lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2cccc(Cl)c2)CCC1(O)c1cccc(O)c1
InChIKey: OUHGHFXEMHKVJE-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 19.7 nM (pChEMBL 7.710000038146973)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): C#CCCCCCCN1CCC(OC(=O)Nc2ccc(F)cc2-c2ccc(F)c(Cl)c2)CC1
InChIKey: FLUDDWGSVPESJK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 474.98, ALogP 6.88, HBA 3, HBD 1, PSA 41.57, QED 0.32
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-SFHVURJKSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): COc1ccc(CCC(=O)N2CCN(c3ccc(O)cn3)CC2)cc1
InChIKey: PSOALEIIKIAZMH-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 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 341.41, ALogP 2.08, HBA 5, HBD 1, PSA 65.9, QED 0.9
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCCNC(=O)[C@H](CCC(=O)O)NC(=O)c1ccc(N(C)Cc2cnc3nc(N)nc(N)c3n2)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)[C@@H](C)CC
InChIKey: CKBSFTZJAYRRQQ-USSPWNEHSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Agonist activity at human Y2R expressed in myo-[2-3H]-inositol labelled African green monkey COS7 cells coexpressing chimeric Galphadelta6qi4myr protein assessed as accumulation of [2-3H]-IP after 1 hr by scintillation counting analysis
Measurement: EC50 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 4734.29
Compound (SMILES): CNC(=O)[C@]12C[C@@H]1[C@@H](n1cnc3c(NC(C4CC4)C4CC4)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: PWANAKRSKQRVSS-WRQNOASSSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Binding affinity to 5HT2C receptor (unknown origin) assessed as inhibition constant
Measurement: Ki = 269 nM (pChEMBL 6.570000171661377)
Descriptors: MW 432.91, ALogP 1.11, HBA 8, HBD 4, PSA 125.19, QED 0.5
Compound (SMILES): C=CC(=O)N1CC[C@H](c2nc(-c3cc4cc(Br)cc(OC)c4s3)c3c(N)nccn23)C1
InChIKey: ZYBQELLBNQSEEB-LBPRGKRZSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human recombinant FGFR3
Measurement: IC50 < 0.3 nM (pChEMBL 9.52299976348877)
Descriptors: MW 498.41, ALogP 4.47, HBA 7, HBD 1, PSA 85.75, QED 0.42
Compound (SMILES): Cc1cc(N2CCOCC2)cnc1NC(=O)c1cc(C(=O)NCc2ccc(F)c(F)c2)c(F)cc1Cl
InChIKey: GBAXCPGBQNNUHB-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as increase in luciferase activity incubated for 24 hrs by luminescence based analysis
Measurement: IC50 > 49800 nM (pChEMBL 4.302999973297119)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 83.56, QED 0.5
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(=O)N1CCC[C@H]1C(N)=O
InChIKey: CIYDWUJZZVUIJH-LBURKSJTSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant
Measurement: Ki = 243.5 nM (pChEMBL 6.610000133514404)
Descriptors: MW 554.63, ALogP -1.68, HBA 9, HBD 5, PSA 223.58, QED 0.14
Compound (SMILES): Cn1cnc2c(c(-c3ccc(O)c(C(N)=O)c3)cn2CC(=O)Nc2cc(N3CCOCC3)ncc2Cl)c1=O
InChIKey: YBIRSGSQXIUNKC-UHFFFAOYSA-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 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 537.96, ALogP 1.73, HBA 10, HBD 3, PSA 157.6, QED 0.34
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(F)c(Nc4ccc5[nH]ccc5c4)n3)cc2)CC1
InChIKey: GULVHNBTUFJZLT-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 417.49, ALogP 4.34, HBA 6, HBD 3, PSA 72.11, QED 0.45
