lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N=C(N)NS(=O)(=O)c1ccc(C2C[C@H]2C(=O)Nc2ccc3cnccc3c2)cc1
InChIKey: ZTBJDQDNHPHYGS-QRWMCTBCSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: ROCK Kinase Inhibition Assays: All compounds were initially prepared as 10 mM stocks in anhydrous dimethylsulfoxide (DMSO). A 20 μl aliquot of the 10 mM solutions was transferred to individual wells in column 1 of a 96-well polypropylene microtiter plate (Corning #3363) and diluted with DMSO to give a final compound concentration of 4 mM. Test compounds were then serially diluted 1:5 in DMSO for an 11-point concentration response and further diluted in the assay buffer bringing all compound concentrations to a final range of 100 μM to 10 pM in 2.5% DMSO. The assay was performed in white 96-well, flat-bottom, half-area, non-binding assay plate (Corning #3642) in assay buffer consisting of 20 mM HEPES (pH 7.5), 10 mM MgCl2*6H2O, 100 μM sodium orthovanadate, 0.05% CHAPS and 0.1% bovine serum albumin. A 10 μL aliquot of compound from each well of the intermediate dilution plate and 20 μL of a 2× substrate/enzyme solution containing acceptor substrate (800 nM RSK2 peptide KRRRLSSLRA (SEQ ID NO: 1)), ROCK2 enzyme (10 nM), or ROCK1 enzyme, and 1,4-Dithiothreitol (DTT, 2 μM) were added to all wells. The reaction was initiated by the addition of 10 μL of 4× stock solution ATP (2 ∥M). Reactions were thoroughly mixed manually, covered and allowed to incubate at room temperature for 75 min. Protein kinase activity was quantitated using Promega's KINASE-GLO luminescent Kinase Assay Kit according to the manufacturer's directions. ATP concentrations remaining in Test wells following the termination of the enzymatic reaction were compared against control wells containing equivalent amounts of DMSO containing no inhibitor (CTRL). ATP concentrations in both Test wells and CTRL wells were normalized against background (BKG) ATP concentrations in wells containing concentrations of inhibitor that completely inhibited the protein kinase under investigation (i.e. a concentration that prevented any consumption of ATP over the course of the incubation). Percent of Control (POC) values were determined for each concentration of compound tested according to the equation: POC=((Test well value−BKG)/(CTRL−BKG))*100IC50 values were calculated using the following 4-parameter logistic curve-fitting algorithm: f(x)=(A+((B−A)/(1+((x/C){circumflex over ( )}D))))IC50 values were converted to Ki values using the Cheng-Prusoff Equation: Ki=IC50/(1+([ATP]/Km ATP])).
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 409.47, ALogP 2.15, HBA 5, HBD 4, PSA 138.03, QED 0.38
Compound (SMILES): N#CC[C@]1(n2cc(-c3ncnc4[nH]ccc34)cn2)C[C@H](N2CCC(Oc3cc(CN4CC(O)C4)cc(C(F)(F)F)n3)CC2)C1
InChIKey: LLZWKZMRVJFITC-CNZDGBQKSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: TAM Enzymatic Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl, or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu-W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 607.64, ALogP 3.73, HBA 10, HBD 2, PSA 132.01, QED 0.31
Compound (SMILES): Cc1cc(C(=O)Nc2ccc(Oc3ccnc4[nH]nc(N[C@H](C)CO)c34)c(F)c2)c(=O)n(-c2cccc(F)c2)c1
