lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN1CCN(C(=O)CS(=O)(=O)c2ccc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)c(OC)c2)CC1
InChIKey: MAKLQLGGXQPLRV-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK L1196M mutant (unknown origin) using peptide substrate incubated for 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 651.21, ALogP 3.75, HBA 11, HBD 2, PSA 150.9, QED 0.31
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)c(-c3ccc(N4CCN(C)CC4)cc3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: YGKQELHBAUZPPA-HMIXDJPHSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 1a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.113 nM (pChEMBL 9.949999809265137)
Descriptors: MW 919.1, ALogP 6.43, HBA 10, HBD 4, PSA 181.12, QED 0.11
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(C)(F)F
InChIKey: YJZXOHCPDWISMV-GYCJOSAFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Binding Assay: hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials [Sanguinetti et al., Nature, 2006, 440, 463-469.] and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 472.56, ALogP 4.4, HBA 5, HBD 2, PSA 60.08, QED 0.51
Compound (SMILES): Cc1ccc(-c2nnc(-c3ccc(C#N)cc3)o2)cc1S(N)(=O)=O
InChIKey: JNFQGORLTRRYND-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of recombinant human carbonic anhydrase 13 by stopped flow CO2 hydrase assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 340.36, ALogP 2.23, HBA 6, HBD 1, PSA 122.87, QED 0.78
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)C(Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)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(C)C
InChIKey: OQWWPGFZOFJMCP-DCKQJDKTSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30082
Assay: Agonist activity at rat glucagon receptor expressed in HEK293 cells assessed as stimulation of cAMP accumulation by FRET assay
Measurement: EC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 5223.88
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cnc(N)cc2C(F)F)nc(N2[C@H](C)COC[C@@H]2C)n1
InChIKey: YXQKBQLVKBUCLZ-UPJWGTAASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Binding affinity to wild-type human partial length PIK3CA (R108 to N1068 residues) expressed in HEK293 cells measured after 1 hr by Kinomescan method
Measurement: Kd = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 435.48, ALogP 2.29, HBA 9, HBD 1, PSA 102.52, QED 0.77
Compound (SMILES): CN[C@H]1CN[C@@](CCCCB(O)O)(C(=O)O)C1
InChIKey: ALIDHAHGIJCPSV-PSASIEDQSA-N
Target: Arginase-2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P78540
Assay: Inhibition of Arg2 (unknown origin)
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 244.1
Compound (SMILES): CNC(=O)[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: YZNCNMQLYFVHNO-DLBZAZTESA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Mus musculus
UniProt: Q91XA9
Assay: Inhibition of full-length C-terminal his-tagged mouse AMCase expressed in expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N'-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 433.94, ALogP 1.07, HBA 7, HBD 3, PSA 112.4, QED 0.65
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(-c5ncccn5)c4n3)cc(C(F)(F)F)c2C1=O
InChIKey: QWLPXHNNUXMBRO-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 479.47, ALogP 4.21, HBA 7, HBD 1, PSA 102.3, QED 0.47
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2ccccc2NCc2ccc(C(=O)Nc3ccccc3N)cc2)cc1
InChIKey: HPPZWGKNLWSQRW-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using RHKAcKAc-AMC as substrate measured after 60 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 502.6, ALogP 4.94, HBA 6, HBD 4, PSA 122.55, QED 0.24
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)c(F)n2)N1CC(F)(F)F
