lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccccc1N1CCC2(CCN(CCCSc3nnc(-c4cccnc4)n3C)CC2)CC1
InChIKey: WFUOLXWLKCINBD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [125I]IABN from recombinant human D2 long receptor stably expressed in HEK293 cell membranes measured after 60 mins by scintillation counting analysis
Measurement: Ki = 48584 nM (pChEMBL 4.309999942779541)
Descriptors: MW 492.69, ALogP 4.75, HBA 8, HBD 0, PSA 59.31, QED 0.33
Compound (SMILES): Cl.NC[C@H]1C[C@]1(F)c1cccc(Cl)c1
InChIKey: KVNKDSQPWALVKE-SCYNACPDSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at recombinant human 5HT2B receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 21.88 nM (pChEMBL 7.659999847412109)
Descriptors: MW 199.66, ALogP 2.48, HBA 1, HBD 1, PSA 26.02, QED 0.78
Compound (SMILES): COC1=CC(=O)N(C(=O)/C=C/[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2CCCCC2)NC(=O)[C@H](C(C)C)N(C)C)C2CCCCC2)[C@H]1Cc1c[nH]c2ccccc12.O=C(O)C(F)(F)F
InChIKey: QIYSMJMILRBSNA-AUAZNUPCSA-N
Target: Cysteine protease falcipain-3 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q9NAW4
Assay: Inhibition of Plasmodium falciparum N-terminal His-tagged falcipain-3 (33 residues) expressed in Escherichia coli M15 pREP4 using Z-Leu-Arg-AMC as substrate measured after 30 mins by spectrofluorometric method
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 801.09, ALogP 6.17, HBA 7, HBD 4, PSA 152.94, QED 0.13
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)cc(=O)n(Cc2cc(C#N)ccc2C(=O)O)c1=O
InChIKey: BXJCLYZXPDLVFN-QGZVFWFLSA-N
Target: Dipeptidyl peptidase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6V1X1
Assay: Inhibition of recombinant full-length human N-terminal GST-tagged DPP8 expressed in Sf9 insect cells using Gly-Pro-AMC as substrate measured at 60 secs interval for 20 mins by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 421.46, ALogP 0.58, HBA 8, HBD 2, PSA 134.35, QED 0.67
Compound (SMILES): Oc1ccc2c(c1)CCCC(c1ccncc1)=C2c1ccc(O[C@H]2CCN(CCCF)C2)cc1
InChIKey: VQJJJXIRLQIHGO-SANMLTNESA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Estrogen Receptor Coactivator Assay: It is a competition assay, where binding of a test compound to a complex comprised of (i) His6-ERα298-554 protein representing ERα ligand-binding domain, (ii) Tb-labeled His6 antibody, (iii) a fluorescein-labeled PGC1α coactivator peptide (EAEEPSLLKKLLLAPANTQ), and (iv) estradiol, results in a decrease of the TR-FRET signal due to dissociation of the coactivator peptide. His6-ERα298-554 proteins were expressed as WT or D538G or Y537S mutants in E. coli and purified by affinity chromatography. The assay works in a homogeneous mix-and-read format. In a typical experiment, a 4 μL mixture of 0.5 nM His6-ERα298-554, 0.5 nM Tb-labeled His6 antibody, 250 nM PGC1a peptide, and 3 nM estradiol in 100 mM potassium phosphate, pH 7.4, 0.01% Tween-20, 0.02% NaN3, 5 mM DTT, was added to 40 nL test compound in DMSO and incubated overnight at room temperature. The TR-FRET 520:495 nm emission ratio was calculated and used to determine the IC50 value from a dose response curve fit to the 4-parameter logistic equation. The antagonist activity with respect to estrogen receptors in this test is given by the concentration which inhibits 50% of the estrogen receptor activity (or IC50) in nM.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 458.58, ALogP 5.9, HBA 4, HBD 1, PSA 45.59, QED 0.48
Compound (SMILES): CN1CCN(C(=O)[C@H]2CC(=O)N(c3ccc(S(N)(=O)=O)cc3)[C@@H]2c2ccc(Cl)cc2)CC1
InChIKey: CIXRBVPFMWBGEY-PZJWPPBQSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 476.99, ALogP 1.86, HBA 5, HBD 1, PSA 104.02, QED 0.72
Compound (SMILES): CCOCCn1cc(C(=O)Nc2ccc(-n3nc(-c4cccnc4)cc3C(F)(F)F)cn2)ccc1=O
InChIKey: KMESAVNRPDKZCQ-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Affinity Biochemical interaction (Human soluble epoxide hydrolase inhibition) EUB0000542a EPHX2
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 498.47, ALogP 3.8, HBA 8, HBD 1, PSA 103.93, QED 0.37
