lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCOC(=O)c1cnc2ccc(C)cc2c1N1CCN(CC(=O)Nc2n[nH]c3ncccc23)CC1
InChIKey: UNZLOHMKHJXERK-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate pretreated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 473.54, ALogP 2.75, HBA 8, HBD 2, PSA 116.34, QED 0.41
Compound (SMILES): CN1C[C@H](Nc2nc3cc[nH]c3c(=O)n2C)C[C@H](c2ccc(OC(F)(F)F)cc2)C1
InChIKey: GKIIOLVMXQWUTJ-UONOGXRCSA-N
Target: Histone acetyltransferase KAT2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q92831
Assay: Binding affinity to human N-terminal His-tagged PCAF by isothermal titration calorimetry
Measurement: Kd = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 421.42, ALogP 3.06, HBA 6, HBD 2, PSA 75.18, QED 0.68
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)[C@@H](C)O
InChIKey: CGCHUERLXMTAEN-WGPKIHSISA-N
Target: Dickkopf WNT-signaling pathway inhibitor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: A6I0Z0
Assay: Inhibition of biotin-labeled rat recombinant DKK1 assessed as reduction in DKK1 interaction with LRP-6/Fc incubated overnight by chemiluminescence based Alpha-screen assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 4727.19
Compound (SMILES): Oc1cccc(OCCC2CCCCC2)c1-c1cnc[nH]1
InChIKey: XOMMGYPJJYEBPO-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 expressed in T-REx-293 cells assessed as reduction in kynurenine level measured after 16 hrs
Measurement: EC50 = 80000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 286.37, ALogP 4.13, HBA 3, HBD 2, PSA 58.14, QED 0.87
Compound (SMILES): O=C(c1ccc(-c2ccc(F)cc2Cl)cc1)N1CCN(C(=O)C2(O)CC2)CC1
InChIKey: KPYMGJDBFZANBT-UHFFFAOYSA-N
Target: Fatty acid synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P49327
Assay: Inhibition of FASN in human BT474 cells preincubated for 1 hr followed by [14C]-acetate addition and measured after 4 hrs by scintillation counting assay
Measurement: IC50 = 4960 nM (pChEMBL 5.300000190734863)
Descriptors: MW 402.85, ALogP 2.96, HBA 3, HBD 1, PSA 60.85, QED 0.86
Compound (SMILES): CS(=O)(=O)c1cc(Br)cc(-c2nnc(-c3ccc(C(=O)N[C@@H](Cn4ccnc4)c4ccc(-c5ccc(F)cc5)cc4Cl)cc3)o2)c1
InChIKey: GWNWIEYNTYTQJX-PMERELPUSA-N
Target: Lanosterol 14-alpha demethylase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16850
Assay: Inhibition of recombinant full length human CYP51 expressed in Escherichia coli incubated for 1 hr using [3H] lanosterol as substrate by HPLC analysis
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 721.01, ALogP 7.4, HBA 8, HBD 1, PSA 119.98, QED 0.17
Compound (SMILES): C[C@H](NC(=O)c1c(-c2ccccc2)nnn1CCOc1ccc(F)cc1)c1ccc(C(=O)O)cc1
InChIKey: KACXHPIOLAFDNG-KRWDZBQOSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Mus musculus
UniProt: P32240
Assay: Antagonist activity at mouse EP4 expressed in CHO cells coexpressing G16-alpha assessed as intracellular calcium flux preincubated for 15 mins followed by addition of PGE2 by calcium flux assay
Measurement: IC50 = 132.3 nM (pChEMBL 6.880000114440918)
Descriptors: MW 474.49, ALogP 4.35, HBA 6, HBD 2, PSA 106.34, QED 0.37
Compound (SMILES): CCOC(=O)N1CCC(=CC#Cc2cccc(C#N)c2)CC1
InChIKey: QWWMNIZBTUYTCH-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6 using 3-[2-(N,N-diethylamino)ethyl]-7-methoxy-4-methylcoumarin as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 294.35, ALogP 3.09, HBA 3, HBD 0, PSA 53.33, QED 0.75
Compound (SMILES): CN1CCC(CNC(=O)c2ccncc2Nc2cc(-c3ccc4ccn(C)c4c3)c3nccnc3c2)C1
InChIKey: HOOQIXYPPUPSGW-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3 in human HCT116 cell lysates assessed as reduction in glycolytic-flux induced fructose-2,6-bisphosphate formation using fructose-6-phosphate as substrate treated with cells prior to glucose stimulation followed by PFK1 and substrate addition and measured at 0.5 mins interval for 45 mins
Measurement: IC50 = 24010 nM (pChEMBL 4.619999885559082)
Descriptors: MW 491.6, ALogP 4.61, HBA 7, HBD 2, PSA 87.97, QED 0.36
Compound (SMILES): CC(C)NC[C@@H](O)COc1ccc(O)c(O)c1
InChIKey: BTOQOGYPRARWDT-SECBINFHSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Mus musculus
UniProt: P34971
Assay: Displacement of [3H]-CGP-12177 from murine beta1-adrenergic receptor expressed in HEK293T cells after 60 mins by radioligand competition binding assay
Measurement: Ki = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 241.29, ALogP 0.84, HBA 5, HBD 4, PSA 81.95, QED 0.55
Compound (SMILES): CN1CCc2c1nc(N1CCC3(CC1)C(=O)N(CCO)c1cc(F)cc(F)c13)[nH]c2=O
