediately followed by plate sealing and centrifugation. Two pre-mixes were prepared from reagents thawed immediately before addition to assay plates. Pre-mix one comprised human Arginase 1 or human Arginase 2, at a final concentration of 5 nM and 0.5 mM DTNB in assay buffer, 45 mM HEPES pH7.5, brij 35, 0.045% (w/v) and 100 μM MnCl2. Pre-mix two comprised freshly thawed 0.5 mM thioarginine in assay buffer. Fifteen microlitres of pre-mix one was dispensed to assay plates containing Examples 1 to 30, centrifuged and incubated for 30 minutes at room temperature prior to adding fifteen microlitres of pre-mix two.Assay plates were centrifuged prior to reading absorbance at 412 nm in a Pherastar multi-mode plate reader to collect data at time point 0 (T0). The plates were incubated at room temperature for 60 min prior to reading again to collect data at time point 1 (T1). Data is derived by subtracting the A412 signal measured at T0 (time point 0) from that measured at T1 (time point 1). The data was transformed to % effect using the equation:Compound % effect=100*[(X−min)/(max−min)], where X represents the normalized value for the compound based on the Min (vehicle) and Max (reference compound) inhibition control.
Measurement: IC50 = 6410 nM (pChEMBL 5.190000057220459)
Descriptors: MW 230.07
Compound (SMILES): O=C(Nc1ccc(OC(CO)CO)nc1)c1n[nH]c2ccc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: JRKXYICQDHOPTH-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 502.58, ALogP 2.99, HBA 8, HBD 4, PSA 136.49, QED 0.27
Compound (SMILES): Cc1cc(-c2ccn3nc(N)nc3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: IBRQJCOMQXDQQV-LBPRGKRZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 347.42, ALogP 3.04, HBA 5, HBD 1, PSA 76.52, QED 0.79
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(C#Cc4ccc(Cl)s4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: ADWCKXIAWARNSR-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 653.18, ALogP 6.14, HBA 8, HBD 2, PSA 128.17, QED 0.19
Compound (SMILES): COc1cccc(O)c1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: BUYXRPOASRGKHF-QFIPXVFZSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli using BML-KI178 as substrate and SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 555.66, ALogP 5.47, HBA 7, HBD 4, PSA 129.23, QED 0.16
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCC(O)C1
InChIKey: USGWWFWAYIOOFO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 51286.14 nM (pChEMBL 4.289999961853027)
Descriptors: MW 274.36, ALogP 1.42, HBA 3, HBD 1, PSA 43.78, QED 0.91
Compound (SMILES): CC[C@H]1OC2(CCN(CCc3ccccc3)CC2)CN(C)C1=O
InChIKey: QKSGTKTUVCNJNZ-QGZVFWFLSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHOK1 cell membranes incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 192 nM (pChEMBL 6.71999979019165)
Descriptors: MW 316.45, ALogP 2.33, HBA 3, HBD 0, PSA 32.78, QED 0.85
Compound (SMILES): COCCCCC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: ZJPSQGKCYKMKSJ-VOQZNFBZSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at human recombinant S1P1 expressed in CHO cells assessed as stimulation of ERK phosphorylation incubated for 7 mins by microplate reader analysis
Measurement: EC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 425.51, ALogP 4.07, HBA 4, HBD 3, PSA 102.01, QED 0.39
Compound (SMILES): CCCOc1ccc2c(c1[C@H]1C[C@@H]1CN)CCO2.Cl
InChIKey: UWVLPYSRFUDFMR-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 247.34, ALogP 2.47, HBA 3, HBD 1, PSA 44.48, QED 0.87