Compound (SMILES): CC(C)(C)ONC(=O)C[C@H](NC(=O)CCc1ccccc1)C(=O)N[C@@H](Cc1ccc(F)cc1)C(=O)NCc1cccc2ccccc12
InChIKey: DDEQIWLWJUDFKG-ACHIHNKUSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human constitutive 20S proteasome beta 5 chymotrypsin-like activity
Measurement: IC50 = 32400 nM (pChEMBL 4.489999771118164)
Descriptors: MW 640.76, ALogP 4.68, HBA 5, HBD 4, PSA 125.63, QED 0.15
Compound (SMILES): CN1CCc2cc(Nc3ncc(C4CC4)c(NCCCNC(=O)C4CCC4)n3)ccc2C1
InChIKey: KKISLZKMBSCLSS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: Inhibition of wild type GST-tagged ULK1 (unknown origin) after 5 mins in presence of gamma-[32]P-ATP by immunoblot analysis
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 434.59, ALogP 3.8, HBA 6, HBD 3, PSA 82.18, QED 0.52
Compound (SMILES): COc1ccc(Cl)cc1N1CCN(CCCCc2nc3ccsc3c(=O)[nH]2)CC1
InChIKey: KLCMFCQMTRDNFR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor expressed in CHO-K1 cells incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 13.4 nM (pChEMBL 7.869999885559082)
Descriptors: MW 432.98, ALogP 3.79, HBA 6, HBD 1, PSA 61.46, QED 0.58
Compound (SMILES): COc1ccc(-c2c(CO)n(Cc3ccccc3Cl)c3cc(OC(F)(F)F)ccc23)cn1
InChIKey: UYKDOBMAEWQAIT-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI0
Assay: Antagonist activity against PAR4 activating peptide domain in human platelets assessed as inhibition of alpha2bbeta3 activation level by PAC1 binding assay
Measurement: IC50 = 812.83 nM (pChEMBL 6.090000152587891)
Descriptors: MW 462.86, ALogP 5.8, HBA 5, HBD 1, PSA 56.51, QED 0.39
Compound (SMILES): O=C(Nc1cccc(F)c1)Nc1cccc(C2CCCN(c3ncnc4[nH]ccc34)C2)c1
InChIKey: BCLPMAXCXRQJNB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: In Vitro BTK Kinase Assay: The purpose of the BTK in vitro assay is to determine compound potency against BTK through the measurement of IC50. Compound inhibition is measured after monitoring the amount of phosphorylation of a fluorescein-labeled polyGAT peptide (Invitrogen PV3611) in the presence of active BTK enzyme (Upstate 14-552), ATP, and inhibitor. The BTK kinase reaction was done in a black 96 well plate (costar 3694). For a typical assay, a 24 μL aliquot of a ATP/peptide master mix (final concentration; ATP 10 μM, polyGAT 100 nM) in kinase buffer (10 mM Tris-HCl pH 7.5, 10 mM MgCl2, 200 μM Na3PO4, 5 mM DTT, 0.01% Triton X-100, and 0.2 mg/ml casein) is added to each well. Next, 1 μL of a 4-fold, 40× compound titration in 100% DMSO solvent is added, followed by adding 15 uL of BTK enzyme mix in 1× kinase buffer (with a final concentration of 0.25 nM). The assay is incubated for 30 minutes before being stopped with 28 μL of a 50 mM EDTA solution. Aliquots (5 μL) of the kinase reaction are transferred to a low volume white 384 well plate (Corning 3674), and 5 μL of a 2× detection buffer (Invitrogen PV3574, with 4 nM Tb-PY20 antibody, Invitrogen PV3552) is added. The plate is covered and incubated for 45 minutes at room temperature. Time resolved fluorescence (TRF) on Molecular Devices M5 (332 nm excitation; 488 nm emission; 518 nm fluorescein emission) is measured. IC50 values are calculated using a four parameter fit with 100% enzyme activity determined from the DMSO control and 0% activity from the EDTA control.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 430.49, ALogP 5.13, HBA 4, HBD 3, PSA 85.94, QED 0.42
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)[C@@H](C)O
InChIKey: PEZZIJHARVHXLT-RWXRVXIYSA-N
Target: Dickkopf WNT-signaling pathway inhibitor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: A6I0Z0
Assay: Inhibition of biotin-labeled rat recombinant DKK1 assessed as reduction in DKK1 interaction with LRP-6/Fc incubated overnight by chemiluminescence based Alpha-screen assay
Measurement: IC50 <= 1 nM (pChEMBL 9)
Descriptors: MW 4778.32
Compound (SMILES): Cc1cc(-c2cccc3nccn23)ccc1Oc1nccc2occc12