InChIKey: RSDNLMODCLIZFE-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of recombinant human N-terminal TEV cleavage site-fused/FLAG-poly his-tagged TNKS2 ARC5-SAM-PARP domain (613 to 1166 residues) expressed in Escherichia coli assessed as reduction in auto-PARylation preincubated for 10 mins followed by biotinylated-NAD+ addition and measured after 45 mins by ELISA
Measurement: IC50 = 27.6 nM (pChEMBL 7.559999942779541)
Descriptors: MW 431.44, ALogP 0.92, HBA 6, HBD 2, PSA 92.77, QED 0.75
Compound (SMILES): Cn1cc(C2C3CC4CC2CN(C4)C3)c2ccc(C(=O)NS(=O)(=O)C3CC3)cc21
InChIKey: WDRXHDZPFLDCKI-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 at -50 mV holding potential by cell-based IonWorks barracuda automated electrophysiology method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 413.54, ALogP 2.46, HBA 5, HBD 1, PSA 71.41, QED 0.84
Compound (SMILES): O=C(Cc1ccc(Oc2nc3ccccc3s2)cc1F)NCc1c[nH]c2cc(F)ccc12
InChIKey: URDNGEHEARGIJN-UHFFFAOYSA-N
Target: Leukotriene A-4 hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P09960
Assay: Inhibition of (His)6 tagged human recombinant LTA4H expressed in Escherichia coli BL21(DE3) using non-fluorescent L-arginine-7-amino-4-methylcoumarine as substrate preincubated for 30 mins followed by substrate addition and measured for 30 mins by fluorescence based assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 449.48, ALogP 5.71, HBA 4, HBD 2, PSA 67.01, QED 0.35
Compound (SMILES): C[C@@]1(CO)Cc2cc(NC(=O)c3cnn4cccnc34)c(N3CCOCC3)cc2O1
InChIKey: JLKSBHRAVFWETB-NRFANRHFSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human THP1-Xblue-MD2-CD14 cells assessed as reduction in LPS-induced NFkappaB transcription by measuring alkaline phosphatase level preincubated for 1 hr followed by LPS stimulation and measured after 20 hrs by quanti-blue reagent based reporter assay
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 409.45, ALogP 1.5, HBA 8, HBD 2, PSA 101.22, QED 0.67
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCOCC1)c(=O)n2C
InChIKey: XISVSTPEXYIKJL-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK in human A549 cells assessed as reduction in irradiation-induced autophosphorylation at S2056 residue preincubated for 1 hr followed by 8 Gy irradiation and measured after 1 hr by ELISA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 380.41, ALogP 1.58, HBA 10, HBD 1, PSA 104.16, QED 0.58
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)C[S+]([O-])Cc2c(C)noc2C)CC1
InChIKey: TZCJHPQHEHWFTO-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 375.49, ALogP 2.2, HBA 5, HBD 0, PSA 72.64, QED 0.75
Compound (SMILES): Cc1c(-c2c(-c3ccc(F)o3)sc3ncnc(O[C@H](Cc4ccccc4OCc4ccnn4CC(F)(F)F)C(=O)O)c23)ccc(OCCN2CCN(C)CC2)c1Cl
InChIKey: ZFBHXVOCZBPADE-SSEXGKCCSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of MCl-1 (unknown origin)
Measurement: Ki = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 829.27, ALogP 7.76, HBA 12, HBD 1, PSA 128.21, QED 0.1
Compound (SMILES): NC(=O)c1c(Nc2ccc(Cl)cc2Cl)[nH]c2c(Cl)ccc(Cl)c2c1=O
InChIKey: WSTLBEWBBCSETN-UHFFFAOYSA-N
Target: Protein lin-28 homolog A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9Z2
Assay: Binding affinity to recombinant human N-terminal His6-tagged Lin28a expressed in Escherichia coli Rosetta2 (DE3) pLysS by surface plasmon resonance analysis
Measurement: Kd = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 417.08, ALogP 4.98, HBA 3, HBD 3, PSA 87.98, QED 0.56
Compound (SMILES): O=C(CCc1cccc(C(F)(F)F)c1)Nc1cc(Oc2ccc3nc(NC(=O)C4CC4)sc3c2)ccc1F
InChIKey: UEHMGSTWWBKBBG-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Binding affinity to wild-type human partial length RIPK3 (M1 to Q307 residues) expressed in bacterial expression system after 1 hr by quantitative PCR based KINOMEscan assay
Measurement: Kd = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 543.54, ALogP 7.17, HBA 5, HBD 2, PSA 80.32, QED 0.23
Compound (SMILES): COc1nn2cc(-c3cc4c(OC)cccc4o3)nc2s1
InChIKey: HDUZNTFLTHRWAF-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI0
Assay: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay
Measurement: IC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 301.33, ALogP 3.22, HBA 7, HBD 0, PSA 61.79, QED 0.58
Compound (SMILES): COCC1OC2(CCN(CCc3ccccc3)CC2)CN(c2ccccc2)C1=O
InChIKey: CAXQLHIXVZVOAJ-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHOK1 cells assessed as stimulation of cAMP accumulation incubated for 45 mins by HTRF assay
Measurement: EC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 394.52, ALogP 3.14, HBA 4, HBD 0, PSA 42.01, QED 0.75
Compound (SMILES): Cc1ccc(-n2ccc3c(Nc4cccc(NC(=O)c5ccc(NC(=O)/C=C/CN(C)C)cc5)c4)ncnc32)cc1
