lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CNC(=O)[C@]1(C)CC[C@@H](Nc2ncc3c(Br)nn(-c4ccc(-c5nnc(C)s5)c(CCO)c4)c3n2)C1
InChIKey: WAYMNYVTTBCOHI-OYLFLEFRSA-N
Target: eIF-2-alpha kinase GCN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2K8
Assay: Inhibition of GCN2 (unknown origin)
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 571.51, ALogP 3.66, HBA 10, HBD 3, PSA 130.74, QED 0.31
Compound (SMILES): Cn1c(Cn2ccc(C(F)(F)F)c(Oc3ccc(-c4ccc(C#N)cc4)cc3)c2=O)n[nH]c1=O
InChIKey: JSIGOVKCQFVLPU-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild type HIV-1 Reverse transcriptase
Measurement: IC50 = 15920 nM (pChEMBL 4.800000190734863)
Descriptors: MW 467.41, ALogP 3.67, HBA 7, HBD 1, PSA 105.7, QED 0.48
Compound (SMILES): C=CC(=O)Nc1ccc(-c2cn([C@@H]3CN[C@H](C(=O)Nc4ccc(Cl)c(C(F)(F)F)c4)C3)nn2)cn1
InChIKey: QDXRELOFIZDHGS-YOEHRIQHSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 9.26 nM (pChEMBL 8.029999732971191)
Descriptors: MW 505.89, ALogP 3.68, HBA 7, HBD 3, PSA 113.83, QED 0.44
Compound (SMILES): COc1ccc2ncc(F)c(CCCN3CCN(CCSc4cccs4)C[C@@H]3C(N)=O)c2c1
InChIKey: XCTXSIYQDRJNHM-JOCHJYFZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG by fluorescence polarization assay
Measurement: EC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 488.65, ALogP 3.64, HBA 7, HBD 1, PSA 71.69, QED 0.44
Compound (SMILES): CCOC(=O)N1CCN(C(=O)[C@H](CC(C(=O)O)C(=O)O)NC(=O)c2cc(OC3(C(=O)OCC)CCC3)n(-c3ccccc3)n2)CC1
InChIKey: CXJJOGUHWFGENF-QFIPXVFZSA-N
Target: P2Y purinoceptor 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H244
Assay: Displacement of [33P]2MeSADP from human P2Y12 expressed in CHO cell membranes preincubated for 15 mins followed by [33P]2MeSADP addition and measured after 20 mins by microbeta scintillation counting method
Measurement: IC50 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 643.65, ALogP 1.31, HBA 11, HBD 3, PSA 206.9, QED 0.21
Compound (SMILES): O=C1C(=O)N(CCc2ccccc2)c2ccc(F)cc21
InChIKey: FMQVEHDXVCRVTP-UHFFFAOYSA-N
Target: Parkinson disease protein 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99497
Assay: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate
Measurement: IC50 = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 269.27, ALogP 2.6, HBA 2, HBD 0, PSA 37.38, QED 0.8
Compound (SMILES): CCCCc1nc(C2CCN(CCc3c[nH]c4ccc(C#N)cc34)CC2)cn1-c1ccc(Oc2ccc(Cl)cc2)cc1
InChIKey: NSTCHFNFLIONCS-UHFFFAOYSA-N
Target: Advanced glycosylation end product-specific receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q15109
Assay: Inhibition of biotinylated human RAGE/amyloid beta interaction incubated for 120 mins by ELISA assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 578.16, ALogP 8.44, HBA 5, HBD 1, PSA 69.87, QED 0.18
Compound (SMILES): Cn1c(=O)[nH]c(=O)c2c1nc(Sc1nc3ccccc3[nH]1)n2Cc1cnco1
InChIKey: AGMWNRMJABUMDS-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17752
Assay: In Vitro Enzyme Activity Assay: These compounds according to the afore-mentioned examples were tested for tryptophan hydroxylase (TPH) inhibitory activity in a fluorescence-based in vitro assay, using recombinant human TPH1 (Swiss-Prot: P17752) and TPH2 (Swiss-Prot: Q8IWU9).The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, MA, USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).TPH1 and TPH2 inhibition was determined by measuring a compound dose response, using a serial dilution of a 5 mM DMSO stock solution. The potency of a given compound was calculated in GraphPad PRISM 6 software (San Diego, USA) with a Nonlinear Regression fit (log(inhibitor) vs. response-variable slope) using the relative fluorescence units (RFU) of the sample triplicates.