InChIKey: CRBIBFLRQNHOTI-PEBXRYMYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding Assay : hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.The assay was conducted as follows with all reagents used at room temperature unless otherwise stated.Reagent Preparations Include:1. Internal IC700 solution used to perfuse the underside of chip (in mM), KF 130, KCl 20, MgCl2 1, EGTA 10 and HEPES 10, (all Sigma-Aldrich; pH 7.2-7.3 using 10 M KOH, 320 mOsm) and supplemented with 25 □M escin.2. External and cell buffer (in mM), NaCl 137, KCl 4, HEPES 10, D-glucose 10, CaCl2 2, MgCl2 1 (pH7.4, NaOH)3. NMDG reference buffer used to establish a stable baseline prior to the addition of test compounds, NaCl 80, KCl 4, CaCl2 2, MgCl2 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 NaOH 298 mOsm)4. Seal enhancer used to improve seal quality of cells, NaCl 80, KCl 3, CaCl2 10, HEPES 10, MgCl2 1 (pH7.4 NaOH)
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 494.51, ALogP 4.45, HBA 5, HBD 2, PSA 60.08, QED 0.38
Compound (SMILES): CC1(C)C(=O)C(C#N)=C[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@@](C)(C(=O)N6CCN(c7ccc(NC(=O)CCCCCCC(=O)NO)cc7)CC6)CC[C@]5(C)CC[C@@]4(C)[C@]3(C)CC[C@@H]12
InChIKey: WNAHLDHLRFYMBG-FJCZYIGASA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant C-terminal FLAG-tagged full length human HDAC6 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 368 nM (pChEMBL 6.429999828338623)
Descriptors: MW 822.1, ALogP 8.34, HBA 8, HBD 3, PSA 159.91, QED 0.12
Compound (SMILES): Cc1sc(C(=O)N[C@@H]2CCOC2)cc1-n1cc(NC(=O)Nc2c(F)cccc2Cl)cn1
InChIKey: VPVAOTNNZQMZSM-GFCCVEGCSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3alpha1 (unknown origin) using ATF2 as substrate after 22 mins in presence of ATP by HTRF assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 463.92, ALogP 4.2, HBA 6, HBD 3, PSA 97.28, QED 0.53
Compound (SMILES): CSCC[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: JHLDGEVEPFCIIL-FZUWRBLYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at kappa opioid receptor (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 2454.71 nM (pChEMBL 5.610000133514404)
Descriptors: MW 1115.33
Compound (SMILES): CC(C)c1ccn2ncnc(N[C@H]3CC[C@@H](N4CCN(C(=O)CCC(=O)N5CCC(CCN6CCN(c7ccc8c(c7)C(=O)N(C7CCC(=O)NC7=O)C8=O)CC6)CC5)CC4)CC3)c12
InChIKey: ZUODKONSNNHSAJ-AMLBMYBGSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Inhibition of GSG2 (unknown origin)
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 878.09, ALogP 3.35, HBA 13, HBD 2, PSA 176.11, QED 0.25
Compound (SMILES): O=C(CCCCCCn1cnc2c(N3CCOCC3)nc(-c3cccc(CO)c3)nc21)NO
InChIKey: JBFFDSGEOZGWCK-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full-length recombinant p110alpha/p85alpha co-expressed in baculovirus expression system using PIP2:PS lipid as substrate incubated for 1 hr in presence of ATP by ADP-Glo assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 454.53, ALogP 2.28, HBA 9, HBD 3, PSA 125.63, QED 0.24
Compound (SMILES): COc1ccc2cc(C(C)C(=O)Nc3cc(C)ccn3)ccc2c1
InChIKey: QUOGFPPPCZTQAX-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of recombinant human GSK3alpha S449A mutant (2 to end residues) using YRRAAVPPSPSLSR peptide as substrate incubated for 40 mins in presence of [gamma33P]ATP by radiometric scintillation analysis
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 320.39, ALogP 4.29, HBA 3, HBD 1, PSA 51.22, QED 0.78
Compound (SMILES): Cc1noc(C)c1-c1ccc2nc(-c3cnn(CC(C)(C)O)c3)nc(N3CCOC[C@@H]3c3ccccc3)c2c1
InChIKey: SUFVOUWYHJXPBW-AREMUKBSSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to human partial length BRD2 (BD1) (K71 to N194 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 524.63, ALogP 5.11, HBA 9, HBD 1, PSA 102.33, QED 0.33
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NCC1CCN(Cc2ccc(OC)cc2)CC1
InChIKey: WNRSNGYSTQQFNW-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 407.52, ALogP 3.26, HBA 5, HBD 3, PSA 82.28, QED 0.56