InChIKey: QSHQSGKUSRNJPU-VMPITWQZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P78356
Assay: Inhibition of PI5P4Kbeta (unknown origin) incubated for 15 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 9900 nM (pChEMBL 5)
Descriptors: MW 545.65, ALogP 5.78, HBA 7, HBD 3, PSA 104.18, QED 0.2
Compound (SMILES): N#Cc1cccc(C(=O)Nc2cccc3c2CCC3N2CCN(C(=O)C3CCCC3)CC2)c1
InChIKey: YYMICDVHCXFIBG-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: Inverse agonist activity at RORgammat in mouse CD4 positive T cells assessed as inhibition of Th17 cell differentiation by measuring IL-17 release after 4 days by cellular staining based flow cytometry
Measurement: IC50 = 1782.5 nM (pChEMBL 5.75)
Descriptors: MW 442.56, ALogP 4.13, HBA 4, HBD 1, PSA 76.44, QED 0.77
Compound (SMILES): CC1(C)Cc2cc(NC(=O)c3cnn4cccnc34)c(N3CCOCC3)cc2C1O
InChIKey: RATMYVYGSCVTEW-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full-length N-terminal His6-tagged human IRAK4 expressed in baculovirus expression system using H-KKARFSRFAGSSPSQSSMVAR peptide as substrate after 90 mins by fluorescence polarisation assay
Measurement: Ki = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 407.47, ALogP 2.43, HBA 7, HBD 2, PSA 91.99, QED 0.69
Compound (SMILES): O[C@@H]1c2ccnn2CC[C@H]1[C@H]1c2ccccc2-c2cncn21
InChIKey: IFVZLNHSMBKMSZ-XKQJLSEDSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human A172 cells after 24 hrs in presence of IFNgamma by NFK green reagent based assay
Measurement: EC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 292.34, ALogP 2.4, HBA 5, HBD 1, PSA 55.87, QED 0.75
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(F)cn3)ccc2F)Cc2ncncc2C(N)=N1
InChIKey: BRCYVPIMBJJFFF-FQEVSTJZSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Time-Resolved Endpoint Proteolysis aAssay: Inhibitor IC50s at purified human autoBACE-2 are determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light. Inhibitor compounds, prepared at 3× the desired final concentration in 1×BACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO are pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1×BACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30° C. The assay is initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 μM for 4 μM for autoBACE-2) prepared in 1×BACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30° C. DMSO is present at 5% final concentration in the assay. Following laser excitation of sample wells at 320 nm, the fluorescence signal at 620 nm is collected for 400 ms following a 50 μs delay on a RUBYstar HTRF plate reader (BMG Labtechnologies). Raw RFU data is normalized to maximum (1.0 nM BACE/DMSO) and minimum (no enzyme/DMSO) RFU values.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 394.39, ALogP 2.58, HBA 6, HBD 2, PSA 106.15, QED 0.71
Compound (SMILES): O=C(NO)c1ccc(Cc2nnc[nH]2)cc1
InChIKey: LAZDRBDEOWORSZ-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489) expressed in baculovirus infected sf9 insect cells pretreated with compound followed by Fluor de Lys deacetylase substrate addition by fluorescence method
Measurement: IC50 = 2896 nM (pChEMBL 5.539999961853027)
Descriptors: MW 218.22, ALogP 0.51, HBA 4, HBD 3, PSA 90.9, QED 0.52
Compound (SMILES): CC(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)[C@@H](C)O)[C@@H](C)O
InChIKey: WTLNDVBCNUJPBR-ITKBPXBPSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 1558.76
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc2ccc(Cl)cc2)NC(=O)CCCSC[C@@H](C(=O)N2CSC[C@H]2C(=O)N[C@H](CCCNC(=N)N)C(=O)NCCc2cccs2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: AQCUQKJQKKRGGY-GUPRDMPJSA-N
Target: Vasopressin V1b receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47901
Assay: Agonist activity at recombinant human V1B receptor expressed in HEK293 cells measured after 5 hrs by luciferase reporter gene assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 1129.8
Compound (SMILES): Cc1c(C)c2ccc(OCC3CCCN(Cc4ccc(F)cc4)C3)cc2oc1=O.Cl
InChIKey: YOWUEPXICGUKNK-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB expressed in microsomes of baculovirus-infected insect cell using kynuramine as substrate preincubated for 20 mins followed by protein addition measured after 30 mins by fluorescence assay
Measurement: IC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 395.47, ALogP 4.84, HBA 4, HBD 0, PSA 42.68, QED 0.58
Compound (SMILES): COc1cc(F)ccc1-c1ncnc(Nc2cccc(C[S@](C)(=N)=O)c2)n1