InChIKey: DRQYCGYQGUZWJX-MRXNPFEDSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Enzyme Assay: The affinity of compound binding to wild type and mutant human MET kinases is measured using Invitrogen's LanthaScreen Eu Kinase Binding technology. Briefly, GST-tagged recombinant human MET kinase domain from Signal Chem (see Table 8 below for concentration in assay) is incubated with 50 nM Alexa-Fluor® Tracer 236 (Invitrogen Cat No. PR9078A) and 2 nM Europium-anti-GST (Invitrogen Cat. No. A151 6) along with test compound in a buffer consisting of 25 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% Triton X-100, 1 mM DTT, and 2% DMSO. Compounds are typically prepared in a three-fold serial dilution in DMSO and added to the assay to give the appropriate final concentration. After a 60-minute incubation at 22° C., the reaction is measured using a PerkinElmer EnVision multimode plate reader via TR-FRET dual wavelength detection, and the percent of control (POC) calculated using a ratiometric emission factor. 100 POC is determined using no test compounds and 0 POC is determined using a concentration of control compound that completely inhibits the enzyme
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 546.53, ALogP 4.53, HBA 8, HBD 4, PSA 134.16, QED 0.22
Compound (SMILES): Cc1[nH]c(/C=C2/C(=O)Nc3ccc(S(=O)(=O)N(C)c4cccc(Cl)c4)cc32)c(C)c1C(=O)N1CCN(C)CC1
InChIKey: FPYJSJDOHRDAMT-XQNSMLJCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met in Melphalan Resistant human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay
Measurement: IC50 = 8913.5 nM (pChEMBL 5.050000190734863)
Descriptors: MW 568.1, ALogP 3.99, HBA 5, HBD 2, PSA 105.82, QED 0.45
Compound (SMILES): CN1CCc2c(c3ccccc3n2Cc2ccc(C(=O)NO)cc2)C1.O=C(O)C(F)(F)F
InChIKey: AVAOVICSJJIYRZ-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant human HDAC11 using fluorogenic RHKKAc peptide as substrate by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 335.41, ALogP 2.8, HBA 4, HBD 2, PSA 57.5, QED 0.57
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Inhibition of recombinant PDK1 (unknown origin) using peptide as substrate
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): N[C@H]1CC[C@H](S(=O)(=O)N2[C@@H]3CC[C@H]2C[C@@H](NC(=O)c2cc(C4CC4)on2)C3)CC1
InChIKey: JYZQPJRVTADXNE-BSBCAUIJSA-N
Target: Protein arginine N-methyltransferase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR22
Assay: Inhibition of PRMT8 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.55, ALogP 1.88, HBA 6, HBD 2, PSA 118.53, QED 0.75
Compound (SMILES): COc1cc2nc(C)nc(NC(C)c3ccc(-c4cnc5n4CCC5)s3)c2cc1OC
InChIKey: XRGDXPBYPNBGJI-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of SOS1 in human K562 cells assessed as reduction in pERK level incubated for 60 mins by HTRF analysis
Measurement: IC50 = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 435.55, ALogP 5, HBA 8, HBD 1, PSA 74.09, QED 0.46
Compound (SMILES): CCN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(/C=C/c4cnc5[nH]ccc5c4OC)c3)cc2C(F)(F)F)CC1
InChIKey: UMBFDGUGXMOMHX-BQYQJAHWSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of ABL (unknown origin) ACT labeling site by KiNativ Profiling analysis
Measurement: IC50 = 51.5 nM (pChEMBL 7.289999961853027)
Descriptors: MW 577.65, ALogP 6.46, HBA 5, HBD 2, PSA 73.49, QED 0.25
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of His-tagged recombinant TRKA (441 to 796 residues) (unknown origin) expressed in Insect cell
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(C)=O)C(C)C)C(=O)N[C@H](C=O)CC(=O)O.O=C(O)C(F)(F)F
