lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccc(N)nc2)nc2c1C[C@@H]1COCCN21
InChIKey: FFFOZOQSDJISHN-TZMCWYRMSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to human wild-type partial length PI3Kdelta (R108 to Q1044 residues) expressed in mammalian expression system by kinome scan assay
Measurement: Kd = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 368.44, ALogP 1.11, HBA 8, HBD 1, PSA 89.63, QED 0.84
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: ROCK-II(h) In Vitro Inhibition Activity: Table 2: ROCK-II(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-II(h) was incubated with the test compound in assay buffer containing 50 mM Tris pH 7.5 (VWR cat #103157P), 0.1 mM EGTA (VWR cat #20308), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(-n3nnc(-c4cc(OC)c(OC)cc4NC(=O)c4cc(=O)c5ccccc5o4)n3)cc1)CC2
InChIKey: AHJUHHDDCJQACA-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in MCF7 cells assessed as increase in reversal of resistance to paclitaxel-induced cytotoxicity by measuring reduction in paclitaxel EC50 at 50 nM incubated for 72 hrs in presence of paclitaxel by SRB assay (Rvb = 11.5 nM)
Measurement: EC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 688.74, ALogP 5.32, HBA 12, HBD 1, PSA 143.07, QED 0.19
Compound (SMILES): C=C(F)C(=O)N1CCN(c2nc(OC[C@@H]3CCCN3C)nc3c2CCN(c2cccc4cccc(Cl)c24)C3)C[C@@H]1CC#N
InChIKey: PEMUGDMSUDYLHU-ZEQRLZLVSA-N
Target: SOS1-KRAS (PROTEIN COMPLEX), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant/SOS1 (unknown origin) interaction incubated for 2 hrs in presence of GTP by HTRF assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 604.13, ALogP 4.73, HBA 8, HBD 0, PSA 88.83, QED 0.36
Compound (SMILES): CCO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CS[C@H]12)c1nsc(N)n1
InChIKey: RGFBRLNVZCCMSV-BIRGHMBHSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: Binding affinity towards human ADRA2A in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 604.72, ALogP -0.04, HBA 14, HBD 2, PSA 179.7, QED 0.14
Compound (SMILES): CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](Nc2ncnc3cc(C(C)(C)C)nn23)C1=O
InChIKey: CMVHFGNTABZQJU-HCXYKTFWSA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: Displacement of [125I]chemokine from CCR4 (unknown origin) by gamma counter method
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 484.65, ALogP 2.25, HBA 8, HBD 3, PSA 116.55, QED 0.6
Compound (SMILES): COc1cc(OC)c(F)c(COc2cnc(Nc3cnn(CCO)c3)nc2)c1F
InChIKey: VDZZYOJYLLNBTD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) in presence of ATP at Km concentration by mobility shift assay
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 407.38, ALogP 2.28, HBA 9, HBD 2, PSA 103.55, QED 0.56
Compound (SMILES): CC(C)n1c(=O)n(C)c2cnc3cc(F)c(-c4ccc(OCCCN5CCCCC5)nc4)cc3c21
InChIKey: VQSZIPCGAGVRRP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR in human MDA-MB-468 cells incubated for 2.5 hrs by Alexa Fluor 488 staining based fluorescence analysis
Measurement: IC50 > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 477.58, ALogP 4.93, HBA 7, HBD 0, PSA 65.18, QED 0.35
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1F
InChIKey: OYFMQDVLFYKOPZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human recombinant GST-tagged JAK3 catalytic domain (781 to 1124 residues) expressed in baculovirus expression system by Z'-lyte assay
Measurement: IC50 = 923 nM (pChEMBL 6.039999961853027)
Descriptors: MW 395.39, ALogP 4.16, HBA 7, HBD 3, PSA 105.07, QED 0.47
Compound (SMILES): Cc1cc(-c2nnc(N)nc2-c2ccc(F)cc2)cc(Cl)n1
InChIKey: NCWQLHHDGDXIJN-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Binding Assay: All test compounds were prepared as a stock solution of 10 mM in 100% DMSO.Inhibition binding assays were performed using 2.5 μg of membranes prepared from HEK293 cells transiently transfected with human adenosine A2a receptor or 10 μg of membranes prepared from CHO cells stably transfected with human adenosine A1 receptor. Membranes were incubated in 50 mM Tris-HCl (HEK293-hA2a; pH 7.4) or 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2 (CHO-hA1; pH 7.4) in the presence of varying concentrations of test compound and 1 nM [3H]ZM241385 (HEK293-hA2a) or [3H]DPCPX (CHO-hA1) at 25° C. for 1 h. The assay was then terminated by rapid filtration onto GF/B grade Unifilter plates using a TomTec cell harvester, followed by 5×0.5 ml washes with double distilled H2O. Nonspecific binding was defined in the presence of 1 μM CGS15943 (HEK293-hA2a) or 1 μM DPCPX (CHO-hA1). Bound radioactivity was determined by liquid scintillation counting (Trilux Microbeta® Counter) and inhibition curves were analysed using a four-parameter logistic equation.
