lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc5c(cnn5CCN(C)C)c4)c(-c4c(Cl)c(C)cc5[nH]ncc45)c3C)C2)C1
InChIKey: OAQUOYUTTVTTQF-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Scintillation Proximity Assay (SPA): Assays were run using 384-well plates (781207/Greiner) in which one column was designated as the high signal (no inhibition) control, and contained DMSO with no test compound, and another column was designated as the low signal control (maximal inhibition), and contained no protein. Serial dilutions of compounds to be tested were added to the assay plate (resulting in duplicate 11-point dose response with semi-log compound dilutions from 50 μM to 0.5 nM or from 5 μM to 0.05 nM for the most potent compounds). A 1/20 isotopic dilution of labeled (Compound B) and non-labeled covalent (Compound A) probe was prepared and added to all wells on the plate. The reaction was started by addition of KRasG12C (M1-K169, biotinylated on the N-terminus) to the compounds and incubated for 2 hours with continuous agitation allowing for full modification of KRasG12C with probe or test compounds. Final concentrations in an assay volume of 40 μL were 10 nM KRasG12C, 25 nM radio-ligand and 475 nM unlabelled ligand. The assay buffer contained 20 mM Tris-HCl pH 7.5 (Invitrogen), 150 mM NaCl (Sigma Aldrich), 0.1 mM MgCl2 (Sigma Aldrich), and 0.01% Tween-20 (Sigma Aldrich). Following addition of 50 μL of a 400 μg/ml. suspension of streptavidin-coated YSi beads (Perkin Elmer), plates were incubated for a further 30 min with continuous agitation before reading the plates on a scintillation counter (Topcount NXT 384 (Packard).
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 583.14, ALogP 5.62, HBA 7, HBD 1, PSA 87.87, QED 0.25
Compound (SMILES): CCc1ccc(N(CC(C)C)S(=O)(=O)c2ccc3c(c2)C(O)CC(C2CCN(C)CC2)O3)cc1
InChIKey: XCCVQQVLLHLAAH-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inhibition of RORgammat in human Jurkat cells assessed as inhibition of RORgammat transcriptional activity incubated for 10 mins by luciferase reporter gene assay
Measurement: IC50 = 3638 nM (pChEMBL 5.440000057220459)
Descriptors: MW 486.68, ALogP 4.63, HBA 5, HBD 1, PSA 70.08, QED 0.62
Compound (SMILES): Cl.Cl.O=C(c1ccc(O[C@H]2CCNC2)c(-c2ccc3ccccc3c2)c1)N1CCC(Oc2cc(F)cc(N3CCNCC3)c2)CC1
InChIKey: PCJFFLKPDFFAEY-GDCSGTLQSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of full length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)/N-terminal biotinylated human BCL9 HD2 (350 to 375 residues) protein-protein interaction assessed as inhibition constant incubated for 1 hr by Alphascreen assay
Measurement: Ki = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 594.73, ALogP 5.48, HBA 6, HBD 2, PSA 66.07, QED 0.3
Compound (SMILES): Cc1csc([C@@]2(CN)[C@@H]3CN(c4cnc5c(-c6ccn7nccc7c6Cl)n[nH]c5n4)C[C@@H]32)n1
InChIKey: CHLHMGGBVMLLOD-KOBKJTCASA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 477.99, ALogP 3.05, HBA 9, HBD 2, PSA 113.91, QED 0.41
Compound (SMILES): C/C=C1/CN2CC[C@@]34c5cc(O)c(Br)cc5N(C)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: UPIPYHXXEKEQBW-ZLUQDIKLSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]DAMGO from mu opioid receptor (unknown origin) assessed as inhibition constant incubated for 180 mins by competitive radioligand binding assay
Measurement: Ki = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 461.36, ALogP 2.78, HBA 6, HBD 1, PSA 62.24, QED 0.51
Compound (SMILES): C[C@H]1Nc2ccc3ncc(n3n2)C(=O)NC2(CC2)COc2ccccc21
InChIKey: JBBAPLLCPKVUSU-GFCCVEGCSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK G1202R mutant (unknown origin)
Measurement: IC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 349.39, ALogP 2.56, HBA 6, HBD 2, PSA 80.55, QED 0.65
Compound (SMILES): Cc1ccc(-c2noc(-c3cccc(OCC4CCN(Cc5ccc(C(C)(C)C)cc5)CC4)c3)n2)cn1
InChIKey: HQTQXRVUVNCUOH-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using ATC and BTC iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by DTNB reagent based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 496.66, ALogP 6.7, HBA 6, HBD 0, PSA 64.28, QED 0.28
Compound (SMILES): N#Cc1cn(C2CC2)c2c(N3CCN(CCc4c[nH]c5ccccc45)CC3)ncnc12
InChIKey: PHGFMAYCTYWBIS-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 in human NCI-H69AR cells incubated for 180 mins in presence of daunorubicin by flow cytometry analysis
Measurement: IC50 = 316 nM (pChEMBL 6.5)
Descriptors: MW 411.51, ALogP 3.48, HBA 6, HBD 1, PSA 76.77, QED 0.54