Measurement: IC50 = 42220 nM (pChEMBL 4.369999885559082)
Descriptors: MW 395.4, ALogP 1.49, HBA 9, HBD 2, PSA 127.39, QED 0.47
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)N[C@H]5CC[C@](O)(C(F)(F)F)CC5)c4n3)cc(NS(C)(=O)=O)c2C1=O
InChIKey: HGSPCVJTIYJJKQ-BMEKPBSDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) in rhMPC1 stimulated human THP-1 cells assessed as reduction in Akt phosphorylation level at Ser473 residue preincubated for 60 mins followed by rhMCP-1 stimulation and measured after 2 mins by AlphaLisa assay
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 635.67, ALogP 3.07, HBA 9, HBD 4, PSA 172.02, QED 0.31
Compound (SMILES): Cn1cc(S(N)(=O)=O)c2cc(NC(=O)c3cc(-c4ccc(Cl)cc4)nc4ccccc34)ccc21
InChIKey: AILQJRPKMBKQQX-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 by stopped flow CO2 assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 490.97, ALogP 4.95, HBA 5, HBD 2, PSA 107.08, QED 0.37
Compound (SMILES): COC1CN(c2cc(NC(=O)c3cccc(-c4cnn(C)c4)n3)c(C(F)(F)F)cn2)C1
InChIKey: KHTCIOWVELAJLF-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST20 tagged truncated LRRK2 G2019S mutant assessed as substrate phosphorylation preincubated for 15 mins followed by substrate addition and measured after 90 mins using fluorescein-labeled LRRK2tide as substrate in presence of ATP by TR-FRET based Lanthascreen kinase activity assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 432.41, ALogP 2.98, HBA 7, HBD 1, PSA 85.17, QED 0.67
Compound (SMILES): Cc1cc(Oc2ccc(Cn3nc4ccc(Cl)cc4c3C(=O)NS(=O)(=O)c3ccc(NCc4ccco4)c([N+](=O)[O-])c3)cc2)cc(C)c1Cl
InChIKey: IMUMIQGNKAABEB-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of MCL-1 (unknown origin) by fluorescence polarization competition assay
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 720.59, ALogP 8.03, HBA 10, HBD 2, PSA 158.6, QED 0.1
Compound (SMILES): O=C(O)CNC(=O)CNS(=O)(=O)c1cc2c(c(O)c1O)C(=O)c1ccccc1C2=O
InChIKey: KXQNRTCNXMVTJL-UHFFFAOYSA-N
Target: Pyruvate kinase PKLR (SINGLE PROTEIN), Homo sapiens
UniProt: P30613
Assay: Inhibition of PKL (unknown origin) for 30 mins by Kinase-Glo Max reagent based luminescence assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 434.38, ALogP -0.65, HBA 8, HBD 5, PSA 187.17, QED 0.31
Compound (SMILES): N#Cc1cn(Cc2ccccc2F)c2ccc(NC(=O)c3cc(=O)[nH]cn3)cc12
InChIKey: KLDXBFAJDZXXPG-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P47989
Assay: Inhibition of xanthine oxidase (unknown origin) using xanthine as substrate incubated for 15 mins followed by substrate addition by spectrophotometric analysis
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 387.37, ALogP 3.04, HBA 5, HBD 2, PSA 103.57, QED 0.56
Compound (SMILES): COc1cc(N2CCN(CCCCCCCCCCCCNC(=O)CC34CC5CC(CC(C5)C3)C4)CC2)ccc1Nc1ncc2c(C)cc(=O)n(-c3cccc(NC(C)=O)c3)c2n1
InChIKey: SOOCPBLZCOVDIQ-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Induction of AKT1 degradation in human NCI-H1975 cells assessed as reduction in AKT1 protein level incubated for 24 hrs under serum free medium by Western blot analysis
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 859.17, ALogP 9.55, HBA 10, HBD 3, PSA 133.72, QED 0.07
Compound (SMILES): c1ccc2c(Cc3nncn3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: CHUTZBIFVIDRGL-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST2A receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 306.37, ALogP 2.71, HBA 4, HBD 2, PSA 75.18, QED 0.57
Compound (SMILES): CN(c1ccnc(C(F)(F)F)n1)[C@H]1CC[C@@H](Nc2ccc3nnc(Cl)n3n2)CC1
InChIKey: JZWOPQIXJGYIGY-PHIMTYICSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of human MALT1 assessed as cleavage of substrate using fluorescent labeled Ac-LRSR-Rh110 peptide as substrate incubated for 30 mins followed by substrate addition and measured after 3 to 4 hrs by FRET assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 426.83, ALogP 3.45, HBA 8, HBD 1, PSA 84.13, QED 0.68
Compound (SMILES): C#CCNC(=O)c1ccc(Oc2cc(NC(=O)N3CCN(CC(CC)CC)CC3)cc(Oc3ccc(F)cc3)c2)cc1
InChIKey: XCMUKCHMYJBOAX-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis
Measurement: Kd > 1000 nM (pChEMBL 6)
Descriptors: MW 572.68, ALogP 6.36, HBA 5, HBD 2, PSA 83.14, QED 0.26
Compound (SMILES): Cc1ccc(F)cc1C(=O)Nc1ccc(C(=O)N2CCCN(CCCN3CCOCC3)c3ccccc32)cc1
InChIKey: CRXBUFVNUNBIKE-UHFFFAOYSA-N
Target: Vasopressin V2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30518
Assay: Displacement of conivaptan-red from SNAP-tagged human V2 receptor expressed in HEK293 cells measured after 1 hr by HTRF assay
Measurement: Ki = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 530.64, ALogP 4.97, HBA 5, HBD 1, PSA 65.12, QED 0.47
