lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](O)C(F)(F)F)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: JXGGHGLZZYBWNG-XMMPIXPASA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 501.51, ALogP 5.15, HBA 8, HBD 1, PSA 85.53, QED 0.36
Compound (SMILES): COc1cccc(/C=N/Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c1
InChIKey: GYQWOGHOBIBGDV-WYMPLXKRSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using peptide as substrate after 60 mins by HTRF assay
Measurement: IC50 = 376 nM (pChEMBL 6.420000076293945)
Descriptors: MW 459.96, ALogP 4.51, HBA 8, HBD 2, PSA 105.57, QED 0.38
Compound (SMILES): Cc1cc(Nc2cc(N3CC(F)(C4CC4)C3)nc(O[C@H]3CCN(C(=O)OC(C)(C)C)C3)n2)[nH]n1
InChIKey: XASNWGIYRRYMHU-INIZCTEOSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) using poly(Glu)4Tyr substrate and and [gamma-33P]-ATP incubated for 20 mins by Top-count assay
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 473.55, ALogP 3.58, HBA 8, HBD 2, PSA 108.5, QED 0.66
Compound (SMILES): CCC(=O)N1CC[C@H](Oc2ccnc3ccc(-c4ccc(OC)nc4)cc23)C1
InChIKey: GKVUBNGBTYQPGF-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3K-alpha (unknown origin) by KinaseGlo assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 377.44, ALogP 3.7, HBA 5, HBD 0, PSA 64.55, QED 0.68
Compound (SMILES): C(=C/c1ccco1)\CN1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: ZOHRQKUBVIZFBG-HNQUOIGGSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 348.41, ALogP 3.09, HBA 6, HBD 1, PSA 75.25, QED 0.61
Compound (SMILES): Cc1cnc(C(=O)N2CCC[C@@H](Nc3cnc(C(F)(F)F)cn3)[C@@H]2C)c(-n2nccn2)c1
InChIKey: AXADKMWRPJJTBF-UONOGXRCSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor(Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, IX Pen/Strep, IX sodium pyruvate, 10 mM HEPES, 600 ug/mL G418 and DMEM/F12 (Gibco, Cat #1 1039), 10%FBS, IX Pen/Strep, 600 ug/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phoshpate Buffered Saline IX with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 5 min at 4 C), the supernatant was aspirated and the pellets frozen and stored at -80C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #1 1836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL.
Measurement: Ki = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 446.44, ALogP 2.88, HBA 8, HBD 1, PSA 101.72, QED 0.66
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(C(F)(F)F)c(F)c4)cs3)ccnc2n(C)c1=O
InChIKey: LVNGBBYMWXDSCD-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 = 619.5 nM (pChEMBL 6.210000038146973)
Descriptors: MW 493.44, ALogP 3.09, HBA 8, HBD 1, PSA 98.88, QED 0.44
Compound (SMILES): COc1cc(C2CCN(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: YBLOETFEIHBENF-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 737.83, ALogP 6.97, HBA 10, HBD 2, PSA 130.82, QED 0.14
Compound (SMILES): CC#CC(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc21
InChIKey: MCHPKOULFPNIOZ-IBGZPJMESA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 3.82 nM (pChEMBL 8.420000076293945)
Descriptors: MW 452.52, ALogP 3.88, HBA 7, HBD 1, PSA 99.16, QED 0.46
Compound (SMILES): Cc1oc2c(c1CC(=O)Nc1nc(-c3cc(F)cc(C(F)(F)F)c3)cs1)c(=O)n(C)c(=O)n2C
InChIKey: OZYWCNZZAGZNJD-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 496.44, ALogP 3.6, HBA 8, HBD 1, PSA 99.13, QED 0.44
Compound (SMILES): CN[C@@H](C)C(=O)Nc1ccc(-c2c(-c3cncn3C)nc3cc(C)ccn23)c(C#Cc2ccc3c(C)nccc3c2)n1
InChIKey: MKBRPDBPQLDLIT-QFIPXVFZSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition Assays: The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