Compound (SMILES): COc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: ZBGMKBKMVOGMLL-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]MSX2 from adenosine receptor A2A in rat brain striatum membranes incubated for 30 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 520.57, ALogP 6.03, HBA 8, HBD 1, PSA 99.25, QED 0.29
Compound (SMILES): Cn1ncc(-c2ccc3cnc(NC(=O)[C@H]4CC[C@H](CO)CC4)cc3c2)c1CN1CCCCC1
InChIKey: AFXZSFRQUZCOKK-MXVIHJGJSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. response-variable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 594 nM (pChEMBL 6.230000019073486)
Descriptors: MW 461.61, ALogP 4.36, HBA 6, HBD 2, PSA 83.28, QED 0.57
Compound (SMILES): COc1ccc2nc3c(c(NCCCCCCN(CC(=O)NCCc4c[nH]c5ccc(OC)cc45)C(=O)CCCC[C@@H]4CCSS4)c2c1)CCCC3
InChIKey: ZYKIOUVTAQGDKW-JGCGQSQUSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BuChE in human erythrocyte hemo-lyzates pre-incubated for 5 mins before addition of butyrylthiocholine iodide substrate by Ellman's method
Measurement: IC50 = 1880 nM (pChEMBL 5.730000019073486)
Descriptors: MW 746.06, ALogP 8.49, HBA 8, HBD 3, PSA 108.58, QED 0.06
Compound (SMILES): CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2sc(CN3CCN(C(=O)C4CCC4)CC3=O)cc2n1
InChIKey: FANCMOGTFZXBFZ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin)
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 559.7, ALogP 3.4, HBA 9, HBD 0, PSA 96.69, QED 0.36
Compound (SMILES): Cc1cc(-c2ccn3nc(N)c(-c4ccccn4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: SOTXCCDMWLOUTG-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 424.51, ALogP 4.1, HBA 6, HBD 1, PSA 89.41, QED 0.53
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(CN4CC[C@@H](N(C)C)C4=O)c(C=O)nc32)ncc1C#N
InChIKey: IINODIWIEGKWRS-OAQYLSRUSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant non-phosphorylated FGFR4 kinase domain (442 to 753) (unknown origin) expressed in Sf9 insect cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 peptide as substrate in presence of ATP measured after 60 mins by caliper microfluidic mobility shift assay
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 521.58, ALogP 1.83, HBA 9, HBD 1, PSA 140.99, QED 0.39
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)/C=C/c1nccs1
InChIKey: BHWDYFGTRWGKRI-JXMROGBWSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in human THP1 cells assessed as inhibition of IL-1beta release in presence of nigericin
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 389.5, ALogP 3.24, HBA 5, HBD 2, PSA 88.16, QED 0.84
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2c(c1)C(=C(C)C)C(=O)N2
InChIKey: CDERLIUJSXSXFH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of BRD2 BD2 (unknown origin) preincubated for 15 mins followed by peptide addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 358.42, ALogP 3.24, HBA 4, HBD 2, PSA 84.5, QED 0.82
Compound (SMILES): O=C(NO)c1ccc(Nc2ccnc3ccccc23)cc1
InChIKey: CRQRFXAGXWHWTJ-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC9 (604 to 1066 residues) expressed in baculovirus infected Sf9 cells using fluorogenic HDAC 2A substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 13230 nM (pChEMBL 4.880000114440918)
Descriptors: MW 279.3, ALogP 3.1, HBA 4, HBD 3, PSA 74.25, QED 0.51
Compound (SMILES): OC/C=C/[C@H]1[C@@H]2CCC[C@@]1(c1cccc(O)c1)CCN2CCc1ccccc1
InChIKey: FTDOOEOFAZGQEK-ZADLEFMZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Activity at human MOR expressed in CHOK1 cells co-expressing beta-arrestin2 EFC assessed as beta-arrestin2 EFC recruitment measured after 90 mins by PathHunter assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 377.53, ALogP 4.3, HBA 3, HBD 2, PSA 43.7, QED 0.74