Measurement: Ki = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 315.74, ALogP 3.28, HBA 5, HBD 1, PSA 77.58, QED 0.73
Compound (SMILES): C[C@H](O)c1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nn1-c1cccc(Cl)c1
InChIKey: AZXOTZCWQDJCLY-SJCJKPOMSA-N
Target: Vasopressin V1b receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47901
Assay: Radiometric AVPR1B binding assay (Eurofins #287560)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 543.33, ALogP 3.62, HBA 9, HBD 2, PSA 110.99, QED 0.37
Compound (SMILES): CCO[C@H]1CCN(Cc2c(OC)cc(C)c3[nH]ccc23)[C@H](c2ccc(C(=O)O)cc2)C1
InChIKey: RENRQMCACQEWFC-UGKGYDQZSA-N
Target: Complement factor B (SINGLE PROTEIN), Homo sapiens
UniProt: P00751
Assay: Human Complement Factor B TR-FRET Assay: CVF-Bb complex prepared from purified cobra venom factor (1 μM), recombinant human complement factor B (expressed in drosophila cells and purified using standard methods) and human complement factor D (expressed in E. Coli, refolded and purified using standard methods). CVF-Bb complex at 3 nM concentration was incubated with test compound at various concentrations for 1 hour at room temperature in PBS pH 7.4 containing 10 mM MgCl2 and 0.05% (w/v) CHAPS. Human complement C3 substrate purified from plasma was added to a final concentration of 1 μM. After 1 hour incubation at room temperature, the enzyme reaction was stopped by addition of a cocktail of concentrated pan-protease inhibitors. The product of the reaction, C3a, was quantified by means of an enzyme-linked-immunosorbent assay. IC50 values were calculated from percentage of inhibition of CVF-Bb activity as a function of test compound concentration.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 422.53, ALogP 4.93, HBA 4, HBD 2, PSA 74.79, QED 0.56
Compound (SMILES): COC1=CC(=O)N(C(=O)/C=C/[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)C2CCN(C)CC2)[C@H]1Cc1c[nH]c2ccccc12
InChIKey: IMTIJVSUXSYPRE-OAMSZMPYSA-N
Target: Procathepsin L (SINGLE PROTEIN), Mus musculus
UniProt: P06797
Assay: Inhibition of mouse Cathepsin L assessed as Apparent inhibition constant using Z-FR-AMC as substrate inubated for 30 mins by fluorometric assay
Measurement: Ki = 3.95 nM (pChEMBL 8.399999618530273)
Descriptors: MW 690.89, ALogP 3.44, HBA 7, HBD 4, PSA 152.94, QED 0.21
Compound (SMILES): COC1=CC(=O)N(C(=O)/C=C/[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2CCCCC2)NC(=O)C2CCN(C)CC2)[C@H]1Cc1c[nH]c2ccccc12
InChIKey: ZJLUYWUYIFDQKX-YGVSIWEKSA-N
Target: Procathepsin L (SINGLE PROTEIN), Mus musculus
UniProt: P06797
Assay: Inhibition of mouse Cathepsin L assessed as Apparent inhibition constant using Z-FR-AMC as substrate inubated for 30 mins by fluorometric assay
Measurement: Ki = 29.3 nM (pChEMBL 7.53000020980835)
Descriptors: MW 730.95, ALogP 4.37, HBA 7, HBD 4, PSA 152.94, QED 0.2
Compound (SMILES): O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1cccc2cc[nH]c12
InChIKey: ZFHQLTFHZHQXAS-BCTJHDQDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO-K1 cells with holding potential of -80 mV by automated patch clamp assay
Measurement: IC50 = 0.021 nM (pChEMBL 10.680000305175781)
Descriptors: MW 485.58, ALogP 3.24, HBA 5, HBD 4, PSA 97.82, QED 0.46
Compound (SMILES): Cn1nccc1-c1ccc(C(=O)N[C@@H]2CNCC[C@H]2c2ccc(F)c(F)c2)c(F)c1
InChIKey: PALTUSLCLFDFQQ-MGPUTAFESA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Inhibition of CHK1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 414.43, ALogP 3.38, HBA 4, HBD 2, PSA 58.95, QED 0.69