Measurement: IC50 = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 554.66, ALogP 4.91, HBA 8, HBD 2, PSA 102.03, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCCC2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: SIWFRERSMYFRNO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 500.65, ALogP 5.45, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): c1c(N2CCCC2)nc(N2CCCC2)nc1N1CCNCC1
InChIKey: XTPTVAPEXHUUDR-UHFFFAOYSA-N
Target: Caspase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P49662
Assay: Inhibition of human recombinant N-terminal His-tagged DTT-activated caspase-4 expressed in Escherichia coli using Ac-LEVD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: Ki = 207 nM (pChEMBL 6.679999828338623)
Descriptors: MW 302.43, ALogP 1.09, HBA 6, HBD 1, PSA 47.53, QED 0.9
Compound (SMILES): c1cc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)ccn1
InChIKey: HKEYBHDQWXZWSU-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 333.4, ALogP 2.38, HBA 6, HBD 1, PSA 75, QED 0.62
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3Cl)ncnc2cc1OC[C@@H]1CN2CCOC[C@H]2CO1
InChIKey: QPNYAXXXUXFKDG-KBPBESRZSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 570.27, ALogP 4.93, HBA 8, HBD 1, PSA 77.97, QED 0.42
Compound (SMILES): CCc1cncc(-c2cc3c(cn2)cnn3-c2cccc(N3CCNCC(O)C3)n2)n1
InChIKey: PSCVBRQZWNSBAR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: In Vitro Cell Proliferation Potency Assay: BaF3, a murine interleukin-3 dependent pro-B cell line, parental cells, BaF3 PIM1 cells, BaF3 PIM2 cells, and MM1.S (multiple myeloma) cells were seeded at 2 k/well, 5 k/well, 5 k/well, and 10 k/well respectively, in a 384-well plate, at 45 μL/well. Test compound was added at 5 μL/well. BaF3 cells (parental and transfected) were incubated overnight, while MM1.S cells were incubated for 72 hours at 37° C., 5% CO2. CELL TITER GLO® Reagent (Promega) was added at 50 μL/well, the plates were incubated for 30 minutes, and their luminescence read on an HT Analyst.
Measurement: IC50 = 111 nM (pChEMBL 6.960000038146973)
Descriptors: MW 416.49, ALogP 1.61, HBA 9, HBD 2, PSA 104.88, QED 0.52
Compound (SMILES): Cc1noc(C)c1-c1cc(C(O)(c2ccccn2)c2ccccn2)c2nc(C3CC3)[nH]c2c1F
InChIKey: QRMLXMNLPJVQQA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Ligand KI Assay: The labeled ligand specifically binds BRD4-1 and BRD4-2 and can be displaced by a small molecule inhibitor that shares a similar or overlapping binding site. BRD4-I and BRD4-2 were expressed and purified from Escherichia coli as N-terminal His6, tagged proteins. A Eu-cryptate labeled anti-His antibody (Perkin Elmer) was used to specifically bind BRD4. Binding of BRD4 to the labeled probe/ligand resulted in an increase in FRET signal whereas displacement of this labeled ligand from BRD4 with a small molecule inhibitor resulted in a decrease in FRET signal. Assays were performed in 50 mM Hepes (pH 7.5), 150 mM NaCl, 0.1 mg/ml BSA, 0.01% (v/v) Brij, 0.5% (v/v) DMSO and 10 nM labeled ligand at the following concentrations for each BRD4 isoform: 2 nM BRD4-1 and 0.5 nM BRD4-2. After an assay reaction time of 60 minutes at 25° C., binding was measured with 2 nM Eu-cryptate labeled anti-His antibody. TR-FRET signal was detected on an Envision plate reader (Ex: 320 nm; Em: 615/665 nm; 100 us delay and 200 us read window). Data were normalized based on a positive (2 uM I-BET) and negative (DMSO) controls and IC50 values were calculated from the fit of the dose-response curves to a four-parameter equation. All IC50 values represent geometric mean values of a minimum of four determinations. The IC50 values were converted to Ki values (dissociation constant for BRD4-inhibitor complex) using the Cheng and Prusoff equation for a competitive inhibitor mode of action.