InChIKey: DMUVMYXFMMONRW-NVOIZEPQSA-N
Target: Caspase-6 (SINGLE PROTEIN), Homo sapiens
UniProt: P55212
Assay: Affinity On-target Cellular interaction: (Fluorogenic cell-permeable peptidic substrate, staurosporine-treated SKNAS neuroblastoma cells) EUB0002178aAD CASP6
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 500.55, ALogP -0.81, HBA 7, HBD 6, PSA 208.07, QED 0.15
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type IV (SINGLE PROTEIN), Homo sapiens
UniProt: Q16566
Assay: Inhibition of CAMK4 (unknown origin) incubated for 120 mins in presence of 33P-ATP by radiometric kinase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): Cn1cc(-c2cnc3nnn(Cc4cc5cccnc5cc4F)c3n2)cn1
InChIKey: JLNMOXLBPUEIPE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human c-Met H1094R mutant expressed in mouse 3T3 cells assessed as reduction in cellular c-Met phosphorylation incubated for 1 hr followed by 20 mins stimulation with HGF by ELISA
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 360.36, ALogP 2.36, HBA 8, HBD 0, PSA 87.2, QED 0.49
Compound (SMILES): COc1cccc(OC)c1S(=O)(=O)Nc1noc2cc(Cn3cccn3)cc(OC)c12
InChIKey: VNSQFPFWUAZOTQ-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Kat6A Assay 2: A. Compound preparation    1. Prepare 10 mM stock solutions in 100% DMSO from solid material    2. Serial dilute 10 mM, 1 mM or 0.1 mM compound stocks 3-fold in 100% DMSO for 11-point dose responseB. Reagent preparation    1. Prepare 1× assay buffer containing 10 mM Tris HCL pH 8.0, 2.5 mM NaCl, 0.5 mM EDTA, 0.005% BSG and 0.02% Tween-20    2. Dilute Histone peptide (CPC Scientific) and AcCoA (Sigma) together in assay buffer to 2×.    3. Dilute KAT enzyme in assay buffer to 2×.C. Enzyme reaction    1. Final reaction conditions for each KAT assay in a 20 ul assay reaction volume:  KAT6A 15 nM, 10 uM AcCoA, 2 uM H3 1-21 peptide, 45-minute reaction   2. Add 0.5 ul of diluted compound to the assay plate (384-well V-bottom polypropylene plates) or 0.5 ul of DMSO for control wells.    3. Add 10 ul of 2× Histone peptide/2×AcCoA mix to the assay plate.    4. Add 10 ul of 2× enzyme to the assay plate.    5. Stop the reaction after the indicated time with the addition of 2 ul of 5% formic acid    6. Each reaction was analyzed using self-assembled monolayer desorption/ionization time-of-flight mass spectrometry (Mrksich, Milan (2008) Mass Spectrometry of Self-Assembled Monolayers: A New Tool for Molecular Surface Science ACS Nano 2008 2 (1), 7-18; SAMDI Tech, Inc. (Chicago, Ill.)).    7. Area under the curve (AUC) for both substrate and product peaks was determined for KAT5 at M.W. 2561 [Substrate+H]+ and 2603 [Product+H]+ with a +/−1 Da tolerance, respectively    8. Area under the curve (AUC) for both substrate and product peaks was determined for KAT6a, KAT6B, KAT7 and KAT8 at M.W. 2723 [Substrate+H]+ and 2765 [Product+H]+ with a +/−1 Da tolerance, respectively. 9. Percent conversion to product was calculated by: AUCProduct/(AUCsubstrate+AUCProduct).D. Data analysis    1. IC50 values were determined by fitting the % conversion at each inhibitor concentration to the 4-parameter IC50 equation using Pfizer proprietary curve fitting software.    2. Ki values were determined by fitting the % conversion at each inhibitor concentration to the Morrison equation for tightbinding competitive inhibitors using Pfizer proprietary curve fitting software.