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(C(N)=O)c(O)c(F)c3F)c3c(=O)n(C)cnc32)c(Cl)c(F)n1
InChIKey: WUNZYZWWEBYSRT-LBPRGKRZSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Inhibition of BCL6 (unknown origin) stably expressed in human SU-DHL-4 cells incubated for 2 days by luminescence based microplate reader analysis
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 619, ALogP 2.45, HBA 10, HBD 3, PSA 151.61, QED 0.28
Compound (SMILES): COc1ccccc1-n1c(=O)c2cnc(Nc3ccc4c(c3)CN(C)CC4(C)C)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: KEQAEPQFWOQEKT-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of human full length GST-tagged WEE1 expressed in insect cells incubated for 15 mins followed by ATP addition by ADP Glo luminescent assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 565.68, ALogP 4.67, HBA 10, HBD 2, PSA 110.33, QED 0.31
Compound (SMILES): COc1ccc(C2=NN(C(=O)c3ccc(S(N)(=O)=O)cc3)C(c3ccc(OC)cc3)C2)cc1
InChIKey: ZTZZFLHUQWXMPB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2
Measurement: Ki = 31.7 nM (pChEMBL 7.5)
Descriptors: MW 465.53, ALogP 3.34, HBA 6, HBD 1, PSA 111.29, QED 0.6
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)N(C)C
InChIKey: NHUYRIDWSHPVGA-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of TNF-alpha induced NF-kappaB signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 437.95, ALogP 3.89, HBA 4, HBD 1, PSA 78.95, QED 0.79
Compound (SMILES): CCCCOc1nc(N)c2[nH]c(=O)n(CCCCN3CCCC3)c2n1
InChIKey: YRRMMLIQTVCYBS-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at TLR7 in human PBMC assessed as TFN-alpha production after 24 hrs by electrochemiluminescence assay
Measurement: EC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 348.45, ALogP 1.76, HBA 7, HBD 2, PSA 102.06, QED 0.67
Compound (SMILES): C=CC(=O)N1CC[C@@H](n2cc(-c3cnc4ccccc4c3)c3c(N)ncnc32)C1
InChIKey: IQJPWAAWPFBLPZ-MRXNPFEDSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human EGFR del19/T790M using biotinEEPLYWSFPAKKK-NH2 as substrate incubated for 120 mins by TR-FRET assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 384.44, ALogP 3.19, HBA 6, HBD 1, PSA 89.93, QED 0.55
Compound (SMILES): COC[C@@H]1C[C@H]2[C@@H]3CCc4cc(O)ccc4[C@H]3CC[C@]2(C)C1NN
InChIKey: ZZPUNGNICWACST-KIQLNDKJSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of wild type B-Raf (unknown origin)
Measurement: IC50 = 4320 nM (pChEMBL 5.369999885559082)
Descriptors: MW 330.47, ALogP 2.95, HBA 4, HBD 3, PSA 67.51, QED 0.59
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(NC(C)=O)c(C(=O)NCc3cncnc3)cc21
InChIKey: OVENXINRYODYBV-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2:PS as substrate preincubated for 1 hr followed by ATP and substate addition and measured after 1 hr by ADP-glo reagent based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 405.42, ALogP 1.35, HBA 8, HBD 2, PSA 123.28, QED 0.52
Compound (SMILES): CN1CCC2(CC1)c1ccccc1N(Cc1ccc(C(=O)NO)cc1)C2c1ccc(Cl)cc1
InChIKey: YJDINAAEZXWQRK-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant HDAC6 using ZMAL (Z-(Ac)Lys-AMC) as fluorogenic substrate incubated for 120 mins by microplate reader assay
Measurement: IC50 = 164.8 nM (pChEMBL 6.78000020980835)
Descriptors: MW 461.99, ALogP 5.18, HBA 4, HBD 2, PSA 55.81, QED 0.41
Compound (SMILES): CC(C)(O)[C@H]1CC[C@H](NC(=O)c2cnc3ccccc3c2)CC1
InChIKey: PHLUYNGCRCAAOS-WKILWMFISA-N
Target: Hematopoietic prostaglandin D synthase (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35543
Assay: Inhibition of H-PGDS in rat RBL cells assessed as reduction in A23187-induced PGD2 production pretreated for 30 mins followed by A23187 addition for 30 mins by RapidFire Mass spectrometry
Measurement: EC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 312.41, ALogP 3.29, HBA 3, HBD 2, PSA 62.22, QED 0.91
Compound (SMILES): CN1Cc2ccc(Nc3ncc4c(=O)n(C5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2C1
InChIKey: OLLXANSJPNHXRT-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of human full length GST-tagged WEE1 expressed in insect cells incubated for 15 mins followed by ATP addition by ADP Glo luminescent assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 497.6, ALogP 4.17, HBA 9, HBD 2, PSA 101.1, QED 0.4
Compound (SMILES): CCC(=O)Nc1cc(Nc2ncc(Br)c(Nc3ccc4cc[nH]c4c3)n2)c(OC)cc1N1CCN(C)CC1
InChIKey: DHLPFNUQGIEEHA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) expressed in baculovirus expression system by ELISA
Measurement: IC50 = 92.1 nM (pChEMBL 7.039999961853027)