Compound (SMILES): C#CCCCCN1C(=O)C2=C(SC[C@@H]3NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc4c[nH]c5ccccc45)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](Cc4cnc[nH]4)NC(=O)CNC(=O)[C@H](CCCC)NC(=O)[C@H](CS2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2c[nH]c4ccccc24)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC3=O)C1=O
InChIKey: HRTHPANNFOMYJE-LPRGXNBOSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC1R expressed in HEK2936E cell membrane measured after 16 to 23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 2230.59
Compound (SMILES): CCOC(=O)[C@@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)C(=O)c1c(-c2ccccc2)[nH]c2ccccc12
InChIKey: TXTXUJCZFZSISJ-RRPNLBNLSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Displacement of [3H] PK11195 from TSPO (unknown origin) assessed as inhibition constant
Measurement: Ki = 438 nM (pChEMBL 6.360000133514404)
Descriptors: MW 553.66, ALogP 4.84, HBA 5, HBD 3, PSA 117.36, QED 0.13
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2[C@@H]1CCCN(C(=O)C2(C(=O)N3CCN(CC#Cc4ccc5c(c4)CN(C4CCC(=O)NC4=O)C5=O)CC3)CC2)C1
InChIKey: BGQBVRALQOTAKM-VCIADJTKSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin)
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 846.95, ALogP 3.77, HBA 12, HBD 2, PSA 189.19, QED 0.13
Compound (SMILES): COc1cc2nc(NCCCN(C)C)nc(OC3CCN(Cc4ccccc4)CC3)c2cc1OC
InChIKey: GMIMRINGJXMLEA-UHFFFAOYSA-N
Target: LSD1/CoREST complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UKL0
Assay: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay
Measurement: Kd = 2849 nM (pChEMBL 5.539999961853027)
Descriptors: MW 479.63, ALogP 4.05, HBA 8, HBD 1, PSA 71.98, QED 0.41
Compound (SMILES): CCOC(c1ccc2nc(-c3cccc4[nH]ccc34)nc(N3CCOC[C@H]3C)c2c1)n1cccn1
InChIKey: PGCPDAYNCWGINY-XZATXCMXSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of human recombinant full length ATR using GST-cMyc-p53 as substrate incubated for 40 mins in presence of ATP by HTRF assay
Measurement: IC50 = 901 nM (pChEMBL 6.039999961853027)
Descriptors: MW 468.56, ALogP 4.78, HBA 7, HBD 1, PSA 81.09, QED 0.39
Compound (SMILES): COc1cc(-c2ccn3nc(N)c(C(=O)NC4CC4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: XANZNPICXVINSW-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) in rhMPC1 stimulated human THP-1 cells assessed as reduction in Akt phosphorylation level at Ser473 residue preincubated for 60 mins followed by rhMCP-1 stimulation and measured after 2 mins by AlphaLisa assay
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 446.51, ALogP 2.63, HBA 7, HBD 2, PSA 114.85, QED 0.6
Compound (SMILES): CCOC(=O)c1cn(Cc2ccc(F)cc2)c2ccc(OCc3cccc4ccccc34)cc2c1=O
InChIKey: SWFYRRCYIDSQGP-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant His-tagged wild-type HIV-1 group M subtype B BH10 reverse transcriptase-associated RNase H activity harboring p66/p51 hetrodimer expressed in Escherichia coli M15 using GTTTTCTTTTCCCCCCTGAC-30 fluorescein/50-CAAAAGAAAAGGGGGGACUG-30 Dabcyl RNA/DNA template-primer as substrate incubated for 1 hr by multilabel counter plate reader analysis
Measurement: IC50 = 1490 nM (pChEMBL 5.829999923706055)
Descriptors: MW 481.52, ALogP 6.1, HBA 5, HBD 0, PSA 57.53, QED 0.26
Compound (SMILES): N=C(N)NCCC[C@H](NCc1ccccn1)C(=O)NCc1ccc(CNCCCNC2CCCCC2)cc1
InChIKey: AMGQQWNQWHMPHG-MHZLTWQESA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Antagonist activity at CXCR4 receptor in SDF-1alpha-stimulated human SUP-T1 cells measured by calcium mobilization assay
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 522.74, ALogP 2.52, HBA 6, HBD 7, PSA 139.98, QED 0.1
Compound (SMILES): Cl.Nc1c(Cl)cc(C(CO)NC2CCCC2)cc1C(F)(F)F
InChIKey: FQQOLPPAGWDOAG-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at beta2 adrenoceptor (unknown origin) expressed in HEK293 cells assessed as cAMP accumulation incubated for 60 mins by microplate reader analysis
Measurement: EC50 = 586.8 nM (pChEMBL 6.230000019073486)
Descriptors: MW 322.76, ALogP 3.51, HBA 3, HBD 3, PSA 58.28, QED 0.74
Compound (SMILES): C=CC(=O)Nc1cccc(C)c1Nc1cc2c(cn1)cc(-c1c(Cl)c(OC)cc(OC)c1Cl)c(=O)n2CC
InChIKey: RNRSRGHTQPAPQD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of wild type FGFR1 (unknown origin) using Poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA
Measurement: IC50 = 637 nM (pChEMBL 6.199999809265137)
Descriptors: MW 553.45, ALogP 6.58, HBA 7, HBD 2, PSA 94.48, QED 0.24
Compound (SMILES): CC(=O)NCC1CCN(Cc2cc(Oc3ccc(N4CCN(CC(=O)O)CC4)nc3)nc(-c3cc(Cl)cc(Cl)c3)c2)CC1
InChIKey: WGRNTRPTSUMYAD-UHFFFAOYSA-N
Target: Furin (SINGLE PROTEIN), Homo sapiens
UniProt: P09958