Compound (SMILES): CN(C)C(=O)Cn1ccc2ncc(-c3ccc(F)c(Cl)c3)cc21
InChIKey: OZQNCCZSWDCRSH-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 331.78, ALogP 3.58, HBA 3, HBD 0, PSA 38.13, QED 0.74
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(Sc2ccccc2)cc1Br
InChIKey: PRYBEVSATZDKFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 431.33, ALogP 1.97, HBA 5, HBD 3, PSA 109.49, QED 0.65
Compound (SMILES): Cl.Cl.O=C(CN1CCOCC1)Nc1ccc(OC2CCN(C3CCC3)CC2)cc1
InChIKey: LCPQCTBHZPMVFX-UHFFFAOYSA-N
Target: Cytochrome P450 2E1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05181
Assay: Inhibition of CYP2E1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 373.5, ALogP 2.35, HBA 5, HBD 1, PSA 54.04, QED 0.83
Compound (SMILES): O=C(NO)[C@H](Cc1ccccc1)n1nnc(-c2ccccc2)c1C#Cc1ccccc1
InChIKey: JMEPDOCHFSIAAG-QHCPKHFHSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant full length human C-terminal FLAG/His-tagged HDAC1 expressed in baculovirus expression system using fluorophore-conjugated substrate by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 408.46, ALogP 3.63, HBA 5, HBD 2, PSA 80.04, QED 0.3
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccc(N)nc2)nc2c1C[C@@H]1COCCN21
InChIKey: FFFOZOQSDJISHN-TZMCWYRMSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Binding affinity to human wild-type partial length PI3Kgamma (S144 to A1102 residues) expressed in mammalian expression system by kinome scan assay
Measurement: Kd = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 368.44, ALogP 1.11, HBA 8, HBD 1, PSA 89.63, QED 0.84
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(-n3nnc(-c4cc(OC)c(OC)cc4NC(=O)c4cc(=O)c5ccccc5o4)n3)cc1)CC2
InChIKey: AHJUHHDDCJQACA-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in MES-SA/DX5 cells assessed as increase in reversal of resistance to paclitaxel-induced cytotoxicity by measuring reduction in paclitaxel EC50 at 50 nM incubated for 72 hrs in presence of paclitaxel by SRB assay (Rvb = 294.6 nM)
Measurement: EC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 688.74, ALogP 5.32, HBA 12, HBD 1, PSA 143.07, QED 0.19
Compound (SMILES): C=C(F)C(=O)N1CCN(c2nc(OC[C@@H]3CCCN3C)nc3c2CCN(c2cccc4cccc(Cl)c24)C3)C[C@@H]1CC#N
InChIKey: PEMUGDMSUDYLHU-ZEQRLZLVSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Binding affinity to human KRAS G12C mutant (1 to 169 residues) extracted from Escherichia coli BL21 cells incubated for 20 to 24 hrs by LC-MS/MS analysis
Measurement: IC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 604.13, ALogP 4.73, HBA 8, HBD 0, PSA 88.83, QED 0.36
Compound (SMILES): CCO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CS[C@H]12)c1nsc(N)n1
InChIKey: RGFBRLNVZCCMSV-BIRGHMBHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Binding affinity towards human OPRM1 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 604.72, ALogP -0.04, HBA 14, HBD 2, PSA 179.7, QED 0.14
Compound (SMILES): CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](Nc2ncnc3cc(C(C)(C)C)nn23)C1=O
InChIKey: CMVHFGNTABZQJU-HCXYKTFWSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Displacement of [125I]-interleukin-8 from human CXCR2 expressed in human pEAK rapid cells incubated for 90 mins by microscintillation counting analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 484.65, ALogP 2.25, HBA 8, HBD 3, PSA 116.55, QED 0.6
Compound (SMILES): CC(C)n1c(=O)n(C)c2cnc3cc(F)c(-c4ccc(OCCCN5CCCCC5)nc4)cc3c21
InChIKey: VQSZIPCGAGVRRP-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK (unknown origin)