Compound (SMILES): Nc1nc(N2CCC3(CC2)Cc2cnccc2[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: HESMLNQOTOVZRA-QGZVFWFLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by manual patch clamp method
Measurement: IC50 = 11700 nM (pChEMBL 4.929999828338623)
Descriptors: MW 454.99, ALogP 3.08, HBA 9, HBD 3, PSA 132.86, QED 0.55
Compound (SMILES): Cl.NC[C@@H]1C[C@H]1c1c(OCC2CC2)ccc2occc12
InChIKey: HMLRTUGCQZRYDU-STEACBGWSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 524 nM (pChEMBL 6.28000020980835)
Descriptors: MW 257.33, ALogP 3.28, HBA 3, HBD 1, PSA 48.39, QED 0.89
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CC[C@@]2(O)c1cn(-c2cccc(O)c2)nn1
InChIKey: CNCYPHLGQIATRW-YWBWYGPRSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at full length human ERbeta receptor assessed as inhibition of estradiol-induced activation incubated for 22 to 24 hrs by cell based luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 431.54, ALogP 4.42, HBA 6, HBD 3, PSA 91.4, QED 0.56
Compound (SMILES): COC[C@@H](C)Oc1ccc2c(c1)Cc1cccc(-c3cc(=O)cc(N4CCOCC4)o3)c1S2
InChIKey: SYVQAQHCFMTBNA-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HeLa cells incubated for 4 hrs
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 465.57, ALogP 4.61, HBA 7, HBD 0, PSA 61.14, QED 0.41
Compound (SMILES): COC(=O)N1CC[C@](CO)(Nc2nc(N3CCOCC3)nc(-c3cnc(N)nc3)c2F)C1
InChIKey: RTAAXWKPLMSXJJ-IBGZPJMESA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 448.46, ALogP 0.11, HBA 11, HBD 3, PSA 151.85, QED 0.57
Compound (SMILES): CCc1cc(-c2ccc3c(c2)-c2nnc(Nc4cccc(C(F)(F)F)c4)n2CCO3)ccn1
InChIKey: BKGOKPQNNKWLHW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells assessed as reduction in S35-MK-0499 binding
Measurement: IC50 = 334 nM (pChEMBL 6.480000019073486)
Descriptors: MW 451.45, ALogP 5.72, HBA 6, HBD 1, PSA 64.86, QED 0.43
Compound (SMILES): C=CC(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4cc(CC)ccn4)cc3)c2c1
InChIKey: VYZQSAKXLMEDCB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of His-tagged recombinant human His-tagged full length BTK expressed in baculovirus expression system using Tyr01 peptide as substrate preincubated for 1 hr by Z'lyte assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 438.49, ALogP 5.36, HBA 5, HBD 2, PSA 93.21, QED 0.38
Compound (SMILES): C=CC(=O)N[C@H]1COC[C@H]1Nc1ncc2cc(-c3c(F)c(OC)cc(OC)c3F)c(=O)n(C)c2n1
InChIKey: PSKWUEAQZZDBSQ-UONOGXRCSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) expressed in human Huh7 cells assessed as autophosphorylation after 1 hr incubation measured by Mesoscale discovery (MSD) assay
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 487.46, ALogP 1.77, HBA 9, HBD 2, PSA 116.6, QED 0.48
Compound (SMILES): O=C(O)CCNC(=O)/C(Cc1ccc(O)c(Br)c1)=N/O
InChIKey: NWSKLDYVCQCAPY-OQLLNIDSSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant full length C-terminal FLAG/His-tagged human HDAC1 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.15, ALogP 1.12, HBA 5, HBD 4, PSA 119.22, QED 0.35
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)CC4)c(F)cn2)C1
InChIKey: ZNUJHRYFOFHSMX-JKSUJKDBSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (ATP Concentration at Km): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (3 nM CDK9/CycT1, 6 μM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 427.52, ALogP 3.69, HBA 5, HBD 2, PSA 88.91, QED 0.78