Compound (SMILES): Cc1noc(-c2ccccc2)c1C#CCCCCNC(=O)C(C)(C)S
InChIKey: VHNISSUREJJHQB-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 356.49, ALogP 4, HBA 4, HBD 2, PSA 55.13, QED 0.47
Compound (SMILES): CC(C)n1nc(C(=O)NCC2C3CN(C4CCOCC4)CC23)c2ccccc21.O=C(O)C(=O)O
InChIKey: CXCUAXXCKFHCAF-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 12 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 382.51, ALogP 2.7, HBA 5, HBD 1, PSA 59.39, QED 0.86
Compound (SMILES): CC(=O)N1c2ccc(NC(=O)OCC(C)(C)C)cc2C2(CCCCC2)C1(C)C
InChIKey: DCKSHOASDSPSRS-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 2550 nM (pChEMBL 5.590000152587891)
Descriptors: MW 386.54, ALogP 5.63, HBA 3, HBD 1, PSA 58.64, QED 0.72
Compound (SMILES): Cc1ccc2c(=O)[nH]c(-c3ccc(C4(O)CC4)cc3)cn12
InChIKey: UIPJAQKAZCQVPU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 280.33, ALogP 2.58, HBA 3, HBD 2, PSA 57.5, QED 0.76
Compound (SMILES): CC(C)N(CC(N)=O)C(=O)c1cc2c(N(C)C)nc(NCCc3c[nH]c4ccccc34)nc2n1CCCc1ccc(Cl)cc1Cl
InChIKey: DGYXXVVLRDGURB-UHFFFAOYSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Binding affinity to human MDM4 assessed as dissociation constant
Measurement: Ki = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 649.63, ALogP 5.91, HBA 7, HBD 3, PSA 125.17, QED 0.15
Compound (SMILES): CNC(C)c1cc(C)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(F)c1
InChIKey: ZGISJMLTGDSYRS-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: HPK1 Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μl of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech).
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 364.43, ALogP 3.75, HBA 5, HBD 2, PSA 71.42, QED 0.58
Compound (SMILES): CN(C)c1cccc2c(SNCCCCCC(=O)NO)cccc12
InChIKey: IOJSHUPVMUJFRE-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 4890 nM (pChEMBL 5.309999942779541)
Descriptors: MW 347.48, ALogP 3.57, HBA 5, HBD 3, PSA 64.6, QED 0.28
Compound (SMILES): O=C1[C@@H]2Cc3c([nH]c4ccccc34)[C@@H](c3ccc4c(c3)OCO4)N2C(=O)CN1CCC1CCN(Cc2ccccc2)CC1
InChIKey: KVANOXIAOYTXBY-ZBWWXOROSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) by Ellman's method
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 576.7, ALogP 4.88, HBA 5, HBD 1, PSA 78.11, QED 0.35
Compound (SMILES): COc1cc(/C=c2\c(=O)[nH]n3c(=O)c4ccccc4nc23)cc(OC)c1OC
InChIKey: SBBHTKBJRAVMMH-JYRVWZFOSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin) by fluorometric analysis
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 379.37, ALogP 1.11, HBA 7, HBD 1, PSA 94.92, QED 0.57
Compound (SMILES): N#Cc1c2n(c3c(N4CCN(Cc5ccc6c(c5)OCO6)CC4)ncnc13)CCCCC2
InChIKey: AEQOQBBHDZTQQV-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 = 23700 nM (pChEMBL 4.619999885559082)
Descriptors: MW 430.51, ALogP 3.08, HBA 8, HBD 0, PSA 79.44, QED 0.63
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: FXWMKOAMGUIHEX-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 398.45, ALogP 5.07, HBA 4, HBD 3, PSA 82.28, QED 0.39
Compound (SMILES): c1cncc(C[C@H]2[C@H](Oc3cnc(-c4ccc5[nH]ccc5c4)cn3)C3CCN2CC3)c1
InChIKey: MYGGRYSOINDCAP-UKILVPOCSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Binding affinity to alpha3beta4 nAChR (unknown origin) assessed as dissociation constant