Assay: Inhibition of Tev-FLAG-His-tagged furin (108 to 574 residues) (unknown origin) using FAM-QRVRRAVGIDK-TAMRA as substrate and measured after 2 hrs
Measurement: IC50 = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 627.57, ALogP 4.8, HBA 8, HBD 2, PSA 111.13, QED 0.33
Compound (SMILES): COc1ccc(C(=O)Nc2cccc([C@@]3(C)O[C@@H]4CO[C@H]5N4[C@@H]3O[C@]5(C)c3cccc(NC(=O)c4ccc(OC)cc4)c3)c2)cc1
InChIKey: CEFZLJAZLPOVTE-VNCSWJDHSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at human OX1R expressed in CHO-K1 cells assessed as inhibition of orexin-A-induced increase in calcium mobilization preincubated for 15 mins followed orexin-A stimulation by Fura-2-AM dye based fluorescence assay
Measurement: Ki = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 621.69, ALogP 5.71, HBA 8, HBD 2, PSA 107.59, QED 0.26
Compound (SMILES): COc1ccc(-c2ccc3[nH]c(=O)c4nnn(-c5ccc(N6CCNCC6)c(C(F)(F)F)c5)c4c3c2)cn1
InChIKey: RGHLRMNPUGUZEY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase RIO2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BVS4
Assay: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay
Measurement: Kd = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 521.5, ALogP 3.76, HBA 8, HBD 2, PSA 100.96, QED 0.37
Compound (SMILES): O=C(Nc1ccn(-c2cncc(F)c2)n1)C1(c2ccccc2)CC1
InChIKey: MGVVGJUNHTXTGR-UHFFFAOYSA-N
Target: Very long chain fatty acid elongase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BW60
Assay: Inhibition of ELOVL1 (unknown origin) using C22-acyl-CoA as substrate by radiometric enzyme assay
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 322.34, ALogP 3.08, HBA 4, HBD 1, PSA 59.81, QED 0.8
Compound (SMILES): Cc1noc(C)c1-c1ccc2ccn(Cc3ccccc3)c2c1
InChIKey: YOLNCPSNENGUCN-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged full length recombinant BRD4 (unknown origin) (21 to 153 residues) using SGRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHRK(Biotin)-OH as substrate measured after 1 hr by HTRF assay
Measurement: IC50 = 2654 nM (pChEMBL 5.579999923706055)
Descriptors: MW 302.38, ALogP 4.96, HBA 3, HBD 0, PSA 30.96, QED 0.54
Compound (SMILES): CCOc1cccnc1Oc1cncc(-c2ncc(C(=O)NC3(CO)CCOC3)cn2)c1
InChIKey: DFNKRIPGDXQUEM-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: In Vitro DGAT2 Assay: For determination of IC50 values, the reactions were carried out in 384-well white Polyplates (Perkin Elmer) in a total volume of 20 μL. To 1 μL of compounds dissolved in 100% DMSO and spotted at the bottom of each well, 5 μL of 0.04% bovine serum albumin (BSA) (fatty acid free, Sigma Aldrich) was added and the mixture was incubated at room temperature for 15 minutes. hDGAT2 membrane fractions were diluted in 100 mM Hepes-NaOH, pH 7.4, 20 mM MgCl2 containing 200 nM methyl arachidonyl fluorophosphonate (Cayman Chemical; dried from ethyl acetate stock solution under argon gas and dissolved in DMSO as 5 mM stock). 10 μL of this enzyme working solution was added to the plates and incubation continued for 2 hours at room temperature. DGAT2 reactions were initiated by the addition of 4 μL of substrates containing 30 μM [1-14C]decanoyl-CoA (custom-synthesized by Perkin Elmer, 50 mCi/mmol) and 125 μM 1,2-didecanoyl-sn-glycerol (Avanti Polar Lipids) dissolved in 12.5% acetone. The reaction mixtures were incubated at room temperature for 40 min and the reactions were stopped by addition of 5 μL of 1% H3PO4. After the addition of 45 μL MicroScint-E (Perkin-Elmer), plates were sealed with Top Seal-A covers (Perkin-Elmer) and phase partitioning of substrates and products was achieved using a HT-91100 microplate orbital shaker (Big Bear Automation, Santa Clara, Calif.). Plates were centrifuged at 2,000×g for 1 minute in an Allegra 6R Centrifuge (Beckman Coulter) and then were sealed again with fresh covers before reading in a 1450 Microbeta Wallac Trilux Scintillation Counter (Perkin Elmer). DGAT2 activity was measured by quantifying the generated product [14C]tridecanoylglycerol in the upper organic phase.Background activity obtained using 50 μM of (R)-1-(2-((S)-1-(4-Chloro-1H-pyrazol-1-yl)ethyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (WO 2013150416, Example 196-A) for complete inhibition of DGAT2 was subtracted from all reactions. Inhibitors were tested at eleven different concentrations to generate IC50 values for each compound. The eleven inhibitor concentrations employed typically included 50, 15.8, 5, 1.58, 0.50, 0.16, 0.05, 0.016, 0.005, 0.0016, and 0.0005 μM. The data were plotted as percentage of inhibition versus inhibitor concentration and fit to the equation, y=100/[1+(x/IC50)z], where IC50 is the inhibitor concentration at 50% inhibition and z is the Hill slope (the slope of the curve at its inflection point).