InChIKey: UBJHHHAOUCEOFG-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at recombinant human D1 receptor expressed in HEK29T cells assessed as induction of stimulatory G-protein-mediated cAMP accumulation measured after 15 mins by Glosensor-based FLIPR assay
Measurement: EC50 = 537.03 nM (pChEMBL 6.269999980926514)
Descriptors: MW 341.37, ALogP 5.24, HBA 5, HBD 0, PSA 52.56, QED 0.45
Compound (SMILES): CO[C@H]1CN(C#N)C[C@@H]1N(C)C(=O)c1ccc(-c2cnn(C)c2)cc1
InChIKey: FZTPNRYAJIZXCY-IRXDYDNUSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 339.4, ALogP 1.34, HBA 6, HBD 0, PSA 74.39, QED 0.79
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3cnc(NCc4cccnc4)nc3)c(O)c(F)c2Br)C1=O
InChIKey: YQVQKHZFMXRBQU-SOFYXZRVSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with interferon stimulatory DNA and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 546.38, ALogP 4.34, HBA 9, HBD 2, PSA 117.54, QED 0.42
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2ccc(Cl)c(Cl)c2)C(=O)NC(C)(C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: VFQKTVGHCSXJJH-GETCDGGFSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1653.63
Compound (SMILES): Nc1ncnc2c1c(Sc1ccc3c(c1)OCC3)nn2[C@H]1C[C@H](O)[C@@H](COS(N)(=O)=O)O1
InChIKey: LCGDXBNJQIQUGD-IACUBPJLSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 480.53, ALogP 0.36, HBA 12, HBD 3, PSA 177.7, QED 0.44
Compound (SMILES): C=CC(=O)N1CCCC(Cn2nc(Br)c3c(N)ncnc32)C1
InChIKey: JUKXZGJYTMCCBR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62689
Assay: Inhibition of JAK2 in Lewis rat T cells assessed as reduction in IL-2-induced cell proliferation measured after 72 hrs by alamar blue staining based fluorescence assay
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 365.24, ALogP 1.6, HBA 6, HBD 1, PSA 89.93, QED 0.83
Compound (SMILES): O=C(COc1ccc(C(F)(F)F)cc1)N1CCN(c2ccccc2[N+](=O)[O-])CC1
InChIKey: YVIPFEAAAGWZPX-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of C-terminal FLAG tagged human recombinant ATX expressed in insect sf9 cells using pNP-TMP as substrate measured every 2 mins for 60 mins by fluorescence analysis
Measurement: IC50 = 11300 nM (pChEMBL 4.949999809265137)
Descriptors: MW 409.36, ALogP 3.34, HBA 5, HBD 0, PSA 75.92, QED 0.56
Compound (SMILES): Cc1cnc(C(C)(C)C#Cc2ccc3c(c2)-c2nc(C(N)=O)c(C4CC4)n2C2CC3C2)o1
InChIKey: IAXMTTOIYPZWFX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin) using ATP as substrate by transcreener ADP assay based fluorescence correlation spectroscopic analysis
Measurement: Ki > 1250 nM (pChEMBL 5.9029998779296875)
Descriptors: MW 426.52, ALogP 4.58, HBA 5, HBD 1, PSA 86.94, QED 0.62
Compound (SMILES): COc1ccccc1C1CCN(c2nc(C3CC3)nc3c(C)cc(N(C)CCO)cc23)CC1
InChIKey: KJRIJBVRTOLCQH-UHFFFAOYSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: NTR1 Ca2+ Flux Dose Response: NTSR1 (NTR1) CHO cells are plated in 20 uL of assay media containing Ham's F12 supplemented with 10% fetal bovine serum and 0.4 mg/mL G418 at a concentration of 1.0×106 cells per mL into black, 384-well assay plates with clear bottoms using a Multidrop liquid handler. Assay plates are incubated at 37° C. in 5% CO2. The next day, the assay plates are aspirated to remove growth media and washed once with 20 uL of DPBS. The DPBS is then aspirated from the assay plate and replaced with 25 uL of Fluo-4 NW calcium dye prepared according to the manufacturer's recommendations then the plates are incubated for 1 hour at 37° C. Following the incubation in the presence of dye, the assay is run on a Molecular Devices FlexStation-III using 494 excitation and 516 emission wavelengths set to read for 90 seconds with the addition at 18 seconds of 5 uL of 6× final concentration of test compounds and peptide control diluted in assay media containing 0.1% BSA and no more than 9% DMSO to yield a maximum final DMSO concentration of 1.5%. Percent activation is calculated based on the maximum response minus the minimum value over the time course relative to the neurotensin 1 control peptide at 100 pM. EC50 values were calculated for those compounds tested in 8-point dose dependent response.
