lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): FC(F)(F)c1ccc(Nc2nc(Nc3ccc(-c4ccsc4)cn3)ncc2Cl)cc1
InChIKey: CNTRCGCSHPFXBU-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 1 hr followed by substrate addition and incubated for 60 mins by microplate reader assay
Measurement: IC50 = 149.6 nM (pChEMBL 6.829999923706055)
Descriptors: MW 447.87, ALogP 6.76, HBA 6, HBD 2, PSA 62.73, QED 0.35
Compound (SMILES): COc1cc(/C=C/c2cc(=O)oc3c2ccc2oc(-c4cccc(F)c4)cc23)cc(OC)c1
InChIKey: SVFJYZVSHWUWHU-VOTSOKGWSA-N
Target: Cytochrome c oxidase subunit 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00403
Assay: Inhibition of cox-2 (unknown origin) incubated for 5 mins by 96-well plate method
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 442.44, ALogP 6.53, HBA 5, HBD 0, PSA 61.81, QED 0.29
Compound (SMILES): Cc1nc2cnc3ccc(-c4cc(C(F)(F)F)cc(C(F)(F)F)c4)cc3c2n1-c1ccc(F)cc1
InChIKey: LAKQAGYHGGECLQ-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 as substrate incubated for 2 hrs in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 489.39, ALogP 7.73, HBA 3, HBD 0, PSA 30.71, QED 0.24
Compound (SMILES): C[C@@H]1CN(c2ccc(-c3n[nH]c4cnc(N5[C@H](C)CN(C(=O)N(C)C)C[C@@H]5C)nc34)cn2)CCN1
InChIKey: RWYJMMHOMKOPEY-ZACQAIPSSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (3 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 3 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 478.61, ALogP 1.79, HBA 8, HBD 2, PSA 109.41, QED 0.59
Compound (SMILES): O=C1CCCc2[nH]c(-c3ccncc3)cc21
InChIKey: FQYKIBPUNQVZRF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16512
Assay: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis
Measurement: Ki = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 212.25, ALogP 2.6, HBA 2, HBD 1, PSA 45.75, QED 0.79
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)CCc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
InChIKey: ULZGIJQWFIUBKB-VZVHPENPSA-N
Target: Interleukin-1 receptor antagonist protein (SINGLE PROTEIN), Homo sapiens
UniProt: P18510
Assay: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 508.62, ALogP 2.13, HBA 5, HBD 6, PSA 157.54, QED 0.21
Compound (SMILES): N#Cc1ccc(C[C@@H](NC(=O)Nc2ccc(F)cc2)C(=O)N2CCc3ccccc32)cc1
InChIKey: ZVHTWRPQYTXGOD-JOCHJYFZSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Antagonist activity at human FPR2 transfected in human HL-60 cells assessed as inhibition of WKYMVM-induced intracellular calcium mobilization preincubated for 10 mins followed by WKYMVM addition measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 428.47, ALogP 4.02, HBA 3, HBD 2, PSA 85.23, QED 0.64
Compound (SMILES): Cc1ccc(CC(C)CNC(=O)/N=C(\N)NCCCc2cnc(N)s2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ZZDDLWVPLCUTER-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Ki = 64.57 nM (pChEMBL 7.190000057220459)
Descriptors: MW 388.54, ALogP 2.46, HBA 4, HBD 4, PSA 118.42, QED 0.31
Compound (SMILES): CC(C)CN(Cc1ccc(C(=O)NO)cc1)S(=O)(=O)c1cc(F)c(F)c(F)c1F
InChIKey: ORRALXXDFMZZIR-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length human recombinant HDAC8 expressed in Sf9 baculovirus system using FAM-labeled acetylated peptide as substrate by measuring fluorescence intensity by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 434.41, ALogP 3.21, HBA 4, HBD 2, PSA 86.71, QED 0.23
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)NC5CC5)c4n3)cc(S(C)(=O)=O)c2C1=O
InChIKey: NLRPOLHEDYFDBC-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 351 nM (pChEMBL 6.460000038146973)
Descriptors: MW 494.58, ALogP 2.03, HBA 8, HBD 2, PSA 139.76, QED 0.53
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CCNS(=O)(=O)c1ccc(Oc2ccccc2)cc1)C(=O)N1CCC[C@H]1C(N)=O
InChIKey: ZIKBROOIDUARGQ-YXKTVTGNSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition by fluroscence based assay
Measurement: IC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 962.12, ALogP -0.78, HBA 13, HBD 9, PSA 344.69, QED 0.05
Compound (SMILES): COc1cc2c(NC3CCN(Cc4ccccc4)CC3)nc(NCCCN(C)C)nc2cc1OCc1ccccc1
InChIKey: CLMKFAVBRRFUGX-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a (unknown origin) assessed as reduction in substrate methylation using histone H3 and SAM as substrate measured after 15 to 60 mins by microfluidic capillary electrophoresis analysis
Measurement: Ki = 39400 nM (pChEMBL 4.409999847412109)
Descriptors: MW 554.74, ALogP 5.66, HBA 8, HBD 2, PSA 74.78, QED 0.21
Compound (SMILES): O=C(N[C@@H](Cc1coc2ccccc12)B(O)O)[C@H]1CCOC1
InChIKey: LPDJLONKZFUKOX-HZMBPMFUSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human A549 cells using Suc-LLVY-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 2996 nM (pChEMBL 5.519999980926514)
Descriptors: MW 303.12