Measurement: IC50 = 20.2 nM (pChEMBL 7.699999809265137)
Descriptors: MW 455.49, ALogP 4.93, HBA 6, HBD 2, PSA 100.72, QED 0.39
Compound (SMILES): COC(=O)Nc1ccc(-c2ccc3nc(C(=O)c4nnc(CNS(N)(=O)=O)o4)sc3c2)cc1
InChIKey: DMPVUNBZJQKAFR-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Enzymatic Assay: The enzymatic assay was measured using white, opaque 96-well half area plates. Each well contained 60 μL of assay buffer (50 mM HEPES pH 8.0, 50 mM NaCl and 1 mM CaCl2) and 2 ul of a DMSO solution containing compound of interest. Conditioned media obtained from HT-1080 cells, which were transformed by RAGE technology (Athersys) to overexpress endogenous EL, was added and the reaction was allowed to incubate for 20 min at 37° C. with gentle agitation. The reaction was started by the addition of 20 μL of a 1:4 dilution of vesicles. The final total reaction volume was 100 μL. The reaction rates were measured on a Gemini plate reader with an excitation wavelength of 488 nm and an emission of 530 nm. Readings were taken every 20 seconds for 10 min with agitation between each reading.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 488.51, ALogP 2.05, HBA 10, HBD 3, PSA 179.4, QED 0.33
Compound (SMILES): COc1cccc2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c12
InChIKey: RIZNRXQIXARGMI-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.39, ALogP 2.82, HBA 4, HBD 1, PSA 54.56, QED 0.88
Compound (SMILES): CCCc1nc2ccccc2n1C(=O)c1ccc(OC)cc1
InChIKey: AWXPIFQUFWZVAF-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cell membranes incubated for 1.5 hrs
Measurement: Ki = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 294.35, ALogP 3.69, HBA 4, HBD 0, PSA 44.12, QED 0.74
Compound (SMILES): Cc1cccc2cc(Cn3nc(C#N)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: MPLCQEUUJAOLFE-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.43, ALogP 3.08, HBA 8, HBD 1, PSA 115.41, QED 0.47
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1csnn1
InChIKey: KDMBMLINAPXLCW-UZLBHIALSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human dopamine D3 receptor expressed in CHO cell membranes after 90 mins in presence of quinelorane by [35S]-GTPgammaS binding assay
Measurement: Ki = 1.445 nM (pChEMBL 8.84000015258789)
Descriptors: MW 480.59, ALogP 4.71, HBA 8, HBD 0, PSA 59.73, QED 0.36
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3cccc(Cl)c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: QFVCJCFTEZUZGZ-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 507, ALogP 5.7, HBA 7, HBD 1, PSA 91.62, QED 0.33
Compound (SMILES): Cc1cccc2cc(Cn3nc(-c4cccc(O)c4)c4c(N)ncnc43)n(-c3ccccc3OCCN3CCOCC3)c(=O)c12
InChIKey: OTIHXEJGGZQROI-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 603.68, ALogP 4.15, HBA 11, HBD 2, PSA 133.55, QED 0.26
Compound (SMILES): CC(C)(C)OC(=O)N1CCC(CNC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)CC1
InChIKey: CUDIXZDMIROSIC-UAPYVXQJSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 710 nM (pChEMBL 6.150000095367432)
Descriptors: MW 467.62, ALogP 4.12, HBA 7, HBD 2, PSA 100.44, QED 0.59
Compound (SMILES): CC(=O)SC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: FNTDWLPCWWDDJQ-HAQNSBGRSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 329.43, ALogP 3.16, HBA 6, HBD 1, PSA 75.94, QED 0.8
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc3ncccc3o2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RYLYPXANRHKWKH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 4365.16 nM (pChEMBL 5.360000133514404)
Descriptors: MW 492.54, ALogP 5.53, HBA 9, HBD 0, PSA 91.33, QED 0.29
Compound (SMILES): COc1nc2ccc(C(O)(c3ccc(C)nc3C)c3cnnn3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
InChIKey: HVSWHSCHDKSPHW-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: ThermoFluor® Assay: Bar-coded assay plates are robotically loaded onto a thermostatically controlled PCR-type thermal block and then heated at a typical ramp-rate of 1 °C./min for all experiments. Fluorescence was measured by continuous illumination with UV light (Hamamatsu LC6) supplied via fiber optic and filtered through a band-pass filter (380-400 nm; >6 OD cutoff). Fluorescence emission of the entire 384-well plate was detected by measuring light intensity using a CCD camera (Sensys, Roper Scientific) filtered to detect 500±25 nm, resulting in simultaneous and independent readings of all 384 wells. Images were collected at each temperature, and the sum of the pixel intensity in a given area of the assay plate was recorded versus temperature. Reference wells contained RORγt without compounds, and the assay conditions were as follows: 0.065 mg/mL RORγt, 60 μM 1,8-ANS, 100 mM Hepes, pH 7.0, 10 mM NaCl, 2.5 mM GSH, 0.002% Tween-20. Project compounds were arranged in a pre-dosed mother plate (Greiner Bio-one) wherein compounds are serially diluted in 100% DMSO by 1:2 from a high concentration of 10 mM over 12 columns within a series (column 12 is a reference well containing DMSO, no compound). The compounds were robotically dispensed directly into assay plates (1×=46 nL) using a Hummingbird capillary liquid handling instrument (Digilab). Following compound dispense, protein and dye in buffer was added to achieve the final assay volume of 3 μL, followed by 1 μL of silicone oil.