Measurement: Ki = 0.75 nM (pChEMBL 9.119999885559082)
Descriptors: MW 444.47, ALogP 2.9, HBA 9, HBD 1, PSA 117.71, QED 0.44
Compound (SMILES): CCCCC(=O)N1CC2(C1)CN(c1ccccc1-c1nnn[nH]1)C2
InChIKey: RIEBAXQZOMUWKX-UHFFFAOYSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: IP-One assay (AGTR1), antagonist mode at up to 50 µM (  vs. 10 nM Val5-Angiotensin II)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 326.4, ALogP 1.71, HBA 5, HBD 1, PSA 78.01, QED 0.9
Compound (SMILES): Cc1cc(C(=O)N2CC[C@@H](C)[C@H](c3cc(C(F)F)nc4ncnn34)C2)cc(C)n1
InChIKey: OKZITNMVZCTKEZ-IAQYHMDHSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q01064
Assay: IC50 of hPDE1B1 in the PDE screen at 1.0 µM
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 400.43, ALogP 3.34, HBA 6, HBD 0, PSA 76.28, QED 0.67
Compound (SMILES): N#CC[C@]1(n2cc(-c3ncnc4[nH]ccc34)cn2)C[C@H](N2CCC(Oc3cc(CN4CC(O)C4)cc(C(F)(F)F)n3)CC2)C1
InChIKey: LLZWKZMRVJFITC-CNZDGBQKSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: The kinase reaction was conducted in clear-bottom 96-well plate from Thermo Fisher Scientific in a final volume of 24 μL. Inhibitors were first diluted serially in DMSO and added to the plate wells before the addition of other reaction components. The final concentration of DMSO in the assay was 0.5%. The PI3K assays were carried out at room temperature in 20 mM MOPS, pH 6.7, 10 mM MgCl2, 5 mM DTT and CHAPS 0.03%. The reaction mixture was prepared containing 50 μM PIP2, kinase and varying concentration of inhibitors. Reactions were initiated by the addition of ATP containing 2.2 μCi [γ-33P]ATP to a final concentration of 1000 μM. The final concentration of PI3K isoforms α, β, δ and γ in the assay were 1.3, 9.4, 2.9 and 10.8 nM respectively. Reactions were incubated for 180 min and terminated by the addition of 100 μL of 1 M potassium phosphate pH 8.0, 30 mM EDTA quench buffer. A 100 μL aliquot of the reaction solution was then transferred to 96-well Millipore MultiScreen IP 0.45 μm PVDF filter plate (The filter plate was prewetted with 200 μL 100% ethanol, distilled water, and 1 M potassium phosphate pH 8.0, respectively). The filter plate was aspirated on a Millipore Manifold under vacuum and washed with 18×200 μL wash buffer containing 1 M potassium phosphate pH 8.0 and 1 mM ATP. After drying by aspiration and blotting, the plate was air dried in an incubator at 37° C. overnight. Packard TopCount adapter (Millipore) was then attached to the plate followed with addition of 120 μL Microscint 20 scintillation cocktail (Perkin Elmer) in each well. After the plate sealing, the radioactivity of the product was determined by scintillation counting on Topcount (Perkin-Elmer).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 607.64, ALogP 3.73, HBA 10, HBD 2, PSA 132.01, QED 0.31
Compound (SMILES): Cc1cc(C(=O)Nc2ccc(Oc3ccnc4[nH]nc(N[C@H](C)CO)c34)c(F)c2)c(=O)n(-c2cccc(F)c2)c1
InChIKey: DRQYCGYQGUZWJX-MRXNPFEDSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Enzyme Assay: The affinity of compound binding to wild type and mutant human MET kinases is measured using Invitrogen's LanthaScreen Eu Kinase Binding technology. Briefly, GST-tagged recombinant human MET kinase domain from Signal Chem (see Table 8 below for concentration in assay) is incubated with 50 nM Alexa-Fluor® Tracer 236 (Invitrogen Cat No. PR9078A) and 2 nM Europium-anti-GST (Invitrogen Cat. No. A151 6) along with test compound in a buffer consisting of 25 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% Triton X-100, 1 mM DTT, and 2% DMSO. Compounds are typically prepared in a three-fold serial dilution in DMSO and added to the assay to give the appropriate final concentration. After a 60-minute incubation at 22° C., the reaction is measured using a PerkinElmer EnVision multimode plate reader via TR-FRET dual wavelength detection, and the percent of control (POC) calculated using a ratiometric emission factor. 