lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(NC(=O)CN2CCC3(CCCN3Cc3ccc(F)c(F)c3)C2)ccc1F
InChIKey: GTHHJVJOWMXRBS-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from D3 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 512 nM (pChEMBL 6.289999961853027)
Descriptors: MW 417.48, ALogP 4.09, HBA 3, HBD 1, PSA 35.58, QED 0.8
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)N[C@@H](C)CO
InChIKey: POMBIFQUJUHXAV-AWEZNQCLSA-N
Target: Bone morphogenetic protein receptor type-1A (SINGLE PROTEIN), Homo sapiens
UniProt: P36894
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): COc1ccc(Nc2ncnc3c2ccn3-c2ccc(C)c(C)c2)cc1Cl
InChIKey: DZIHITUUUPJMOQ-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TBX8
Assay: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 378.86, ALogP 5.44, HBA 5, HBD 1, PSA 51.97, QED 0.51
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC2(CCCN2Cc2ccc(F)c(F)c2)C1
InChIKey: QXQOZVSPURYOAI-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 1698.24 nM (pChEMBL 5.769999980926514)
Descriptors: MW 433.93, ALogP 4.61, HBA 3, HBD 1, PSA 35.58, QED 0.75
Compound (SMILES): COc1ccc2c(c1)OC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)CC2=O
InChIKey: JHNNUPWYLCFGLP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 447.47, ALogP 2.26, HBA 8, HBD 1, PSA 142.07, QED 0.56
Compound (SMILES): CN1CCN(C(=O)C(C)(C)c2ccc(C(=O)Cc3cn4cc(-c5ccncc5)ccc4n3)cc2)CC1
InChIKey: AOLMNCAPVYTEHC-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 146.6 nM (pChEMBL 6.829999923706055)
Descriptors: MW 481.6, ALogP 3.87, HBA 6, HBD 0, PSA 70.81, QED 0.39
Compound (SMILES): CCCOc1ccc(NC(=O)C(C)(C)c2csc(NS(=O)(=O)C3CC3)n2)cc1
InChIKey: BOEWQRNBSGZWMC-UHFFFAOYSA-N
Target: CTP synthase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P70303
Assay: Inhibition of mouse CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 423.56, ALogP 3.75, HBA 6, HBD 2, PSA 97.39, QED 0.64
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(C[C@H](C)C(=O)O)c2C#N)cc1
InChIKey: ZOCYJBFYLLNYQK-KRWDZBQOSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 13400 nM (pChEMBL 4.869999885559082)
Descriptors: MW 437.5, ALogP 5.5, HBA 5, HBD 1, PSA 96.1, QED 0.41
Compound (SMILES): CC1(C)[C@@H]2[C@@H](C(=O)N[C@H](C=O)C[C@@H]3CCNC3=O)N(C(=O)COc3ccc(Cl)cc3Cl)C[C@@H]21
InChIKey: BDFIPRXCQILSGM-ZUHDPNGNSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant SARS-CoV-2 3CLp using fluorogenic substrate by microplate reader
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 496.39, ALogP 2.07, HBA 5, HBD 2, PSA 104.81, QED 0.54
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3ccc(Cl)cc3)C4=O)nn2)cc1
InChIKey: CLELLOLWPKLTHX-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 48.91 nM (pChEMBL 7.309999942779541)
Descriptors: MW 537.94, ALogP 2.73, HBA 9, HBD 1, PSA 154.55, QED 0.29
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4nc5ccccc5[nH]4)c3c2)Cn2nnnc2N1C
InChIKey: XULTUONTNLFTDL-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 426.44, ALogP 2.46, HBA 8, HBD 3, PSA 133.3, QED 0.4
Compound (SMILES): CC(C)n1nc(-c2nnc(C3CCN(CC4(O)CCCC4)CC3)o2)c2ccccc21.O=C(O)C(=O)O
InChIKey: IWULMJQXAMPTDP-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 12 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 409.53, ALogP 4.15, HBA 7, HBD 1, PSA 80.21, QED 0.68