Measurement: EC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 446.6, ALogP 4.64, HBA 6, HBD 1, PSA 61.72, QED 0.57
Compound (SMILES): N#Cc1ccc(O[C@H]2CN(S(=O)(=O)c3ccc(Cl)cc3Cl)C[C@@]2(O)CN)cc1F
InChIKey: CSBJRNIFYKMMRY-ROUUACIJSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 460.31, ALogP 2.15, HBA 6, HBD 2, PSA 116.65, QED 0.71
Compound (SMILES): CCc1cccc(N2CCN(CC(O)CCNC(=O)c3cc4ccccc4o3)CC2)c1Cl
InChIKey: ANDAVALYLUYQOC-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human dopamine D3 receptor expressed in HEK293 cell membranes incubated for 1 hr by liquid scintillation counting analysis
Measurement: Ki = 0.985 nM (pChEMBL 9.010000228881836)
Descriptors: MW 455.99, ALogP 3.95, HBA 5, HBD 2, PSA 68.95, QED 0.54
Compound (SMILES): CCC(C(=O)Nc1ccc(Cl)cc1)n1nc(C)cc(Cc2ccccc2OC)c1=O
InChIKey: RKRGAKKSRRSDNI-UHFFFAOYSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Biased agonist activity at human FPR1 expressed in FlpIn-CHO cells assessed as intracellular calcium mobilization by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 425.92, ALogP 4.39, HBA 5, HBD 1, PSA 73.22, QED 0.61
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(N)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: ZTXRTGHTKGEDQY-CCSAZDPQSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1579.76
Compound (SMILES): CN(Cc1ccc2c(c1)OCO2)c1nc(-c2cccnc2)nc2ccccc12
InChIKey: KDTNSRXPGJKLNO-UHFFFAOYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: High Throughput Screening (HTS) by Fluorescence Polarization (pH = 7.2): The enzyme in GCase enzyme activity buffer (25 μL/well) was added to a 384-well black plate. The fluorescent probe 3 (25 nL/well, 50 nM final concentration) was transferred to a 384-well black plate using a Labcyte Echo 550 Liquid Handler system. Compounds in DMSO stock solution (50 nL) were transferred to the plate. The plate was shaken at room temperature in dark for 20 min. The final concentration was 19.5 nM to 10 μM, 10 concentrations, 2 times dilution. The fluorescence polarization was measured in a Molecular Devices Analyst GT with Ex=535 nm and Em=580 nm, G Factor=1.05. To the recombinant wild type enzyme (22 μM, 95 μL, 1 equiv) in 0.1 M phosphate buffer (pH 7.2) was added 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(4-(4-(2,4-dimethylpyrrolo [1,2-a]pyrimidine-8-carboxamido)phenyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)propanoate (4) in DMSO (0.89 mM, 5 μL, 2 equiv) in one portion, and was vortexed for 5 sec immediately. At indicated time points, the reaction solution (2 μL) was sampled and diluted (1:3125 dilution) into the assay buffer (50 mM citric acid, 176 mM K2HPO4, and 0.01% Tween-20 at pH 5.9). After 2 h the reaction solution was dialyzed three times with 0.1 M phosphate buffer (pH 7.2). The enzyme was adjusted to the same concentration and sampled for activity. The dilution solutions were assayed with three substrates, resorufin substrate, 4-MU substrate, and natural substrate using the methods described in the examples above without adding compounds.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 370.41, ALogP 4.06, HBA 6, HBD 0, PSA 60.37, QED 0.54
Compound (SMILES): Cc1c(N2CCN(Cc3ccc(Cl)nc3)CC2)c(=O)n(C[C@H](N)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
InChIKey: DZOVNTYYKAGTON-SANMLTNESA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Displacement of [125I]D-Trp6-LHRH from human GnRH receptor expressed in CHO-K1 cell membranes incubated for 1 hr by competitive binding assay
Measurement: IC50 = 3.77 nM (pChEMBL 8.420000076293945)
Descriptors: MW 631.07, ALogP 4.6, HBA 8, HBD 1, PSA 89.39, QED 0.23
Compound (SMILES): CCOc1c(Cl)cc(-c2cnc(-c3ccc(C(=O)O)cc3)o2)cc1Cl
InChIKey: PNCYUHNQVYHNOF-UHFFFAOYSA-N
Target: Retinoic acid receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P11416
Assay: Transactivation of GAL4-fused mouse RARalpha-LBD expressed in COS-7 cells after 24 hrs by bright-Glo reagent based assay
Measurement: EC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 378.21, ALogP 5.41, HBA 4, HBD 1, PSA 72.56, QED 0.64
Compound (SMILES): Cc1c(C(=O)N2CC[C@H](N(C)C)C2)nc(-c2ccc(C#N)c(F)c2)n1-c1cc(F)c2nn(C)cc2c1
InChIKey: UOAGHSGZZDCNBF-IBGZPJMESA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 in human THP1 cells assessed as induction of CD11b expression after 4 days by LIVE/DEAD violet staining based FACS analysis
Measurement: EC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 489.53, ALogP 3.66, HBA 7, HBD 0, PSA 82.98, QED 0.44