Compound (SMILES): CC(=O)Nc1cccc(-c2cnc(Nc3ccc(-c4ccsc4)cn3)nc2Nc2cccc(C(F)(F)F)c2)c1
InChIKey: HSKMGPMYKVEFJG-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 1 hr followed by substrate addition and incubated for 60 mins by microplate reader assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 546.58, ALogP 7.73, HBA 7, HBD 3, PSA 91.83, QED 0.19
Compound (SMILES): Clc1cc(Cl)cc(Cc2nnc(CCc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: DWNKUUCRZQVTHP-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 51.7 nM (pChEMBL 7.289999961853027)
Descriptors: MW 479.42, ALogP 5.8, HBA 4, HBD 2, PSA 75.18, QED 0.28
Compound (SMILES): Cc1[nH]c2cc(Nc3ncc(Cl)c(Nc4ccccc4NS(C)(=O)=O)n3)ccc2c1C(=O)N1CCC(C)CC1
InChIKey: IDOYZDKYHYCQEW-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human wild type ALK (1058 to 1620 residues) cytoplasmic domain expressed in baculovirus infected Sf21 cells incubated for 1 hrs in the presence of ATP by mobility shift assay
Measurement: IC50 = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 568.1, ALogP 5.65, HBA 7, HBD 4, PSA 132.11, QED 0.23
Compound (SMILES): O=C(c1cnc2c(cnn2CC2CC2)c1C(F)(F)F)N1CCN(c2ccc(F)cc2F)CC1
InChIKey: QZBSALDEUVKOGG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Agonist activity at mGlu3 receptor (unknown origin) expressed in human Flp-In-T-REx-293 cells by luciferase based GloSensor cAMP Assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 465.43, ALogP 4.1, HBA 5, HBD 0, PSA 54.26, QED 0.54
Compound (SMILES): COc1ccc2[nH]c(=O)c(C(c3nnnn3CCc3ccccc3)N3CCN(c4cccc(C(F)(F)F)c4)CC3)cc2c1
InChIKey: FAUBXPJKRZBEGW-UHFFFAOYSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Activation of human EAAT2 expressed in rat Astrocytes assessed as glutamate uptake by ELISA
Measurement: EC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 589.62, ALogP 4.7, HBA 8, HBD 1, PSA 92.17, QED 0.28
Compound (SMILES): C[N+]1(C)CCC(Oc2ccc(/C=C/c3ccccc3)cc2)C1.[I-]
InChIKey: VUPBXVOBUWSAOS-HRNDJLQDSA-M
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Displacement of [3H]-epibatidine from human alpha4beta2 nAChR expressed in HEK293 cells membrane assessed as inhibition constant preincubated for 5 mins followed by overnight incubation with [3H]-epibatidine by gamma liquid scintilation counting analysis
Measurement: Ki = 10.7 nM (pChEMBL 7.96999979019165)
Descriptors: MW 294.42, ALogP 4.08, HBA 1, HBD 0, PSA 9.23, QED 0.61
Compound (SMILES): COC(=O)C1CN(Cc2ccc(-c3cn(-c4ccc(OC(C)C)c(Cl)c4)nn3)cc2)C1
InChIKey: OXYWVGALKMSARL-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.93, ALogP 3.98, HBA 7, HBD 0, PSA 69.48, QED 0.52
Compound (SMILES): CCCCCCNNC(=O)c1cnc(NCCc2ccccc2)nc1
InChIKey: DDAMDJOJXKOHBK-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3 using p53 (Ac-RHKK(Acetyl)-AMC) as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 341.46, ALogP 2.95, HBA 5, HBD 3, PSA 78.94, QED 0.43
Compound (SMILES): CCCCCCCCCCCOc1cccc(CCC(=O)NC[C@@H](O)COP(=O)(O)OC[C@H](NC(=O)CCCC)C(=O)O)c1
InChIKey: BMRCIIZGJWUFPB-IAPPQJPRSA-N
Target: Probable G-protein coupled receptor 174 (SINGLE PROTEIN), Mus musculus
UniProt: Q3U507
Assay: Antagonist activity at mouse GPR174 transfected in human HEK293FT cells co-transfected with AP-TGFalpha assessed as inhibition of LysoPalloT-NH-C3-ph-m-O-C11-induced AP-TGFalpha release incubated for 90 mins by TGFalpha shedding assay
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 644.74, ALogP 4.9, HBA 8, HBD 5, PSA 180.72, QED 0.07
Compound (SMILES): Cc1nc2cnc3ccc(-c4cc(Cl)c(O)c(Cl)c4)cc3c2n1[C@H]1CC[C@H](CO)CC1
InChIKey: VYYJXVQJCSGHTK-CZIWCDLHSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Kinase/Tyr 6 peptide as substrate incubated for 1 hrs in presence of ATP by fluorescence microplate reader analysis
Measurement: IC50 = 15.4 nM (pChEMBL 7.809999942779541)
Descriptors: MW 456.37, ALogP 6.3, HBA 5, HBD 2, PSA 71.17, QED 0.38
Compound (SMILES): O=C(Nc1nc2cccc([C@@H]3CCC4(C3)CN(C(=O)[C@@H]3CC3(F)F)C4)n2n1)C1CC1
InChIKey: SOKYMLHPKZYWKI-KGLIPLIRSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 415.44, ALogP 2.83, HBA 5, HBD 1, PSA 79.6, QED 0.83
Compound (SMILES): Cc1ccc(O)c(C)c1-n1c(N)c(C(N)=O)c2nc3ccccc3nc21
InChIKey: KBWZVVPCJMAFMN-UHFFFAOYSA-N
Target: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99640
Assay: Inhibition of N-terminal recombinant PKMYT1 (76 to 362 residues) in CCNE1 amplified human FU-OV-1 cells assessed as phosphorylation of CDK1 at Thr14 incubated for 2 hrs by AlphaLisa assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 347.38, ALogP 2.58, HBA 6, HBD 3, PSA 120.05, QED 0.51
Compound (SMILES): Cc1c(-c2ccc(-c3c[nH]nc3-c3ccnc(N4CCOCC4)c3)cc2)ccc(S(N)(=O)=O)c1C
InChIKey: OUWOAMPJEASGND-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q5S006