InChIKey: ACWKGTGIJRCOOM-HHHXNRCGSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant full length His-tagged human CDK9/cyclin-T1 expressed in insect cells using biotin-Ttds-YISPLKSPYKISEG as substrate preincubated for 15 mins followed by substrate addition and measured after 25 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 387.44, ALogP 3.61, HBA 7, HBD 2, PSA 100.85, QED 0.67
Compound (SMILES): O=C(NCc1ccccc1OC(F)(F)F)c1csc(CCNCc2nc3ccccc3[nH]2)n1
InChIKey: VZGRANMISMQZGK-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 475.5, ALogP 4.18, HBA 6, HBD 3, PSA 91.93, QED 0.32
Compound (SMILES): Oc1ccc2c(O)ncc(-c3cc(F)c(F)c(F)c3)c2c1
InChIKey: CMNAKAUBHYLUQT-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Displacement of [3H]-R1881 from androgen receptor (unknown origin) expressed in human HeLa cells harboring AR3A-PSA-(ARE)4-Luc13 incubated for 2 hrs by scintillation counting
Measurement: IC50 = 80000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 291.23, ALogP 3.73, HBA 3, HBD 2, PSA 53.35, QED 0.67
Compound (SMILES): Cn1cc(-c2cc3nccnc3c(NC[C@@H]3CNCCC3(F)F)n2)cn1
InChIKey: KNGBPOUPNSUJPG-LBPRGKRZSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of N-terminal-6His-tagged full length human Aurora B expressed in baculovirus using 5FAM-PKA-tide as substrate after 120 mins by fluorescence polarization assay
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 359.38, ALogP 2.08, HBA 7, HBD 2, PSA 80.55, QED 0.74
Compound (SMILES): CC(C)C(C)Sc1nn([C@@H]2O[C@H](COS(N)(=O)=O)[C@@H](O)[C@@H]2F)c2ncnc(N)c12
InChIKey: BBPAZQCPQCGORX-XAZCMVNQSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 450.52, ALogP 0.36, HBA 11, HBD 3, PSA 168.47, QED 0.5
Compound (SMILES): Cc1cc(Oc2nccc3occc23)ccc1-c1c(C)nc2cnccn12
InChIKey: QKBXFUHRWRJTOQ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at recombinant human D1 receptor expressed in HEK29T cells assessed as induction of stimulatory G-protein-mediated cAMP accumulation measured after 15 mins by Glosensor-based FLIPR assay
Measurement: EC50 = 5.754 nM (pChEMBL 8.239999771118164)
Descriptors: MW 356.39, ALogP 4.95, HBA 6, HBD 0, PSA 65.45, QED 0.46
Compound (SMILES): CCCn1c(=O)c2c(nc3cc(OC)ccn32)n(CCCNC(=O)c2ccc(S(=O)(=O)F)cc2)c1=O
InChIKey: QNCALQNHCSHYFR-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from human A1 adenosine receptor expressed in CHO cell membranes measured after 2 hrs by scintillation spectrometric method
Measurement: Ki = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 517.54, ALogP 1.71, HBA 10, HBD 1, PSA 133.77, QED 0.26
Compound (SMILES): COc1cc2ncnc(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2cc1OCCCN1CCNCCNCC1
InChIKey: JBSDBYXRHGAOIT-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of wild type human N-terminal His-tagged HER2 cytoplasmic domain (676 to 1255 residues) expressed in baculovirus expression system after 1 hr in presence of ULight-labeled peptide substrate and ATP by LANCE ultra kinase assay
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 595.12, ALogP 5.02, HBA 9, HBD 3, PSA 92.8, QED 0.21
Compound (SMILES): O=C(Cc1cccc(OC(F)(F)F)c1)Nc1cc(Oc2ccc3nc(NC(=O)C4CC4)sc3c2)ccc1F
InChIKey: PZBUOCXBGCVSAF-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Binding affinity to wild-type human partial length RIPK3 (M1 to Q307 residues) expressed in bacterial expression system after 1 hr by quantitative PCR based KINOMEscan assay
Measurement: Kd = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 545.51, ALogP 6.66, HBA 6, HBD 2, PSA 89.55, QED 0.24
Compound (SMILES): Cc1ccc(N2C(=O)C(O)=C(C(=O)C(C)C)C2C2CCCCC2)cc1
InChIKey: PUKIAWNJPGVZPZ-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Displacement of [3H]-CCR2-RA-[R] from human TEV protease site linked CCR1 expressed in human U20S cell membranes co-expressing Gal4-VP16 transcription factor after 120 mins by scintillation spectrometry
Measurement: Ki = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 341.45, ALogP 4.33, HBA 3, HBD 1, PSA 57.61, QED 0.89
Compound (SMILES): Cl.O=C(CCN1CCOCC1)c1cc2cc(Br)c(O)c(Br)c2oc1=O
InChIKey: LQWIPXBJGTXBON-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by horse-radish peroxidase-coupled amplex red reagent-based fluorescence spectrophotometric method
Measurement: IC50 = 14080 nM (pChEMBL 4.849999904632568)
Descriptors: MW 461.11, ALogP 2.93, HBA 6, HBD 1, PSA 79.98, QED 0.56
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: UKSUKCFAXQZWEG-RPHQFHTDSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in absence of albumin by CRE luciferase reporter gene assay
Measurement: EC50 = 0.032 nM (pChEMBL 10.489999771118164)
Descriptors: MW 3718.27
Compound (SMILES): O=c1c(-c2ccccc2F)c2ccccn2c(=O)n1CCCCN1CCCC(c2c[nH]c3ccc(F)cc23)C1