Descriptors: MW 579.5, ALogP 5.32, HBA 8, HBD 4, PSA 110.44, QED 0.22
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccc3c(c2)B(O)OC3)n1
InChIKey: XLZSJJOKIGHAHP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ALK cytoplasmic domain (1058 to 1620 residues) C1156Y mutant expressed in baculovirus-infected Sf21 cells using LANCE Ultra ULight-PolyGT substrate incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 77.2 nM (pChEMBL 7.110000133514404)
Descriptors: MW 480.77
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1CCCCN1CCCCC1
InChIKey: BYPQEUFUCCZAJU-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 2090 nM (pChEMBL 5.679999828338623)
Descriptors: MW 345.51, ALogP 3.51, HBA 4, HBD 0, PSA 35.91, QED 0.77
Compound (SMILES): COc1ccc(Nc2ncnc3c2cnn3-c2ccc(C)c(C)c2)cn1
InChIKey: DBETYCCNDHCTNK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant PI5P4Kgamma (unknown origin) expressed in Escherichia coli BL21(DE3) by ADP-Glo reagent based assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 346.39, ALogP 3.58, HBA 7, HBD 1, PSA 77.75, QED 0.61
Compound (SMILES): CCNC(=S)N1N=C(c2ccccc2)CC1c1ccc(F)cc1
InChIKey: XUDIUPYCNUIVEO-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B by spectrofluorimetric analysis
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 327.43, ALogP 3.87, HBA 2, HBD 1, PSA 27.63, QED 0.87
Compound (SMILES): COc1cc(F)c([C@@H]2CNC(=O)[C@H]2Nc2cc(-c3ccc(C(F)F)cc3)on2)c(F)c1
InChIKey: IXGFRCAYDKCZPZ-DJJJIMSYSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Agonist activity at human FPR1 expressed in CHO cells assessed as cAMP level incubated for 1.5 hr by HTRF assay
Measurement: EC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 435.38, ALogP 4.26, HBA 5, HBD 2, PSA 76.39, QED 0.57
Compound (SMILES): O=C(NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O)C1CCOCC1.O=C(O)C(F)(F)F
InChIKey: GJISLSPZZIQUSJ-GNAFDRTKSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Antagonist activity against recombinant human H1 receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 509.05, ALogP 3.65, HBA 6, HBD 1, PSA 76.46, QED 0.5
Compound (SMILES): COC(=O)[C@]1(c2ccccc2)C[C@@H]1CN1CC[C@]2(C)c3cc(O)ccc3C[C@@H]1[C@@H]2C
InChIKey: ZQZLNUMNWMAXIZ-RVYZHTKBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-Diprenorphine from DOR receptor (unknown origin) assessed as inhibition constant
Measurement: Ki > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 405.54, ALogP 4.05, HBA 4, HBD 1, PSA 49.77, QED 0.78
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(C(N)=O)c(O)c(F)c3F)c3c(=O)n(C)cnc32)c(Cl)cn1
InChIKey: UWECVQGTVIRVDC-ZDUSSCGKSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Inhibition of BCL6 (unknown origin) stably expressed in human SU-DHL-4 cells incubated for 2 days by luminescence based microplate reader analysis
Measurement: IC50 = 382 nM (pChEMBL 6.420000076293945)
Descriptors: MW 601.01, ALogP 2.31, HBA 10, HBD 3, PSA 151.61, QED 0.3
Compound (SMILES): Cc1c(NC(=O)CN2C(=O)S/C(=C\c3ccc(Br)cc3)C2=O)c(=O)n(-c2ccccc2)n1C
InChIKey: PILUXIJYFKKUDT-PDGQHHTCSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) by ELISA assay
Measurement: IC50 = 3849 nM (pChEMBL 5.420000076293945)
Descriptors: MW 527.4, ALogP 3.92, HBA 7, HBD 1, PSA 93.41, QED 0.51
Compound (SMILES): CN(C)CCCN1C(=O)c2cc([N+](=O)[O-])ccc2Oc2ccccc21
InChIKey: CGYWLLGTCBIGSR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Compound was evaluated for inhibition of human KCNH2 in an in vitro assay with cellular components measured by membrane filtration, radioactivity method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 341.37, ALogP 3.3, HBA 5, HBD 0, PSA 75.92, QED 0.62
Compound (SMILES): C[N@+]1(CCF)[C@@H]2CC[C@H]1C[C@@H](OC(=O)C(O)(c1ccccc1)c1ccccc1)C2
InChIKey: OATDVDIMNNZTEY-DAXLTYESSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Rattus norvegicus
UniProt: P22002
Assay: Compound was evaluated for inhibition of rat Cacna1c in an in vitro assay with cellular components measured by membrane filtration
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 398.5, ALogP 3.58, HBA 3, HBD 1, PSA 46.53, QED 0.6
Compound (SMILES): CCc1ccc(-c2ncn(CC3(F)CCN(C)CC3)c2-c2ccnc3[nH]ccc23)nc1
InChIKey: SRSOVGVHVNSXTC-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Affinity On-target Cellular interaction: (NanoBRET asssay (HEK293T cells)) EUB0001201a CSNK1E
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 418.52, ALogP 4.48, HBA 5, HBD 1, PSA 62.63, QED 0.52