Assay: Inhibition of mouse full-length LRRK2 G2019S mutant transfected in HEK293 cells using LRRKtide as substrate in presence of ATP by incubated for 1 hr TR-FRET based ADAPTA assay
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 489.6, ALogP 3.91, HBA 6, HBD 2, PSA 114.2, QED 0.44
Compound (SMILES): CCCCn1cc(C(=O)N[C@H](C(N)=O)C(C)(C)C)c2ccccc21
InChIKey: JXGXKMDAAOWHLR-MRXNPFEDSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from N-terminal 3HA-tagged human CB2 receptor expressed in human HEK293-EBNA cells incubated for 60 mins by radioligand competitive binding assay based liquid scintillation counter
Measurement: Ki = 1.318 nM (pChEMBL 8.880000114440918)
Descriptors: MW 329.44, ALogP 3.07, HBA 3, HBD 2, PSA 77.12, QED 0.85
Compound (SMILES): NS(=O)(=O)c1cccc(N/C=C/C(=O)c2ccc(Cl)cc2)c1
InChIKey: CDNDGWRDBIEZRJ-CMDGGOBGSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to human CA4 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 336.8, ALogP 2.8, HBA 4, HBD 2, PSA 89.26, QED 0.65
Compound (SMILES): COC(C)(C)C(=O)NC(=O)Nc1ccc(Oc2ccnc(-c3ccc(C)nc3)c2)c(C)n1
InChIKey: PCXFPRAKEYSDMS-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of N-terminal GST-tagged PDGFRbeta (unknown origin) (557 to 1106 residues) measured by spectrophotometric analysis
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 435.48, ALogP 4.02, HBA 7, HBD 2, PSA 115.33, QED 0.6
Compound (SMILES): CN1C(=O)[C@@H](N2CCc3c(nn(Cc4ccccc4)c3C(N)=O)C2=O)COc2cc(Cl)ccc21
InChIKey: KIBQDIDFPAQGOU-SFHVURJKSA-N
Target: LIM domain kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53667
Assay: Inhibition of PAK mediated recombinant LIMK1 phosphorylation (330 to 637 residues) (unknown origin) incubated for 45 mins followed by ATP addition measured after 105 mins by RapidFire Mass Spectrometry kinase assay
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 479.92, ALogP 2.11, HBA 6, HBD 1, PSA 110.76, QED 0.62
Compound (SMILES): COc1cc2cnnc(N[C@H](C)c3cccc(C(F)(F)F)c3C)c2cc1OC
InChIKey: FZGCUSRTDSOYLS-GFCCVEGCSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: HTRF Displacement Assay: Table 21: This Example illustrates that exemplary compounds of the present invention bind to SOS1 and prevent a labeled tracer ligand from occupying the SOS1 binding site. The ability of a compound of Formula (I) to bind to SOS1 was measured using a HTRF displacement assay. A recombinant human SOS1 polypeptide (corresponding to amino acids 564-1049, expressed in E. Coli with N-terminal StrepII-TEV, C-terminal His-tag. MW=60.59 kDa) was incubated with an exemplary compound of Formula (I) (in a DMSO stock solution) in buffer (25 mM HEPES pH 7.5, 25 mM NaCl, 1 mM DTT, 0.01% Brij 35, 0.02% BSA, 0.1% DMSO). After a 15-minute incubation at room temperature, a solution comprised of a custom-made Cy5 labelled tracer and MAb Anti-6HIS Tb cryptate Gold (Cisbio 61HI2TLA) in buffer was added to the solution containing the SOS1 polypeptide and exemplary compound of Formula (I). After a 1-hour incubation at room temperature, the HTRF signal was measured using Envision plate reader (Perkin Elmer) according to the manufacturer's instructions. Excitation was from over a range of 245-395 nm, and emission 1 was detected at (657.5-672.5) nm and emission 2 detected at (606.5-623.5) nm. The HTRF ratio was calculated using the formula: [emission 1/emission 2]*10000.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 391.39, ALogP 5.15, HBA 5, HBD 1, PSA 56.27, QED 0.65
Compound (SMILES): CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CC(C)(C)C)C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O
InChIKey: KAQZTNGABLBVAD-CMOCDZPBSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of His/SUMO tagged SARS-CoV2 main protease expressed in Escherichia coli BL21 (DE3) cells using Dabcyl-KTSAVLQSGFRKME-Edans as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence plate reader analysis
Measurement: IC50 = 17.9 nM (pChEMBL 7.75)
Descriptors: MW 516.64, ALogP 2.07, HBA 6, HBD 4, PSA 142.7, QED 0.31
Compound (SMILES): Nc1ncc(-c2cc(N3CCOCC3)nc(N3C[C@@H](CO)OC3=O)n2)c(C(F)(F)F)n1
InChIKey: DWKKLVKWBYBYKI-VIFPVBQESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9Z1L0
Assay: Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction in phosphorylation of AKT at Ser473 residue incubated for 1 hr by cellular assay
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 441.37, ALogP 0.69, HBA 10, HBD 2, PSA 139.82, QED 0.7
Compound (SMILES): NS(=O)(=O)c1cccc(NC(=O)c2cc(-c3cccc(Cl)c3)nc3ccc(Cl)cc23)c1
InChIKey: WULCZDMQCWOIQB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 348.7 nM (pChEMBL 6.460000038146973)
Descriptors: MW 472.35, ALogP 5.11, HBA 4, HBD 2, PSA 102.15, QED 0.43