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C)cc4n3[C@@H](C)c3ccc(C)cc3)cc2)cc1
InChIKey: IGPRUALXJOEVNF-DEOSSOPVSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at human GAL4-fused RORbeta LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 551.71, ALogP 6.9, HBA 5, HBD 1, PSA 81.06, QED 0.23
Compound (SMILES): Cc1ccc(-c2cc(-c3ccc(S(=O)(=O)N[C@H](C(=O)O)C(C)C)cc3)no2)s1
InChIKey: NNCVCMDUQDAWGY-SFHVURJKSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of MMP12 (unknown origin)
Measurement: IC50 = 0.368 nM (pChEMBL 9.430000305175781)
Descriptors: MW 420.51, ALogP 3.77, HBA 6, HBD 2, PSA 109.5, QED 0.6
Compound (SMILES): C[C@@H]1CN(CCOc2cc(CC(=O)O)ccc2Cl)CCN1c1nc2ccc(Cl)cc2s1
InChIKey: DORQQPRGWXDMDY-CQSZACIVSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(Cc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: GHNOYQGNCIPRAH-OIAMUCEYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from kappa opioid receptor (unknown origin) assessed as inhibition constant incubated for 180 mins by competitive radioligand binding assay
Measurement: Ki = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 442.56, ALogP 3.88, HBA 5, HBD 0, PSA 42.01, QED 0.53
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N[C@H](CC)C(=O)NS(=O)(=O)C3CC3)c2C#N)cc1
InChIKey: VTAXIHMISZQRAG-RUZDIDTESA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 3360 nM (pChEMBL 5.46999979019165)
Descriptors: MW 555.66, ALogP 5.03, HBA 8, HBD 2, PSA 134.07, QED 0.28
Compound (SMILES): CCCOc1c(CCC)cc(-c2ccccc2C(=O)O)cc1NC(=O)Nc1ccc(C)cc1
InChIKey: UYODUNYIATWXJO-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 446.55, ALogP 6.75, HBA 3, HBD 3, PSA 87.66, QED 0.34
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(F)cc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: AMINIFOLNFYOOD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin) by Ambit kinase assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 376.39, ALogP 3.88, HBA 4, HBD 2, PSA 83.98, QED 0.71
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c5ccoc5c4)nn32)CC1
InChIKey: RRDIEPDENZRYJK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 241.4 nM (pChEMBL 6.619999885559082)
Descriptors: MW 449.51, ALogP 3.19, HBA 7, HBD 2, PSA 115.62, QED 0.58
Compound (SMILES): COc1ccc2sc(-c3cncc(NC(C)=O)c3)nc2c1
InChIKey: JLUXIHDOQQZMIZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 4409 nM (pChEMBL 5.360000133514404)
Descriptors: MW 299.36, ALogP 3.33, HBA 5, HBD 1, PSA 64.11, QED 0.81
Compound (SMILES): COCCOc1cc(F)c2c(c1)CC[C@@H]2Nc1nc2nc(O[C@@H]3CO[C@H]4[C@@H]3OC[C@H]4O)[nH]c2cc1Cl
InChIKey: RWALQNUYYICDCM-UMBWAWJWSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 520.95, ALogP 2.78, HBA 9, HBD 3, PSA 119.98, QED 0.38
Compound (SMILES): Nc1cc(Oc2ccc3c(C(=O)Nc4cccc(C(F)(F)F)c4)cccc3c2)ncn1
InChIKey: IOYGAWXBNPFOKF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGF-induced human VEGFR2 autophosphorylation transfected in CHO cells measured after 2 hrs by chemiluminescence assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 424.38, ALogP 5.28, HBA 5, HBD 2, PSA 90.13, QED 0.47
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNc3c(C(N)=O)c(-c4cc(OC)c(C5CC5)c(OC)c4)nn32)CC1
InChIKey: NVDXHXCRQAOJQR-SFHVURJKSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 479.58, ALogP 3.32, HBA 7, HBD 2, PSA 111.71, QED 0.59