Compound (SMILES): Cc1cc(CN)cc(C)c1-c1ncn(C)c1-c1ccnc2cc(F)ccc12.Cl
InChIKey: RKTOBFVDHMUFAM-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZ95
Assay: Affinity Biochemical interaction: (SPR) EUB0000269cCl NSD3
Measurement: Kd = 166 nM (pChEMBL 6.78000020980835)
Descriptors: MW 360.44, ALogP 4.52, HBA 4, HBD 1, PSA 56.73, QED 0.58
Compound (SMILES): Cc1ccc(S(=O)(=O)O)cc1.Cn1cc(Nc2nccc(N3CC4CCC(C3)N4C(=O)[C@@H]3CC3(F)F)n2)cn1
InChIKey: FAKGOYNHHHOTEN-WTMFEIAXSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Human Whole Blood Assay (IFN+- induced pSTAT3 (lymphocytes), TYK2/JAK1 signaling)) EUB0001542aTs JAK1
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 389.41, ALogP 1.79, HBA 7, HBD 1, PSA 79.18, QED 0.86
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4CCN(C(C)C)CC4)cc3)c2C)cc(F)c1C(=O)N1CCCC1
InChIKey: WFJOMSKCDAOJBT-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Affinity Phenotypic Cellular interaction: (Western Blot (inhibition of ALK2 catalysed phosphorylation of SMAD1/5/8, BMP branch signalling)) EUB0001465a ACVR1
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 516.66, ALogP 5.64, HBA 5, HBD 0, PSA 48.91, QED 0.42
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2nc(C(=O)Nc3ccc(CC(=O)N(C)C)c(C)c3C)c3c(N)ncnc32)C1
InChIKey: JCCIICHPRAAMGK-GOSISDBHSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin)
Measurement: IC50 = 16.36 nM (pChEMBL 7.789999961853027)
Descriptors: MW 504.6, ALogP 2.26, HBA 8, HBD 2, PSA 139.34, QED 0.49
Compound (SMILES): C[C@H](CCOc1cccc(CC(=O)O)c1)N(Cc1cccc(C(F)(F)F)c1Cl)CC(c1ccccc1)c1ccccc1.Cl
InChIKey: LCMIYQOJZLRHTO-GJFSDDNBSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Affinity On-target Cellular interaction: (Reporter gene assay (HEK293T cells)) EUB0001482aCl NR1H3
Measurement: EC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 596.09, ALogP 8.48, HBA 3, HBD 1, PSA 49.77, QED 0.17
Compound (SMILES): Fc1ccc(-c2nc(-c3ccc4ccccc4c3F)[nH]c2-c2ccncc2)cc1
InChIKey: PUQAFIILJICJRR-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Homo sapiens
UniProt: P48730
Assay: Kinase Assay : Table 2: The p38 MAPK IC50 values of selected compounds except IM-32 to IM-44 were determined using the HitHunter p38 MAP kinase binding assay from DiscoveRx Corporation (Fremont, Calif., USA). The p38 MAPK IC50 values of IM-32 to IM-44 and the CK1 IC50 values of selected compounds were determined using LanthaScreen Eu kinase binding assay from Invitrogen (Life Technologies, Carlsbad, Calif., USA). The assays were performed following the manufacturers' protocols in white 384-well plates (Cat. No. 3572; Corning Incorporated, Corning, N.Y., USA). SB203580 was used as the control in all assays. For the HitHunter p38 MAP kinase binding assay the compounds were dissolved in DMSO (5 mM stocks) and diluted to a final concentration of 2% (vol/vol) DMSO for all assays. Recombinant GST-tagged active p38α MAP kinase enzyme (Millipore, Billerica, Mass., USA) was used for the HitHunter p38 MAP kinase binding assay. For the LanthaScreen Eu kinase binding assay the compounds were dissolved in DMSO (5 mM stocks) and diluted to a final concentration of 1% (vol/vol) DMSO for all assays. Each data point was done in triplicate. The assay was run using JANUS Automated Workstation according to the protocol developed using WinPREP software (Perkin Elmer Inc., Waltham, Mass., USA). Tecan Infinite® M1000 microplate reader (Tecan Group Ltd., Minnedorf, Switzerland) was used for luminescence measurements (HitHunter p38 MAP kinase binding assay) and fluorescence measurements (LanthaScreen Eu kinase binding assay; ex=340 nm, em=665, 615 nm). All data analysis was performed using GraphPad Prism 5 software (GraphPad Software Inc.). Inhibition curves and IC50 values were generated by nonlinear regression analysis and data represent mean±SEM.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 383.4, ALogP 6.24, HBA 2, HBD 1, PSA 41.57, QED 0.4
Compound (SMILES): CN1Cc2nccc(-c3cn(C)nc3-c3ccc(F)cc3)c2C1=O.Cl
InChIKey: CLDJMFXSCFWXDI-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Affinity On-target Cellular interaction: (Translocation Assay (CSNK1E mediated PER3 nuclear translocation in COS-7 cells)) EUB0001199aCl CSNK1E
Measurement: EC50 = 318 nM (pChEMBL 6.5)
Descriptors: MW 322.34, ALogP 2.87, HBA 4, HBD 0, PSA 51.02, QED 0.73
Compound (SMILES): CN(C)c1ncc2cc(-c3ccc(-c4ncccc4F)cc3Cl)c(=O)n(C[C@H]3OC[C@H](N)CO3)c2n1
InChIKey: RRFFBKGCCWPMLK-OQIWPSSASA-N