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(OC(F)(F)F)c2)ccn1
InChIKey: HAPXQAGUUXSYBV-FQEVSTJZSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of full length human AAK1 expressed in HEK293F cells assessed as suppression of AP2 phosphorylation measured after 3 hrs by Western blot analysis based cellular assay
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 441.45, ALogP 4.97, HBA 6, HBD 2, PSA 95.7, QED 0.6
Compound (SMILES): Cc1[nH]nc(-c2ccncc2)c1-c1ccc(-c2cccc(S(N)(=O)=O)c2)c(C(F)(F)F)c1
InChIKey: QVWRYNBRCWCJRD-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q5S006
Assay: Inhibition of mouse full-length LRRK2 G2019S mutant transfected in HEK293 cells using LRRKtide as substrate in presence of ATP by incubated for 1 hr TR-FRET based ADAPTA assay
Measurement: EC50 = 4780 nM (pChEMBL 5.320000171661377)
Descriptors: MW 458.47, ALogP 4.78, HBA 4, HBD 2, PSA 101.73, QED 0.46
Compound (SMILES): COCCOc1ccnc(C#Cc2ccc3c4c(oc3c2)C(C)(C)c2cc(OCCN3CCOCC3)ccc2C4=O)c1
InChIKey: IPFQMFOPNXOZJB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: IC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 566.65, ALogP 4.83, HBA 8, HBD 0, PSA 83.26, QED 0.22
Compound (SMILES): CC/C(=C(/c1ccc(/C=C/C(=O)O)cc1)c1[nH]c2ccccc2c1Cl)c1ccc(F)cc1Cl
InChIKey: HUQVRIJCSRWPQV-CCDJVQBGSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 10100 nM (pChEMBL 5)
Descriptors: MW 480.37, ALogP 8.08, HBA 1, HBD 2, PSA 53.09, QED 0.22
Compound (SMILES): CNC(=O)c1cccc(-c2cnc3cc(-c4cnn(C)c4)c(OC4COC4)nn23)c1
InChIKey: KCWGQPNZUSKGQY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61851
Assay: Inhibition of TEL-FGFR3 in mouse BaF3 cells incubated for 125 mins by plate reader analysis
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 404.43, ALogP 1.93, HBA 8, HBD 1, PSA 95.57, QED 0.55
Compound (SMILES): CCCCCC[Si](C)(C)c1cc(OC)c([C@H]2C=C(CO)[C@H]3C[C@@H]2C3(C)C)c(OC)c1
InChIKey: XWDCFKORUHOXRS-BDTNDASRSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at recombinant human CB2 receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin stimulation and measured after 15 mins by HTRF assay
Measurement: EC50 = 460.2 nM (pChEMBL 6.340000152587891)
Descriptors: MW 430.71
Compound (SMILES): CCN(Cc1ccc(C(=O)N2CCC[C@@H]2C#N)s1)c1ccc(F)cc1
InChIKey: AQYKGKLKIQVGOS-MRXNPFEDSA-N
Target: Glutamate receptor ionotropic, NMDA 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q12879
Assay: Positive allosteric modulator activity at GluN2A receptor (unknown origin) by FLIPR assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 357.45, ALogP 4.04, HBA 4, HBD 0, PSA 47.34, QED 0.81
Compound (SMILES): COc1cc(OCC(=O)Nc2cc(OC(F)(F)F)ccc2-n2cncn2)ccc1OC1COC1
InChIKey: KGZJVSVIUHWKQW-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay
Measurement: IC50 = 819 nM (pChEMBL 6.090000152587891)
Descriptors: MW 480.4, ALogP 2.97, HBA 9, HBD 1, PSA 105.96, QED 0.5
Compound (SMILES): Fc1ccc2c(c1CNc1ncc(-c3cccnc3)c3nncn13)CCO2
InChIKey: GNJGTNXXYAEHGW-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: EED LC-MS Assay: Representative compounds of the present disclosure were serially and separately diluted 3-fold in DMSO to obtain a total of eight or twelve concentrations. Then the test compounds at each concentration (120 nL of each) were transferred by Mosquito into a 384-well Perkin Elmer ProxiPlate 384 plus plates. Solutions (6 μL) of 24 nM the wild type PRC2 (wtPRC2) complex and 2 μM SAM in reaction buffer (20 mM Tris, pH 8.0, 0.1% BSA, 0.01% Triton, 0.5 mM DTT) were added to the wells that were then incubated with the test compound for 20 min. A 6 μL solution of 3 μM of the peptide substrate H3K27Me0 (histone H3[21-44]-biotin) in reaction buffer was added to initiate each reaction. The final components in the reaction solution include 12 nM wtPRC2 complex, 1 μM SAM, and 1.5 μM H3K27me0 peptide with varying concentration of the compounds. A positive control consisted of the enzyme, 1 μM SAM and 1.5 μM substrate in the absence of the test compound, and a negative control consisted of 1 μM SAM and 1.5 μM substrate only. Each reaction was incubated at rt for 120 min, then stopped by addition of 3 μL per of quench solution (2.5% TFA with 320 nM d4-SAH). The reaction mixture was centrifuged (Eppendorf centrifuge 5810, Rotor A-4-62) for 2 min at 2000 rpm and read on an API 4000 triple quadrupole mass spec with Turbulon Spray (Applied Biosystem) coupled with Prominence UFLC (Shimadzu). The levels of SAH production were then normalized based on the values coming from the positive and negative controls to give percent enzyme activities. The data were then fit to a dose response equation using the program Helios to get the IC50 values of the test compound.