Measurement: Kd = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 568, ALogP 5.93, HBA 7, HBD 1, PSA 85.95, QED 0.27
Compound (SMILES): Cc1cccc(C(=O)c2cnn(-c3cc(O)ccc3Cl)c2N)c1
InChIKey: HHUATYYBFHVSMC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 by time-resolved fluorescence or time-resolved fluorescence assay
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 327.77, ALogP 3.35, HBA 5, HBD 2, PSA 81.14, QED 0.72
Compound (SMILES): CC(=O)N1CCC2(CCC(Nc3nc(Nc4cnn(C)c4)ncc3Cl)CC2)CC1
InChIKey: ZXAFLEVWBXJCQF-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Kinase Assay: TYK2 (h) is incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 250 μM GGMEDIYFEFMGGKKK, 10 mM MgAcetate and [γ-33P-ATP](specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 3% phosphoric acid solution. 10 μL of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 417.95, ALogP 3.59, HBA 7, HBD 2, PSA 87.97, QED 0.79
Compound (SMILES): COC1CCC(CNc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccc4[nH]ccc4c3)cc2[N+](=O)[O-])CC1
InChIKey: MFBQDUKJZTVUAS-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q64373
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The inhibition constant (Ki) is the dissociation constant of an enzyme-inhibitor complex or a protein/small molecule complex, wherein the small molecule is inhibiting binding of one protein to another protein or peptide. Where the Ki for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-XL) is greater than the limits of detection of the assay used. Where the binding selectivity ratio for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the selectivity of a particular compound for Bcl-2 over Bcl-XL is at least as great as the number indicated. Where the Ki for a compound is represented as < (less than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-2) is lower than the limit of detection of the assay used. Inhibition constants were determined using Wang's equation (Wang Z-X).
Measurement: Ki = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 895.52, ALogP 10.04, HBA 10, HBD 3, PSA 159.14, QED 0.07
Compound (SMILES): Cc1cc2cc(Nc3nccc(Oc4ccc(NC(=O)Nc5cc(C(C)(C)C)nn5-c5ccc(OCCN6CCOCC6)cc5)c5ccccc45)n3)ccc2[nH]1
InChIKey: QJLFDDXFGSEKEP-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: GSK 3α Enzyme Inhibition Assay: The inhibitory activities of compounds of the invention against the GSK 3α enzyme isoform (Invitrogen), are evaluated by determining the level of activation/phosphorylation of the target peptide. The GSK3-α protein (500 ng/mL, 2.5 uL) is mixed with the test compound (2.5 uL at either 4 ug/mL, 0.4 ug/mL, 0.04 ug/mL, or 0.004 ug/mL) for 2 hr at RT. The FRET peptide (8 uM, 2.5 uL), which is a phosphorylation target for GSK3α, and ATP (40 uM, 2.5 uL) are then added to the enzyme/compound mixture and the resulting mixture incubated for 1 hr. Development reagent (protease, 5 uL) is added for 1 hr prior to detection in a fluorescence microplate reader (Varioskan Flash, ThermoFisher Scientific).