Target: Serine/threonine-protein kinase SIK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H0K1
Assay: Affinity On-target Cellular interaction: (NanoBRET assay (HEK293T cells)) EUB0001479a SIK2
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 510.96, ALogP 3.08, HBA 9, HBD 1, PSA 108.39, QED 0.44
Compound (SMILES): O=C(Nc1ccccc1C(=O)O)c1cc(S(=O)(=O)c2ccccc2)ccc1Cl
InChIKey: CLAUJSRBKSRTGQ-UHFFFAOYSA-N
Target: Monocarboxylate transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53985
Assay: Affinity Biochemical interaction: (Displacement of radiolabelled [3H]-BAY-8002) EUB0001677b SLC16A1
Measurement: IC50 = 11.04 nM (pChEMBL 7.960000038146973)
Descriptors: MW 415.85, ALogP 4.12, HBA 4, HBD 2, PSA 100.54, QED 0.65
Compound (SMILES): C[C@@H]1C[C@H](C)CN(c2ncc(Cl)c(Nc3ccc4c(c3)cc(OC(C)(C)C(=O)O)c(=O)n4C)n2)C1
InChIKey: KWMGIHUWUIICDA-GASCZTMLSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: SPR (BCL6), Ontario institute for cancer research
Measurement: Kd = 1409 nM (pChEMBL 5.849999904632568)
Descriptors: MW 500, ALogP 4.45, HBA 8, HBD 2, PSA 109.58, QED 0.51
Compound (SMILES): CN1CCC(F)(Cn2cnc(-c3ccc(F)cn3)c2-c2ccnc3[nH]ccc23)CC1
InChIKey: SWOIFXHMBKFCRM-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human P38alpha incubated for 30 mins in presence of ATP by ADP-GLO reagent based multimode microplate reader analysis
Measurement: IC50 = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 408.46, ALogP 4.06, HBA 5, HBD 1, PSA 62.63, QED 0.55
Compound (SMILES): CN1CCC(C#N)(NC(=O)[C@@H](NC(=O)N2CCOCC2)C(C)(C)C)CC1
InChIKey: ZJHRRAJHJNQDON-CQSZACIVSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Luminescent based enzymatic assay (CTSS)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 365.48, ALogP 0.55, HBA 5, HBD 2, PSA 97.7, QED 0.76
Compound (SMILES): COc1cc(-c2cn[nH]c2)ccc1C(=O)Nc1ccc2c(c1)CCNCC2.Cl
InChIKey: OXRWZUUCCUDKJJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Affinity Phenotypic Cellular interaction: (Immunoblot (proteasome-mediated degradation of MELK protein), Alamar Blue assay (proliferatio in FLT3-driven Ba/F3 cell lines)) EUB0001485aCl FLT3
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 362.43, ALogP 3.03, HBA 4, HBD 3, PSA 79.04, QED 0.67
Compound (SMILES): CCn1c(CNC(=O)c2nc(Cl)cnc2N)[n+](CC)c2ccc(C(=O)N(C)CCN(C)C)cc21.[Cl-]
InChIKey: PJKRNPPUSQSCHN-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: GPCRScan assay: inhibition of D5
Measurement: Ki = 4066.31 nM (pChEMBL 5.389999866485596)
Descriptors: MW 488.02, ALogP 1.56, HBA 7, HBD 2, PSA 113.26, QED 0.44
Compound (SMILES): Cc1nnc2n1-c1sc3c(c1C(c1ccccc1Cl)=NC2)C[C@@H](C(=O)N1CCOCC1)C3
InChIKey: FWYVRZOREBYLCY-CQSZACIVSA-N
Target: Platelet-activating factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25105
Assay: PAF Receptor Binding
Measurement: Kd = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 467.98, ALogP 3.22, HBA 7, HBD 0, PSA 72.61, QED 0.58
Compound (SMILES): CC(Sc1nc2c(cnn2-c2cccc(Cl)c2)c(=O)[nH]1)C(N)=O
InChIKey: NASYEGAVCTZSDO-UHFFFAOYSA-N
Target: Death-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53355
Assay: Inhibition of DAPK1 (unknown origin) by (33P-ATP) filter-binding assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 349.8, ALogP 1.73, HBA 6, HBD 2, PSA 106.66, QED 0.55
Compound (SMILES): O=C(/N=c1\sccn1Cc1ccccc1)c1c[nH]c2ncccc12
InChIKey: VTXBMVZVPUSAJF-UZYVYHOESA-N
Target: Serine/threonine-protein kinase LATS2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRM7
Assay: Inhibition of human LATS2 incubated for 40 mins in presence of ATP by Eurofins kinase profiler method
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 334.4, ALogP 3.22, HBA 4, HBD 1, PSA 63.04, QED 0.63
Compound (SMILES): CC1(C)C(=O)N([C@H]2CCc3c(O)cccc32)c2nc(Nc3cccc(CN4CCCC4)c3)ncc21
InChIKey: OFIFLUFVENTCNZ-QHCPKHFHSA-N
Target: Serine/threonine-protein kinase SIK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H0K1
Assay: Inhibition of SIK2 (unknown origin)
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 469.59, ALogP 4.83, HBA 6, HBD 2, PSA 81.59, QED 0.56
Compound (SMILES): C[C@H]1CN(c2nc3ccc(C(F)(F)F)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: FERGAQDBZAJZNY-AWEZNQCLSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 513.97, ALogP 5.19, HBA 6, HBD 1, PSA 65.9, QED 0.47
Compound (SMILES): c1cncc(-c2csc(-c3csc(Nc4ccc(N5CCOCC5)cc4)n3)n2)c1
InChIKey: IZQVMCKIZHVNEF-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 2553 nM (pChEMBL 5.590000152587891)