100 POC is determined using no test compounds and 0 POC is determined using a concentration of control compound that completely inhibits the enzyme
Measurement: IC50 = 10.2 nM (pChEMBL 7.989999771118164)
Descriptors: MW 546.53, ALogP 4.53, HBA 8, HBD 4, PSA 134.16, QED 0.22
Compound (SMILES): Cc1[nH]c(/C=C2/C(=O)Nc3ccc(S(=O)(=O)N(C)c4cccc(Cl)c4)cc32)c(C)c1C(=O)N1CCN(C)CC1
InChIKey: FPYJSJDOHRDAMT-XQNSMLJCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met in human ANBL-6 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 568.1, ALogP 3.99, HBA 5, HBD 2, PSA 105.82, QED 0.45
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of recombinant c-Raf (unknown origin) using protein as substrate
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): N[C@H]1CC[C@H](S(=O)(=O)N2[C@@H]3CC[C@H]2C[C@@H](NC(=O)c2cc(C4CC4)on2)C3)CC1
InChIKey: JYZQPJRVTADXNE-BSBCAUIJSA-N
Target: Histone-lysine N-methyltransferase SETD2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BYW2
Assay: Inhibition of SETD2 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.55, ALogP 1.88, HBA 6, HBD 2, PSA 118.53, QED 0.75
Compound (SMILES): COc1cc2nc(C)nc(NC(C)c3ccc(-c4cnc5n4CCC5)s3)c2cc1OC
InChIKey: XRGDXPBYPNBGJI-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of SOS1 in human Calu-1 cells assessed as reduction in pERK level incubated for 24 hrs by HTRF analysis
Measurement: IC50 = 4460 nM (pChEMBL 5.349999904632568)
Descriptors: MW 435.55, ALogP 5, HBA 8, HBD 1, PSA 74.09, QED 0.46
Compound (SMILES): CCN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(/C=C/c4cnc5[nH]ccc5c4OC)c3)cc2C(F)(F)F)CC1
InChIKey: UMBFDGUGXMOMHX-BQYQJAHWSA-N
Target: Tyrosine-protein kinase ABL2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42684
Assay: Inhibition of ARG (unknown origin) ACT labeling site by KiNativ Profiling analysis
Measurement: IC50 = 51.5 nM (pChEMBL 7.289999961853027)
Descriptors: MW 577.65, ALogP 6.46, HBA 5, HBD 2, PSA 73.49, QED 0.25
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of His-tagged recombinant TRKC (510 to 825 residues) (unknown origin) expressed in baculovirus expression system
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): Cn1cc(-c2cnc3nnn(Cc4cc5cccnc5cc4F)c3n2)cn1
InChIKey: JLNMOXLBPUEIPE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human c-Met Y1230C mutant expressed in mouse 3T3 cells assessed as reduction in cellular c-Met phosphorylation incubated for 1 hr followed by 20 mins stimulation with HGF by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 360.36, ALogP 2.36, HBA 8, HBD 0, PSA 87.2, QED 0.49
Compound (SMILES): COc1cccc(OC)c1S(=O)(=O)Nc1noc2cc(Cn3cccn3)cc(OC)c12
InChIKey: VNSQFPFWUAZOTQ-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WYB5