InChIKey: WWJIYPPDCNQYTL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from recombinant human 5HT1A receptor expressed in CHO cell membranes measured after 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 218 nM (pChEMBL 6.659999847412109)
Descriptors: MW 528.6, ALogP 5.55, HBA 5, HBD 1, PSA 62.51, QED 0.28
Compound (SMILES): Cl.O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1ccc2occc2c1
InChIKey: JGLHXQXUHKJCKZ-HBJKKLOVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Displacement of [3H]-Naltrindole from mouse kappa opioid receptor expressed in CHO cells incubated for 1.5 hrs by competitive radioligand binding assay
Measurement: Ki = 4.23 nM (pChEMBL 8.369999885559082)
Descriptors: MW 486.57, ALogP 3.5, HBA 6, HBD 3, PSA 95.17, QED 0.52
Compound (SMILES): CN1CCCc2c1nc(N1CCC3(CC1)C(=O)N(C)c1cc(F)cc(F)c13)[nH]c2=O
InChIKey: FAANBVRTVUGZKM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of recombinant human N-terminal TEV cleavage site-fused/FLAG-poly his-tagged TNKS2 ARC5-SAM-PARP domain (613 to 1166 residues) expressed in Escherichia coli assessed as reduction in auto-PARylation preincubated for 10 mins followed by biotinylated-NAD+ addition and measured after 45 mins by ELISA
Measurement: IC50 = 10.7 nM (pChEMBL 7.96999979019165)
Descriptors: MW 415.44, ALogP 1.95, HBA 5, HBD 1, PSA 72.54, QED 0.77
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)NCCc3ccc(O)cc3)cc12
InChIKey: ISSAIUVNVQGNCG-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Displacement of fluormone PPAR green tracer ligand from recombinant GST-tagged PPARgamma ligand binding domain (unknown origin) incubated for 4 hrs by competitive fluorescence polarization binding assay
Measurement: Ki = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 518.61, ALogP 6.35, HBA 4, HBD 3, PSA 91.56, QED 0.22
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nc(C(=O)OCCN3CCOCC3)cc2-c2ccc(F)cc2)cc1
InChIKey: MAKADFGVDFFLRX-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P12527
Assay: Inhibition of Sprague-Dawley rat 5-LOX assessed as calcium ionophore A23187-stimulated LTB4 production preincubated for 30 mins followed by calcium ionophore A23187 addition and measured after 30 mins by ELISA
Measurement: IC50 = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 474.51, ALogP 1.81, HBA 8, HBD 1, PSA 116.75, QED 0.52
Compound (SMILES): CS(=O)(=O)c1cccc(S(=O)(=O)c2ccc(CN)s2)n1.Cl
InChIKey: UZXDBFFOUKCIJH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB expressed in baculovirus infected BTI insect cells incubated for 1 hr by luminescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 332.43, ALogP 0.84, HBA 7, HBD 1, PSA 107.19, QED 0.89
Compound (SMILES): COCCn1cc(-c2c(-c3ccc(Cl)cc3)nc3c(N4CCOCC4)nccn23)cn1
InChIKey: TXZWJUACJCVHQE-UHFFFAOYSA-N
Target: GRIA1/CACNG8 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WXS5
Assay: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 438.92, ALogP 3.4, HBA 8, HBD 0, PSA 69.71, QED 0.46
Compound (SMILES): COc1cccc(C(C)(C)NC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)c2cc(C(=O)NCCO)cc(N3CCCCC3)c2)c1
InChIKey: FTVBVWNZKYPGOY-AJQTZOPKSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human cathepsin D using DABCYL-Glu-Arg-Nle-Phe-Leu-Ser-Phe-Pro-EDANS as substrate preincubated for 30 mins followed by substrate addition and measured every min for 8 to 15 mins by FRET assay
Measurement: IC50 = 1420 nM (pChEMBL 5.849999904632568)
Descriptors: MW 602.78, ALogP 3.63, HBA 7, HBD 5, PSA 123.16, QED 0.19
Compound (SMILES): O=C(Cc1ccc(-c2ccccc2)cc1)Nc1cc(C2CCC2)[nH]n1
InChIKey: DTNFOGMAASDEQI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/CyclinE (unknown origin) in presence of ATP
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 331.42, ALogP 4.53, HBA 2, HBD 2, PSA 57.78, QED 0.72
Compound (SMILES): COc1ccc2c(c1)c(CC(=O)N[C@@H](Cc1ccc(OCc3ccc(Br)cc3)cc1)C(=O)NS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1)c(C)n2C(=O)c1ccc(Cl)cc1
InChIKey: UCKJHWQRSPPAHM-BHVANESWSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of 5-FAM-tagged Bid-BH3 peptide binding to Mcl1 (unknown origin) by fluorescence polarization assay
Measurement: Ki = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 908.61, ALogP 7.98, HBA 10, HBD 2, PSA 175.94, QED 0.08
Compound (SMILES): O=C(O)c1ccc(-c2noc(-c3cc4c(C(F)(F)F)ccc(F)c4o3)n2)cc1
InChIKey: FXUBADJBEQLXCF-UHFFFAOYSA-N
Target: Retinoic acid receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P11416
Assay: Transactivation of GAL4-fused mouse RARalpha-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
Measurement: EC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 392.26, ALogP 5.01, HBA 5, HBD 1, PSA 89.36, QED 0.49