Measurement: IC50 = 2850 nM (pChEMBL 5.539999961853027)
Descriptors: MW 751.89, ALogP 8.79, HBA 10, HBD 4, PSA 143.48, QED 0.1
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cc4c(cn3)OC(CO)n3c-4cc4c(F)cccc43)cc12
InChIKey: IGLDGEOGVDCZEA-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1b (isolate Japanese) (HCV)
UniProt: P26662
Assay: ELISA-Based Assay: Measurement of inhibition by compounds was performed using the HCV replicon system. Several different replicons encoding different HCV genotypes or mutations were used. In addition, potency measurements were made using different formats of the replicon assay, including different ways of measurements and different plating formats. See Jan M. Vrolijk et al., A replicons-based bioassay for the measurement of interferons in patients with chronic hepatitis C, 110 J. VIROLOGICAL METHODS 201 (2003); Steven S. Carroll et al., Inhibition of Hepatitis C Virus RNA Replication by 2'-Modified Nucleoside Analogs, 278(14) J. BIOLOGICAL CHEMISTRY 11979 (2003). However, the underlying principles are common to all of these determinations, and are outlined below.Stable neomycin phosphotransferase encoding replicons-harboring cell lines were used, so all cell lines were maintained under G418 selection prior to the assay. Potency was determined using a cell ELISA assay with an antibody to the replicons encoded NS3/4a protease. See Caterina Trozzi et al., In Vitro Selection and Characterization of Hepatitis C Virus Serine Protease Variants Resistant to an Active-Site Peptide Inhibitor, 77(6) J. Virol. 3669 (2003).
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 644.66, ALogP 5.7, HBA 8, HBD 2, PSA 126.9, QED 0.24
Compound (SMILES): COc1ncnc(N2Cc3cn(-c4cccc(S(C)(=O)=O)c4)nc3[C@H]2C(C)C)c1F
InChIKey: XOTHLYNSDMSVGX-GOSISDBHSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at LXRbeta LBD (unknown origin) fused with Gal4-DNA binding domain expressed in HEK293 cells assessed as modulation of receptor transcription activity by luciferase reporter gene assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 431.49, ALogP 2.93, HBA 8, HBD 0, PSA 90.21, QED 0.61
Compound (SMILES): Fc1ccc2c(CN3CCC(F)(F)[C@H](CCc4ccccc4)C3)c[nH]c2c1
InChIKey: PFOWCBUJJWGNHA-GOSISDBHSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 372.43, ALogP 5.4, HBA 1, HBD 1, PSA 19.03, QED 0.64
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#Cc1ccccc1)c1nc2cccc(F)c2c(=O)n1-c1cccnc1
InChIKey: HZXDUOBIELHOKT-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: PI3K isoforms were assayed under initial rate conditions in the presence of 25 mM Hepes (pH 7.4), and 2xKm ATP (100-300 uM), 10 uM PIP2, 5% glycerol, 5 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 1% (v/v) DMSO at the following concentrations for each isoform: PI3K alpha, beta, delta, and gamma at 50 picomolar (pM) and PI3Kgamma at 2 nanomolar (nM). After an assay reaction time of 30 minutes at 25° C., reactions were terminated with a final concentration of 10 mM EDTA, 10 nM labeled-PIP3, and 35 nM Europium labeled GRP-1 detector protein before reading TR-FRET on an Envision plate reader (Ex: 340 nm; Em: 615/665 nm; 100 us delay and 500 us read window).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 477.5, ALogP 3.86, HBA 8, HBD 2, PSA 111.61, QED 0.38
Compound (SMILES): Cc1c(Cc2ccccc2)nnc(N2CCN(c3cnc(C(=O)NCCN4CCCC4)cn3)[C@H](C)C2)c1C
InChIKey: UBNIZTBXTXRRTF-OAQYLSRUSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Displacement of radio-labeled smoothened agonist from human Smo by radio-ligand competition binding assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 514.68, ALogP 3.01, HBA 8, HBD 1, PSA 90.38, QED 0.49
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(F)c(C(F)(F)F)c4F)cs3)csc2n(C)c1=O
InChIKey: XOPMVFNBFICPDB-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 516.47, ALogP 3.9, HBA 8, HBD 1, PSA 85.99, QED 0.42