Measurement: IC50 = 20.9 nM (pChEMBL 7.679999828338623)
Descriptors: MW 437.46, ALogP 2.01, HBA 9, HBD 2, PSA 128.58, QED 0.54
Compound (SMILES): C#CCNS(=O)(=O)c1ccc(CCN(Cc2cc(Cl)ccc2OCCC)C(=O)c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)cc1
InChIKey: UWIFJGKAWZQZHS-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R4B8
Assay: Inhibition of NLRP3 inflammasome in LPS-primed mouse J774.A1 cells assessed as reduction in IL-1beta secretion preincubated for 30 mins followed by ATP addition and measured after 30 mins by ELISA
Measurement: IC50 = 2490 nM (pChEMBL 5.599999904632568)
Descriptors: MW 651.03
Compound (SMILES): CC(C)c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4ccc(Cl)c(O)c4)c4ccccc43)cn12
InChIKey: AWHBCWYBAZTHBN-AHKZPQOWSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human recombinant full length GST-tagged p38alpha expressed in Escherichia coli preincubated for 2 hrs followed by ATP addition and measured after 1 hr by Alpha screen assay
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 614.15, ALogP 7.47, HBA 8, HBD 3, PSA 118.6, QED 0.18
Compound (SMILES): CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(C(=O)N(C)C)c(C)[nH]c3c2)ncc1Cl
InChIKey: NQJLJKFROUEMTA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR (669 to 1210 residues) cytoplasmic domain expressed in baculovirus infected Sf21 cells incubated for 1 hrs in the presence of ATP by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 477.96, ALogP 4.47, HBA 6, HBD 4, PSA 115.04, QED 0.33
Compound (SMILES): CC(=O)OCC1=CC[C@@H]2C(C(=O)NCCC#N)=CO[C@@H](O[C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)[C@H]12
InChIKey: XQBNFNTVJPEWSV-QSGYYAINSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P80457
Assay: Inhibition of bovine XOD assessed as inhibition of uric acid formation using xanthine as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured for 30 mins by microplate reader analysis
Measurement: IC50 = 15840 nM (pChEMBL 4.800000190734863)
Descriptors: MW 636.61, ALogP 0.48, HBA 15, HBD 1, PSA 212.08, QED 0.13
Compound (SMILES): O=C(Nc1ccc(F)cc1)c1cc2cccnc2n(CCCCF)c1=O
InChIKey: HLXDVVAGNXDIJA-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-SR141716A from recombinant human CB1 receptor expressed in CHO cells membrane incubated for 90 mins
Measurement: Ki = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 357.36, ALogP 3.54, HBA 4, HBD 1, PSA 63.99, QED 0.69
Compound (SMILES): O=C(CNCc1ccccc1)Nc1ccc(-c2nc(-c3ccnc(Nc4ccc(OC(F)(F)F)cc4)c3)no2)cc1
InChIKey: NFSPTCJOLBERPO-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured after 5 mins by DTNB-reagent based Ellman's method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 560.54, ALogP 6.17, HBA 8, HBD 3, PSA 114.2, QED 0.19
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: MPISIZFSGAZROV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR Del19/T790M/C797S triple mutant (unknown origin)
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 601.18, ALogP 4.21, HBA 10, HBD 3, PSA 114.96, QED 0.33
Compound (SMILES): COc1ccc(CNC(=O)C2CN(S(=O)(=O)c3ccc(N)cc3)CCN2C(=O)c2cc(O)c(O)c(O)c2)cc1
InChIKey: SBRDGWFDBGXWDJ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type recombinant HIV-1 group M subtype B BH10 reverse transcriptase RNase-associated RNase H activity expressed in Escherichia coli XL1 blue using 32P-labeled 5'-UUUUUUUUUAGGAUACAUAUGGUUAAAGUAU-3'/5'-ATACTTTAACCATATGTATCC-3' RNA/DNA template-primer as substrate preincubated for 5 mins followed by substrate addition and measured after 15 mins by phosphorimaging analysis
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 556.6, ALogP 1.23, HBA 9, HBD 5, PSA 182.73, QED 0.21
Compound (SMILES): CCCCN(CCC1CCCCCC1)Cc1cc(OC(=O)N(C)C)c2ccccc2c1
InChIKey: YFKHDWWVYBTYBD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of recombinant human BChE using butyrylthiocholine iodide as substrate preincubated for 1 to 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 424.63, ALogP 6.86, HBA 3, HBD 0, PSA 32.78, QED 0.41
Compound (SMILES): Cc1cc(Nc2nc(NCc3c(F)cccc3F)nc3ccccc23)n[nH]1
InChIKey: NEGLWIYSEXNMHG-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of N-terminal human TRKA (436 to 790 residues) expressed in baculovirus expression system using TK as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 366.38, ALogP 4.3, HBA 5, HBD 3, PSA 78.52, QED 0.49
Compound (SMILES): O=C(c1ccc(Nc2nccc(-c3ccc(Cl)s3)n2)cc1)N1CCC(N2CCCC2)CC1
InChIKey: RUJUBLPCSJOYSF-UHFFFAOYSA-N
Target: Glycogen synthase kinase 3 (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: O77344
Assay: Inhibition of Plasmodium falciparum GSK3 measured after 2 hrs by luciferin-based luminescence assay
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 468.03, ALogP 5.3, HBA 6, HBD 1, PSA 61.36, QED 0.55
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(-c3ccccc3)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2[C@@H](c3ccccc3)CCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)CSSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: CXUBHHHIXIUVDV-XXUUABCDSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of recombinant biotinylated KRAS G12D mutant (unknown origin) assessed as inhibition of SOS-catalyzed nucleotide exchange preincubated for 60 mins followed by addition of human SOS protein and unlabeled GTP and measured after 60 mins by TR-FRET analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 2072.5