Measurement: Ki = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 411.51, ALogP 4.1, HBA 5, HBD 1, PSA 66.93, QED 0.54
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3C)c3c(N)ncnc32)C1
InChIKey: BJMXICGJKUALLN-SFHVURJKSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Inhibition of BLK (unknown origin) by Z'LYTE assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 454.53, ALogP 4.53, HBA 7, HBD 1, PSA 99.16, QED 0.45
Compound (SMILES): CC(C)C[C@H]1CN(c2nc3ccc(Cl)cc3s2)CCC1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: QJANOKPCWNKQDB-GGYWPGCISA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 521.51, ALogP 7.19, HBA 5, HBD 1, PSA 62.66, QED 0.32
Compound (SMILES): O=C(/C=C/c1cccc(Nc2ncnc3cc4c(cc23)OCCO4)c1)NO
InChIKey: OJRNZGDFYZRJBM-SNAWJCMRSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 364.36, ALogP 2.66, HBA 7, HBD 3, PSA 105.6, QED 0.37
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)ccc2N2CC[C@@H](N)C2)n1
InChIKey: PZWKQEQSYRXWEJ-CQSZACIVSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 425.44, ALogP 3.22, HBA 6, HBD 2, PSA 93.37, QED 0.65
Compound (SMILES): CC1(C)C(/C=C/C=C/C=C2/N(CCCCS(=O)(=O)O)c3ccccc3C2(C)C)=[N+](CCCCCC(=O)NCCCCCCCCN2CCC(OC(=O)Nc3ccc(F)cc3-c3ccc(F)c(Cl)c3)CC2)c2ccc(S(=O)(=O)[O-])cc21
InChIKey: BMNOFIWIZFZYES-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 1160.89
Compound (SMILES): COc1cccc(/C=C/C(=O)NC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)c1
InChIKey: YOLVZOJWYFHBDZ-RCJYHZQCSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 529.46, ALogP 4.18, HBA 4, HBD 2, PSA 84.5, QED 0.39
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(N(C)C)c(C(=O)NCc3cccnc3)cc21
InChIKey: OXBZWMNEKIHBRX-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 = 15040 nM (pChEMBL 4.820000171661377)
Descriptors: MW 390.45, ALogP 2.06, HBA 7, HBD 1, PSA 84.53, QED 0.56
Compound (SMILES): O=c1cc(CO)n(-c2c(Cl)cccc2Cl)c2c(Cl)cnc(OC[C@@H](O)CO)c12
InChIKey: DDDSGZFENQKDDY-JTQLQIEISA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of recombinant human Cav1.2
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 445.69, ALogP 2.57, HBA 7, HBD 3, PSA 104.81, QED 0.54
Compound (SMILES): CN(C)CCNC1=CC(=O)c2nc(-c3cc(F)ccc3F)oc2C1=O
InChIKey: FOJHTOMZWUIILB-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P30307
Assay: Inhibition of recombinant CDC25C (unknown origin)
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 347.32, ALogP 2.03, HBA 6, HBD 1, PSA 75.44, QED 0.89
Compound (SMILES): Cc1cc(C)cc(-c2cncc(C(=O)Nc3cccc(O)c3)c2NCCCN)c1
InChIKey: NUUWLGXOHGOZLE-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 390.49, ALogP 4.08, HBA 5, HBD 4, PSA 100.27, QED 0.46
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CN(C)C1)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: YOCBGMVQRJHNRU-QHCPKHFHSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 expressed in baculovirus infected insect cells using FLUOR DE LYS-SIRT1 as fluorogenic substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by spectrophotometer based analysis
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 478.59, ALogP 4.55, HBA 7, HBD 1, PSA 97.56, QED 0.38
Compound (SMILES): Cc1ccc(CC(=O)O)cc1OCCN1CCN(c2nc3ccc(Cl)cc3s2)C[C@@H]1C