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)NCC(F)F)[C@@H](O)[C@H]1O
InChIKey: IXDUYFCEDCWAOL-FLNNQWSLSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 344.28, ALogP -1.59, HBA 9, HBD 4, PSA 148.41, QED 0.52
Compound (SMILES): CC(C)SC[C@@H]1[C@@H](O)[C@H]2[C@H](C(=O)O)[C@H]2[C@]1(N)C(=O)O
InChIKey: DSQKRTLZZWIIIR-NZHJENJMSA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method
Measurement: Ki = 614 nM (pChEMBL 6.210000038146973)
Descriptors: MW 289.35, ALogP -0.15, HBA 5, HBD 4, PSA 120.85, QED 0.55
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)NCCCN1C(=O)CC(SC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](CCSC)NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(N)=O)C1=O
InChIKey: PXKVDJONXZSCHP-FVSZKLDUSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at DOP (unknown origin) expressed in SH-SY5Y cell membranes co-expressing beta-arrestin2-RGFP protein assessed as induction of beta-arrestin2 activation incubated for 15 mins by BRET assay
Measurement: EC50 = 22.39 nM (pChEMBL 7.650000095367432)
Descriptors: MW 1450.9
Compound (SMILES): Cn1cc(-c2cc(C(C)(C)O)ccc2Oc2ccc(F)cc2F)c2cc(C(=O)NCCCCCCC(=O)NO)[nH]c2c1=O
InChIKey: REHHQXJAWXFUSZ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 596.63, ALogP 5.02, HBA 7, HBD 5, PSA 145.68, QED 0.09
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NCC(CCC(=O)O)c1c(F)ccc(F)c1Cl
InChIKey: YZDHMNSJTDELSQ-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 587.85, ALogP 7.28, HBA 3, HBD 2, PSA 79.29, QED 0.21
Compound (SMILES): COc1cc2ncnc(Nc3cnc(OCCC4CC4)nc3)c2cc1OCC1CCNCC1
InChIKey: PLIIPGVTCVYGIU-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of His6/TEV fused-GST-tagged Flt3 (unknown origin) (H564 to S993 residues) using Axltide (CKKSRGDYMTMQJ-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 75 mins by RapidFire LC-MS analysis
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 450.54, ALogP 3.73, HBA 9, HBD 2, PSA 103.31, QED 0.48
Compound (SMILES): COc1ccc(S(=O)(=O)N2c3ccc(C(=O)NCc4ccccc4Cl)cc3C3(CCN(C(C)=O)CC3)C2C)cc1
InChIKey: NSPKPBVUVFCVKY-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity at human GnRH receptor expressed in CHO-K1 cells assessed as inhibition of buserelin-induced response preincubated for 20 mins followed by buserelin addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 582.12, ALogP 4.76, HBA 5, HBD 1, PSA 96.02, QED 0.45
Compound (SMILES): COc1cccc2[nH]c3c(c12)CCN=C3C(=O)O
InChIKey: HSDIVHBEPMALRN-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q05769
Assay: Inhibition of mouse COX2 using 2-arachidonylglycerol as substrate preincubated for 3 mins followed by substrate addition and measured for 30 sec by LC/MS analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 244.25, ALogP 1.61, HBA 3, HBD 2, PSA 74.68, QED 0.84
Compound (SMILES): Cc1c(N2CCCCC2)nc2ccc(Br)cc2c1C(=O)NCC(CCC(=O)O)c1c(F)ccc(F)c1Cl
InChIKey: VDHJPBNFGKNQMK-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay
Measurement: IC50 = 0.79 nM (pChEMBL 9.100000381469727)
Descriptors: MW 594.88, ALogP 6.61, HBA 4, HBD 2, PSA 82.53, QED 0.29
Compound (SMILES): Cn1ccc2c(S(=O)(=O)N[C@H]3CCN(CCCc4noc5ccccc45)C3)cccc21
InChIKey: RDXPMJJNBGHREI-KRWDZBQOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from recombinant human D2 receptor expressed in CHOK1 cell membranes measured after 60 mins by microbeta counting method
Measurement: Ki = 38.02 nM (pChEMBL 7.420000076293945)
Descriptors: MW 438.55, ALogP 3.3, HBA 6, HBD 1, PSA 80.37, QED 0.48
Compound (SMILES): O=C(c1ccccc1)c1cc(O)c(-c2cccc(C(F)(F)F)c2)c(O)c1
InChIKey: TUGFOURPPWFBHT-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at cannabinoid CB2 receptor in human U2OS cells assessed as induction of beta-arrestin recruitment using CCF4/AM as substrate preincubated for 5 hrs followed by substrate addition and measured after 2 hrs by Tango assay
Measurement: EC50 = 3467.37 nM (pChEMBL 5.460000038146973)