Compound (SMILES): O=C(OC(C(F)(F)F)C(F)(F)F)N1CCN(Cc2ccc(C(F)(F)F)cc2N2[C@@H]3CC[C@H]2COC3)CC1
InChIKey: FHODREPDGXGHBI-IYBDPMFKSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of ABHD6 derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 549.43, ALogP 4.82, HBA 5, HBD 0, PSA 45.25, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(-c3ccc(Cl)c(Cl)c3)o2)cc1
InChIKey: QMMLKYIEFBOHLT-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in insect cells microsomes assessed as inhibition of 4-hydroxyquinoline formation using kynuramine as substrate incubated for 20 mins by fluorescence spectrophotometry analysis
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 370.22, ALogP 3.36, HBA 5, HBD 1, PSA 99.08, QED 0.76
Compound (SMILES): C=CCn1cc(-c2ccc(NC(=O)Nc3cc(C(C)(C)C)on3)cc2)c2c(N)ncnc21
InChIKey: XIMGYPHSYIMHAW-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Binding affinity to wild-type human partial length FLT3 (V592 to Y969 residues) expressed in Escherichia coli after 1 hr by qPCR analysis
Measurement: Kd = 4.37 nM (pChEMBL 8.359999656677246)
Descriptors: MW 431.5, ALogP 4.8, HBA 7, HBD 3, PSA 123.89, QED 0.39
Compound (SMILES): Oc1ccc2c(c1)OCCC1=C2C(c2ccc(OCCN3CC(CF)C3)cc2)Oc2ccc(O)cc21
InChIKey: KLMVORSBCFNPRO-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of ERalpha degradation in human MCF7 cells after 4 hrs by Alexafluor-488 conjugate anti-mouse IgG antibody/Hoechst 33342 staining based immunofluorescence imaging analysis
Measurement: IC50 = 0.021 nM (pChEMBL 10.680000305175781)
Descriptors: MW 489.54, ALogP 5.2, HBA 6, HBD 2, PSA 71.39, QED 0.5
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)NCC(F)(F)F)nc3cnc4[nH]ccc4c32)CC1
InChIKey: JNUDIJJVTYHAPN-JOCQHMNTSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was ≤0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of 2× enzyme and ATP mixture to 10 μL of 2× substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK 3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat #06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction. The assay conditions for the above assays are shown in Table 3 and the results of Ex. 1-209 as tested in these assays are shown in Table 4.TABLE 3Assay conditions for JAK family enzyme assays* [p], [ATP], [Substrate], [IS],Enzyme nM μM μM nMJAK1-JH1JH2 8.0 12.5 200 100JAK2-JH1JH2 7.0 or 3.6 30 40 100JAK3-JH1JH2 2.0 150 40 100Tyk2-JH1JH2   25 or 14.7 50 200 100*Reaction buffer: 50 mM MOPS, pH 7.5 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20; IS stands for internal standard peptide; p stands for phospho-peptide (product); Substrate stands for peptide.
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 418.42, ALogP 3.78, HBA 5, HBD 2, PSA 99.39, QED 0.66
Compound (SMILES): Cc1cn(C23CC(Nc4nc5n(n4)CCCC[C@@H]5c4ccc(Cl)cc4)(C2)C3)cn1
InChIKey: UKAFCWRUMNMSBA-OSFYOIPJSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Cellular gamma-Secretase Assay: Human neuroglioma H4 cells overexpressing human APP695 with the Swedish double mutation (K595N/M596L) were plated at 30,000 cells/well/100 μl in 96-well plates in IMDM media containing 10% FCS, 0.2 mg/l Hygromycin B and incubated at 37° C., 5% CO2.3-4 hr post plating, compounds are a diluted in media and 50 μl is added as 1.5-fold concentrate to achieve the final concentration. Compound incubation is performed for 24 hr. Final doses typically range from 4 μM down to 0.001 μM in half-log steps resulting in a eight point dose response curve.Appropriate controls using vehicle only and reference compound were applied to this assay. The final concentration of Me2SO was 0.4%.After incubation at 37° C., 5% CO2, the supernatant was subjected to quantification of secreted Aβ42 by the means of an AlphaLisa assay kit (Human Amyloid beta 1-42 Kit: Cat #AL203C, Perkin Elmer). 20 μl of the cell culture supernatant was transferred to an assay plate. Then 10 μl of a mixture of the AlphaLisa coupled capture antibody and the biotinylated detection antibody was added and incubated for 3 hours at room temperature while softly shaking the assay plate. After a further addition of 20 μl of the Donor beads the assay plate was incubated for 30 min at room temperature and constant shaking without exposure to direct light. The assay plate was then read on a Paradigm AlphaLisa Reader using the build-in program with excitation at 680 nm and emission at 570 nm.The measured signals were then used to calculate IC50 values for inhibition of Aβ42 secretion by nonlinear regression fit analysis using XLfit 5.3 software (IDBS).