Compound (SMILES): O=C(c1ccccc1-n1nccn1)N1CCC[C@H]1Cc1cccc(-n2nccn2)c1
InChIKey: OFOKYTZDYMGETB-SFHVURJKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at human OX1R expressed in CHO cells preincubated for 120 mins followed by orexin-A addition by FLIPR assay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 399.46, ALogP 2.7, HBA 7, HBD 0, PSA 81.73, QED 0.52
Compound (SMILES): CC(C)C(O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)o2)cc1
InChIKey: RIHOLXRQBXNRMS-QRIPLOBPSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at human recombinant EP2 receptor expressed in HEK-EBNA cells incubated for 30 mins by cAMP accumulation assay
Measurement: EC50 = 1218 nM (pChEMBL 5.909999847412109)
Descriptors: MW 387.43, ALogP 3.38, HBA 5, HBD 2, PSA 100.21, QED 0.72
Compound (SMILES): CC(=O)N1CCN(C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC1
InChIKey: AENFRJUKGBLCPJ-QHCPKHFHSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at LXRalpha (unknown origin) expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 627.55, ALogP 4.77, HBA 4, HBD 0, PSA 78, QED 0.36
Compound (SMILES): CCCCOC(=O)c1cnc(N2CCN(c3nnc(-c4ccncc4)c(C)c3C)C[C@H]2C)cc1C(F)(F)F
InChIKey: RQVJRDTWXMZXIE-QGZVFWFLSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Displacement of radio-labeled smoothened agonist from human Smo by radio-ligand competition binding assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 528.58, ALogP 5.24, HBA 8, HBD 0, PSA 84.34, QED 0.3
Compound (SMILES): Cc1nccn1-c1ccc(-c2cn(CC(=O)Nc3cccc(Cl)c3Cl)nn2)cc1
InChIKey: XSIJYOFJNDFHGL-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Mus musculus
UniProt: Q7TQN9
Assay: Agonist activity at mouse GPR142 expressed in CHO cells measured after 30 to 60 mins by IP-One assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 427.3, ALogP 4.38, HBA 6, HBD 1, PSA 77.63, QED 0.51
Compound (SMILES): CC(C)[C@@H](Nc1nc(Cl)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(CO)C[C@H]12)C1CC1
InChIKey: PSZUVLHNNPZVCD-XRPRFISDSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]N6-phenylisopropyladenosine from recombinant human A1AR expressed in CHO cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 407.9, ALogP 1.6, HBA 8, HBD 4, PSA 116.32, QED 0.54
Compound (SMILES): CCOc1cc(N2CCN(CCS(C)(=O)=O)CC2)c(CC)cc1Nc1nccc(-c2c(-c3ccc(OCC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: QYCFAKRGUGSZPT-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 824.95, ALogP 7.26, HBA 12, HBD 2, PSA 143.29, QED 0.11
Compound (SMILES): COc1cc(OC)cc(N(CCNCC(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NEDQSDMNOSMYHF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 468.51, ALogP 4.04, HBA 8, HBD 1, PSA 77.33, QED 0.35
Compound (SMILES): Cc1cccc(-c2cc(Nc3nn(C)cc3C(F)(F)F)nc3[nH]cc(C#N)c23)n1
InChIKey: IHVBFXAXYRLAMA-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: LanthaScreen Kinase Activity Assay: In the assay, 1 nM LRRK2 WT or 250 pM LRRK2 G2019S kinase is incubated with the test compound (typically at 0 to 30 μM) for 30 minutes before the kinase reaction is initiated by addition of 1.3 mM ATP and 0.4 μM fluorescein-LRRKtide. The reaction mixture (20 μl total volume) is incubated for 2 hours at 30° C. before the reaction is terminated by addition of 10 mM EDTA and 1 nM terbium-labelled anti-phospho-LRRKtide antibody (final volume 20 μl). The mixture is further incubated for 30 minutes at RT. TR-FRET is measured by excitation of the terbium-donor with 340 nm light and subsequent (delay time 100 μs) measurement of terbium and fluorescein emission at 495 nm and 520 nm, respectively, over a time window of 1000 μs. The measurement is repeated 10 times for fluorescein and 10 times for terbium emission with a 2000 μs time window between repeats. TR-FRET measurements are performed on a Biomek Synergy plate. The TR-FRET signal is calculated as the emission-ratio at 520 nm over 495 nm.