Descriptors: MW 358.32, ALogP 5.01, HBA 3, HBD 2, PSA 57.53, QED 0.65
Compound (SMILES): COc1ccc(/C=C/C(=O)Nc2ccc3c(C)cc(=O)oc3c2)cc1OC
InChIKey: OLIHKWFLHDOQRH-WEVVVXLNSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 644.3 nM (pChEMBL 6.190000057220459)
Descriptors: MW 365.39, ALogP 3.77, HBA 5, HBD 1, PSA 77.77, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CC(O)C4CCCC4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: PMOPSSPZFPUDCD-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 652.75, ALogP 5.07, HBA 8, HBD 3, PSA 148.4, QED 0.21
Compound (SMILES): N=S1(=O)CCC2(CC1)c1cc(NC(=O)c3cccnc3)ccc1N(S(=O)(=O)c1ccc(F)cc1)C2C1CC1
InChIKey: JTLIUTFVVQLNNM-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity at human GnRH receptor expressed in CHO-K1 cells assessed as inhibition of buserelin-induced response preincubated for 20 mins followed by buserelin addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 58.5 nM (pChEMBL 7.230000019073486)
Descriptors: MW 554.67, ALogP 4.54, HBA 6, HBD 2, PSA 120.29, QED 0.48
Compound (SMILES): CN1CCN(c2cc(C(=O)Nc3cc4cc(-c5cnc(N)s5)ccc4cn3)ccn2)CC1
InChIKey: BUFVLGIHADJNER-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 445.55, ALogP 3.34, HBA 8, HBD 2, PSA 100.27, QED 0.5
Compound (SMILES): CC(C)(O)COc1ccc2c(Oc3ccc(Nc4nccc5[nH]cc(-c6ccccc6)c(=O)c45)cc3F)ccnc2c1
InChIKey: DGRCFAYRKDYEMX-UHFFFAOYSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Inhibition of TEK (unknown origin) using biotin as substrate preincubated for 5 mins followed by substrate addition and measured after 30 to 60 mins by HTRF assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 562.6, ALogP 6.96, HBA 7, HBD 3, PSA 109.36, QED 0.18
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)c(-c2nc3ccccc3c(=O)n2-c2ccc(Cl)cc2)s1)c1ccco1
InChIKey: OTAAAJWYDQOTRS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 524.99, ALogP 6.67, HBA 7, HBD 1, PSA 90.02, QED 0.27
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)CN(Cc2ccccc2)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: MAJFZWKRKQTSRH-NETOACFBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd = 1 nM (pChEMBL 9)
Descriptors: MW 949.13, ALogP -0.84, HBA 10, HBD 9, PSA 294.35, QED 0.06
Compound (SMILES): N=C(N)NCCCCCC(=O)NC[C@H](NC(=O)[C@@H]1CCCN1S(=O)(=O)c1ccccc1)C(=O)O
InChIKey: ZJLLVRHQFNOZTN-IRXDYDNUSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Cell adhesion assay to Hamster Ovary: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alphavbeta1 (adhesion of Chinese Hamster Ovary cells transfected with human alphav to the latency associated peptide of transforming growth factor beta, a response that is entirely dependent on binding of alphavbeta1 to LAP).
Measurement: IC50 = 5050 nM (pChEMBL 5.300000190734863)
Descriptors: MW 496.59, ALogP -0.43, HBA 6, HBD 6, PSA 194.78, QED 0.12
Compound (SMILES): Cc1c(-c2cc(F)c(N)cc2F)ccc2c3ocnc3c(=O)n(C3CC3)c12
InChIKey: KBUYQPMNHBXXOV-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 367.36, ALogP 4.31, HBA 5, HBD 1, PSA 74.05, QED 0.54
Compound (SMILES): NC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCCC1CCN(Cc2ccc(F)cc2)CC1
InChIKey: LQLBWZJHRARWDB-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin) by ATP competitive based analysis
Measurement: IC50 > 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 537.66, ALogP 4.86, HBA 7, HBD 2, PSA 110.44, QED 0.34
Compound (SMILES): CN(C)C(=O)[C@H]1CN(C2CCCCC2)CC[C@@H]1NC(=O)c1cc(-c2ccc(F)cc2F)on1
InChIKey: WTQZMARGZPHBHA-ICSRJNTNSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at -40 mV holding potential by Q-patch clamp assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 460.53, ALogP 3.46, HBA 5, HBD 1, PSA 78.68, QED 0.74
Compound (SMILES): Cc1cc(/C=C/c2cc3c4c(c2)CCCN4CCC3)cc(C)[n+]1CCN1CCN(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: MYFOSGGTPUMZLP-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes measured after 3 hrs by radioligand competition binding assay