InChIKey: WGVWBIUWHHDYCY-INIZCTEOSA-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 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 460, ALogP 4.47, HBA 6, HBD 1, PSA 65.9, QED 0.56
Compound (SMILES): COc1ccc(/C=C2\SC(=O)N(CCNC(=O)Nc3c(C)n(C)n(-c4ccccc4)c3=O)C2=O)cc1
InChIKey: ADQLECAYDOTLPN-HKWRFOASSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) by ELISA assay
Measurement: IC50 = 517 nM (pChEMBL 6.289999961853027)
Descriptors: MW 507.57, ALogP 3.35, HBA 8, HBD 2, PSA 114.67, QED 0.47
Compound (SMILES): Cc1cccc(C)c1N1C(=O)c2ccc(C(=O)OCc3cn(-c4ccc(S(N)(=O)=O)cc4)nn3)cc2C1=O
InChIKey: OZUYYULYXSVVHQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human transmembrane carbonic anhydrase 4 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 32.5 nM (pChEMBL 7.489999771118164)
Descriptors: MW 531.55, ALogP 2.69, HBA 9, HBD 1, PSA 154.55, QED 0.29
Compound (SMILES): NC(=O)c1cnc(Nc2cccc(O)n2)cc1Nc1ccccc1Cl
InChIKey: PYJOHIHCMNCVLZ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of KDR (unknown origin)
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 355.79, ALogP 3.42, HBA 6, HBD 4, PSA 113.16, QED 0.56
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1cccs1
InChIKey: YLAJTTQGOWTNBK-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 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 477.01, ALogP 5.11, HBA 5, HBD 1, PSA 75.71, QED 0.55
Compound (SMILES): O=C(Nc1cnccc1OCC1CC1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: FYBXDJNRVFIQTH-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 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 352.39, ALogP 2.87, HBA 5, HBD 2, PSA 93.21, QED 0.8
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCN(C)Cc1cccc(O)c1
InChIKey: OIIHAUYKICHNQI-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 422.57, ALogP 5.64, HBA 5, HBD 1, PSA 54.7, QED 0.29
Compound (SMILES): Cc1ccc(N2C[C@@H]3C[C@H]2CN3c2nc(-c3cnc(N)c(OC(F)F)n3)cc(N3CCC(F)(F)C3)n2)nn1
InChIKey: LDWXXJNYXNYPRY-KBPBESRZSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 532.51, ALogP 2.53, HBA 11, HBD 1, PSA 122.31, QED 0.47
Compound (SMILES): COc1cc(N2CCC(N(C)C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccc3c(c2)B(O)OC3)n1
InChIKey: NXBFYHJMYLEINJ-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 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 508.82
Compound (SMILES): O=C1NCCc2ccc(cc2)Nc2nccc(n2)Nc2cc1[nH]n2
InChIKey: JZFLSWUCZKXSQQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of N-terminal NanoLuc-fused full length GSK3A (unknown origin) transfected in HEK293T cells incubated for 2 hrs in presence of tracer K8 by NanoBRET assay
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 321.34, ALogP 1.97, HBA 6, HBD 4, PSA 107.62, QED 0.5
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)c3c(cnn3C)c2N2CC[C@@H](N)C2)n1
InChIKey: PSZVRCRTXCCMNS-CYBMUJFWSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in human Jurkat cells assessed as inhibition of SLP76 phosphorylation by measuring inhibition constant incubated for 1 hr by HTRF assay
Measurement: Ki = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 479.49, ALogP 3.11, HBA 8, HBD 2, PSA 111.19, QED 0.45
Compound (SMILES): CC1(C)CN(C(N)=O)c2ccc(F)c(F)c2N1Cc1ccccc1
InChIKey: GZCUYIORGOWTKF-UHFFFAOYSA-N