Measurement: IC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 477.58, ALogP 4.93, HBA 7, HBD 0, PSA 65.18, QED 0.35
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1F
InChIKey: OYFMQDVLFYKOPZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of human recombinant N-terminal GST-tagged TYK2 (833 to 1187 residues) expressed in baculovirus expression system by Z'-lyte assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 395.39, ALogP 4.16, HBA 7, HBD 3, PSA 105.07, QED 0.47
Compound (SMILES): C[C@H](O)c1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nn1-c1cccc(Cl)c1
InChIKey: AZXOTZCWQDJCLY-SJCJKPOMSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Radiometric OXTR binding assay (Eurofins #260900)
Measurement: Ki = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 543.33, ALogP 3.62, HBA 9, HBD 2, PSA 110.99, QED 0.37
Compound (SMILES): CCO[C@H]1CCN(Cc2c(OC)cc(C)c3[nH]ccc23)[C@H](c2ccc(C(=O)O)cc2)C1
InChIKey: RENRQMCACQEWFC-UGKGYDQZSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Inhibition of adrenergic receptor alpha1a (unknown origin)
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 422.53, ALogP 4.93, HBA 4, HBD 2, PSA 74.79, QED 0.56
Compound (SMILES): COC1=CC(=O)N(C(=O)/C=C/[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)C2CCN(C)CC2)[C@H]1Cc1c[nH]c2ccccc12
InChIKey: IMTIJVSUXSYPRE-OAMSZMPYSA-N
Target: Cruzipain (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P25779
Assay: Inhibition of Trypanosoma cruzi cruzain using Z-FR-AMC as substrate preincubated for 10 mins followed by substrate addition by fluorimetric analysis
Measurement: IC50 = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 690.89, ALogP 3.44, HBA 7, HBD 4, PSA 152.94, QED 0.21
Compound (SMILES): COC1=CC(=O)N(C(=O)/C=C/[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2CCCCC2)NC(=O)C2CCN(C)CC2)[C@H]1Cc1c[nH]c2ccccc12
InChIKey: ZJLUYWUYIFDQKX-YGVSIWEKSA-N
Target: Cruzipain (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P25779
Assay: Inhibition of Trypanosoma cruzi cruzain using Z-FR-AMC as substrate preincubated for 10 mins followed by substrate addition by fluorimetric analysis
Measurement: IC50 = 0.086 nM (pChEMBL 10.069999694824219)
Descriptors: MW 730.95, ALogP 4.37, HBA 7, HBD 4, PSA 152.94, QED 0.2
Compound (SMILES): O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1cccc2cc[nH]c12
InChIKey: ZFHQLTFHZHQXAS-BCTJHDQDSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Competition Binding Assay: The competition binding assay was conducted to determine the affinity and selectivity of the synthesized compounds to MOR over KOR and DOR. The Kd and Bmax values for [3H]NLX at MOR and [3H]DPN at KOR had been determined previously. The Kd and Bmax values for [3H]DPN at DOR were determined using varying concentrations of [3H]DPN and fixed a concentration of 30 μg DOR membrane protein and 5 μM SNC80. [3H]NLX was used to label MOR whilst [3H]DPN was used to label both DOR and KOR. The potency of the new compounds in displacing the specific binding of the radioligand was determined by linear regression analysis of Hill plots. Specific (i.e., opioid receptor-related) binding at MOR, KOR and DOR was determined as the difference in binding obtained in the absence and presence of 5 μM naltrexone, U50,488 and SNC80, respectively. The IC50 values were determined and converted to Ki values using the ChengPrusoff equation (Rosenblum, A. et al. Exp Clin Psychopharmacol. 2008, 16 (5), 405-416).