Descriptors: MW 421.55, ALogP 4.91, HBA 8, HBD 1, PSA 63.17, QED 0.49
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)C[C@H]1CCCN1C
InChIKey: MILBIPKHYWBIPY-JOCHJYFZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 19 Deletion and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR exon 19 deletion and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR exon 19 deletion and T790M mutation. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR E746-A750 deletion and T790M Mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 19 deletion and T790M mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR E746-A750 deletion and T790M Mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR E746-A750 deletion and T790M Mutation (named Ba/F3-EGFR-Del/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR-Del/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 611.75, ALogP 5.61, HBA 10, HBD 2, PSA 113.85, QED 0.17
Compound (SMILES): Cc1ccc(-c2noc(-c3cccc(OCC4CCN(Cc5ccccc5Cl)CC4)c3)n2)cn1
InChIKey: DOTWPYOPUGDXID-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using ATC and BTC iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by DTNB reagent based assay
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 474.99, ALogP 6.05, HBA 6, HBD 0, PSA 64.28, QED 0.32
Compound (SMILES): CC(C)n1nc(-c2nnc(C3CCN(CC4CCOCC4)CC3)o2)c2ccccc21.O=C(O)C(=O)O
InChIKey: YTGJXFMVMWXTCY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 2 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 409.53, ALogP 4.27, HBA 7, HBD 0, PSA 69.21, QED 0.63
Compound (SMILES): CC(C)N1C[C@H](NC(=O)N2Cc3ccccc3[C@@H]2C)[C@@H](C)C1
InChIKey: IMDMWQYWHACQHO-ZQIUZPCESA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-methylspiperone from D4 (unknown origin) receptor expressed in HEK293T cells assessed as inhibition constant
Measurement: Ki = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 301.43, ALogP 3, HBA 2, HBD 1, PSA 35.58, QED 0.91
Compound (SMILES): CC(C)(C)OC(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C=O)Cc1c[nH]cn1
InChIKey: SYSFJLSWEUVDHF-ROUUACIJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Binding affinity to C-terminal His6-tagged recombinant SARS-CoV-2 MPro expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by ITC assay
Measurement: Kd = 442 nM (pChEMBL 6.360000133514404)
Descriptors: MW 443.5, ALogP 0.89, HBA 6, HBD 4, PSA 142.28, QED 0.4
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NCCNS(C)(=O)=O
InChIKey: ATSRJSICZUBQJU-UHFFFAOYSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 506, ALogP 4.08, HBA 6, HBD 3, PSA 113.08, QED 0.38
Compound (SMILES): COc1cc(C)c(C)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccccc1
InChIKey: DRWCQAUIQXYCLK-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 1140 nM (pChEMBL 5.940000057220459)
Descriptors: MW 450.56, ALogP 4.71, HBA 4, HBD 1, PSA 75.71, QED 0.61
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CCC1CCC(CNC(=O)c2cc3ccccc3[nH]2)C1
InChIKey: QIUNPJREZURMGC-RFNIIBAYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylscopolamine from human dopamine D2 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 461.61, ALogP 4.14, HBA 5, HBD 3, PSA 96.27, QED 0.49
Compound (SMILES): O=C(Nc1cccnc1F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: BNMDYIGEWXWOOI-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 300.29, ALogP 2.22, HBA 4, HBD 2, PSA 83.98, QED 0.85
Compound (SMILES): CCCCOc1ccc(CCC(=O)N2CCN(c3ccc(O)cn3)CC2)cc1
InChIKey: YSCNKXDDPMRZQX-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 383.49, ALogP 3.25, HBA 5, HBD 1, PSA 65.9, QED 0.71
Compound (SMILES): O=[N+]([O-])c1ccc(CNc2ccccc2)cc1
InChIKey: BFPIOTHCNQDBNL-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of recombinant TC-PTP (unknown origin)
Measurement: IC50 = 20110 nM (pChEMBL 4.699999809265137)
Descriptors: MW 228.25, ALogP 3.21, HBA 3, HBD 1, PSA 55.17, QED 0.65
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n([C@@H]5C=CCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: LZTPSBCGWGMOMP-JOCHJYFZSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 526.65, ALogP 3.59, HBA 10, HBD 2, PSA 104.34, QED 0.37
Compound (SMILES): CCCOc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2cc(OC)ccc2OC)c1C
InChIKey: XOVXEGAZAJVMDI-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 452.56, ALogP 4.93, HBA 7, HBD 1, PSA 87.5, QED 0.52
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc5c(c4)ncn5C)c(-c4c(Cl)c(C)cc5[nH]ncc45)c3C)C2)C1