Assay: Kat6B Assay 1: A. Compound preparation    1. Prepare 10 mM stock solutions in 100% DMSO from solid material    2. Serial dilute 10 mM, 1 mM or 0.1 mM compound stocks 3-fold in 100% DMSO for 11-point dose responseB. Reagent preparation    1. Prepare 1× assay buffer containing 10 mM Tris HCL pH 8.0, 2.5 mM NaCl, 0.5 mM EDTA, 0.005% BSG and 0.02% Tween-20    2. Dilute Histone peptide (CPC Scientific) and AcCoA (Sigma) together in assay buffer to 2×.    3. Dilute KAT enzyme in assay buffer to 2×.C. Enzyme reaction    1. Final reaction conditions for each KAT assay in a 20 ul assay reaction volume:  KAT6B 25 nM, 1 uM AcCoA, 2 uM H3 1-21 peptide, 60-minute reaction     2. Add 0.5 ul of diluted compound to the assay plate (384-well V-bottom polypropylene plates) or 0.5 ul of DMSO for control wells.    3. Add 10 ul of 2× Histone peptide/2×AcCoA mix to the assay plate.    4. Add 10 ul of 2× enzyme to the assay plate.    5. Stop the reaction after the indicated time with the addition of 2 ul of 5% formic acid    6. Each reaction was analyzed using self-assembled monolayer desorption/ionization time-of-flight mass spectrometry (Mrksich, Milan (2008) Mass Spectrometry of Self-Assembled Monolayers: A New Tool for Molecular Surface Science ACS Nano 2008 2 (1), 7-18; SAMDI Tech, Inc. (Chicago, Ill.)).    7. Area under the curve (AUC) for both substrate and product peaks was determined for KAT5 at M.W. 2561 [Substrate+H]+ and 2603 [Product+H]+ with a +/−1 Da tolerance, respectively    8. Area under the curve (AUC) for both substrate and product peaks was determined for KAT6a, KAT6B, KAT7 and KAT8 at M.W. 2723 [Substrate+H]+ and 2765 [Product+H]+ with a +/−1 Da tolerance, respectively. 9. Percent conversion to product was calculated by: AUCProduct/(AUCsubstrate+AUCProduct).D. Data analysis    1. IC50 values were determined by fitting the % conversion at each inhibitor concentration to the 4-parameter IC50 equation using Pfizer proprietary curve fitting software.    2. Ki values were determined by fitting the % conversion at each inhibitor concentration to the Morrison equation for tightbinding competitive inhibitors using Pfizer proprietary curve fitting software.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 444.47, ALogP 2.9, HBA 9, HBD 1, PSA 117.71, QED 0.44
Compound (SMILES): CCCCC(=O)N1CC2(C1)CN(c1ccccc1-c1nnn[nH]1)C2
InChIKey: RIEBAXQZOMUWKX-UHFFFAOYSA-N
Target: Leukotriene B4 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPC1
Assay: Inhibition of human LTB4R2 in CHO-K1 cells overexpressing LTB4R2 and GNA using cAMP assay  ( cAMP HIRANGE kit (62AM6PEx Cisbio Bioassays, Codolet, France))
Measurement: EC50 = 0.51 nM (pChEMBL 9.289999961853027)
Descriptors: MW 326.4, ALogP 1.71, HBA 5, HBD 1, PSA 78.01, QED 0.9
Compound (SMILES): Cc1cc(C(=O)N2CC[C@@H](C)[C@H](c3cc(C(F)F)nc4ncnn34)C2)cc(C)n1
InChIKey: OKZITNMVZCTKEZ-IAQYHMDHSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: IC50 of hPDE4D3 in the PDE screen at 1.0 µM
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 400.43, ALogP 3.34, HBA 6, HBD 0, PSA 76.28, QED 0.67
Compound (SMILES): N=C(N)NS(=O)(=O)c1ccc(C2C[C@H]2C(=O)Nc2ccc3cnccc3c2)cc1
InChIKey: ZTBJDQDNHPHYGS-QRWMCTBCSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: JAK Kinase Assays: Compounds were prepared in the exact same manner as described in the ROCK Kinase Assay with the exception to the substrate and enzyme. The JAK 2× substrate/enzyme solution consisted of acceptor substrate (800 nM Abl peptide EAIYAAPFAKKK (SEQ ID NO: 2)), JAK2 or JAK3 enzyme (10 nM) and DTT (2 μM). All other steps and solutions remain identical to the ROCK Kinase Assay above.