Compound (SMILES): O=C(O)c1ccc2c(c1)nc(NCc1ccccc1)c1ncncc12
InChIKey: HEVVNKYNJCSHFA-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Inhibition of wild type human CK2alpha' in presence of ATP by radiometric kinase assay
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 330.35, ALogP 3.49, HBA 5, HBD 2, PSA 88, QED 0.56
Compound (SMILES): O=C(NCCN1CCOCC1)Nc1nc2ccc(Sc3nnc4ccc(-c5ccccc5)nn34)cc2s1
InChIKey: WTVCPJCTIVZLQJ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human MET L1195V mutant incubated for 1 hrs by ELISA assay
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 532.66, ALogP 4.01, HBA 10, HBD 2, PSA 109.57, QED 0.32
Compound (SMILES): CCCCNNC(=O)c1ccc(Cl)cc1
InChIKey: SOFXANVWFFBJSR-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 5820 nM (pChEMBL 5.239999771118164)
Descriptors: MW 226.71, ALogP 2.37, HBA 2, HBD 2, PSA 41.13, QED 0.6
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(Cc3ccc5c(c3)OCO5)C4=O)nn2)cc1
InChIKey: QNJQVLYQHWMMHP-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human transmembrane carbonic anhydrase 12 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 27.55 nM (pChEMBL 7.559999942779541)
Descriptors: MW 561.53, ALogP 1.8, HBA 11, HBD 1, PSA 173.01, QED 0.26
Compound (SMILES): Cc1cc(F)cc(-c2cnc3ccc(-c4cccc(C#N)c4O)cc3c2N2CCC(N)CC2)c1
InChIKey: UJWVFOZDAGJLCH-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 452.53, ALogP 5.52, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccncc4)c3c2)[C@@H](C)n2nnnc2N1C
InChIKey: AGBHROMNNPQXGK-GFCCVEGCSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 401.43, ALogP 2.53, HBA 8, HBD 2, PSA 117.51, QED 0.54
Compound (SMILES): CN1C[C@@H]2CC[C@H](C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CCC4)c3)c2n1
InChIKey: OXJWXQVCCWDQJS-DZGCQCFKSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of recombinant human ALK2 (147 to end residues) expressed in Sf9 infected baculovirus expression system using TRF0130 as substrate incubated for 3 hrs in presence of APT
Measurement: IC50 = 477 nM (pChEMBL 6.320000171661377)
Descriptors: MW 378.44, ALogP 1.75, HBA 7, HBD 1, PSA 95.83, QED 0.75
Compound (SMILES): O=C(c1cccnc1Oc1cc(Cl)ccc1Cl)N1CCN(C2COC2)c2ccccc21
InChIKey: KPXRVFTXTHPVCY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 456.33, ALogP 5.05, HBA 5, HBD 0, PSA 54.9, QED 0.55
Compound (SMILES): CNCc1ccc(-c2cc3cc(F)cc(C(N)=O)c3o2)cc1.Cl
InChIKey: GPFWTAVHQKERKY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Affinity On-target Cellular interaction: (Inhibition of H2O2 induced PAR formation in Capan-1 cells) EUB0002633aCl PARP1
Measurement: IC50 = 69.87 nM (pChEMBL 7.159999847412109)
Descriptors: MW 298.32, ALogP 3.06, HBA 3, HBD 2, PSA 68.26, QED 0.78
Compound (SMILES): N#Cc1ccc(N2C(=O)c3ccc(C(=O)OCc4cn(-c5ccc(S(N)(=O)=O)cc5)nn4)cc3C2=O)cc1
InChIKey: WNAIWAZVDQQDMK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human transmembrane carbonic anhydrase 12 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 14.39 nM (pChEMBL 7.840000152587891)
Descriptors: MW 528.51, ALogP 1.94, HBA 10, HBD 1, PSA 178.34, QED 0.29
Compound (SMILES): CN(C)C[C@H]1CN(C(=O)Cc2cc(F)c(F)cc2F)CC[C@]1(O)c1cccc(O)c1
InChIKey: JMDFENKDWRFUQU-AOMKIAJQSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at KOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 500.2 nM (pChEMBL 6.300000190734863)