Measurement: IC50 = 19.2 nM (pChEMBL 7.71999979019165)
Descriptors: MW 362.37, ALogP 2.87, HBA 7, HBD 1, PSA 77.23, QED 0.6
Compound (SMILES): N#Cc1ccc(Nc2cnccc2SCc2ccccc2C(=O)[O-])c2ccccc12.[Na+]
InChIKey: VFQCYGPPRZHSKX-UHFFFAOYSA-M
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin) expressed in HEK293 cells membrane vesicles assessed as inhibition of ATP-induced 14C-uric acid uptake preincubated for 15 mins followed by incubation with ATP and substrate for 5 mins by liquid scintillation counting analysis
Measurement: IC50 = 26740 nM (pChEMBL 4.570000171661377)
Descriptors: MW 411.49, ALogP 5.84, HBA 5, HBD 2, PSA 86.01, QED 0.39
Compound (SMILES): O=C(NO)c1ccc2c(c1)CCN(S(=O)(=O)c1cc(F)c(F)c(F)c1F)C2
InChIKey: YGSMPRINJCSYQS-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length human recombinant HDAC8 expressed in Sf9 baculovirus system using FAM-labeled acetylated peptide as substrate by measuring fluorescence intensity by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 404.34, ALogP 2.11, HBA 4, HBD 2, PSA 86.71, QED 0.27
Compound (SMILES): O=c1[nH]cc([C@@H]2COc3cc(F)ccc3S2)[nH]c1=O
InChIKey: OTKFYQJEXKHMQT-JTQLQIEISA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Mus musculus
UniProt: P18894
Assay: Inhibition of full length mouse DAO transfected with CHO-K1 cells incubated for 30 mins by Amplex red and horseradish peroxidase based fluorescence assay
Measurement: EC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 280.28, ALogP 1.43, HBA 4, HBD 2, PSA 74.95, QED 0.77
Compound (SMILES): O=P(O)(O)OP(=O)(O)OP(=O)(O)OC[C@H]1O[C@@H](n2cnc3c(Nc4ccccc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: MXSCITZYHDRLLP-XNIJJKJLSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Agonist activity at human P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: IC50 = 208.93 nM (pChEMBL 6.679999828338623)
Descriptors: MW 583.28, ALogP 0.53, HBA 14, HBD 7, PSA 265.14, QED 0.16
Compound (SMILES): CCCc1ccc(-c2cn(-c3ccc(CN4CC(C(=O)O)C4)cc3)nn2)cc1
InChIKey: OXYDFIRCOQWIJF-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 376.46, ALogP 3.4, HBA 5, HBD 1, PSA 71.25, QED 0.68
Compound (SMILES): Cc1nc(Nc2cccc(N3CCCCC3=O)n2)sc1-c1cc2c(c(S(=O)(=O)NC3COC3)c1)C(=O)N([C@@H](C)C(F)(F)F)C2
InChIKey: ZTXDHUWPUMVZCM-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Enzymatic Activity Assay : The activity of recombinant human PI3Kγ ((aa144-1102)-6His) and PI3Kα, β, δ (6-His(p110-p85α)) was determined by measuring the ADP level after phosphorylation of DiC8-PIP2 using a commercially available ADP-Glo kit from Promega. The assay was carried out in white low volume 384 well plates in a final volume of 14 μl at R.T. The assay conditions contained the following: 50 mM Tris buffer pH 7.4, 2.1 mM DTT, 3 mM MgCl2, 0.05% CHAPS, 20 μM ATP, 80 μM DiC8-PIP2 and 1.2 nM PI3Kα, β, γ or 0.6 nM PI3Kδ. Potential inhibitors were made up in DMSO and then diluted in the assay to give a final concentration of not exceeding 1% (v/v) DMSO. A 10-point half-log dilution series of the inhibitors (highest concentration typically 0.1 μM for δ or γ and 33 μM for a or 1) was tested and the pIC50 determined using a 4-parameter logistic equation in a non-linear curve fitting routine. Routinely, inhibitors were pre-incubated with 3 μl of enzyme for 15 min prior to the addition of 2 μl substrate mixture for a further 60 min enzyme reaction. The phosphorylation was stopped with the addition of 3 μl ADP-Glo reagent (stop solution) followed by a 40 min incubation. Prior to detection 6 μl of ADP-Glo Kinase Detection Reagent was added and the plates were read in a micro plate reader using a Luminescence filter. All additions were followed by a short centrifugation step.