Compound (SMILES): C/C=C/c1cc(-c2nn(-c3nc(C(=O)O)cs3)c(CC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)ccc1F
InChIKey: AYXFVSAODMCRBM-NSCUHMNNSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 570.64, ALogP 5.2, HBA 7, HBD 2, PSA 128.17, QED 0.28
Compound (SMILES): CC[C@H](C)C(=O)N1CCC(NC(=O)Nc2ccc(OC(F)(F)F)c(F)c2)CC1
InChIKey: LHRXHTKENPCGSZ-NSHDSACASA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of human recombinant sEH using CMNPC as substrate incubated for 5 mins by fluorescent based assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 405.39, ALogP 3.88, HBA 3, HBD 2, PSA 70.67, QED 0.73
Compound (SMILES): O=C(O)CSc1ncnc2cc(-c3cc4ccccc4s3)sc12
InChIKey: BNYXRPMABDQJJR-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human MET in presence of ATP at Km level
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 358.47, ALogP 4.75, HBA 6, HBD 1, PSA 63.08, QED 0.42
Compound (SMILES): N#Cc1c(-c2ccc(Cl)cc2)cn(-c2ccc(S(N)(=O)=O)cc2)c1N
InChIKey: YTUJINOQEQGXDS-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 88.5 nM (pChEMBL 7.050000190734863)
Descriptors: MW 372.84, ALogP 2.9, HBA 5, HBD 2, PSA 114.9, QED 0.73
Compound (SMILES): Cl.Oc1ccccc1C1NCCc2c1[nH]c1ccc(Cl)cc21
InChIKey: GWTYJHNSTXGCFP-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 = 15.49 nM (pChEMBL 7.809999942779541)
Descriptors: MW 298.77, ALogP 3.76, HBA 2, HBD 3, PSA 48.05, QED 0.64
Compound (SMILES): O=[N+]([O-])c1ccc(N/C(Cc2ccc(Cl)cc2)=N\O)c2nonc12
InChIKey: BIUHMRRXHQWMMV-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 assessed as N-formylkynurenine formation using L-tryptophan as substrate measured after 1.5 hrs by HPLC analysis
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 347.72, ALogP 3.23, HBA 7, HBD 2, PSA 126.68, QED 0.24
Compound (SMILES): CCCCNNC(=O)c1cccnc1
InChIKey: NBKPFBBNYBOQPN-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Allosteric inhibition of C-terminal His-tagged recombinant human HDAC3 expressed in Sf9 cells pre-incubated for 2 hrs before acetylated lysine-aminomethyl coumarin-BOC addition and measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 1547 nM (pChEMBL 5.809999942779541)
Descriptors: MW 193.25, ALogP 1.12, HBA 3, HBD 2, PSA 54.02, QED 0.54
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4c(OC)ncnc4C4CC4)nc3n([C@H](C)C3CC3)c2=O)nc1
InChIKey: LYWORTORILMZIS-OAHLLOKOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Reporter Gene Assay: A nuclear receptor transactivation assay is performed to quantitate the ability of test compounds to inhibit RORγ transactivation of a luciferase reporter. A similar assay is described in: Khan et al., Bioorganic & Medicinal Chemistry Letters 23 (2013), 532-536. The system uses transiently transfected HEK 293 cells cotransfected with two plasmids (pGL4.3, luc2P/GAL4UAS/Hygro, and pBIND, Gal4DBD hRORC LBD1-3). The positive control is co-transiently transfected with both plasmids, and the negative control contains the pGL4.3 promoter sequence. Assays are assembled in 384 well plates where transiently transfected cells and test compound at varying concentrations are incubated for 20-24 h.The next day, assays plates are taken out and equilibrated at RT for 20-30 minutes. Bright-Glo Luciferase Assay System is used to detect Luciferase production. After addition of Bright GLO detection reagent, the plates are incubated at RT for 20 minutes. The plates are read on an Envision plate reader to measure luminescence signal. The RLU signal is converted to POC relative to control and blank wells.