Descriptors: MW 422.45, ALogP 2.65, HBA 4, HBD 2, PSA 64.01, QED 0.73
Compound (SMILES): CC(=O)NC1CSCc2cc3cc(c2)CSC(C(N)=O)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CCC(N)=O)NC(=O)C(Cc2c[nH]cn2)NCC(C)NC(=O)C(CSC3)NC(=O)C(CCCNC(=N)N)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C2CCN2C(=O)C(Cc2ccccc2)NC(=O)C(CO)NC1=O
InChIKey: NATBJNOLJXJRBB-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human fXIIa using Z-GGR-AMC as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1655.95
Compound (SMILES): O=C1C2=C(CCN(Cc3ccccc3)C2)N2CCN=C2N1Cc1ccc(C(F)(F)F)cc1
InChIKey: DFULPGUTXZTYKA-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 132 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNW8
Assay: Agonist activity at human G2A expressed in CHO-K1 cells co-expressing human GNA11 assessed as accumulation of IP-1 incubated for 90 mins by HTRF based FRET assay
Measurement: EC50 = 3920 nM (pChEMBL 5.409999847412109)
Descriptors: MW 440.47, ALogP 3.88, HBA 4, HBD 0, PSA 39.15, QED 0.72
Compound (SMILES): CN(C)CC1CN(C(=O)CCc2cccc(C(F)(F)F)c2)CCC1(O)c1cccc(O)c1
InChIKey: BTTDVYVTDTUALJ-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at KOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 105.4 nM (pChEMBL 6.980000019073486)
Descriptors: MW 450.5, ALogP 3.64, HBA 4, HBD 2, PSA 64.01, QED 0.71
Compound (SMILES): COc1cc(O)c2c(=O)cc(-c3ccc(N4CCN(C)CC4)cc3)oc2c1N1CCNCC1
InChIKey: FXIMIJCGTDGDFQ-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/CyclinD1 (unknown origin) by ADP-Glo assay
Measurement: IC50 = 2217 nM (pChEMBL 5.650000095367432)
Descriptors: MW 450.54, ALogP 2.34, HBA 8, HBD 2, PSA 81.42, QED 0.63
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc5[nH]ncc5c4)c(-c4c(Cl)c(C)cc5[nH]ncc45)c3C)C2)C1
InChIKey: APRMCKQFBKENDU-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Scintillation Proximity Assay (SPA): Assays were run using 384-well plates (781207/Greiner) in which one column was designated as the high signal (no inhibition) control, and contained DMSO with no test compound, and another column was designated as the low signal control (maximal inhibition), and contained no protein. Serial dilutions of compounds to be tested were added to the assay plate (resulting in duplicate 11-point dose response with semi-log compound dilutions from 50 μM to 0.5 nM or from 5 μM to 0.05 nM for the most potent compounds). A 1/20 isotopic dilution of labeled (Compound B) and non-labeled covalent (Compound A) probe was prepared and added to all wells on the plate. The reaction was started by addition of KRasG12C (M1-K169, biotinylated on the N-terminus) to the compounds and incubated for 2 hours with continuous agitation allowing for full modification of KRasG12C with probe or test compounds. Final concentrations in an assay volume of 40 μL were 10 nM KRasG12C, 25 nM radio-ligand and 475 nM unlabelled ligand. The assay buffer contained 20 mM Tris-HCl pH 7.5 (Invitrogen), 150 mM NaCl (Sigma Aldrich), 0.1 mM MgCl2 (Sigma Aldrich), and 0.01% Tween-20 (Sigma Aldrich). Following addition of 50 μL of a 400 μg/ml. suspension of streptavidin-coated YSi beads (Perkin Elmer), plates were incubated for a further 30 min with continuous agitation before reading the plates on a scintillation counter (Topcount NXT 384 (Packard).