Measurement: Ki = 0.229 nM (pChEMBL 9.640000343322754)
Descriptors: MW 485.58, ALogP 3.24, HBA 5, HBD 4, PSA 97.82, QED 0.46
Compound (SMILES): Cn1nccc1-c1ccc(C(=O)N[C@@H]2CNCC[C@H]2c2ccc(F)c(F)c2)c(F)c1
InChIKey: PALTUSLCLFDFQQ-MGPUTAFESA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 414.43, ALogP 3.38, HBA 4, HBD 2, PSA 58.95, QED 0.69
Compound (SMILES): CN(C)C(=O)Cn1ccc2ncc(-c3ccc(F)c(Cl)c3)cc21
InChIKey: OZQNCCZSWDCRSH-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG expressed in HEK293 cell membranes measured after 80 mins by TopCount scintillation analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 331.78, ALogP 3.58, HBA 3, HBD 0, PSA 38.13, QED 0.74
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(Sc2ccccc2)cc1Br
InChIKey: PRYBEVSATZDKFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 431.33, ALogP 1.97, HBA 5, HBD 3, PSA 109.49, QED 0.65
Compound (SMILES): Cl.Cl.O=C(CN1CCOCC1)Nc1ccc(OC2CCN(C3CCC3)CC2)cc1
InChIKey: LCPQCTBHZPMVFX-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate after 12 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 373.5, ALogP 2.35, HBA 5, HBD 1, PSA 54.04, QED 0.83
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccc(N)nc2)nc2c1C[C@@H]1COCCN21
InChIKey: FFFOZOQSDJISHN-TZMCWYRMSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Binding affinity to wild-type human full-length PI4Kbeta (M1 to M828 residues) expressed in mammalian expression system by kinome scan assay
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 368.44, ALogP 1.11, HBA 8, HBD 1, PSA 89.63, QED 0.84
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: ROCK-II(h) In Vitro Inhibition Activity: Table 2: ROCK-II(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-II(h) was incubated with the test compound in assay buffer containing 50 mM Tris pH 7.5 (VWR cat #103157P), 0.1 mM EGTA (VWR cat #20308), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(-n3nnc(-c4cc(OC)c(OC)cc4NC(=O)c4cc(=O)c5ccccc5o4)n3)cc1)CC2
InChIKey: AHJUHHDDCJQACA-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp in human Caco-2 cells assessed as reduction in paclitaxel efflux pre-incubated for 30 mins and measured after 120 mins by LC-MS/MS analysis
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 688.74, ALogP 5.32, HBA 12, HBD 1, PSA 143.07, QED 0.19
Compound (SMILES): CCO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CS[C@H]12)c1nsc(N)n1
InChIKey: RGFBRLNVZCCMSV-BIRGHMBHSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Compound was evaluated for inhibition of human MAOA in an in vitro cell free assay measured by fluorescence spectroscopy
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 604.72, ALogP -0.04, HBA 14, HBD 2, PSA 179.7, QED 0.14
Compound (SMILES): CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1CC[C@H](Nc2ncnc3cc(C(C)(C)C)nn23)C1=O
InChIKey: CMVHFGNTABZQJU-HCXYKTFWSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Mus musculus
UniProt: P51683
Assay: Displacement of [125I]-CCL2 from mouse CCR2
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 484.65, ALogP 2.25, HBA 8, HBD 3, PSA 116.55, QED 0.6
Compound (SMILES): CC(C)n1c(=O)n(C)c2cnc3cc(F)c(-c4ccc(OCCCN5CCCCC5)nc4)cc3c21
InChIKey: VQSZIPCGAGVRRP-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of ATM (unknown origin)
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 477.58, ALogP 4.93, HBA 7, HBD 0, PSA 65.18, QED 0.35
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1F
InChIKey: OYFMQDVLFYKOPZ-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 signaling pathway in human primary T-cells assessed as reduction of IL-2 induced cell proliferation
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 395.39, ALogP 4.16, HBA 7, HBD 3, PSA 105.07, QED 0.47
Compound (SMILES): C[C@H](O)c1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nn1-c1cccc(Cl)c1
InChIKey: AZXOTZCWQDJCLY-SJCJKPOMSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Assay with bioluminescence detection (AVPR1). (The vasopressin receptor cells react to stimulation of the recombinantly expressed V1a receptors by intracellular release of calcium ions, which can be quantified by the resulting photoprotein luminescence).