Compound (SMILES): CCCN(CCCCOCCOCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)C)C[C@@H](C)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: LNVXIMZTYRLPDR-UYNIEJFQSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant HDAC4 (unknown origin) using Boc-Lys(TFA)-AMC as substrate by fluorescence based plate reader assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 987.16, ALogP 5.66, HBA 14, HBD 4, PSA 210.58, QED 0.06
Compound (SMILES): CCC[C@H](C)COc1ccc([C@H](Cn2cc(CO)nn2)NC(=O)[C@@H](C)c2ccccc2)cc1
InChIKey: JFKYLVWNOYDKGA-RLSLOFABSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay
Measurement: EC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 450.58, ALogP 4.25, HBA 6, HBD 2, PSA 89.27, QED 0.43
Compound (SMILES): Cc1ccc(COc2ccc(-c3ncc4c(=O)[nH][nH]c4n3)cc2C#N)cc1
InChIKey: QUBQJNNFJHIQGZ-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P47989
Assay: Inhibition of xanthine oxidase (unknown origin) using xanthine as substrate preincubated for 15 mins followed by substrate addition by UV spectrophotometric analysis
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 357.37, ALogP 3.07, HBA 5, HBD 2, PSA 107.45, QED 0.58
Compound (SMILES): O=C(NC(=O)c1ccsc1NC(=O)c1nc2ccccc2s1)OCC1CCCCC1
InChIKey: ZFZUXEVYZVMQAH-UHFFFAOYSA-N
Target: Decaprenylphosphoryl-beta-D-ribose oxidase (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: P9WJF1
Assay: Inhibition of Mycobacterium tuberculosis wild type DprE1 expressed in Escherichia coli BL21 DE3 assessed as formation of resorufin using FPR as substrate incubated for 10 mins by Amplex Red dye microplate assay
Measurement: IC50 > 64000 nM (pChEMBL 4.193999767303467)
Descriptors: MW 443.55, ALogP 5.06, HBA 7, HBD 2, PSA 97.39, QED 0.57
Compound (SMILES): CS(=O)(=O)c1cccc(Cc2nnc(Cc3c[nH]c4cc(F)ccc34)n2CCCc2c[nH]cn2)c1
InChIKey: UROWFMUIRALGKF-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST2A receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 492.58, ALogP 3.84, HBA 6, HBD 2, PSA 109.32, QED 0.32
Compound (SMILES): NCCCNCCCCNc1ccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3c2ncn3C2CCCC2)cc1
InChIKey: IWXVPEORISOBQZ-SAIGFBBZSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin)
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 534.76, ALogP 4.5, HBA 10, HBD 6, PSA 143.76, QED 0.16
Compound (SMILES): CC(=O)OCC1Cc2c(-c3ccc(Br)cn3)cccc2-c2c(O)ccc(-c3ccc(Br)cc3)c21
InChIKey: OIFKWXNGHNKROP-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CL protease using Dabcyl-KNSTLQSGLRKE-Edan as substrate incubated for 30 mins and measured by FRET assay
Measurement: IC50 = 6730 nM (pChEMBL 5.170000076293945)
Descriptors: MW 579.29, ALogP 7.52, HBA 4, HBD 1, PSA 59.42, QED 0.25
Compound (SMILES): Cc1cn(-c2ccc(C#N)c(C(F)(F)F)c2)nc1CNC(=O)c1ccc(C#N)cc1
InChIKey: OCGRTINHAXTSGM-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at androgen receptor (unknown origin) in human LNCap-ARR2PB-eGFP cells by measuring fluorescence intensity measured after 3 days by transcriptional assay
Measurement: IC50 = 14900 nM (pChEMBL 4.829999923706055)
Descriptors: MW 409.37, ALogP 3.87, HBA 5, HBD 1, PSA 94.5, QED 0.71
Compound (SMILES): O=C1CCc2ccc(OCCCCN3CCN(C(=O)c4ccccn4)CC3)cc2N1
InChIKey: NKPZUJWHJYTWEE-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L receptor expressed in HEK293 cells measured after 1 hr by Microbeta plate reader method
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 408.5, ALogP 2.58, HBA 5, HBD 1, PSA 74.77, QED 0.71
Compound (SMILES): O=C(Nc1ccc2c(ccn2-c2ccccc2)c1)c1c(O)nn2ccccc12
InChIKey: IHUCMILCWJLWCF-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human N-terminal GST-fusion tagged DHODH (31 to 395 residues) expressed in Escherichia coli BL21-GOLD (DE3) using dihydroorotate as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by DCIP assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 368.4, ALogP 4.24, HBA 5, HBD 2, PSA 71.56, QED 0.5
Compound (SMILES): CN1CCC(N(Cc2ccc(F)cn2)C(=O)NCc2ccc(OCC(F)F)cc2)CC1
InChIKey: HHKZUYBSKLUYKA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) expressed in CHO-K1 cells assessed as reduction in intracellular Ca2+ mobilization incubated for 15 mins by FLIPR assay
Measurement: IC50 = 2.17 nM (pChEMBL 8.65999984741211)
Descriptors: MW 436.48, ALogP 3.67, HBA 4, HBD 1, PSA 57.7, QED 0.69
Compound (SMILES): O=C(NCC#Cc1ccc(Nc2ncnc3c2ncn3[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc1)c1ccccc1
InChIKey: PLMNEORRSOTQPT-RKCWLVDCSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Agonist activity at human A1 receptor expressed in Flp-In-CHO cells assessed as inhibition of forskolin stimulated cAMP accumulation incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 500.52, ALogP 0.96, HBA 10, HBD 5, PSA 154.65, QED 0.24
Compound (SMILES): Cn1c(=O)[nH]c(=O)c2c1nc(Cc1nc3cc(NC(=O)CC[C@H](N)C(=O)O)ccc3[nH]1)n2Cc1ccccc1
InChIKey: YQQGCBNTUKQEBJ-INIZCTEOSA-N
Target: Tryptophan 5-hydroxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17752
Assay: In Vitro Enzyme Activity Assay: These compounds according to the afore-mentioned examples were tested for tryptophan hydroxylase (TPH) inhibitory activity in a fluorescence-based in vitro assay, using recombinant human TPH1 (Swiss-Prot: P17752) and TPH2 (Swiss-Prot: Q8IWU9).The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, MA, USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).TPH1 and TPH2 inhibition was determined by measuring a compound dose response, using a serial dilution of a 5 mM DMSO stock solution. The potency of a given compound was calculated in GraphPad PRISM 6 software (San Diego, USA) with a Nonlinear Regression fit (log(inhibitor) vs. response-variable slope) using the relative fluorescence units (RFU) of the sample triplicates.