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 512.02, ALogP 5.59, HBA 5, HBD 2, PSA 95.49, QED 0.31
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CC#N)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: IRIKLLIKMPLYCS-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 430.53, ALogP 1.81, HBA 8, HBD 1, PSA 120.98, QED 0.77
Compound (SMILES): CC(N)C(=O)NC1CSCc2cc3cc(c2)CSCC(C(=O)NC(C)C(N)=O)NC(=O)C(CCCNC(=N)N)NC(=O)C(C(C)C)NC(=O)C(CC(N)=O)NC(=O)C(CSC3)NC(=O)C(C)NC(=O)C(CCCCN)NC(=O)C(Cc2ccccc2)NC1=O
InChIKey: KECRAMBCZUQJGL-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human fXIIa using Z-GGR-AMC as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1298.63
Compound (SMILES): CC[C@@H]1CN2CCc3c([nH]c4cccc(O[C@@H]5O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]5O)c34)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: PRYHOGCYPICMAJ-IRERNMKVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Agonist activity at mouse KOR expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding incubated for 60 mins by scintillation spectroscopy analysis
Measurement: EC50 = 1143.5 nM (pChEMBL 5.940000057220459)
Descriptors: MW 560.6, ALogP 1.09, HBA 10, HBD 5, PSA 171.01, QED 0.19
Compound (SMILES): [11CH3]n1cc(CCNCc2ccc(/C=C/C(=O)NO)cc2)c2ccccc21
InChIKey: AEDUBEGTPWKDCX-UQCBPKKGSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of HDAC5 (unknown origin)
Measurement: IC50 = 99 nM (pChEMBL 7)
Descriptors: MW 349.43, ALogP 3.03, HBA 4, HBD 3, PSA 66.29, QED 0.27
Compound (SMILES): Cc1ccc(CS(=O)(=O)NC(=O)C2(C)CCN(c3nc4c(cc3C#N)C(=O)OC4)CC2)cc1
InChIKey: UDMPNYKEHCRGIV-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using Midazolam as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 468.54, ALogP 2.18, HBA 8, HBD 1, PSA 129.46, QED 0.66
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3c(N4CCOCC4)cc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: XMRMYIYEEWALOZ-UHFFFAOYSA-N
Target: DNA topoisomerase 2-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P11388
Assay: Inhibition of human DNA topoisomerase 2alpha relaxation
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 455.32, ALogP 4.03, HBA 6, HBD 3, PSA 107.55, QED 0.55
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn([C@H]4CC[C@H](O)CC4)c3)c2n1
InChIKey: GKEASMTXYHOIFG-NYKLAOPUSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 422.49, ALogP 1.5, HBA 8, HBD 2, PSA 116.06, QED 0.66
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)Nc2n[nH]c3ccc(-c4cncc(NC[C@@H](O)c5ccccc5)c4)cc23)cc1
InChIKey: VSTRBHWJZOVRDC-HHHXNRCGSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of CDK5 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.58, ALogP 5.15, HBA 6, HBD 5, PSA 132.03, QED 0.17
Compound (SMILES): Cc1cc(NC(=O)CN2CCC3(CCCN3Cc3ccc(F)c(F)c3)C2)ccc1F
InChIKey: GTHHJVJOWMXRBS-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from D5 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 417.48, ALogP 4.09, HBA 3, HBD 1, PSA 35.58, QED 0.8
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)N[C@@H](C)CO
InChIKey: POMBIFQUJUHXAV-AWEZNQCLSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC2(CCCN2Cc2ccc(F)c(F)c2)C1
InChIKey: QXQOZVSPURYOAI-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma-2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 433.93, ALogP 4.61, HBA 3, HBD 1, PSA 35.58, QED 0.75
Compound (SMILES): CN1CCN(C(=O)C(C)(C)c2ccc(C(=O)Cc3cn4cc(-c5ccncc5)ccc4n3)cc2)CC1
InChIKey: AOLMNCAPVYTEHC-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 739.6 nM (pChEMBL 6.130000114440918)