InChIKey: NKVZWTXEIRYGIH-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Scintillation Proximity Assay (SPA): Assays were run using 384-well plates (781207/Greiner) in which one column was designated as the high signal (no inhibition) control, and contained DMSO with no test compound, and another column was designated as the low signal control (maximal inhibition), and contained no protein. Serial dilutions of compounds to be tested were added to the assay plate (resulting in duplicate 11-point dose response with semi-log compound dilutions from 50 μM to 0.5 nM or from 5 μM to 0.05 nM for the most potent compounds). A 1/20 isotopic dilution of labeled (Compound B) and non-labeled covalent (Compound A) probe was prepared and added to all wells on the plate. The reaction was started by addition of KRasG12C (M1-K169, biotinylated on the N-terminus) to the compounds and incubated for 2 hours with continuous agitation allowing for full modification of KRasG12C with probe or test compounds. Final concentrations in an assay volume of 40 μL were 10 nM KRasG12C, 25 nM radio-ligand and 475 nM unlabelled ligand. The assay buffer contained 20 mM Tris-HCl pH 7.5 (Invitrogen), 150 mM NaCl (Sigma Aldrich), 0.1 mM MgCl2 (Sigma Aldrich), and 0.01% Tween-20 (Sigma Aldrich). Following addition of 50 μL of a 400 μg/ml. suspension of streptavidin-coated YSi beads (Perkin Elmer), plates were incubated for a further 30 min with continuous agitation before reading the plates on a scintillation counter (Topcount NXT 384 (Packard).
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 526.04, ALogP 5.6, HBA 6, HBD 1, PSA 84.63, QED 0.31
Compound (SMILES): O=C(NCc1cn2cc(CNCC3CCCCC3)ccc2n1)c1cc(=O)n2ccccc2n1
InChIKey: OBERVORNENYOLE-UHFFFAOYSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9HCE5
Assay: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5'P-UACACUCGAUCUGGACUAAAGCUGCUC-3' and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RapidFire mass spectrometry
Measurement: IC50 = 16.9 nM (pChEMBL 7.769999980926514)
Descriptors: MW 444.54, ALogP 2.94, HBA 7, HBD 2, PSA 92.8, QED 0.46
Compound (SMILES): CCN1CCN(Cc2cccc3ccccc23)[C@H](CCO)C1
InChIKey: FDUWKETXXFSWBN-GOSISDBHSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Binding affinity to sigma 1 receptor (unknown origin) expressed in human RPMI-8226 cells
Measurement: Ki = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 298.43, ALogP 2.73, HBA 3, HBD 1, PSA 26.71, QED 0.92
Compound (SMILES): O=C1CCc2cc(NC(=O)c3scnc3-c3ccccc3F)ccc2N1
InChIKey: DESVQADCPXYUHA-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of full length human ALDH1A1 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis
Measurement: IC50 >= 100000 nM (pChEMBL 4)
Descriptors: MW 367.41, ALogP 4.09, HBA 4, HBD 2, PSA 71.09, QED 0.73
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc5c(cnn5CCN(C)C)c4)c(-c4c(Cl)c(C)cc5[nH]ncc45)c3C)C2)C1
InChIKey: OAQUOYUTTVTTQF-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Scintillation Proximity Assay (SPA): Assays were run using 384-well plates (781207/Greiner) in which one column was designated as the high signal (no inhibition) control, and contained DMSO with no test compound, and another column was designated as the low signal control (maximal inhibition), and contained no protein. Serial dilutions of compounds to be tested were added to the assay plate (resulting in duplicate 11-point dose response with semi-log compound dilutions from 50 μM to 0.5 nM or from 5 μM to 0.05 nM for the most potent compounds). A 1/20 isotopic dilution of labeled (Compound B) and non-labeled covalent (Compound A) probe was prepared and added to all wells on the plate. The reaction was started by addition of KRasG12C (M1-K169, biotinylated on the N-terminus) to the compounds and incubated for 2 hours with continuous agitation allowing for full modification of KRasG12C with probe or test compounds. Final concentrations in an assay volume of 40 μL were 10 nM KRasG12C, 25 nM radio-ligand and 475 nM unlabelled ligand. The assay buffer contained 20 mM Tris-HCl pH 7.5 (Invitrogen), 150 mM NaCl (Sigma Aldrich), 0.1 mM MgCl2 (Sigma Aldrich), and 0.01% Tween-20 (Sigma Aldrich). Following addition of 50 μL of a 400 μg/ml. suspension of streptavidin-coated YSi beads (Perkin Elmer), plates were incubated for a further 30 min with continuous agitation before reading the plates on a scintillation counter (Topcount NXT 384 (Packard).