Measurement: EC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 408.94, ALogP 4.5, HBA 6, HBD 1, PSA 60.56, QED 0.69
Compound (SMILES): Cc1cc([C@@H](C)Nc2nc(N3C(=O)OC[C@@H]3C(C)C)c3cc[nH]c3n2)ncc1-c1ccnc(C(F)(F)F)c1
InChIKey: NCCNQXYOCGUIQW-FOIQADDNSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R172K mutant (unknown origin) using alpha-KG as substrate after 90 mins in presence of NADPH by RF/MS analysis
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 525.54, ALogP 5.9, HBA 7, HBD 2, PSA 108.92, QED 0.32
Compound (SMILES): O=C(O)CCc1nc(-c2ccccc2Cl)c(-c2ccccc2)o1
InChIKey: KCXXPIVBPKZWHN-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Agonist activity at human RXRalpha transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 36000 nM (pChEMBL 4.440000057220459)
Descriptors: MW 327.77, ALogP 4.68, HBA 3, HBD 1, PSA 63.33, QED 0.74
Compound (SMILES): CN1CCN(Cc2ccc(NC(=O)CCSc3ccc4c(/C=C/c5ccccn5)n[nH]c4c3)cc2C(F)(F)F)CC1
InChIKey: UDEAKWSKOGAXIJ-JXMROGBWSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of BCR/ABL in human MEG01 cells assessed as inhibition of BCR/ABL autophosphorylation at Y245 site after 1 hr by immunoblotting analysis
Measurement: EC50 < 10 nM (pChEMBL 8)
Descriptors: MW 580.68, ALogP 6.02, HBA 6, HBD 2, PSA 77.15, QED 0.24
Compound (SMILES): Oc1ccc(-c2cc3cccnc3[nH]2)cc1
InChIKey: XZQLYCMLGSOHOX-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Binding affinity to human RIPK1 by kinome scan based method
Measurement: Kd = 218 nM (pChEMBL 6.659999847412109)
Descriptors: MW 210.24, ALogP 2.94, HBA 2, HBD 2, PSA 48.91, QED 0.65
Compound (SMILES): COc1ccc2c3c1O[C@H]1/C(=N\OCC(=O)NCCCCCCNC(=O)CCCCCn4cc(C(=O)c5cccc6ccccc56)c5ccccc54)CC[C@@]4(O)[C@@H](C2)N(C)CC[C@]314
InChIKey: DNFQAWUDLDDLDB-BLEUKKESSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]Ile5,6-deltorphin-2 from DOR in Wistar rat brain membranes after 60 mins by liquid scintillation analysis
Measurement: Ki = 263 nM (pChEMBL 6.579999923706055)
Descriptors: MW 854.06, ALogP 7.24, HBA 10, HBD 3, PSA 143.72, QED 0.04
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(OC/C(F)=C/CN)cc1)c1ccccc1.Cl
InChIKey: KIFNERWFYOPRCT-TZLGVYDDSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P33072
Assay: Inhibition of LOX in bovine aorta using putrescine as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured every 2.5 mins for 30 mins by Amplex-Red oxidation assay
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 364.44, ALogP 2.92, HBA 4, HBD 2, PSA 81.42, QED 0.75
Compound (SMILES): Cl.Cl.O=C(Nc1ccc(O[C@H]2CCNC2)c(-c2ccc(-c3nn[nH]n3)cc2)c1)c1ccc(O[C@H]2CCNC2)c(-c2ccc(F)c(F)c2)c1
InChIKey: LXPRCJXPXKPNAU-HWTGJJCHSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of protein interaction between C-terminal 6x-histidine tagged full-length beta-catenin (1 to 781 residues) (unknown origin)/N-terminal biotinylated human BCL9 ( 350 to 375 residues) incubated for 1 hr by Alpha-screen competitive inhibition assay
Measurement: Ki = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 623.66, ALogP 5.21, HBA 8, HBD 4, PSA 126.08, QED 0.18
Compound (SMILES): CCOC(=O)c1cc2c(cc1C(=O)OCC)CN1C(=O)CCC1C2
InChIKey: ONBUEBPFKSYJFJ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of N-terminal GST-tagged recombinant human AKR1C3 expressed in Escherichia coli BL21 (DE) Codon Plus RP cells assessed as reduction in NADPH production using S-tetralol as substrate in presence of NADP+ by fluorimetry assay
Measurement: IC50 = 11690 nM (pChEMBL 4.929999828338623)
Descriptors: MW 331.37, ALogP 2.09, HBA 5, HBD 0, PSA 72.91, QED 0.79
Compound (SMILES): N#Cc1ccc(S(=O)(=O)[C@H]2CN(S(=O)(=O)c3ccc(Cl)cc3Cl)C[C@@]2(O)CO)cc1F
InChIKey: RYDOPOXKOPOTSC-ZWKOTPCHSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: FLIPR Assay for hTRPV4 Expressed in BHK Cells: TRPV4 channel activation results in an influx of divalent and monovalent cations including calcium. The resulting changes in intracellular calcium were monitored using a calcium specific fluorescent dye Fluo-4 (MDS Analytical Technologies). BHK/AC9 cells transduced with BacMam virus expressing the human TRPV4 gene at a MOI of 78 were plated in a 384 well poly-D lysine coated plate (15,000 cells/well in 50 μL culture medium containing DMEM/F12 with 15 mM HEPES, 10% FBS, 1% Penicillin-Streptomycin and 1% L-glutamine). Cells were incubated for 24 hours at 37° C. and 5% CO2. Culture medium was then aspirated using a Tecan plate-washer and replaced with 20 μL/well of dye loading buffer: HBSS, 500 μM Brilliant Black (MDS Analytical Technologies), and 2 μM Fluo-4 AM. Dye loaded plates were then incubated in the dark at room temperature for 11.5 hours. 