Compound (SMILES): Cc1ccc(CN2CCC(c3noc(CN(C)c4ncc(C(=O)NO)cn4)n3)CC2)cc1
InChIKey: DSDPQMCYEOZWTA-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant full length human HDAC2 expressed in sf9 insect cells using Ac-peptide-AMC as substrate after 1 hr by fluorescence assay
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 437.5, ALogP 2.3, HBA 9, HBD 2, PSA 120.51, QED 0.42
Compound (SMILES): CCN(C(=O)Nc1ccc(C(F)(F)F)cc1)[C@@H]1CCN(C#N)C1
InChIKey: BFPDNVZTOHYERD-CYBMUJFWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 326.32, ALogP 3.11, HBA 3, HBD 1, PSA 59.37, QED 0.87
Compound (SMILES): Cc1c(C(=O)N2CC(c3ccnc(C(F)(F)F)c3)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: AZVZEQOWCQRTAU-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 443.39, ALogP 2.17, HBA 7, HBD 1, PSA 101.18, QED 0.52
Compound (SMILES): Cc1c(C(=O)N2CCC2c2ccc(Cl)cc2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: PCSMKPBEPVODOX-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 408.85, ALogP 2.76, HBA 6, HBD 1, PSA 88.29, QED 0.56
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl)c1ccccc1
InChIKey: JIEBHKJKDRMVCK-NSHDSACASA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 1441 nM (pChEMBL 5.840000152587891)
Descriptors: MW 411.91, ALogP 4.91, HBA 5, HBD 2, PSA 71.09, QED 0.6
Compound (SMILES): OC1CCC(C(O)CC2c3c(F)cccc3-c3cncn32)CC1
InChIKey: YGACXVRLDHEXKY-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of purified human IDO1 using L-tryptophan as substrate preincubated for 5 mins followed by substrate addition and measured after 15 mins by spectrophotometric method
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 316.38, ALogP 2.89, HBA 4, HBD 2, PSA 58.28, QED 0.92
Compound (SMILES): Nc1n[nH]c2cc(-c3ccc(C(=O)NCCNC(=O)c4ccc(F)cc4)cc3)ccc12
InChIKey: AIAPDAKQHMWDTA-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of BCR/ABL T315I mutant (unknown origin) measured after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 61200 nM (pChEMBL 4.210000038146973)
Descriptors: MW 417.44, ALogP 3.11, HBA 4, HBD 4, PSA 112.9, QED 0.36
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCC5(CC4)CNC5)cc3)sc2n1
InChIKey: IEUAIIAIXTZDSA-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 435.6, ALogP 3.35, HBA 6, HBD 3, PSA 83.28, QED 0.57
Compound (SMILES): CC1=C(C(=O)Nc2ccccc2C)C(c2ccc(Br)cc2)C2=C(CCCC2=O)N1
InChIKey: QALKUNGGFMIWBA-UHFFFAOYSA-N
Target: Free fatty acid receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14843
Assay: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay
Measurement: EC50 = 1621.81 nM (pChEMBL 5.789999961853027)
Descriptors: MW 451.36, ALogP 5.36, HBA 3, HBD 2, PSA 58.2, QED 0.66
Compound (SMILES): COc1cccc(CCN2CCn3c(nc4c3c(=O)n(C)c(=O)n4C)C2)c1OC
InChIKey: VLMNZBPNKOSTMT-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]MSX from A2A receptor in rat brain striatum membranes measured after 30 mins by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 399.45, ALogP 0.51, HBA 9, HBD 0, PSA 83.52, QED 0.62
Compound (SMILES): Cc1nc2c(c(-c3ccc4oc(N)nc4c3)nn2C(C)C)c(=O)[nH]1
InChIKey: VYGVLHBRKJFFMR-UHFFFAOYSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BPZ7
Assay: Inhibition of mTORC2 in human A431 cells assessed as AKT phosphorylation at S473 residue incubated for 3 hrs by HTRF assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 324.34, ALogP 2.4, HBA 7, HBD 2, PSA 115.62, QED 0.58
Compound (SMILES): Cc1cc(C)c2c(c1O)C(=O)O[C@H](C)C2
InChIKey: RUANKMKZMDHEOS-MRVPVSSYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB using kynuramine as substrate incubated for 10 mins by UPLC-ESI-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 206.24, ALogP 2.11, HBA 3, HBD 1, PSA 46.53, QED 0.66
Compound (SMILES): COc1ccc(OC)c2c1C(=O)C=C(SCCC(=O)O)C2=O
InChIKey: DIIRLGMLDOPLPV-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of recombinant Cdc25B (unknown origin) using OMFP as substrate measured every 30 sec for 10 mins by fluorometric assay
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 322.34, ALogP 2.17, HBA 6, HBD 1, PSA 89.9, QED 0.86
Compound (SMILES): C=C(c1cc(OC)c(OC)c(OC)c1)c1ccc(OC)cc1/C=C/C(=O)NO
InChIKey: QIATVBMDIPTKHN-RMKNXTFCSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 after 30 mins using fluorogenic substrate by fluorimetric assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 385.42, ALogP 3.3, HBA 6, HBD 2, PSA 86.25, QED 0.41
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2cccc(OC)c2F)c1