Descriptors: MW 481.6, ALogP 3.87, HBA 6, HBD 0, PSA 70.81, QED 0.39
Compound (SMILES): CCCOc1ccc(NC(=O)C(C)(C)c2csc(NS(=O)(=O)C3CC3)n2)cc1
InChIKey: BOEWQRNBSGZWMC-UHFFFAOYSA-N
Target: CTP synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P70698
Assay: Inhibition of mouse CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 423.56, ALogP 3.75, HBA 6, HBD 2, PSA 97.39, QED 0.64
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(C[C@H](C)C(=O)O)c2C#N)cc1
InChIKey: ZOCYJBFYLLNYQK-KRWDZBQOSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 437.5, ALogP 5.5, HBA 5, HBD 1, PSA 96.1, QED 0.41
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3ccc(Cl)cc3)C4=O)nn2)cc1
InChIKey: CLELLOLWPKLTHX-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human transmembrane carbonic anhydrase 12 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 33.89 nM (pChEMBL 7.46999979019165)
Descriptors: MW 537.94, ALogP 2.73, HBA 9, HBD 1, PSA 154.55, QED 0.29
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4nc5ccccc5[nH]4)c3c2)Cn2nnnc2N1C
InChIKey: XULTUONTNLFTDL-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 426.44, ALogP 2.46, HBA 8, HBD 3, PSA 133.3, QED 0.4
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C)cc4n3[C@@H](C)c3ccc(C)cc3)cc2)cc1
InChIKey: IGPRUALXJOEVNF-DEOSSOPVSA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Inverse agonist activity at human GAL4-fused RORalpha LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 551.71, ALogP 6.9, HBA 5, HBD 1, PSA 81.06, QED 0.23
Compound (SMILES): C[C@@H]1CN(CCOc2cc(CC(=O)O)ccc2Cl)CCN1c1nc2ccc(Cl)cc2s1
InChIKey: DORQQPRGWXDMDY-CQSZACIVSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(Cc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: GHNOYQGNCIPRAH-OIAMUCEYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at HA-tagged mouse mu opioid receptor expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by Glo Sensor assay
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 442.56, ALogP 3.88, HBA 5, HBD 0, PSA 42.01, QED 0.53
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N[C@H](CC)C(=O)NS(=O)(=O)C3CC3)c2C#N)cc1
InChIKey: VTAXIHMISZQRAG-RUZDIDTESA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 555.66, ALogP 5.03, HBA 8, HBD 2, PSA 134.07, QED 0.28
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(F)cc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: AMINIFOLNFYOOD-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of FMS (unknown origin) by Ambit kinase assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 376.39, ALogP 3.88, HBA 4, HBD 2, PSA 83.98, QED 0.71
Compound (SMILES): COc1ccc2sc(-c3cncc(NC(C)=O)c3)nc2c1
InChIKey: JLUXIHDOQQZMIZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 299.36, ALogP 3.33, HBA 5, HBD 1, PSA 64.11, QED 0.81
Compound (SMILES): COCCOc1cc(F)c2c(c1)CC[C@@H]2Nc1nc2nc(O[C@@H]3CO[C@H]4[C@@H]3OC[C@H]4O)[nH]c2cc1Cl
InChIKey: RWALQNUYYICDCM-UMBWAWJWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using terfenedine as substrate
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 520.95, ALogP 2.78, HBA 9, HBD 3, PSA 119.98, QED 0.38
Compound (SMILES): Nc1cc(Oc2ccc3c(C(=O)Nc4cccc(C(F)(F)F)c4)cccc3c2)ncn1
InChIKey: IOYGAWXBNPFOKF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human recombinant GST-fused VEGFR2 kinase domain transphosphorylation expressed in baculovirus expression system using poly-Glu-Tyr (4:1) as substrate measured after 10 mins in presence of gamma-[33P]-ATP by scintillation counting analysis