10 μL of test compounds diluted in HBSS (with 1.5 mM Calcium Chloride, 1.5 mM Magnesium Chloride and 10 mM HEPES, pH 7.4)+0.01% Chaps was added to each individual well of the plate, incubated for 10 min at room temperature in the dark and then 10 μL of agonist (N((S)-1-(((R)-1-((2-cyanophenyl)sulfonyl)-3-oxoazepan-4-yl)amino)-4-methyl-1-oxopentan-2-yl)benzo[b]thiophene-2-carboxamide, (Thorneloe et al, Sci. Transl. Med. (2012), 4, 159ra148) (hereinafter: Agonist Compound) was added to have a final concentration equals to the agonist EC80. Calcium signals were measured using FLIPRTETRA (MDS Analytical Technologies) or FLIPR384 (MDS Analytical Technologies) and the inhibition of Agonist Compound-induced calcium signal by the test compound was determined.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 509.36, ALogP 1.57, HBA 7, HBD 2, PSA 135.77, QED 0.62
Compound (SMILES): COc1ccc(CC(=O)Nc2ccc(-n3c4c(c5ncnc(N)c53)CCC4)cc2OC)c(F)c1
InChIKey: IYWWFUMOIKYKIX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Displacement of kinase tracer 236 from recombinant human His-tagged KDR cytoplasmic domain (789 to 1356 residues) expressed in baculovirus-infected insect cells measured after 5 hrs by TR-FRET based LanthaScreen assay
Measurement: IC50 > 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 461.5, ALogP 3.83, HBA 7, HBD 2, PSA 104.29, QED 0.45
Compound (SMILES): CC1=C(C(=O)c2cccc3ccccc23)C2C=CC=C3OC[C@@H](CN4CCOCC4)N1C32
InChIKey: AXLOUOMLETWQQL-GZSFQLOGSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP-55,940 from human CB1 receptor expressed in CHO cell membrane after 90 mins by scintillation counting method
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 428.53, ALogP 3.78, HBA 5, HBD 0, PSA 42.01, QED 0.69
Compound (SMILES): Cc1cc(/C=c2/sc3nc4ccccc4n3c2=O)c(C)n1-c1cccc(C(=O)O)c1
InChIKey: CIUHESIPAWCHNN-UDWIEESQSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Time-dependent irreversible inhibition of N-terminal His-tagged STEP catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells preincubated with enzyme followed by p-nitrophenyl phosphate substrate addition
Measurement: Ki = 21600 nM (pChEMBL 4.670000076293945)
Descriptors: MW 415.47, ALogP 3.56, HBA 6, HBD 1, PSA 76.6, QED 0.49
Compound (SMILES): COc1ccc(-c2coc3cc(OCCCCN4CCCCC4)ccc3c2=O)cc1
InChIKey: MXTJXSPHYQMIRK-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: P21836
Assay: Inhibition of mouse brain AChE using acetylthiocholine iodide as substrate measured after 30 mins by Ellman's method
Measurement: IC50 = 3980 nM (pChEMBL 5.400000095367432)
Descriptors: MW 407.51, ALogP 5.11, HBA 5, HBD 0, PSA 51.91, QED 0.49
Compound (SMILES): COc1ccc(F)c(-c2ccc3c(c2)CC[C@H]3Oc2cccc([C@H](C3CC3)[C@@H](C)C(=O)O)c2)c1
InChIKey: ZKPORIQWWQUQHA-IGOFHWAASA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Positive allosteric modulation of recombinant human GPR40 expressed in HEK293 cells assessed as increase in [3H]-myo-inositol phosphate accumulation measured after 60 mins in absence of human serum by microbeta counting method
Measurement: EC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 460.55, ALogP 6.78, HBA 3, HBD 1, PSA 55.76, QED 0.4
Compound (SMILES): COc1cc(C(=O)N[C@@H]2CCN(C#N)C2)ccc1-c1ccnc(N2CCOCC2)c1
InChIKey: PVTURUFYCWXEGM-GOSISDBHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 407.47, ALogP 1.88, HBA 7, HBD 1, PSA 90.72, QED 0.76
Compound (SMILES): Cl.O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1coc2ccccc12
InChIKey: OWYGBCDGAWXBBK-HBJKKLOVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Displacement of [3H]-Naltrindole from mouse kappa opioid receptor expressed in CHO cells incubated for 1.5 hrs by competitive radioligand binding assay
Measurement: Ki = 3.37 nM (pChEMBL 8.470000267028809)
Descriptors: MW 486.57, ALogP 3.5, HBA 6, HBD 3, PSA 95.17, QED 0.52
Compound (SMILES): CCCN(c1cccc(C(F)(F)F)c1)c1cnc(C(=O)[C@H]2C[C@@H]2C(=O)O)c(OC)c1
InChIKey: YGTKGVVKDYWICA-HOTGVXAUSA-N
Target: Leukotriene C4 synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16873
Assay: Inhibition of LTC4S in zymosan-stimulated human PBMC assessed as inhibition of LTC4 production preincubated for 45 mins followed by zymosan stimulation and measured after 20 mins by LC-MS/MS analysis
Measurement: IC50 = 58.4 nM (pChEMBL 7.230000019073486)
Descriptors: MW 422.4, ALogP 4.56, HBA 5, HBD 1, PSA 79.73, QED 0.63