Measurement: Ki = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 807.12, ALogP 7.89, HBA 6, HBD 1, PSA 66.25, QED 0.12
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(N2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)nc1
InChIKey: BTDWTDGMTNRFHC-CLOLKSBNSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of human recombinant CDK12/CyclinK assessed as reduction in substrate phosphorylation using His-c-Myc as substrate preincubated with enzyme for 5 mins followed by substrate addition for 15 mins in presence of [gamma 32P-ATP] by radioactive kinase assay
Measurement: IC50 = 35.4 nM (pChEMBL 7.449999809265137)
Descriptors: MW 531.06, ALogP 4.81, HBA 7, HBD 3, PSA 102.07, QED 0.28
Compound (SMILES): CO[C@@]12CC[C@H](N[C@H](C(=O)O)C3CCCCC3)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: COJPQLLOMWBEEN-OVRAEGQKSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 20.5 nM (pChEMBL 7.690000057220459)
Descriptors: MW 456.58, ALogP 2.82, HBA 6, HBD 3, PSA 91.26, QED 0.63
Compound (SMILES): CCc1cc2c([C@H]3C[C@@H]3CN)c(OC)ccc2o1.Cl
InChIKey: NLGAYZOAGDGYEH-XQKZEKTMSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 933.25 nM (pChEMBL 6.03000020980835)
Descriptors: MW 245.32, ALogP 3.07, HBA 3, HBD 1, PSA 48.39, QED 0.9
Compound (SMILES): Cc1ccc(Cn2c(Nc3ccc(OC(C)C)c(Cl)c3)nc(=O)n(CCC(=O)O)c2=O)cc1
InChIKey: KRHNDEFYSFIWAD-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7 receptor expressed in HEK293 cells
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 472.93, ALogP 3.42, HBA 8, HBD 2, PSA 115.45, QED 0.49
Compound (SMILES): O=C(Nc1nc(-c2ccccn2)n[nH]1)c1ccccc1
InChIKey: LDGAAMMSVIUSAT-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL using 1,3-dihydroxypropan-2-yl 4-pyren-1-ylbutanoate as substrate measured after 45 mins by reverse-phase HPLC-based fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 265.28, ALogP 2.12, HBA 4, HBD 2, PSA 83.56, QED 0.76
Compound (SMILES): CC1(C)OC(=O)c2ccc(Nc3ncc(-c4nnco4)c(N[C@H](CO)c4ccccc4)n3)cc21
InChIKey: RVSSNRBUPQUIEG-LJQANCHMSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 (unknown origin) using MBP protein as substrate in presence of ATP preincubated for 15 mins followed by substrate addition and measured after 90 mins by ADP-Glo assay
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 458.48, ALogP 3.82, HBA 10, HBD 3, PSA 135.29, QED 0.35
Compound (SMILES): O[C@@H]1[C@H](O)CO[C@H]1Cn1cnc2c(NCc3cccc(Br)c3)nc(Cl)nc21
InChIKey: IWVKHQXTSJJJBY-MBNYWOFBSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Binding affinity to PPAR-delta (unknown origin) by TR-FRET assay
Measurement: Ki = 1430 nM (pChEMBL 5.840000152587891)
Descriptors: MW 454.71, ALogP 1.97, HBA 8, HBD 3, PSA 105.32, QED 0.51
Compound (SMILES): Cc1cc(O[C@H]2CC[C@H](C(C)(C)C)CC2)c(CN2CCC(C(=O)O)CC2)c2ccccc12
InChIKey: KVRMGFKQCUEJMS-HZCBDIJESA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 437.62, ALogP 6.43, HBA 3, HBD 1, PSA 49.77, QED 0.59
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc(F)cc2)nc1C(N)=O
InChIKey: SAJWMIHNHHGFQV-YADHBBJMSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 511.64, ALogP 4.13, HBA 5, HBD 3, PSA 121.18, QED 0.37
Compound (SMILES): CO[C@@H](C)c1c(NC(=O)Nc2cnc(-n3nccn3)c(Cl)c2)cnc2cc(Cl)nn12
InChIKey: GBIASRXDYFFUED-VIFPVBQESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 448.27, ALogP 3.36, HBA 9, HBD 2, PSA 124.15, QED 0.48
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)N1Cc2ccccc2C[C@@H]1C(N)=O
InChIKey: SUYRLPGKCVVVEL-UYEZAFAQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Ki = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 753.91, ALogP 0.34, HBA 7, HBD 10, PSA 274.5, QED 0.05
Compound (SMILES): Cn1ccc2c(NC(=O)CCN3CCCc4ccccc43)cccc21
InChIKey: XBTJKTGWGACFOJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 426.58 nM (pChEMBL 6.369999885559082)
Descriptors: MW 333.44, ALogP 3.96, HBA 3, HBD 1, PSA 37.27, QED 0.78
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C(=O)/C=C/C(=O)c2ccccc2)C3)nc1-c1cnn(C(C)C)c1
InChIKey: NQLNVNONUBTYRF-VAWYXSNFSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808 to end residues) KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting method
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 506.61, ALogP 5.3, HBA 7, HBD 1, PSA 93.01, QED 0.27
Compound (SMILES): COc1cc(OCC2CCCO2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: AOXIGKGAMMGXCX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR (669 to 1210 residues) expressed in baculovirus expression system using Srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 520.01, ALogP 4.56, HBA 9, HBD 3, PSA 123.7, QED 0.35
Compound (SMILES): CC(C)c1cc(C2(C(F)(F)F)N=N2)cc(C(C)C)c1CO
InChIKey: FGQXQCSYLCZOIU-UHFFFAOYSA-N
Target: GABA-A receptor; alpha-1/beta-3/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P28472
Assay: Inhibition of [3H]R-mTFD-MPAB labelling of GABAA alpha1beta3gamma2L (unknown origin) expressed in Xenopus laevis oocytes assessed as reduction in photoincorporation at M227 residues of beta3 subunit measured after 30 mins in presence of GABA by liquid scintillation counting method
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 300.32, ALogP 4.61, HBA 3, HBD 1, PSA 44.95, QED 0.87
Compound (SMILES): CN1CCC(Oc2ccc(C(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)cc2)CC1
InChIKey: FOBNFKZGJDCMND-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSK3 beta kinase assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))].
Measurement: EC50 = 668 nM (pChEMBL 6.170000076293945)
Descriptors: MW 441.54, ALogP 4.36, HBA 6, HBD 1, PSA 72.28, QED 0.5
Compound (SMILES): O=C(NO)c1ccc(CN2C(=O)c3ccccc3C2=O)cc1-c1ccccc1
InChIKey: ONODKKVQHKQFFX-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using Boc-Lys(Ac)-AMC as substrate pre-incubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 372.38, ALogP 3.27, HBA 4, HBD 2, PSA 86.71, QED 0.42
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc(C)nc2OC)[nH]1
InChIKey: RELJJJHPPLUJSV-PKTZIBPZSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 495.67, ALogP 4.61, HBA 6, HBD 2, PSA 100.21, QED 0.42
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4c(OC)ncnc4C4CC4)nc3n(C(C)C)c2=O)nc1
InChIKey: FHDMUNWMIACNJV-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Reporter Gene Assay: A nuclear receptor transactivation assay is performed to quantitate the ability of test compounds to inhibit RORγ transactivation of a luciferase reporter. A similar assay is described in: Khan et al., Bioorganic & Medicinal Chemistry Letters 23 (2013), 532-536. The system uses transiently transfected HEK 293 cells cotransfected with two plasmids (pGL4.3, luc2P/GAL4UAS/Hygro, and pBIND, Gal4DBD hRORC LBD1-3). The positive control is co-transiently transfected with both plasmids, and the negative control contains the pGL4.3 promoter sequence. Assays are assembled in 384 well plates where transiently transfected cells and test compound at varying concentrations are incubated for 20-24 h.The next day, assays plates are taken out and equilibrated at RT for 20-30 minutes. Bright-Glo Luciferase Assay System is used to detect Luciferase production. After addition of Bright GLO detection reagent, the plates are incubated at RT for 20 minutes. The plates are read on an Envision plate reader to measure luminescence signal. The RLU signal is converted to POC relative to control and blank wells.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 536.62, ALogP 2.91, HBA 12, HBD 1, PSA 154.74, QED 0.34
Compound (SMILES): OCCC[C@@H]1[C@H]2CCC[C@]1(c1cccc(O)c1)CCN2CCc1ccccc1