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 583.14, ALogP 5.62, HBA 7, HBD 1, PSA 87.87, QED 0.25
Compound (SMILES): C/C=C1/CN2CC[C@@]34c5cc(O)c(Br)cc5N(C)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: UPIPYHXXEKEQBW-ZLUQDIKLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from kappa opioid receptor (unknown origin) assessed as inhibition constant incubated for 180 mins by competitive radioligand binding assay
Measurement: Ki = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 461.36, ALogP 2.78, HBA 6, HBD 1, PSA 62.24, QED 0.51
Compound (SMILES): N#Cc1cn(C2CC2)c2c(N3CCN(CCc4c[nH]c5ccccc45)CC3)ncnc12
InChIKey: PHGFMAYCTYWBIS-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin) expressed in dog MDCK-II cells using pheophorbide A as substrate preincubated for 20 mins followed by substrate addition and measured after 120 mins by flow cytometry analysis
Measurement: IC50 = 18900 nM (pChEMBL 4.71999979019165)
Descriptors: MW 411.51, ALogP 3.48, HBA 6, HBD 1, PSA 76.77, QED 0.54
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(C(N)=O)c(O)c(F)c3F)c3c(=O)n(C)cnc32)c(Cl)c(F)n1
InChIKey: WUNZYZWWEBYSRT-LBPRGKRZSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 619, ALogP 2.45, HBA 10, HBD 3, PSA 151.61, QED 0.28
Compound (SMILES): COc1ccccc1-n1c(=O)c2cnc(Nc3ccc4c(c3)CN(C)CC4(C)C)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: KEQAEPQFWOQEKT-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 565.68, ALogP 4.67, HBA 10, HBD 2, PSA 110.33, QED 0.31
Compound (SMILES): COc1ccc(C2=NN(C(=O)c3ccc(S(N)(=O)=O)cc3)C(c3ccc(OC)cc3)C2)cc1
InChIKey: ZTZZFLHUQWXMPB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9
Measurement: Ki = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 465.53, ALogP 3.34, HBA 6, HBD 1, PSA 111.29, QED 0.6
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)N(C)C
InChIKey: NHUYRIDWSHPVGA-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 437.95, ALogP 3.89, HBA 4, HBD 1, PSA 78.95, QED 0.79
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(NC(C)=O)c(C(=O)NCc3cncnc3)cc21
InChIKey: OVENXINRYODYBV-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2:PS as substrate preincubated for 1 hr followed by ATP and substate addition and measured after 1 hr by ADP-glo reagent based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 405.42, ALogP 1.35, HBA 8, HBD 2, PSA 123.28, QED 0.52
Compound (SMILES): CN1Cc2ccc(Nc3ncc4c(=O)n(C5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2C1
InChIKey: OLLXANSJPNHXRT-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 267 nM (pChEMBL 6.570000171661377)
Descriptors: MW 497.6, ALogP 4.17, HBA 9, HBD 2, PSA 101.1, QED 0.4
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccc3c(c2)B(O)OC3)n1
InChIKey: XLZSJJOKIGHAHP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ALK cytoplasmic domain (1058 to 1620 residues) L1196M mutant expressed in baculovirus-infected Sf21 cells using LANCE Ultra ULight-PolyGT substrate incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 43.8 nM (pChEMBL 7.360000133514404)
Descriptors: MW 480.77
Compound (SMILES): O=C(NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O)C1CCOCC1.O=C(O)C(F)(F)F
InChIKey: GJISLSPZZIQUSJ-GNAFDRTKSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Antagonist activity against recombinant human adrenergic alpha1A receptor expressed in Rat1 cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 509.05, ALogP 3.65, HBA 6, HBD 1, PSA 76.46, QED 0.5
Compound (SMILES): COC(=O)[C@]1(c2ccccc2)C[C@@H]1CN1CC[C@]2(C)c3cc(O)ccc3C[C@@H]1[C@@H]2C
InChIKey: ZQZLNUMNWMAXIZ-RVYZHTKBSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from KOR receptor (unknown origin) assessed as inhibition constant
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 405.54, ALogP 4.05, HBA 4, HBD 1, PSA 49.77, QED 0.78
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(C(N)=O)c(O)c(F)c3F)c3c(=O)n(C)cnc32)c(Cl)cn1
InChIKey: UWECVQGTVIRVDC-ZDUSSCGKSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 31.9 nM (pChEMBL 7.5)
Descriptors: MW 601.01, ALogP 2.31, HBA 10, HBD 3, PSA 151.61, QED 0.3