Target: AMP deaminase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9DBT5
Assay: Inhibition of recombinant mouse AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 331.37, ALogP 3.65, HBA 2, HBD 1, PSA 49.57, QED 0.91
Compound (SMILES): CCCCNNC(=O)c1ccc(OC(F)(F)F)cc1
InChIKey: JEEFFJUUDNJNDQ-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 1350 nM (pChEMBL 5.869999885559082)
Descriptors: MW 276.26, ALogP 2.62, HBA 3, HBD 2, PSA 50.36, QED 0.62
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)c(Cl)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: PFGMZHAOYLGYMA-DNVCBOLYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: CDK4/Cyclin D3 Mobility Shift Assay: The purpose CDK4/Cyclin D3 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK4/Cyclin D3 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % Conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% TW-20, 3 μM 5-FAM-Dyrktide, 2 nM (active sites) CDK4/Cyclin D3 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK4/Cyclin D3 (LJIC-2007/2010) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 1.12 nM (pChEMBL 8.949999809265137)
Descriptors: MW 455.97, ALogP 1.76, HBA 8, HBD 2, PSA 117.42, QED 0.72
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)[C@@H](C)CC
InChIKey: FLIJYNCTNKGDAO-YKHRJRMHSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Agonist activity at human Y2R expressed in myo-[2-3H]-inositol labelled African green monkey COS7 cells coexpressing chimeric Galphadelta6qi4myr protein assessed as accumulation of [2-3H]-IP after 1 hr by scintillation counting analysis
Measurement: EC50 = 0.3981 nM (pChEMBL 9.399999618530273)
Descriptors: MW 4253.71
Compound (SMILES): CCN1CCN(c2cc(NC(=O)Cn3cc(-c4cc(C(N)=O)c(O)c(F)c4F)c4c(=O)n(C)cnc43)c(Cl)cn2)[C@@H](C)C1
InChIKey: XFPNAULTTRZFPF-AWEZNQCLSA-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 = 28.7 nM (pChEMBL 7.539999961853027)
Descriptors: MW 615.04, ALogP 2.7, HBA 10, HBD 3, PSA 151.61, QED 0.29
Compound (SMILES): O=C(CNC(=O)C1CCCC1)Nc1nnc(Cc2ccc([N+](=O)[O-])cc2)s1
InChIKey: QZXYNOYOWGNZHF-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75604
Assay: Inhibition of human His-tagged USP2 (259 to 605 residues) using ubiquitin rhodamine 110 110 as substrate preincubated for 15 to 20 mins followed by enzyme addition and measured after 25 mins by fluorometric assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 389.44, ALogP 2.28, HBA 7, HBD 2, PSA 127.12, QED 0.55
Compound (SMILES): Cc1nc(N2CCN(C(=O)c3ccco3)CC2)c2c(n1)sc1ccccc12
InChIKey: IHDSHXLLANPSBW-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from human CB2 receptor expressed in HEK293 cell membranes assessed as inhibition constant incubated for 90 mins by liquid scintillation spectrometry analysis
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 378.46, ALogP 3.71, HBA 6, HBD 0, PSA 62.47, QED 0.53
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3ccc(=O)n(C4CCCC4)c3n2)CC1
InChIKey: PPTJJWQOPWUCOH-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 41.3 nM (pChEMBL 7.380000114440918)
Descriptors: MW 391.5, ALogP 1.74, HBA 7, HBD 1, PSA 97.19, QED 0.85
Compound (SMILES): Cn1cnc2c(c(-c3ccc(O)c(C(N)=O)c3)cn2CC(=O)Nc2ccncc2Cl)c1=O