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 424.38, ALogP 5.28, HBA 5, HBD 2, PSA 90.13, QED 0.47
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNc3c(C(N)=O)c(-c4cc(OC)c(C5CC5)c(OC)c4)nn32)CC1
InChIKey: NVDXHXCRQAOJQR-SFHVURJKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR autophosphorylation at Tyr1068 residue in EGFR-amplified human A-431 cells preincubated with compound for 1 hrs followed by stimulation with human recombinant EGF and measured after 10 mins by HTRF-based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.58, ALogP 3.32, HBA 7, HBD 2, PSA 111.71, QED 0.59
Compound (SMILES): O=C(NCCN1CCOCC1)Nc1nc2ccc(Sc3nnc4ccc(-c5ccccc5)nn34)cc2s1
InChIKey: WTVCPJCTIVZLQJ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human MET D1228H mutant incubated for 1 hrs by ELISA assay
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 532.66, ALogP 4.01, HBA 10, HBD 2, PSA 109.57, QED 0.32
Compound (SMILES): CCCCNNC(=O)c1ccc(Cl)cc1
InChIKey: SOFXANVWFFBJSR-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 226.71, ALogP 2.37, HBA 2, HBD 2, PSA 41.13, QED 0.6
Compound (SMILES): Cc1cc(F)cc(-c2cnc3ccc(-c4cccc(C#N)c4O)cc3c2N2CCC(N)CC2)c1
InChIKey: UJWVFOZDAGJLCH-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Agonist activity at human SST5 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 452.53, ALogP 5.52, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccncc4)c3c2)[C@@H](C)n2nnnc2N1C
InChIKey: AGBHROMNNPQXGK-GFCCVEGCSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 12.1 nM (pChEMBL 7.920000076293945)
Descriptors: MW 401.43, ALogP 2.53, HBA 8, HBD 2, PSA 117.51, QED 0.54
Compound (SMILES): CN1C[C@@H]2CC[C@H](C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CCC4)c3)c2n1
InChIKey: OXJWXQVCCWDQJS-DZGCQCFKSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant N-terminal His-tagged human FGFR3 V555L mutant using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by HTRF assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 378.44, ALogP 1.75, HBA 7, HBD 1, PSA 95.83, QED 0.75
Compound (SMILES): O=C1C2=C(CCN(Cc3ccccc3)C2)N2CCN=C2N1Cc1ccc(C(F)(F)F)cc1
InChIKey: DFULPGUTXZTYKA-UHFFFAOYSA-N
Target: ATP-dependent Clp protease proteolytic subunit, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16740
Assay: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis
Measurement: EC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 440.47, ALogP 3.88, HBA 4, HBD 0, PSA 39.15, QED 0.72
Compound (SMILES): COc1cc(O)c2c(=O)cc(-c3ccc(N4CCN(C)CC4)cc3)oc2c1N1CCNCC1
InChIKey: FXIMIJCGTDGDFQ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) by ADP-Glo assay
Measurement: IC50 = 4524 nM (pChEMBL 5.340000152587891)
Descriptors: MW 450.54, ALogP 2.34, HBA 8, HBD 2, PSA 81.42, QED 0.63
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CC#N)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: IRIKLLIKMPLYCS-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 16.3 nM (pChEMBL 7.789999961853027)
Descriptors: MW 430.53, ALogP 1.81, HBA 8, HBD 1, PSA 120.98, QED 0.77
Compound (SMILES): [11CH3]n1cc(CCNCc2ccc(/C=C/C(=O)NO)cc2)c2ccccc21
InChIKey: AEDUBEGTPWKDCX-UQCBPKKGSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 349.43, ALogP 3.03, HBA 4, HBD 3, PSA 66.29, QED 0.27
Compound (SMILES): Cc1ccc(CS(=O)(=O)NC(=O)C2(C)CCN(c3nc4c(cc3C#N)C(=O)OC4)CC2)cc1
InChIKey: UDMPNYKEHCRGIV-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 468.54, ALogP 2.18, HBA 8, HBD 1, PSA 129.46, QED 0.66
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)Nc2n[nH]c3ccc(-c4cncc(NC[C@@H](O)c5ccccc5)c4)cc23)cc1