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 543.33, ALogP 3.62, HBA 9, HBD 2, PSA 110.99, QED 0.37
Compound (SMILES): O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1cccc2cc[nH]c12
InChIKey: ZFHQLTFHZHQXAS-BCTJHDQDSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Competition Binding Assay: The competition binding assay was conducted to determine the affinity and selectivity of the synthesized compounds to MOR over KOR and DOR. The Kd and Bmax values for [3H]NLX at MOR and [3H]DPN at KOR had been determined previously. The Kd and Bmax values for [3H]DPN at DOR were determined using varying concentrations of [3H]DPN and fixed a concentration of 30 μg DOR membrane protein and 5 μM SNC80. [3H]NLX was used to label MOR whilst [3H]DPN was used to label both DOR and KOR. The potency of the new compounds in displacing the specific binding of the radioligand was determined by linear regression analysis of Hill plots. Specific (i.e., opioid receptor-related) binding at MOR, KOR and DOR was determined as the difference in binding obtained in the absence and presence of 5 μM naltrexone, U50,488 and SNC80, respectively. The IC50 values were determined and converted to Ki values using the ChengPrusoff equation (Rosenblum, A. et al. Exp Clin Psychopharmacol. 2008, 16 (5), 405-416).
Measurement: Ki = 1.69 nM (pChEMBL 8.770000457763672)
Descriptors: MW 485.58, ALogP 3.24, HBA 5, HBD 4, PSA 97.82, QED 0.46
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(Sc2ccccc2)cc1Br
InChIKey: PRYBEVSATZDKFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human carbonic anhydrase 13 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 431.33, ALogP 1.97, HBA 5, HBD 3, PSA 109.49, QED 0.65
Compound (SMILES): Cl.Cl.O=C(CN1CCOCC1)Nc1ccc(OC2CCN(C3CCC3)CC2)cc1
InChIKey: LCPQCTBHZPMVFX-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate after 2 mins by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 373.5, ALogP 2.35, HBA 5, HBD 1, PSA 54.04, QED 0.83
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccc(N)nc2)nc2c1C[C@@H]1COCCN21
InChIKey: FFFOZOQSDJISHN-TZMCWYRMSA-N
Target: Phosphatidylinositol 3-kinase catalytic subunit type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NEB9
Assay: Binding affinity to human wild-type partial length VPS34 (S282 to H879 residues) expressed in mammalian expression system by kinome scan assay
Measurement: Kd = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 368.44, ALogP 1.11, HBA 8, HBD 1, PSA 89.63, QED 0.84
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(-n3nnc(-c4cc(OC)c(OC)cc4NC(=O)c4cc(=O)c5ccccc5o4)n3)cc1)CC2
InChIKey: AHJUHHDDCJQACA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using IPA as substrate preincubated for 10 mins followed by NADPH generating system addition and measured after 20 mins
Measurement: IC50 > 9000 nM (pChEMBL 5.046000003814697)
Descriptors: MW 688.74, ALogP 5.32, HBA 12, HBD 1, PSA 143.07, QED 0.19
Compound (SMILES): CCO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CS[C@H]12)c1nsc(N)n1
InChIKey: RGFBRLNVZCCMSV-BIRGHMBHSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity towards human HTR1A in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 604.72, ALogP -0.04, HBA 14, HBD 2, PSA 179.7, QED 0.14
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1F
InChIKey: OYFMQDVLFYKOPZ-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 signaling pathway in human primary T-cells assessed as reduction of IFN-alpha induced STAT1 phosphorylation
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 395.39, ALogP 4.16, HBA 7, HBD 3, PSA 105.07, QED 0.47
Compound (SMILES): C[C@H](O)c1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nn1-c1cccc(Cl)c1
InChIKey: AZXOTZCWQDJCLY-SJCJKPOMSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Assay with bioluminescence detection (AVPR). (The vasopressin receptor cells react to stimulation of the recombinantly expressed V1a receptors by intracellular release of calcium ions, which can be quantified by the resulting photoprotein luminescence).