InChIKey: BRGBSNFNWHEGOM-UBFVSLLYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Activity at human MOR expressed in U2OS cells co-expressing beta-arrestin2 EFC assessed as beta-arrestin2 EFC recruitment by Tango assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 379.54, ALogP 4.52, HBA 3, HBD 2, PSA 43.7, QED 0.74
Compound (SMILES): Cn1nc(-c2ccc(OCC34CCC(N)(CC3)CC4)c(F)c2)c2cnc(N)nc21
InChIKey: JGBLHVKRSBVZJG-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonist activity at TLR9 in human PBMC assessed as inhibition of ODN2216-induced IFNalpha production
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 396.47, ALogP 3.18, HBA 7, HBD 2, PSA 104.87, QED 0.7
Compound (SMILES): CCNc1ccc2c(n1)N(C)CCN(c1cccc(O[C@@H](CCNC)c3cccs3)c1)C2=O
InChIKey: DZLGMNWIHGPMMA-NRFANRHFSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding Assay: Human norepinephrine transporter (NET) enriched membranes (5 μg) were incubated with 5 nM of radiolabeled [3H]-Nisoxetin in assay buffer containing 50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH 7.4.NSB (non specific binding) was measured by adding 10 μM desipramine. The binding of the test compound was measured in five different concentrations. After 60 min incubation at 4° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, 0.9% NaCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 465.62, ALogP 4.4, HBA 7, HBD 2, PSA 69.73, QED 0.49
Compound (SMILES): Nc1ccccc1NC(=O)/C=C/c1cnn(C/C=C/c2ccccc2)c1
InChIKey: KOESHVZEHKMOIK-UXKPLKHMSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Enzyme Inhibition: The HDAC activity inhibition assay was performed as follows to determine the ability of a test compound to inhibit HDAC enzymatic activity. Serial dilutions of HDAC inhibitors were prepared in HDAC assay buffer (25 mM Tris/HCl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, pH 8) in 96-well assay plates (Fisher scientific, #07-200-309) and were pre-incubated for 2 hours at room temperature in the presence of 1254 μg/ml BSA and purified HDAC1 (BPS Bioscience, San Diego, Calif., #50051), HDAC2 (BPS Bioscience, #50053), or HDAC3/NcoR2 (BPS Bioscience, #50003) at concentrations of 1.25, 1.32, and 0.167 vg/mL, respectively. Following pre-incubation, Fluor-de-Lys™ substrate (Enzo Life Sciences, Plymouth Meeting, Pa., BML-KI104-0050) was added to a final concentration of 10 μM and plates were further incubated for 30 minutes at room temperature. The enzymatic reaction was stopped by addition of Trichostatin A (Sigma-Aldrich, St Louis, Mo., #T8552, final concentration: 100 nM) and trypsin (MP Biomedicals, Solon, Ohio, #02101179) was added to reach a final concentration of 100 μg/mL. After a 15 minute incubation at room temperature, fluorescence was recorded using a Spectramax M2 fluorometer (Molecular Devices, Sunnyvale, Calif.) with excitation at 365 nm and emission at 460 nm.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 344.42, ALogP 3.83, HBA 4, HBD 2, PSA 72.94, QED 0.53
Compound (SMILES): COc1cc(OCc2ccnc(Nc3cnn(C)c3)n2)cc2sc(N[C@H]3CCCC[C@@H]3O)nc12
InChIKey: MUHWRSWKWURVPP-ROUUACIJSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-TetR cells incubated for 1 hr followed by PDGF-DD stimulation and measured after 5 mins by HTRF assay
Measurement: IC50 = 3560 nM (pChEMBL 5.449999809265137)
Descriptors: MW 481.58, ALogP 3.87, HBA 11, HBD 3, PSA 119.24, QED 0.34
Compound (SMILES): C[C@@H]1CN(c2ccc(S(C)(=O)=O)cc2F)CCN1c1nccc(C(=O)NC2C3CC4CC2CC(O)(C4)C3)n1
InChIKey: SSKKTEYBWOVEET-REKAHOPZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in pooled human liver microsomes using dextromethorphan as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 543.67, ALogP 2.4, HBA 8, HBD 2, PSA 115.73, QED 0.59
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCCC1
InChIKey: KWEPNMOOHUNVKC-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 1819.7 nM (pChEMBL 5.739999771118164)