Measurement: EC50 = 393 nM (pChEMBL 6.409999847412109)
Descriptors: MW 397.36, ALogP 4.3, HBA 6, HBD 2, PSA 95.21, QED 0.54
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccc(C(F)(F)F)cc4Cl)oc23)[C@@H]1CO
InChIKey: MRPGRAKIAJJGMM-OCCSQVGLSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin)
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 469.84, ALogP 4.32, HBA 6, HBD 3, PSA 94.14, QED 0.53
Compound (SMILES): O=C(c1cccc(Cl)c1Cl)N1CCc2c(nnn2-c2ncccn2)C1
InChIKey: WRWQBLDTEKJZRA-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Ca2+ flux assay: 1321N1 cells expressing the recombinant human or rat P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 375.22, ALogP 2.56, HBA 6, HBD 0, PSA 76.8, QED 0.69
Compound (SMILES): COc1cc(N2CCC(N3CCCCC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4ccc(F)cc4Cl)c3)nc3ccccn23)n1
InChIKey: BMTLGYPQYJNECV-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 731.28, ALogP 8.71, HBA 9, HBD 2, PSA 99.92, QED 0.15
Compound (SMILES): CCn1nc(-c2cccc(-c3ccc(CC(=O)NCCN4CCCCC4)cc3)c2)cc(NC(=O)Nc2c(Cl)cncc2Cl)c1=O
InChIKey: XQZLVDUQQNPSEH-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at adenosine A2b receptor (unknown origin)
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 648.59, ALogP 6.09, HBA 7, HBD 3, PSA 121.25, QED 0.19
Compound (SMILES): O=C(CCCNc1ccccn1)Nc1ccc(C[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)cc1
InChIKey: KNSPFVAZTITFFW-DQEYMECFSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of human integrin alphaVbeta3-mediated human SW480 cell adhesion to fibrinogen preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 579.68, ALogP 2.88, HBA 7, HBD 4, PSA 157.8, QED 0.23
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cnc(C(F)(F)F)cn3)CC2)C1
InChIKey: HFWDXHOUYDIMKS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CCOC(=O)N1CCN(CCCNC(=O)c2cc3nccc(Oc4ccc(NC(=O)Nc5cc(C)ccc5F)c(F)c4)c3s2)CC1
InChIKey: QEUXOHWRZLJLKW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: FLIPR (Fluorometric Imaging Plate Reader) Technology Assay: Automated FLIPR (Fluorometric Imaging Plate Reader) technology was used to screen for inhibitors of PDGF induced increases in intracellular calcium levels in fluorescent dye loaded endothelial cells. NHDF-Ad (Normal human dermal fibroblasts) (Lonza) were seeded in 384-well fibronectin coated black-walled plates overnight at 37° C./5% CO2. Cells were loaded with calcium indicator Fluo-4 for 45 minutes at 37° C. Cells were washed 4 times (ELx405-CW, Bio-Tek) to remove extracellular dye. Test compounds were reconstituted in 100% DMSO and added to the cells to give a final DMSO concentration of 0.1%. For screening, cells were pre-incubated with test agents for 30 minutes, at a single concentration (10 μM) or at concentrations ranging from 0.001 nM to 10 μM followed by PDGF stimulation (10 ng/mL). Changes in fluorescence at 515 nm were measured simultaneously in all 384 wells using a cooled CCD camera.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 652.72, ALogP 6.21, HBA 8, HBD 3, PSA 125.13, QED 0.17
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3cccc(C(F)(F)F)n3)CC2)C1
InChIKey: RHDKBFDYKYQBOL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 550.55, ALogP 3.86, HBA 8, HBD 2, PSA 131.65, QED 0.39
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4cc(F)c(OCC(F)(F)F)c(F)c4)cs3)cccc2n(C)c1=O
InChIKey: RLSJFZMRRVZYOG-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 540.47, ALogP 3.76, HBA 8, HBD 1, PSA 95.22, QED 0.38