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 543.33, ALogP 3.62, HBA 9, HBD 2, PSA 110.99, QED 0.37
Compound (SMILES): O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1cccc2cc[nH]c12
InChIKey: ZFHQLTFHZHQXAS-BCTJHDQDSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Competition Binding Assay: The competition binding assay was conducted to determine the affinity and selectivity of the synthesized compounds to MOR over KOR and DOR. The Kd and Bmax values for [3H]NLX at MOR and [3H]DPN at KOR had been determined previously. The Kd and Bmax values for [3H]DPN at DOR were determined using varying concentrations of [3H]DPN and fixed a concentration of 30 μg DOR membrane protein and 5 μM SNC80. [3H]NLX was used to label MOR whilst [3H]DPN was used to label both DOR and KOR. The potency of the new compounds in displacing the specific binding of the radioligand was determined by linear regression analysis of Hill plots. Specific (i.e., opioid receptor-related) binding at MOR, KOR and DOR was determined as the difference in binding obtained in the absence and presence of 5 μM naltrexone, U50,488 and SNC80, respectively. The IC50 values were determined and converted to Ki values using the ChengPrusoff equation (Rosenblum, A. et al. Exp Clin Psychopharmacol. 2008, 16 (5), 405-416).
Measurement: Ki = 10.9 nM (pChEMBL 7.960000038146973)
Descriptors: MW 485.58, ALogP 3.24, HBA 5, HBD 4, PSA 97.82, QED 0.46
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(Sc2ccccc2)cc1Br
InChIKey: PRYBEVSATZDKFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Binding affinity to recombinant human carbonic anhydrase 14 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 431.33, ALogP 1.97, HBA 5, HBD 3, PSA 109.49, QED 0.65
Compound (SMILES): Cl.Cl.O=C(CN1CCOCC1)Nc1ccc(OC2CCN(C3CCC3)CC2)cc1
InChIKey: LCPQCTBHZPMVFX-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Inverse agonist activity at recombinant human Histamine 3 receptor expressed in CHO-K1 cells assessed as inhibition of RAMH-induced agonist activity preincubated for 20 mins and measured after 60 mins by [35S]-GTPgammaS binding assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 373.5, ALogP 2.35, HBA 5, HBD 1, PSA 54.04, QED 0.83
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: ROCK-II(h) In Vitro Inhibition Activity: Table 2: ROCK-II(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-II(h) was incubated with the test compound in assay buffer containing 50 mM Tris pH 7.5 (VWR cat #103157P), 0.1 mM EGTA (VWR cat #20308), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(-n3nnc(-c4cc(OC)c(OC)cc4NC(=O)c4cc(=O)c5ccccc5o4)n3)cc1)CC2
InChIKey: AHJUHHDDCJQACA-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of wild type human P-gp in human MES-SA/Dx5 cells incubated for 3 days by MTT assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 688.74, ALogP 5.32, HBA 12, HBD 1, PSA 143.07, QED 0.19
Compound (SMILES): CCO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CS[C@H]12)c1nsc(N)n1
InChIKey: RGFBRLNVZCCMSV-BIRGHMBHSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Compound was evaluated for inhibition of human KDR in an in vitro cell free assay measured by time-resolved fluorescence resonance energy transfer method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 604.72, ALogP -0.04, HBA 14, HBD 2, PSA 179.7, QED 0.14
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1F
InChIKey: OYFMQDVLFYKOPZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 signaling pathway in human UKE-1 cells assessed as reduction of cell proliferation
Measurement: IC50 = 915 nM (pChEMBL 6.039999961853027)
Descriptors: MW 395.39, ALogP 4.16, HBA 7, HBD 3, PSA 105.07, QED 0.47
Compound (SMILES): C[C@H](O)c1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nn1-c1cccc(Cl)c1
InChIKey: AZXOTZCWQDJCLY-SJCJKPOMSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: GPCRScan assay: inhibition of KOR
Measurement: Ki = 2166.66 nM (pChEMBL 5.659999847412109)
Descriptors: MW 543.33, ALogP 3.62, HBA 9, HBD 2, PSA 110.99, QED 0.37
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(Sc2ccccc2)cc1Br