InChIKey: DLIGCSLDHRTYSK-UHFFFAOYSA-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 = 1330 nM (pChEMBL 5.880000114440918)
Descriptors: MW 452.86, ALogP 1.89, HBA 8, HBD 3, PSA 145.13, QED 0.42
Compound (SMILES): COc1ccc(OC)c(-n2nnc(C(=O)Nc3cc(C#N)cc(C(C)(C)C)c3)c2C)c1
InChIKey: XDGXSEGCGGLQCH-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 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 419.49, ALogP 4.01, HBA 7, HBD 1, PSA 102.06, QED 0.67
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(CCC)c(OC)c4)nn32)CC1
InChIKey: VZOSDPVVDDOWFT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 481.6, ALogP 3.4, HBA 7, HBD 2, PSA 111.71, QED 0.56
Compound (SMILES): CN(C)c1nc(-c2cccc(F)c2)c(C(=O)Nc2ccc3c(c2)CCC(=O)N3)s1
InChIKey: UPJMHXMNZZSWQM-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 410.47, ALogP 4.15, HBA 5, HBD 2, PSA 74.33, QED 0.68
Compound (SMILES): Cc1noc(-c2cccc(F)c2)c1C#CCCCCCNC(=O)C(C)S
InChIKey: ZSCLWKQWMCNIJI-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 374.48, ALogP 4.14, HBA 4, HBD 2, PSA 55.13, QED 0.44
Compound (SMILES): O=C(CCCCCCN(Cc1cc2ccccc2[nH]1)Cc1cc2ccccc2[nH]1)NO
InChIKey: XIBGZRVNDWMMFE-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 expressed in baculovirus by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 418.54, ALogP 5.11, HBA 3, HBD 4, PSA 84.15, QED 0.16
Compound (SMILES): Nc1ncc(-c2cc(N3C[C@@H]4C[C@H]3CO4)nc(N3CC4CC3C4)n2)nc1OC(F)F
InChIKey: PDNZDVAQMFNPMG-QQFIATSDSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 417.42, ALogP 1.69, HBA 9, HBD 1, PSA 102.52, QED 0.78
Compound (SMILES): COc1cccc(S(=O)(=O)N(Cc2ccc(NS(=O)(=O)O)cc2)c2nc(-c3ccccc3)cs2)c1
InChIKey: DLTQFAVGKLFIEF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of recombinant SHP2 (unknown origin)
Measurement: IC50 = 6413 nM (pChEMBL 5.190000057220459)
Descriptors: MW 531.64, ALogP 4.43, HBA 7, HBD 2, PSA 125.9, QED 0.31
Compound (SMILES): CC(Nc1ncnc(N)c1C#N)c1cc2ncc(Cl)n2nc1-c1ccccc1
InChIKey: WKDBRCUUDXLTIM-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)
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 390.84, ALogP 3.47, HBA 8, HBD 2, PSA 117.81, QED 0.55
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCC=CC3c2ccccc2)cc1
InChIKey: ROPDQICAVLKEAY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 = 69000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 514.59, ALogP 6.57, HBA 5, HBD 3, PSA 104.82, QED 0.23
Compound (SMILES): COCCNC(=O)CCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.Cl
InChIKey: FSPHHEQOLOPZPH-VZYDHVRKSA-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 = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 497.04, ALogP 3.65, HBA 6, HBD 1, PSA 76.46, QED 0.41
Compound (SMILES): Cn1ccc(=O)c(O)c1C(=O)NCc1ccc(-c2ccccc2)cc1
InChIKey: FSEDMHXJLQVYKB-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human MMP-9
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 334.38, ALogP 2.69, HBA 4, HBD 2, PSA 71.33, QED 0.77
Compound (SMILES): O=c1cc(CO)n(-c2c(Cl)cccc2Cl)c2c(Cl)cnc(OC[C@H](O)CO)c12
InChIKey: DDDSGZFENQKDDY-SNVBAGLBSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of recombinant human Cav1.2
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 445.69, ALogP 2.57, HBA 7, HBD 3, PSA 104.81, QED 0.54