InChIKey: JEMRXDRYNBPJEK-LJQANCHMSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 459.52, ALogP 3.35, HBA 5, HBD 3, PSA 107.97, QED 0.14
Compound (SMILES): Cn1c(C(N)=O)ccc1-c1cccc(OC(=O)NCCN2CCN(c3ccccc3)CC2)c1
InChIKey: JRYNLQPPXGHRTN-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O08914
Assay: Inhibition of FAAH in mouse brain membranes assessed as inhibitory constant using [14C]-AEA as substrate incubated for 15 mins by scintillation counting method
Measurement: Ki = 203 nM (pChEMBL 6.690000057220459)
Descriptors: MW 447.54, ALogP 2.7, HBA 6, HBD 2, PSA 92.83, QED 0.58
Compound (SMILES): NS(=O)(=O)c1ccc(CN2C(=O)c3ccc(C(=O)Nc4ccc(Cl)cc4C(=O)O)cc3C2=O)cc1
InChIKey: AHEFQWVZVHFUCF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 41.5 nM (pChEMBL 7.380000114440918)
Descriptors: MW 513.92, ALogP 2.73, HBA 6, HBD 3, PSA 163.94, QED 0.43
Compound (SMILES): O=C(NCc1ncco1)c1csc(CCNCc2nc3ccccc3[nH]2)n1
InChIKey: KQGPYGJDFWZUIP-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 1866 nM (pChEMBL 5.730000019073486)
Descriptors: MW 382.45, ALogP 2.27, HBA 7, HBD 3, PSA 108.73, QED 0.4
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCCN3Cc2ccc(Cl)cc2)n(C)c1=O
InChIKey: ZAHHJWITZARPIB-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX2 from recombinant human adenosine A2a receptor expressed in HEK293 cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 373.84, ALogP 1.89, HBA 7, HBD 0, PSA 65.06, QED 0.69
Compound (SMILES): CCC(=O)N[C@@H](Cc1nc2ccc(C(C)C)cc2s1)C(=O)N[C@H](CNC(=O)CCN1CCOCC1)C1CCCCC1
InChIKey: CNJKDQGPBAWNRY-IZZNHLLZSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Binding affinity to DCN1 (unknown origin) assessed as inhibition of constant by fluorescence polarization assay
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 585.82, ALogP 3.76, HBA 7, HBD 3, PSA 112.66, QED 0.33
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: RXFUTTKISACZCN-AKRNDEEESA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 whole cells incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 0.368 nM (pChEMBL 9.430000305175781)
Descriptors: MW 3730.23
Compound (SMILES): Cc1cc(C)c2c(N)c(C(O)c3ccc(O)cc3)sc2n1
InChIKey: CKCRKIDYWQVHLW-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation activity at rat M4 receptor expressed in CHO cells co-expressing Gqi5 protein assessed as potentiation of EC20 acetyl choline-induced response by calcium mobilization assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 300.38, ALogP 3.28, HBA 5, HBD 3, PSA 79.37, QED 0.68
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCc2ccccc2)c(S(=O)(=O)c2ccccc2)cc1Cl
InChIKey: RFMRCPYSBXEKPD-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 464.95, ALogP 2.75, HBA 5, HBD 2, PSA 123.4, QED 0.58
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CO)[C@@H]1CCC2=O
InChIKey: XGUHPTGEXRHMQQ-BGJMDTOESA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 20 mins in presence of NADPH
Measurement: IC50 = 13001.7 nM (pChEMBL 4.889999866485596)
Descriptors: MW 302.41, ALogP 3.06, HBA 3, HBD 1, PSA 54.37, QED 0.81
Compound (SMILES): Cc1cc(CNS(=O)(=O)c2ccc([N+](=O)[O-])cc2)c(C)o1
InChIKey: WIQJCVVQFCUCMR-UHFFFAOYSA-N
Target: Matrix protein 2 (SINGLE PROTEIN), Influenza A virus
UniProt: P06821
Assay: Inhibition of wild type influenza A virus H5N1 (A/chicken/Hubei/327/2004) matrix protein 2 transfected in yeast assessed as yeast growth restoration measured after 46 to 48 hrs
Measurement: EC50 = 1710 nM (pChEMBL 5.769999980926514)
Descriptors: MW 310.33, ALogP 2.28, HBA 5, HBD 1, PSA 102.45, QED 0.67
Compound (SMILES): Cl.N=C(N)c1ccc(C2Cc3ccccc3B(O)O2)cc1OCc1cccc(Cl)c1
InChIKey: DJRBTAGYIUUURP-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibition of human recombinant N-terminal His-tagged and enterokinase cleavage site-fused KLK1 (19 to 262 residues) expressed in baculovirus infected Sf9 insect cells using R110 labelled GSK3162232A as substrate measured at 30 secs interval for 5 mins by FLINT assay
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 406.68
Compound (SMILES): COc1ccccc1Nc1nc(-c2sc(NC(C)=O)nc2C)cs1
InChIKey: ZADCDCMLLGDCRM-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human proMMP9 expressed in African green monkey COS-1 cells assessed as reduction in protein activation incubated for 30 mins prior to catMMP-3 addition for 30 mins and subsequent DQ gelatin addition and measured after 10 mins by fluorescence method
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 360.46, ALogP 4.29, HBA 7, HBD 2, PSA 76.14, QED 0.71
Compound (SMILES): Nc1cccc(Cl)c1Oc1ccc(CNc2ccccc2)cc1