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 562.66, ALogP 3.3, HBA 12, HBD 1, PSA 154.74, QED 0.3
Compound (SMILES): O=C(c1ccc(Cl)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(F)c2)CC1
InChIKey: WQLAYHBUUKJKQO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(N3CCCC(NS(C)(=O)=O)C3)cc2)nc2sccc12
InChIKey: WVWGTOGGUMSNSD-GQCTYLIASA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 4272 nM (pChEMBL 5.369999885559082)
Descriptors: MW 574.73, ALogP 5.9, HBA 9, HBD 2, PSA 120.24, QED 0.25
Compound (SMILES): CCCC#Cc1cc(-c2nn(-c3nc(C(=O)O)cs3)c(CC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)ccc1F
InChIKey: UQVZHAXDYLQVSK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 596.68, ALogP 5.31, HBA 7, HBD 2, PSA 128.17, QED 0.25
Compound (SMILES): O=c1[nH]ncc(N2CCc3c(ncnc3Oc3ccc(F)cc3C(F)(F)F)C2)c1Cl
InChIKey: IQFZADSTVFSHDX-UHFFFAOYSA-N
Target: Short transient receptor potential channel 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN4
Assay: Inhibition of TRPC4 (unknown origin) expressed in HEK293 cells assessed as reduction in englerin A stimulated Ca2+ influx by FLIPR assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 441.77, ALogP 3.73, HBA 6, HBD 1, PSA 84, QED 0.62
Compound (SMILES): Cc1cc(/C=N/O)c(O)c(CNc2ccc(Cn3cncn3)cc2)c1
InChIKey: MSTUXHHGHKBRJQ-LSFURLLWSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Reactivation of dichlorvos-inhibited human AChE assessed as dissociation constant incubated for 30 mins by Ellman's method
Measurement: Kd = 990 nM (pChEMBL 6)
Descriptors: MW 337.38, ALogP 2.76, HBA 7, HBD 3, PSA 95.56, QED 0.37
Compound (SMILES): COc1ccc(-c2cnc3c(c2)C=CS(=O)(=O)O3)cc1
InChIKey: PXHUYCWEZYIHHP-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 289.31, ALogP 2.45, HBA 5, HBD 0, PSA 65.49, QED 0.79
Compound (SMILES): Cc1ncc(-c2ccc3cnc(NC(=O)C4(F)CC4)cc3c2)n1C
InChIKey: JDBSMBPIDCBURU-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: The screening assay for DYRK1A kinase activity : Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.00016 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The DYRK1A kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission.Briefly, recombinant DYRK1A kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control.After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).The Emission ratio (Em) was calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation was then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves were generated and inhibitory concentration (IC50) values were calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 324.36, ALogP 3.38, HBA 4, HBD 1, PSA 59.81, QED 0.8
Compound (SMILES): CC1(C)Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)(F)F
InChIKey: QIMVRHMVKAJIDE-QHCPKHFHSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding Assay : hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.The assay was conducted as follows with all reagents used at room temperature unless otherwise stated.Reagent Preparations Include:1. Internal IC700 solution used to perfuse the underside of chip (in mM), KF 130, KCl 20, MgCl2 1, EGTA 10 and HEPES 10, (all Sigma-Aldrich; pH 7.2-7.3 using 10 M KOH, 320 mOsm) and supplemented with 25 □M escin.2. External and cell buffer (in mM), NaCl 137, KCl 4, HEPES 10, D-glucose 10, CaCl2 2, MgCl2 1 (pH7.4, NaOH)3. NMDG reference buffer used to establish a stable baseline prior to the addition of test compounds, NaCl 80, KCl 4, CaCl2 2, MgCl2 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 NaOH 298 mOsm)4. Seal enhancer used to improve seal quality of cells, NaCl 80, KCl 3, CaCl2 10, HEPES 10, MgCl2 1 (pH7.4 NaOH)
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 490.55, ALogP 4.7, HBA 5, HBD 2, PSA 60.08, QED 0.47