Compound (SMILES): COC/C=C/C(=O)N1CC[C@H](n2nnc3c(O[C@@H](C)[C@@H]4CCCN4C)nc4c(F)c(-c5nn(C)c6ccccc56)c(C)cc4c32)C[C@H]1CC#N
InChIKey: NQTRDANABYJAAI-BHXHEMOUSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human MIA PaCa-2 cells assessed as reduction in whole blood pERK level incubated for 4 hrs by HTRF assay
Measurement: IC50 <= 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 679.8, ALogP 5.49, HBA 11, HBD 0, PSA 127.22, QED 0.19
Compound (SMILES): Fc1cccc(Nc2nc(-c3nc(-c4ccccc4)cs3)cs2)c1
InChIKey: ZOERZVPVEHYAIE-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 = 2165 nM (pChEMBL 5.670000076293945)
Descriptors: MW 353.45, ALogP 5.82, HBA 5, HBD 1, PSA 37.81, QED 0.5
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc([N+](=O)[O-])c(Nc4ccc5[nH]ccc5c4)n3)cc2)CC1
InChIKey: GGCWHBCVZDGOED-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 444.5, ALogP 4.11, HBA 8, HBD 3, PSA 115.25, QED 0.3
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(Cl)c(Br)c(OC)c4)nn32)CC1
InChIKey: ZMCYWNHBOFVQPF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 522.83, ALogP 3.85, HBA 6, HBD 2, PSA 102.48, QED 0.58
Compound (SMILES): OCc1[nH]c2ccccc2c1CN1CCN(c2ccccc2)CC1
InChIKey: RTNHENHQSIAEAI-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-spiperone from human D4 receptor expressed in CHO cells assessed as inhibition constant
Measurement: Ki = 0.66 nM (pChEMBL 9.180000305175781)
Descriptors: MW 321.42, ALogP 2.98, HBA 3, HBD 2, PSA 42.5, QED 0.78
Compound (SMILES): CCCCc1nc2c(N)nc3ccccc3c2s1
InChIKey: XQXNQKAEROQGAD-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 in HEK-Blue hTLR7 cells assessed as activation of NFkappaB by SEAP reporter gene based spectrophotometry assay
Measurement: EC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 257.36, ALogP 3.77, HBA 4, HBD 1, PSA 51.8, QED 0.78
Compound (SMILES): CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCN(C(=O)C4CCC4)CC3=O)n(C)c2n1
InChIKey: ZGZMQKJLWFWWDG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta in presence of [p32-gamma]-ATP measured after 2 hrs by hotspot assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 557.66, ALogP 2.07, HBA 10, HBD 0, PSA 114.51, QED 0.35
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2cccc(OC(F)(F)F)c2)CCC1(O)c1cccc(O)c1
InChIKey: RAHBZLWFKOWESB-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 94.2 nM (pChEMBL 7.03000020980835)
Descriptors: MW 452.47, ALogP 3.13, HBA 5, HBD 2, PSA 73.24, QED 0.7
Compound (SMILES): Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(S(=O)(=O)[N-]C(=O)c3ccccc3)cc2)cc1.[Na+]
InChIKey: VQVAOQIYIYYOJN-UHFFFAOYSA-M
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Inhibition of TRPV1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 485.49, ALogP 4.99, HBA 5, HBD 1, PSA 81.06, QED 0.43
Compound (SMILES): COc1ccc(S(=O)(=O)N(C)c2c(C)cc(Cc3ccc(CN(C)C)cc3)cc2C(=O)NO)cc1
InChIKey: AYTZJEWKGLEPFF-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of MMP-13 (unknown origin)
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 497.62, ALogP 3.6, HBA 6, HBD 2, PSA 99.18, QED 0.35
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(N(S(=O)(=O)c3ccc4c(c3)CCCC4)S(=O)(=O)c3ccc4c(c3)CCCC4)ccc21
InChIKey: KIGOVSDRKYMNKC-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 = 7990 nM (pChEMBL 5.099999904632568)