InChIKey: QVDXMPUCBFHBLV-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition and measured for 6 mins by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 324.81, ALogP 5.33, HBA 3, HBD 2, PSA 47.28, QED 0.62
Compound (SMILES): Cc1ccc(Cl)cc1N1CCN(C(=O)C2CC2c2ccc(F)cc2)CC1
InChIKey: ITRMZYSEZBCBEC-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 372.87, ALogP 4.24, HBA 2, HBD 0, PSA 23.55, QED 0.8
Compound (SMILES): C[C@H](CCC1(O)CC1)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: XDUQIOJDOPDMHF-SZFRISSFSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2A (PROTEIN COMPLEX), Homo sapiens
UniProt: Q12879
Assay: Positive allosteric modulation of recombinant human GluN1/GluN2A receptor stably expressed in HEK293 cells assessed as increase in glycine/L-glutamate-induced channel current at -70 mV holding potential by IonWork two-electrode voltage clamp method
Measurement: EC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 400.65, ALogP 6.26, HBA 2, HBD 2, PSA 40.46, QED 0.55
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](O)[C@H](n5cnc6c(=O)[nH]cnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: FGBPDVXLLDHZTQ-INFSMZHSSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of recombinant human STING haplotype R71H/G230A/R293Q mutant expressed in 293T cells measured after 30 mins in presence of digitonin A by bright Glo-luciferase reporter gene assay
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 675.4, ALogP -2.63, HBA 19, HBD 7, PSA 323.6, QED 0.11
Compound (SMILES): CC1=NC(c2cn(S(=O)(=O)c3ccccc3C)c3ccc(C)cc23)CN1
InChIKey: VIYGPZIYLSPDBJ-UHFFFAOYSA-N
Target: Kallikrein-7 (SINGLE PROTEIN), Mus musculus
UniProt: Q91VE3
Assay: Inhibition of enterokinase activated recombinant mouse C-terminal His6-tagged KLK7 (Gln22 to Arg249 residues) using MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence analysis
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 367.47, ALogP 3.56, HBA 5, HBD 1, PSA 63.46, QED 0.77
Compound (SMILES): Nc1cc(N2CCNCC2)c2ccccc2n1
InChIKey: KNBCGROIEFXNMZ-UHFFFAOYSA-N
Target: Neutrophil cytosol factor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14598
Assay: Binding affinity to immobilized recombinant human His-tagged p47phox SH3A-B domain (151 to 285 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by SPR assay
Measurement: Kd = 78000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 228.3, ALogP 1.23, HBA 4, HBD 2, PSA 54.18, QED 0.77
Compound (SMILES): C[C@@H](O)CNC(=O)c1ccc2nc(C(O)(c3ccccc3)c3ccccc3)n(CCF)c2c1
InChIKey: VFECHVVMLRIBQV-GOSISDBHSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of N-terminal 6x-histidine tagged human ACSS2 expressed in insect cells assessed as reduction in pyrophosphate production using CoA and ATP incubated for 30 mins by pyrophosphatase coupled enzymatic assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 447.51, ALogP 3.4, HBA 5, HBD 3, PSA 87.38, QED 0.39
Compound (SMILES): CCCC[C@H](N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C)C(=O)N[C@H](CO)C(=O)N[C@@H]1CSSC[C@@H]2NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CSSC[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)C(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC2=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC(=O)O)NC(=O)[C@@H](CC(=O)O)NC(=O)[C@@H](CCCNC(=N)N)NC1=O)[C@@H](C)CC)C(C)C)[C@@H](C)O
InChIKey: XQPOQGBASRDUGC-FJOUPPRMSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Inverse agonist activity at SNAP-tagged human GHSR expressed in HEK293T cells assessed as reduction in inositol phosphate production after 30 mins by HTRF assay
Measurement: EC50 = 22.8 nM (pChEMBL 7.639999866485596)
Descriptors: MW 4551.26
Compound (SMILES): CCCCCCCCNCc1ccc(CNC(=O)c2csc3nc[nH]c(=O)c23)cc1
InChIKey: SZWXXUKSELBLQK-UHFFFAOYSA-N
Target: tRNA (guanine-N(1)-)-methyltransferase (SINGLE PROTEIN), Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
UniProt: Q9HXQ1
Assay: Inhibition of Pseudomonas aeruginosa tRNA (guanine(37)-N1)-methyltransferase (Leu5 to Asp25 residues) expressed in Escherichia coli BL21 Rosetta (DE3) assessed as reduction in S-adenosyl-L-homocysteine production preincubated for 15 mins followed by 4.5 uM of tRNALeu(CAG) substrate and SAM addition and measured after 45 mins by MTase-Glo assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 426.59, ALogP 4.36, HBA 5, HBD 3, PSA 86.88, QED 0.38
Compound (SMILES): O=c1cc(N2CCOCC2)nc2n1CC[C@@H](C(F)(F)F)N2C[C@@H](O)c1ccccc1