Descriptors: MW 258.37, ALogP 2.45, HBA 2, HBD 0, PSA 23.55, QED 0.83
Compound (SMILES): Cc1cc(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)cc(N2CCN(C)CC2)n1
InChIKey: ATJIKIOHBGHJFL-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologies-a Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission. Briefly, recombinant DYRKIA kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated ("0% Control") and phosphorylated ("100% control") forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 441.54, ALogP 3.34, HBA 7, HBD 1, PSA 79.18, QED 0.52
Compound (SMILES): Cc1ccc(C#Cc2cc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)ccc2F)s1
InChIKey: ADUJCIPBWYSFQX-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Binding affinity to human His-tagged LDHA by SPR analysis
Measurement: Kd = 0.0667 nM (pChEMBL 10.180000305175781)
Descriptors: MW 650.75, ALogP 5.93, HBA 8, HBD 2, PSA 128.17, QED 0.2
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3CCCCC3C(=O)NCCN)cc2Cl)cccc1-c1ccccc1.Cl.Cl
InChIKey: OUADRWVTCFSKMB-UHFFFAOYSA-N
Target: Programmed cell death 1 ligand 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9EP73
Assay: Binding affinity to mouse PD-L1 by surface plasmon resonance
Measurement: Kd = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 623.2, ALogP 6.77, HBA 6, HBD 2, PSA 100.61, QED 0.18
Compound (SMILES): CN1CCN(c2ccnc(NCCc3ccccc3)n2)CC1
InChIKey: BNXNWRSVYQHTOH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: GPCRScan assay: inhibition of 5-HT5A
Measurement: Ki = 5128.61 nM (pChEMBL 5.289999961853027)
Descriptors: MW 297.41, ALogP 1.88, HBA 5, HBD 1, PSA 44.29, QED 0.91
Compound (SMILES): CN1CCC2(CC1)CN(c1cc(C(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)ccn1)C2
InChIKey: UZWBTUJSENOMKN-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 467.58, ALogP 3.81, HBA 7, HBD 1, PSA 79.18, QED 0.49
Compound (SMILES): CN1CC=C(C2=Nc3cc(Cl)ccc3Nc3ccccc32)CC1
InChIKey: CITBEZAJPJRZNL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Agonist activity at muscarinic M3 receptor (unknown origin) expressed in CHO cells
Measurement: EC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 323.83, ALogP 4.78, HBA 3, HBD 1, PSA 27.63, QED 0.82
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCCCC2)ccc1OC(=O)N(C)C
InChIKey: RVHOEUHHAHFBJU-CSKARUKUSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate after 15 mins by Ellman's method
Measurement: IC50 = 26300 nM (pChEMBL 4.579999923706055)
Descriptors: MW 332.4, ALogP 2.78, HBA 4, HBD 0, PSA 59.08, QED 0.8
Compound (SMILES): C[C@@H](NC(=O)c1ccc(F)cc1)c1ccc2c(n1)CCCN2C(=O)OC1CC1
InChIKey: ZVKVWIFOWYIPEN-CYBMUJFWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 383.42, ALogP 3.76, HBA 4, HBD 1, PSA 71.53, QED 0.87
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)C[C@H](CCCCN)NC(=O)CCN1Cc2ccccc2C[C@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](N)Cc2c(C)cc(O)cc2C)C1=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C
InChIKey: IKZZJCSTDBFLBU-ANITWDKYSA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 0.32 nM (pChEMBL 9.489999771118164)
Descriptors: MW 1380.75
Compound (SMILES): CCn1nc(C2(C)CC2)cc1Nc1nc(-c2ccc(-n3cnc(C)c3)c(OC)n2)cs1
InChIKey: ZLEUKGZKAVGDKU-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 435.56, ALogP 4.72, HBA 9, HBD 1, PSA 82.68, QED 0.45
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccc(Cl)cc4)CC3)cc2C1=O
InChIKey: OFNWXXGHORGIMJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 413.95, ALogP 3.56, HBA 4, HBD 0, PSA 36.02, QED 0.68
Compound (SMILES): Nc1nccn2c([C@@H]3CC[C@H]4COC(=O)N4C3)nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c12
InChIKey: CDISOBGWDHAHGF-AEFFLSMTSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of BMX (unknown origin)
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 537.5, ALogP 4.34, HBA 8, HBD 2, PSA 127.74, QED 0.4