Descriptors: MW 630.79, ALogP 6.21, HBA 6, HBD 0, PSA 104.97, QED 0.25
Compound (SMILES): CC(C)CN(CC(C)C)c1ccc(-c2ccccc2C(=O)O)cc1NC(=O)Nc1ccccc1F
InChIKey: IKFPLKUIOWUYKE-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 477.58, ALogP 6.95, HBA 3, HBD 3, PSA 81.67, QED 0.31
Compound (SMILES): COc1ccc(-c2oc3cc(Br)c(I)cc3c(=O)c2O)cc1
InChIKey: AYKASAIWJOBKAM-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin)
Measurement: IC50 = 15.74 nM (pChEMBL 7.800000190734863)
Descriptors: MW 473.06, ALogP 4.54, HBA 4, HBD 1, PSA 59.67, QED 0.56
Compound (SMILES): O=C(NS(=O)(=O)C1CC1)c1cc(Cl)c(OCCC2CCC3(CCN(Cc4ccccc4)CC3)C2)cc1F
InChIKey: JQZLSWRMJAINEG-UHFFFAOYSA-N
Target: Sodium channel protein type 4 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35499
Assay: Inhibition of Nav1.4 (unknown origin) by whole-cell patch clamp assay
Measurement: IC50 = 4880 nM (pChEMBL 5.309999942779541)
Descriptors: MW 549.11, ALogP 5.55, HBA 5, HBD 1, PSA 75.71, QED 0.44
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccc(Cl)cc2)CCC1(O)c1cccc(O)c1
InChIKey: WAPQGYPGSJNYQW-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 43.1 nM (pChEMBL 7.369999885559082)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CN(CC[C@H](N)C(=O)O)Cc2ccc(Cl)cc2)[C@@H](O)[C@H]1O
InChIKey: WZIBHVZJOMIGLN-SWQDORGXSA-N
Target: tRNA (cytosine(38)-C(5))-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: O14717
Assay: Binding affinity to full-length human DNMT2 expressed in bacteria assessed as apparent dissociation constant by ITC method
Measurement: Kd = 32100 nM (pChEMBL 4.489999771118164)
Descriptors: MW 491.94, ALogP -0.01, HBA 11, HBD 5, PSA 185.87, QED 0.27
Compound (SMILES): O=C(NNCC1CCCC1)c1ccc(Br)cc1
InChIKey: BXLUNIKKCWQZBO-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 6980 nM (pChEMBL 5.159999847412109)
Descriptors: MW 297.2, ALogP 2.87, HBA 2, HBD 2, PSA 41.13, QED 0.84
Compound (SMILES): COc1ccc(C(=O)N2CCCc3cc(NS(=O)(=O)c4cc(Cl)c(C)cc4OC)ccc32)cc1OC
InChIKey: DOCJXKIESOEZAQ-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 = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 531.03, ALogP 5.07, HBA 6, HBD 1, PSA 94.17, QED 0.46
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(NS(=O)(=O)c3ccc(Cl)c(C(F)(F)F)c3)ccc21
InChIKey: FBVKVIIMWGUOBR-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 = 4120 nM (pChEMBL 5.380000114440918)
Descriptors: MW 484.88, ALogP 5.35, HBA 4, HBD 1, PSA 79.62, QED 0.54
Compound (SMILES): C=CCn1c(=O)c2cnc(Nc3ccc(N4CCN(C)CC4)c4ccn(C)c34)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: ITVQDQHPDYLMCH-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 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 553.67, ALogP 3.38, HBA 11, HBD 2, PSA 109.27, QED 0.3
Compound (SMILES): Cc1cc(C(=O)NC2Nc3cccc(C)c3N2[C@H]2CCCCN(C(=O)/C=C/CN(C)C)C2)ccn1
InChIKey: WFAOJPLNRNZXIN-LXARNSNTSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.63, ALogP 3.14, HBA 6, HBD 2, PSA 80.81, QED 0.62
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OCC(C)C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: PDHCFKKUVBCBBI-UHFFFAOYSA-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 599.74, ALogP 5.32, HBA 10, HBD 2, PSA 113.85, QED 0.16