Measurement: IC50 = 2220 nM (pChEMBL 5.650000095367432)
Descriptors: MW 530.55, ALogP 1.07, HBA 9, HBD 5, PSA 193.78, QED 0.19
Compound (SMILES): Cc1ccc(CC(=O)Nc2cccc(O)c2)cc1
InChIKey: QLMQUKIPEUCNQQ-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS/nigericin-stimulated PMA-differentiated human THP-1 macrophages assessed as reduction in pyroptosis pretreated with LPS followed by compound treatment for 30 mins then stimulation with nigericin and measured after 3 hrs by MTT assay
Measurement: IC50 = 2821 nM (pChEMBL 5.550000190734863)
Descriptors: MW 241.29, ALogP 2.88, HBA 2, HBD 2, PSA 49.33, QED 0.87
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](O)[C@H](n5cc(-c6ccc(COc7cccc8ccccc78)cc6)c6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: DBFLURMMWIAUJW-DANBCEJISA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at human wild type STING expressed in 293T cells by digitonin cell based assay
Measurement: EC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 905.71, ALogP 2.66, HBA 20, HBD 7, PSA 325.99, QED 0.12
Compound (SMILES): CNc1ccc(S(=O)(=O)N(CC(C)C)C[C@@H](O)[C@H](Cc2ccccc2)NC(=O)[C@H]2CNCCO2)cc1
InChIKey: NSZQTUIIPYVHSY-ISJGIBHGSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of HIV-1 protease using Arg-Glu (EDANS)-Ser-Gln-Asn-Tyr-Pro-lle-Val-Gln-Lys (DABCYL)-Arg as substrate preincubated for 20 to 30 mins followed by substrate addition and measured by FRET assay
Measurement: IC50 = 90.18 nM (pChEMBL 7.039999961853027)
Descriptors: MW 518.68, ALogP 1.45, HBA 7, HBD 4, PSA 120, QED 0.34
Compound (SMILES): CCOc1ccc2[nH]c(Cc3nc4c(c(=O)[nH]c(=O)n4CC)n3Cc3ccccc3)nc2c1
InChIKey: CPISMKNBAXDQEB-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17752
Assay: Inhibition of N-terminal MBP-tagged full length human TPH1 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 444.5, ALogP 2.82, HBA 7, HBD 2, PSA 110.59, QED 0.4
Compound (SMILES): COc1ccc(S(=O)(=O)n2nc(Oc3ccc(-c4ccccc4)cc3)cc2N)cc1
InChIKey: IHXIUMFQBBESDS-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of DENV2 NS2B-NS3 protease using fluorophore-tagged Bz-nKRR-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 90 mins by microplate reader analysis
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 421.48, ALogP 4.17, HBA 7, HBD 1, PSA 96.44, QED 0.5
Compound (SMILES): O=C(c1ccc(CNCCO)cc1)N1CCc2c(-c3cccc4[nH]ccc34)cccc21
InChIKey: NBJSQXLBXDZCQN-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of Tag2-PD1/Tag1-PD-L1 (unknown origin) protein-protein interaction preincubated for 15 mins followed by addition of anti-Tag1-Eu3+ and anti-Tag2-XL665 and measured after 2 hrs by HTRF analysis
Measurement: IC50 = 635.2 nM (pChEMBL 6.199999809265137)
Descriptors: MW 411.51, ALogP 4.12, HBA 3, HBD 3, PSA 68.36, QED 0.42
Compound (SMILES): O=C(CS(=O)(=O)c1ccc(-c2ccccc2)cc1)NO
InChIKey: HYBHKZKKEGAPOP-UHFFFAOYSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of MMP-1 (unknown origin)
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 291.33, ALogP 1.63, HBA 4, HBD 2, PSA 83.47, QED 0.66
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: JESVEDAOUMZINK-VYDIVQSQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 134.9 nM (pChEMBL 6.869999885559082)
Descriptors: MW 3115.69
Compound (SMILES): CCOc1nc(C(=O)NCC(=O)O)c(O)c2ccc(Oc3ccccc3)cc12
InChIKey: TXMLZQNXTUAMCS-UHFFFAOYSA-N
Target: Thyroid hormone receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10827
Assay: Agonist activity at wild type human TR alpha LBD expressed in Escherichia coli BL21 (DE3) assessed as induction of N-terminal biotinylated coactivator SRC2-3 peptide recruitment by alphascreen assay
Measurement: EC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 382.37, ALogP 2.95, HBA 6, HBD 3, PSA 117.98, QED 0.57
Compound (SMILES): COc1cc(N2CCC3(CCN(C)CC3)CC2)c(C)cc1Nc1ncc(Cl)c(Nc2ccccc2P(C)(C)=O)n1
InChIKey: XQEYPEQDMUAORO-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK C1156Y mutant (unknown origin) using biotinylated substrate incubated for 1 hr in the presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 583.12, ALogP 6.49, HBA 8, HBD 2, PSA 82.62, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(CCn2c(SCC(=O)Nc3ccc(Br)cc3)nc3ccccc3c2=O)cc1
InChIKey: FFDVNPUOGCNTKU-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 25.4 nM (pChEMBL 7.590000152587891)
Descriptors: MW 573.49, ALogP 3.78, HBA 7, HBD 2, PSA 124.15, QED 0.24
Compound (SMILES): Brc1cccc(-c2nccc3c2[nH]c2ccccc23)c1