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 650.7, ALogP 4.36, HBA 9, HBD 2, PSA 133.83, QED 0.37
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1cc(S(=O)(=O)F)ccc1OC)C(=O)N1CCCC[C@H]1C(=O)N[C@@H]1CCc2ccccc21
InChIKey: UUJKVNYGEWQGHG-PVUOONDNSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: Antagonist activity at N-terminal His-tagged cIAP1-BIR3 domain (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 631.73, ALogP 1.36, HBA 8, HBD 4, PSA 163.01, QED 0.27
Compound (SMILES): CNC(=O)c1cncc(-c2cnn3cc(-c4cnn(C(C)C)c4)c(O[C@H]4CCOC4)nc23)c1
InChIKey: XKKGIGFZDVPVNO-SFHVURJKSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 residues) expressed in an Sf9 infected baculovirus expression system using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 447.5, ALogP 2.76, HBA 9, HBD 1, PSA 108.46, QED 0.48
Compound (SMILES): CCOC1CN(C2CCN(c3cc(OC)c(Nc4ncc(Br)c(Nc5ccc6ncnn6c5P(C)(C)=O)n4)cc3CC)CC2)C1
InChIKey: LCYQDTKMLMBXIY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) using TK as substrate incubated for 120 mins in the presence of ATP by HTRF assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 698.61, ALogP 5.28, HBA 12, HBD 2, PSA 122.04, QED 0.2
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2nc(N/N=C/c3ccccn3)nc(Nc3ccccc3)n2)cc1
InChIKey: YARRJWUINHALEQ-ZVHZXABRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA 9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 27.2 nM (pChEMBL 7.570000171661377)
Descriptors: MW 461.51, ALogP 2.85, HBA 10, HBD 4, PSA 160.17, QED 0.23
Compound (SMILES): NS(=O)(=O)c1ccc(NCC/C(=N/CCO)c2ccccc2)cc1
InChIKey: SRRMPHRICLNCLF-JZJYNLBNSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 10.2 nM (pChEMBL 7.989999771118164)
Descriptors: MW 347.44, ALogP 1.62, HBA 5, HBD 3, PSA 104.78, QED 0.63
Compound (SMILES): Cl.Cl.Nc1nc(C(=O)NCc2ccccn2)cn2c1nc1ccccc12
InChIKey: WRWJZCORCAMKGM-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]DPCPX from human A2BAR expressed in HEK293 cells membrane assessed as inhibition constant preincubated for 5 mins followed by [3H]DPCPX addition and measured after 1.5 hrs by TopCount scintillation counting method
Measurement: Ki = 40.6 nM (pChEMBL 7.389999866485596)
Descriptors: MW 318.34, ALogP 1.79, HBA 6, HBD 2, PSA 98.2, QED 0.6
Compound (SMILES): C[C@H]1OC(=O)N(c2nc(-c3cnc(N)nc3C(F)(F)F)cc(N3CCOCC3)n2)[C@H]1CO
InChIKey: GFZKPRZGOZINHQ-SKDRFNHKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9Z1L0
Assay: Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction in phosphorylation of AKT at Ser473 residue incubated for 1 hr by cellular assay
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 455.4, ALogP 1.08, HBA 10, HBD 2, PSA 139.82, QED 0.69
Compound (SMILES): CCC(=O)Nc1ccccc1Nc1n[nH]c2ccc(O[C@H](C)c3c(Cl)cncc3Cl)cc12
InChIKey: VISCPFTZJFACFT-CYBMUJFWSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown orgin) using Tyr 04 peptide as substrate incubated for 1 hr in presence of 5 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 470.36, ALogP 6.5, HBA 5, HBD 3, PSA 91.93, QED 0.29
Compound (SMILES): C[C@H](CO)Nc1nc(SCc2cccc(F)c2F)nc2c1CNCC2
InChIKey: BKSXVRDJSFJSQU-SNVBAGLBSA-N
Target: C-C chemokine receptor type 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P32248
Assay: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 366.44, ALogP 2.49, HBA 6, HBD 3, PSA 70.07, QED 0.54
Compound (SMILES): Cc1cccc(C2NCCc3c2[nH]c2ccc(F)cc32)c1.Cl
InChIKey: NGNCWOWDNFZUSI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 306 nM (pChEMBL 6.510000228881836)
Descriptors: MW 280.35, ALogP 3.85, HBA 1, HBD 2, PSA 27.82, QED 0.7
Compound (SMILES): COc1cc(OCc2cccc(-c3ccccc3)c2C)cc(OC)c1CN(C)CCCC(=O)NO
InChIKey: NOXAXIWAGSLHBX-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/PDL1 interaction (unknown origin) in by HTRF assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 478.59, ALogP 4.98, HBA 6, HBD 2, PSA 80.26, QED 0.28
Compound (SMILES): Cc1c(F)cccc1N(C)C(=O)c1ccc(-c2ccc(O)cc2)o1
InChIKey: DMSXKJVULVZSSZ-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Inhibition of human placental microsomal fraction 17beta-HS2 using [3H]-E2 as substrate in presence of NAD+ measured after 10 mins by HPLC method
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 325.34, ALogP 4.38, HBA 3, HBD 1, PSA 53.68, QED 0.78
Compound (SMILES): Cn1ccnc1SCC1CCN(S(=O)(=O)c2ccc3c(c2)OCO3)CC1
InChIKey: WVSOMULEPSJRTO-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human muscarinic M1 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by by Fluo-4AM staining based fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 395.51, ALogP 2.34, HBA 7, HBD 0, PSA 73.66, QED 0.72
Compound (SMILES): Cc1nc(N[C@H](C)c2cc(N)cc(C(F)(F)F)c2)c2cc(O[C@H]3CCOC3)c(O)cc2n1
InChIKey: GLEBCUSYSCBWKF-BZNIZROVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes at 10 uM using midazolam as substrate preincubated for 10 mins followed by NADPH addition by LC/MS analysis