InChIKey: PZFUMOISBVVUGC-CVEARBPZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3K p110alpha (unknown origin)
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 424.42, ALogP 1.95, HBA 7, HBD 1, PSA 70.83, QED 0.81
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4CCNCC4)cc3)c2C)cc(OC)c1OC
InChIKey: RKBYYWVZFBATHQ-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of ALK2 G328V mutant (unknown origin) by radiometric assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 419.53, ALogP 4.16, HBA 6, HBD 1, PSA 55.85, QED 0.65
Compound (SMILES): Cc1nn(-c2ccc(CN)nc2)c(C)c1-c1ccc(F)cc1
InChIKey: CMYMZIBAHPIODZ-UHFFFAOYSA-N
Target: Acid-sensing ion channel 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q925H0
Assay: Inhibition of pH 5.5-stimulated mouse ASIC2a homomer expressed in CHOK1 cells assessed as reduction in channel activation by VSD fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 296.35, ALogP 3.15, HBA 4, HBD 1, PSA 56.73, QED 0.81
Compound (SMILES): COc1cc(Nc2ccnc3ccc(I)cc23)cc(OC)c1OC
InChIKey: YULUHUJTIHWRMI-UHFFFAOYSA-N
Target: Atypical kinase COQ8A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI60
Assay: Binding affinity to biotinylated full length human ADCK3 expressed in Escherichia coli incubated for 1.5 hrs by fluorescent tracer dependent TR-FRET based competitive ligand binding displacement assay
Measurement: Kd = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 436.25, ALogP 4.61, HBA 5, HBD 1, PSA 52.61, QED 0.59
Compound (SMILES): CC(C)COc1ncc(-c2ccc(C(=O)NS(C)(=O)=O)cc2C2=CCOC2)cc1Cl
InChIKey: PGJCCDDVYSTICD-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells incubated for 3 to 5 mins at -50 mV holding potential by electrophysiology assay
Measurement: IC50 > 42000 nM (pChEMBL 4.376999855041504)
Descriptors: MW 450.94, ALogP 3.54, HBA 6, HBD 1, PSA 94.59, QED 0.69
Compound (SMILES): Cc1nc(-c2ccccc2)c(-c2ccnc(NC(=O)CCn3cnnn3)c2)[nH]1
InChIKey: OSBLXMOEJWVGRZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of P38alpha MAPK (unknown origin) by ADP-Glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 374.41, ALogP 2.46, HBA 7, HBD 2, PSA 114.27, QED 0.54
Compound (SMILES): Cc1ccc(S(=O)(=O)Oc2ccc(-c3ccc4occc4c3)cc2)cc1
InChIKey: YHCRTROKSYQSRE-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant N-HA--tagged carbonic anhydrase 12 expressed in HEK293T cells using p-nitrophenyl acetate as substrate measured after 30 mins by colorimetric analysis
Measurement: IC50 = 1130 nM (pChEMBL 5.949999809265137)
Descriptors: MW 364.42, ALogP 5.18, HBA 4, HBD 0, PSA 56.51, QED 0.47
Compound (SMILES): CN(C1CC1)S(=O)(=O)c1ccc(-c2cnc(N)c(-c3ccc4c(c3)C(C)(C)CNC4=O)n2)cc1
InChIKey: OEQZNQBWTHMIFU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of MST1 (unknown origin) pre-incubated for 10 mins before addition of 50 uM ATP and Z'-Lyte S/T Pep7 and further incubated for 1 hr
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 477.59, ALogP 3.2, HBA 6, HBD 2, PSA 118.28, QED 0.58
Compound (SMILES): Cc1cc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)ccc1C(=O)O
InChIKey: AMWWGPAAICSTSU-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P28702
Assay: Agonist activity at Gal4-LBD fused RXRbeta (unknown origin) expressed in HEK293T cells after 14 to 16 hrs by dual-Glo luciferase assay
Measurement: EC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 348.24, ALogP 5.4, HBA 1, HBD 1, PSA 37.3, QED 0.74
Compound (SMILES): O=C(c1ccccc1)N1CCc2c([nH]c3ccccc23)C1c1ccc(Cl)cc1
InChIKey: ILBXHMLHMLGBPH-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of human ABCG2 expressed in MDCK2 cells assessed as reduction in Hoechst 33342 efflux pre-incubated for 30 mins before Hoechst 33342 addition and measured for 120 mins by microplate reader analysis
Measurement: IC50 = 741 nM (pChEMBL 6.130000114440918)
Descriptors: MW 386.88, ALogP 5.61, HBA 1, HBD 1, PSA 36.1, QED 0.48
Compound (SMILES): Cc1c(C(=O)N2c3ccccc3CC2C)cnn1-c1nc2ccsc2c(=O)[nH]1
InChIKey: GXDGYNVUVVWKTI-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 391.46, ALogP 3.07, HBA 6, HBD 1, PSA 83.88, QED 0.57
Compound (SMILES): CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCc3cc(Cl)ccc3C2)CC1
InChIKey: PWAMOODUNUXEIM-RHDGDCLCSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2L receptor (unknown origin) expressed in human HTLA cells assessed as beta-arrestin2 recruitment after 20 to 22 hrs by brightglo-luciferase reporter gene assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 363.93, ALogP 3.92, HBA 2, HBD 1, PSA 35.58, QED 0.88