InChIKey: LJDAUNCFNFQWMR-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin) assessed as reduction in kynurenine production using L-tryptophan as substrate incubated for 1 hr by absorbance based microplate reader analysis
Measurement: IC50 = 4950 nM (pChEMBL 5.300000190734863)
Descriptors: MW 323.19, ALogP 5.15, HBA 1, HBD 1, PSA 28.68, QED 0.52
Compound (SMILES): CCCCCCCCCCCCC[C@H]1N[C@H](CO)[C@@H](O)[C@@H]1O
InChIKey: UGACFOJZAZEING-BRSBDYLESA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Inhibition of human GCase assessed as reduction of 4-methylumbelliferone liberation using 4-methylumbelliferyl-beta-glucopyranoside as substrate preincubated with enzyme for 45 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometry
Measurement: IC50 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 315.5, ALogP 2.74, HBA 4, HBD 4, PSA 72.72, QED 0.39
Compound (SMILES): O=C(c1ccc(CNCCO)cc1)N1CCc2c(-c3ccc4nccnc4c3)cccc21
InChIKey: GYYYLZJASNTPRD-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of Tag2-PD1/Tag1-PD-L1 (unknown origin) protein-protein interaction preincubated for 15 mins followed by addition of anti-Tag1-Eu3+ and anti-Tag2-XL665 and measured after 2 hrs by HTRF analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 424.5, ALogP 3.58, HBA 5, HBD 2, PSA 78.35, QED 0.46
Compound (SMILES): CCNNC(=O)c1coc(-c2ccc(Br)cc2)c1
InChIKey: HNSSFJBAQLSNOA-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant HDAC1 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 309.16, ALogP 2.96, HBA 3, HBD 2, PSA 54.27, QED 0.85
Compound (SMILES): [O-][n+]1c(-c2ccc(Br)cc2)nc2ccccn21
InChIKey: JRFNVZYJIQMZNX-UHFFFAOYSA-N
Target: Aryl hydrocarbon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35869
Assay: Agonist activity at AhR in human recombinant HepG2-Lucia AhR cell incubated for 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 290.12, ALogP 2.4, HBA 3, HBD 0, PSA 44.24, QED 0.51
Compound (SMILES): CCOc1ccc(C(=O)Cn2c(=O)n(C)c(=O)c3ccccc32)cc1Cl
InChIKey: CZUYGMMGPVJLQL-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Displacement of [32P]S1P from human recombinant S1PR2 incubated for 60 mins by competitive binding assay based scintillation counter
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 372.81, ALogP 2.64, HBA 6, HBD 0, PSA 70.3, QED 0.65
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)NCCCC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)COCCOCCNC(=O)c1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(=O)O)C(=O)NCCOCCOCC(=O)N[C@H]1CSCC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: RXLQPJAGXHHDMC-VMQDGMSWSA-N
Target: Kallikrein-5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y337
Assay: Inhibition of C-terminal poly-His-tagged human recombinant KLK5 (30 to 293 residues) transfected in CHO cells assessed as inhibition constant using Boc-VPR-AMC as fluorogenic substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 2781.11
Compound (SMILES): CCCCC[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2ccc(-c3ccccc3)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2[C@@H](c3ccccc3)CCN2CC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)CSSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC1=O
InChIKey: GMILEDVLYQQFCU-DZKKRDKRSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of recombinant biotinylated KRAS G12D mutant (unknown origin) assessed as inhibition of SOS-catalyzed nucleotide exchange preincubated for 60 mins followed by addition of human SOS protein and unlabeled GTP and measured after 60 mins by TR-FRET analysis
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 2114.58
Compound (SMILES): O=C(NCc1ccccc1C(=O)N[C@H](/C=C/S(=O)(=O)Oc1ccccc1)CCc1ccccc1)c1ccncc1
InChIKey: NRMMQFXZSPQQES-JUTYNXCLSA-N
Target: Rhodesain (SINGLE PROTEIN), Trypanosoma brucei rhodesiense
UniProt: Q95PM0
Assay: Irreversible inhibition of Trypanosoma brucei rhodesiense rhodesain assessed as inhibition constant using Cbz-Phe-Arg-AMC as fluorogenic substrate by fluorometric assay
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 555.66, ALogP 4.67, HBA 6, HBD 2, PSA 114.46, QED 0.25
Compound (SMILES): Cn1nc(C(=O)OCCCCNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)cc1COc1cccc([C@@H](NC(=O)O[C@H]2CN3CCC2CC3)c2ccccc2)c1
InChIKey: YWSIONULMMKTSJ-UZGNFBRWSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-methylscopolamine from human muscarinic M3 receptor expressed in CHO-K1 cell membrane measured after 2 hr by Cheng-prusoff equation analysis
Measurement: Ki = 0.0631 nM (pChEMBL 10.199999809265137)
Descriptors: MW 764.88, ALogP 4.72, HBA 12, HBD 5, PSA 180.27, QED 0.07