InChIKey: VSTRBHWJZOVRDC-HHHXNRCGSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of CDK6 (unknown origin)
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 518.58, ALogP 5.15, HBA 6, HBD 5, PSA 132.03, QED 0.17
Compound (SMILES): Cc1cc(NC(=O)CN2CCC3(CCCN3Cc3ccc(F)c(F)c3)C2)ccc1F
InChIKey: GTHHJVJOWMXRBS-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH23390 from D1 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 417.48, ALogP 4.09, HBA 3, HBD 1, PSA 35.58, QED 0.8
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)N[C@@H](C)CO
InChIKey: POMBIFQUJUHXAV-AWEZNQCLSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 15.7 nM (pChEMBL 7.800000190734863)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC2(CCCN2Cc2ccc(F)c(F)c2)C1
InChIKey: QXQOZVSPURYOAI-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH23390 from D1 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 433.93, ALogP 4.61, HBA 3, HBD 1, PSA 35.58, QED 0.75
Compound (SMILES): CN1CCN(C(=O)C(C)(C)c2ccc(C(=O)Cc3cn4cc(-c5ccncc5)ccc4n3)cc2)CC1
InChIKey: AOLMNCAPVYTEHC-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 49.1 nM (pChEMBL 7.309999942779541)
Descriptors: MW 481.6, ALogP 3.87, HBA 6, HBD 0, PSA 70.81, QED 0.39
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4nc5ccccc5[nH]4)c3c2)Cn2nnnc2N1C
InChIKey: XULTUONTNLFTDL-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pS1292 phosphorylation incubated for 2 hrs by MSD analysis
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 426.44, ALogP 2.46, HBA 8, HBD 3, PSA 133.3, QED 0.4
Compound (SMILES): C[C@@H]1CN(CCOc2cc(CC(=O)O)ccc2Cl)CCN1c1nc2ccc(Cl)cc2s1
InChIKey: DORQQPRGWXDMDY-CQSZACIVSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Agonist activity at Gal4-fused mouse PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(Cc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: GHNOYQGNCIPRAH-OIAMUCEYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at HA-tagged mouse mu opioid receptor expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by Glo Sensor assay
Measurement: EC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 442.56, ALogP 3.88, HBA 5, HBD 0, PSA 42.01, QED 0.53
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(F)cc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: AMINIFOLNFYOOD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) by Ambit kinase assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 376.39, ALogP 3.88, HBA 4, HBD 2, PSA 83.98, QED 0.71
Compound (SMILES): COc1ccc2sc(-c3cncc(NC(C)=O)c3)nc2c1
InChIKey: JLUXIHDOQQZMIZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 339.7 nM (pChEMBL 6.46999979019165)
Descriptors: MW 299.36, ALogP 3.33, HBA 5, HBD 1, PSA 64.11, QED 0.81
Compound (SMILES): Nc1cc(Oc2ccc3c(C(=O)Nc4cccc(C(F)(F)F)c4)cccc3c2)ncn1
InChIKey: IOYGAWXBNPFOKF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGF-induced human VEGFR2 autophosphorylation expressed in HUVEC cells measured after 2 hrs by chemiluminescence assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 424.38, ALogP 5.28, HBA 5, HBD 2, PSA 90.13, QED 0.47
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNc3c(C(N)=O)c(-c4cc(OC)c(C5CC5)c(OC)c4)nn32)CC1
InChIKey: NVDXHXCRQAOJQR-SFHVURJKSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of FLAG-tagged TEC autophosphorylation in HEK293 cells incubated for 2 hrs by MSD electrochemiluminescence immunoassay
Measurement: IC50 = 103.8 nM (pChEMBL 6.980000019073486)
Descriptors: MW 479.58, ALogP 3.32, HBA 7, HBD 2, PSA 111.71, QED 0.59