InChIKey: PRYBEVSATZDKFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 431.33, ALogP 1.97, HBA 5, HBD 3, PSA 109.49, QED 0.65
Compound (SMILES): Cl.Cl.O=C(CN1CCOCC1)Nc1ccc(OC2CCN(C3CCC3)CC2)cc1
InChIKey: LCPQCTBHZPMVFX-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 by whole-cell patch clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 373.5, ALogP 2.35, HBA 5, HBD 1, PSA 54.04, QED 0.83
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1F
InChIKey: OYFMQDVLFYKOPZ-UHFFFAOYSA-N
Target: JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK2/TYK2 signaling pathway in human primary T-cells assessed as reduction of IL-12 induced STAT4 phosphorylation
Measurement: IC50 = 1189 nM (pChEMBL 5.920000076293945)
Descriptors: MW 395.39, ALogP 4.16, HBA 7, HBD 3, PSA 105.07, QED 0.47
Compound (SMILES): C[C@H](O)c1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nn1-c1cccc(Cl)c1
InChIKey: AZXOTZCWQDJCLY-SJCJKPOMSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: GPCRScan assay: inhibition of KOR
Measurement: Ki = 2137.96 nM (pChEMBL 5.670000076293945)
Descriptors: MW 543.33, ALogP 3.62, HBA 9, HBD 2, PSA 110.99, QED 0.37
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(Sc2ccccc2)cc1Br
InChIKey: PRYBEVSATZDKFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.23 nM (pChEMBL 9.640000343322754)
Descriptors: MW 431.33, ALogP 1.97, HBA 5, HBD 3, PSA 109.49, QED 0.65
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1F
InChIKey: OYFMQDVLFYKOPZ-UHFFFAOYSA-N
Target: JAK2/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK2 signaling pathway in human U-937 cells assessed as reduction of IFN-gamma induced ICAM1 expression
Measurement: IC50 = 417 nM (pChEMBL 6.380000114440918)
Descriptors: MW 395.39, ALogP 4.16, HBA 7, HBD 3, PSA 105.07, QED 0.47
Compound (SMILES): C[C@H](O)c1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nn1-c1cccc(Cl)c1
InChIKey: AZXOTZCWQDJCLY-SJCJKPOMSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: GPCRScan assay: inhibition of NET
Measurement: Ki = 1316.15 nM (pChEMBL 5.880000114440918)
Descriptors: MW 543.33, ALogP 3.62, HBA 9, HBD 2, PSA 110.99, QED 0.37
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(Sc2ccccc2)cc1Br
InChIKey: PRYBEVSATZDKFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P07451
Assay: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 431.33, ALogP 1.97, HBA 5, HBD 3, PSA 109.49, QED 0.65
Compound (SMILES): Cc1ccc(C(=O)OCc2ccc([C@@H](CN)C(=O)Nc3ccc4cnccc4c3)cc2)c(C)c1
InChIKey: OURRXQUGYQRVML-AREMUKBSSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK-I(h) In Vitro Inhibition Activity-Method A: Table 2: ROCK-I(h) kinase assays were conducted using the KinaseProfiler service of Eurofins Pharma Discovery Services UK Limited. ROCK-I(h) was incubated with the test compound in assay buffer containing 8 mM MOPS pH 7.0 (VWR cat #441644J) 0.2 mM EDTA (Sigma cat #E5134), 30 μM KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (Pepceuticals), 10 mM magnesium acetate (Merck Millipore cat #105819) and [γ-33P-ATP] (Perkin Elmer cat #NEG602K). Test compound in 100% DMSO (Calbiochem cat #317275) was spotted into a 96-well assay plate prior using a Mosquito X1 (TTP Labtech) prior to addition of the reaction mix. The reaction was initiated by the addition of the Mg/ATP mix using a Matrix Wellmate. After incubation for 40 minutes at room temperature, the reaction was stopped by the addition of a 3% phosphoric acid solution (Fisher Scientific cat #O/0500/PB17) using a Matrix Wellmate. An aliquot of the reaction was then spotted onto a filtermat and washed in phosphoric acid followed by a rinse in methanol prior to drying and scintillation counting in a Trilux Wallac Microbeta detector (Perkin Elmer). Results were expressed in relation to controls containing DMSO only in place of test compound. Where applicable, IC50 curve analysis was performed using XLFit version 5.3 (ID Business Solutions). Sigmoidal dose-response (variable slope) curves are fitted using non-linear regression analysis.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 453.54, ALogP 4.89, HBA 5, HBD 2, PSA 94.31, QED 0.39