Measurement: IC50 = 54300 nM (pChEMBL 4.260000228881836)
Descriptors: MW 448.45, ALogP 4.59, HBA 7, HBD 3, PSA 102.52, QED 0.49
Compound (SMILES): O=C(Cc1ccccc1F)Nc1nc(-c2ccnc(F)c2)cs1
InChIKey: NLVGPTZAAUCTJS-UHFFFAOYSA-N
Target: Very long chain fatty acid elongase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: A1L3X0
Assay: Inhibition of ELOVL7 (unknown origin) using C18-acyl-CoA as substrate by radiometric enzyme assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 331.35, ALogP 3.66, HBA 4, HBD 1, PSA 54.88, QED 0.74
Compound (SMILES): O=C(O)c1ccc2c(c1)C1(CCN(C(=O)c3ccc(Cl)cc3)CC1)C(=O)N2
InChIKey: NBNDZHLPEOMAMK-UHFFFAOYSA-N
Target: Inositol hexakisphosphate kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PC2
Assay: Inhibition of recombinant full length human IP6K3 assessed as inorganic phosphate release measured after 2 hrs by ADP-Glo Max assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 384.82, ALogP 3.16, HBA 3, HBD 2, PSA 86.71, QED 0.83
Compound (SMILES): O[C@H](c1cc(Cl)cc2cncn12)C1CCCCC1
InChIKey: AVJCRIIDMDBAQC-AWEZNQCLSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 264.76, ALogP 3.6, HBA 3, HBD 1, PSA 37.53, QED 0.9
Compound (SMILES): NS(=O)(=O)c1ccc(NNCCC(=O)c2ccc3ccccc3c2)cc1
InChIKey: PUKIVUCMTLVWPO-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 66.7 nM (pChEMBL 7.179999828338623)
Descriptors: MW 369.45, ALogP 2.68, HBA 5, HBD 3, PSA 101.29, QED 0.34
Compound (SMILES): CC1Cc2ccc(C(=O)O)cc2Oc2ccc(OCc3c(-c4c(Cl)cccc4Cl)noc3C3CC3)nc21
InChIKey: ZSGKCBJKVYQMFL-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Receptor Coactivator Assay: Purchasing invitrogen PV4833 kits. The procedure refers to LanthaScreen TR-FRET Farnesoid X Receptor Coactivator AssayFirst, the required amount of the compound was weighed and dissolved in 100% DMSO at the maximum concentration of 3000 μM. The solution at the maximum concentration was diluted by 3-fold serial dilution in DMSO to get 10 concentrations;Second, the above prepared solutions of different concentrations were diluted to 50-fold with a buffer supplied with the kit, to 2× compound solution, followed by mixing and then 10 μL of the diluted solution was added to a 384 well plate;Third, FXR-LBD was diluted with a buffer to 4× solution, and 5 μL of the diluent was added to the 384 well plate of second step;Fourth, Fluorescein-SRC2-2 and Tb anti-GST antibody were diluted to 4× Fluorescein-SRC2-2 and Tb anti-GST antibody solution. Then two reagents were mixed together, and 5 μL of the mixture was added to the 384 well plate of third step;Finally, the solution of the 384 well above was mixed uniformly by centrifuging, and then incubated at room temperature for 1 h. Then the TR-FRET Endpoint method was used for measuring the solution at wavelengths of 520 nm, 495 nm and 337 nm. EC50 values were calculated according to the measured value of ER=520 nm/495 nm.
Measurement: EC50 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 537.4, ALogP 7.65, HBA 6, HBD 1, PSA 94.68, QED 0.27
Compound (SMILES): CCCCc1sc(C2CCN(CCCCc3cn(C)c4ccc(C#N)cc34)CC2)nc1-c1ccc(Oc2ccc(Cl)cc2)cc1
InChIKey: SYSZRZAQHLUSDF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG transfected in CHO cells by manual patch-clamp assay
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 637.29, ALogP 10.16, HBA 6, HBD 0, PSA 54.08, QED 0.13
Compound (SMILES): N#Cc1ccccc1CC(=O)N[C@@H](C[C@@H]1COc2c(Cl)cccc21)B(O)O
InChIKey: ANAHQGZCJNNCQJ-PBHICJAKSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human A549 cells using Suc-LLVY-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 20904 nM (pChEMBL 4.679999828338623)
Descriptors: MW 384.63
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)n2[nH]c(=O)c3c(Br)c(Br)c(Br)c(Br)c3c2=O)cc1
InChIKey: NIXSTVGKKMIUBM-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometry based esterase assay
Measurement: Ki = 6.32 nM (pChEMBL 8.199999809265137)
Descriptors: MW 660.92, ALogP 3.08, HBA 6, HBD 2, PSA 132.09, QED 0.32
Compound (SMILES): O=c1[nH]c2ccccc2nc1N/N=C/c1cccs1
InChIKey: GAXLWQSFFHWRJR-RIYZIHGNSA-N
Target: Phospholipase A2, membrane associated (SINGLE PROTEIN), Homo sapiens
UniProt: P14555
Assay: Inhibition of human PLA2G2A
Measurement: IC50 = 2810 nM (pChEMBL 5.550000190734863)
Descriptors: MW 270.32, ALogP 2.43, HBA 5, HBD 2, PSA 70.14, QED 0.57
Compound (SMILES): NC(=S)c1ccc(C(=O)N2CCN(Cc3ccccc3)CC2)cc1
InChIKey: LRWUYNOAVKINCT-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]-DAMGO from Sprague-Dawley rat brain membrane mu opioid receptor incubated for 45 mins by liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 339.46, ALogP 2.28, HBA 3, HBD 1, PSA 49.57, QED 0.87
Compound (SMILES): O=C(NC1CCN(C(=O)C2(F)CC2)CC1)NC12CC3CC(Cl)(CC(C1)c1ccccc13)C2
InChIKey: WHFWYHDLWCPIQQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human recombinant CYP2C19 using 3-cyano-7-ethoxycoumarin as a substrate preincubated for 5 mins followed by substrate addition by fluorescence plate reader analysis
Measurement: IC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 459.99, ALogP 4.35, HBA 2, HBD 2, PSA 61.44, QED 0.66
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NCCc4ccccc4)nc(C#Cc4ccc(Cl)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: KXUMVOXGLOSYAM-SASJIJFGSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human adenosine A3A receptor stably expressed in HEK293 cells assessed as mini G-alpha recruitment potency by luciferase based NanoBiT assay
Measurement: EC50 = 64.9 nM (pChEMBL 7.190000057220459)
Descriptors: MW 549.06, ALogP 2.62, HBA 9, HBD 4, PSA 125.19, QED 0.27
Compound (SMILES): Cc1ccc(O)cc1-n1c(N)c(C(N)=O)c2cc3ccccc3nc21
InChIKey: CCLATZMUQLEESJ-UHFFFAOYSA-N
Target: Ephrin type-B receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P54753
Assay: Inhibition of full length Nano-luc fused EPHB3 in human HEK-293T cells incubated for 2 hrs by cell based NanoBRET target engagement assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 332.36, ALogP 2.87, HBA 5, HBD 3, PSA 107.16, QED 0.52
Compound (SMILES): COc1cc([SeH])cc(OC)c1OC
InChIKey: AMSHOIFJKIQSFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 180 nM (pChEMBL 6.75)
Descriptors: MW 247.15
Compound (SMILES): CC(C)c1cnc(N2CC(O)C2)c2cnc(Nc3ccnc(N4CC[C@@H](O)[C@@](C)(F)C4)n3)cc12
InChIKey: JREDDTPLOBGIFI-DVECYGJZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGF stimulated EGFR L858R/T790M double mutant phosphorylation in human NCI-H1975 cells preincubated for 4 to 5 hrs followed by EGF stimulation for 10 mins by AlphaLISA method
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 467.55, ALogP 2.77, HBA 9, HBD 3, PSA 110.53, QED 0.52
Compound (SMILES): O=C(O)CC1CCC2(CC1)CCN(c1ccc(NC(=O)c3nnc(Nc4ccc(F)c(F)c4)o3)cn1)CC2
InChIKey: XOFGTUXJGBWWCZ-UHFFFAOYSA-N
Target: Acetyl-CoA acetyltransferase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P24752
Assay: Inhibition of human ACAT1 in HepG2 cells assessed as inhibition of triglyceride synthesis incubated for 1 hrs followed by 13C-addition of 13C-oleic acid pre-complexed with fatty acid free BSA for 6 hrs by LC/MS/MS analysis
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 526.54, ALogP 4.99, HBA 8, HBD 3, PSA 133.48, QED 0.39
Compound (SMILES): CCNNC(=O)c1ccc(CN2c3ccccc3C=Cc3nc(C)nc(C)c32)cc1
InChIKey: ADHUUJWLMKPLLG-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant HDAC3 (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 = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 399.5, ALogP 4.17, HBA 5, HBD 2, PSA 70.15, QED 0.63
Compound (SMILES): Cc1cc(C(=O)C2=C(c3ccc(O)cc3)COc3cc(O)ccc32)ccc1OCCN1C=Cc2cccnc2C1
InChIKey: IWMRBSFBFQITCE-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha in human MCF7 cells assessed as downregulation of ERalpha
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 532.6, ALogP 5.85, HBA 7, HBD 2, PSA 92.12, QED 0.29
Compound (SMILES): Cc1nc2cnc3ccc(-c4ccc(C#N)cc4)cc3c2n1-c1ccc(F)cc1
InChIKey: QBDILWXCGRGTSO-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 as substrate incubated for 2 hrs in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 513.3 nM (pChEMBL 6.289999961853027)
Descriptors: MW 378.41, ALogP 5.56, HBA 4, HBD 0, PSA 54.5, QED 0.4
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)N[C@@H](CO)C5CC5)c4n3)cc(OC(F)F)c2C1=O
InChIKey: SHTQVEFWTQUXFU-SGTLLEGYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in SDF-1alpha stimulated human whole blood assessed as reduction in phospho-AKT kinase activity preincubated for 1 hr followed by SDF-1alpha stimulation and measured after 2 mins by flow cytometric analysis
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 526.54, ALogP 2.83, HBA 8, HBD 3, PSA 135.08, QED 0.39
Compound (SMILES): NC1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1
InChIKey: WKYMGORXOQPTTO-CLTKARDFSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of GST-fused mouse recombinant CLK1 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 231.21, ALogP 0.2, HBA 5, HBD 2, PSA 85.94, QED 0.68
Compound (SMILES): N#Cc1ccc(-n2ccc(CC(=O)Nc3ccc(F)nc3)n2)cc1C(F)(F)F
InChIKey: TUMXUWXQSGSEJW-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at androgen receptor F877L mutant (unknown origin) expressed in PC-3 cells assessed as inhibition of transcriptional activity measured after 24 hrs by dual luciferase assay
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 389.31, ALogP 3.48, HBA 5, HBD 1, PSA 83.6, QED 0.55
Compound (SMILES): CCOCCN1CCN(CCC(=O)Nc2nc3c(C)cccc3s2)CC1
InChIKey: VJFHGIXPLWBJRF-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membrane measured after 120 mins by scintillation counting method
Measurement: Ki = 575 nM (pChEMBL 6.239999771118164)
Descriptors: MW 376.53, ALogP 2.59, HBA 6, HBD 1, PSA 57.7, QED 0.72