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 409.47, ALogP 2.15, HBA 5, HBD 4, PSA 138.03, QED 0.38
Compound (SMILES): N#CC[C@]1(n2cc(-c3ncnc4[nH]ccc34)cn2)C[C@H](N2CCC(Oc3cc(CN4CC(O)C4)cc(C(F)(F)F)n3)CC2)C1
InChIKey: LLZWKZMRVJFITC-CNZDGBQKSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) 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 μL 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 hour 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 PHERA star plate reader (BMG, Cary, N.C.). The data for the JAK1 and/or JAK2 inhibitors were obtained by testing the compounds in the Example A assay at 1 mM ATP.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 607.64, ALogP 3.73, HBA 10, HBD 2, PSA 132.01, QED 0.31
Compound (SMILES): Cc1cc(C(=O)Nc2ccc(Oc3ccnc4[nH]nc(N[C@H](C)CO)c34)c(F)c2)c(=O)n(-c2cccc(F)c2)c1
InChIKey: DRQYCGYQGUZWJX-MRXNPFEDSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Enzyme Assay: The affinity of compound binding to wild type and mutant human MET kinases is measured using Invitrogen's LanthaScreen Eu Kinase Binding technology. Briefly, GST-tagged recombinant human MET kinase domain from Signal Chem (see Table 8 below for concentration in assay) is incubated with 50 nM Alexa-Fluor® Tracer 236 (Invitrogen Cat No. PR9078A) and 2 nM Europium-anti-GST (Invitrogen Cat. No. A151 6) along with test compound in a buffer consisting of 25 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% Triton X-100, 1 mM DTT, and 2% DMSO. Compounds are typically prepared in a three-fold serial dilution in DMSO and added to the assay to give the appropriate final concentration. After a 60-minute incubation at 22° C., the reaction is measured using a PerkinElmer EnVision multimode plate reader via TR-FRET dual wavelength detection, and the percent of control (POC) calculated using a ratiometric emission factor. 100 POC is determined using no test compounds and 0 POC is determined using a concentration of control compound that completely inhibits the enzyme
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 546.53, ALogP 4.53, HBA 8, HBD 4, PSA 134.16, QED 0.22
Compound (SMILES): Cc1[nH]c(/C=C2/C(=O)Nc3ccc(S(=O)(=O)N(C)c4cccc(Cl)c4)cc32)c(C)c1C(=O)N1CCN(C)CC1
InChIKey: FPYJSJDOHRDAMT-XQNSMLJCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met in human bortezomib-resistant ANBL6 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay
Measurement: IC50 = 4678.4 nM (pChEMBL 5.329999923706055)
Descriptors: MW 568.1, ALogP 3.99, HBA 5, HBD 2, PSA 105.82, QED 0.45
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of recombinant Src (unknown origin) using peptide as substrate
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): N[C@H]1CC[C@H](S(=O)(=O)N2[C@@H]3CC[C@H]2C[C@@H](NC(=O)c2cc(C4CC4)on2)C3)CC1
InChIKey: JYZQPJRVTADXNE-BSBCAUIJSA-N
Target: Histone-lysine N-methyltransferase SETD7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WTS6
Assay: Inhibition of SETD7 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.55, ALogP 1.88, HBA 6, HBD 2, PSA 118.53, QED 0.75
Compound (SMILES): COc1cc2nc(C)nc(NC(C)c3ccc(-c4cnc5n4CCC5)s3)c2cc1OC
InChIKey: XRGDXPBYPNBGJI-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of SOS1 in human MOLM-13 cells assessed as reduction in pERK level incubated for 60 mins by HTRF analysis
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 435.55, ALogP 5, HBA 8, HBD 1, PSA 74.09, QED 0.46
Compound (SMILES): CCN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(/C=C/c4cnc5[nH]ccc5c4OC)c3)cc2C(F)(F)F)CC1
InChIKey: UMBFDGUGXMOMHX-BQYQJAHWSA-N
Target: Tyrosine-protein kinase CSK (SINGLE PROTEIN), Homo sapiens
UniProt: P41240
Assay: Inhibition of CSK (unknown origin) ACT labeling site by KiNativ Profiling analysis
Measurement: IC50 = 80.9 nM (pChEMBL 7.090000152587891)
Descriptors: MW 577.65, ALogP 6.46, HBA 5, HBD 2, PSA 73.49, QED 0.25
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: Tyrosine-protein kinase FRK (SINGLE PROTEIN), Homo sapiens
UniProt: P42685
Assay: Inhibition of GST-tagged recombinant full length FRK (unknown origin) expressed in baculovirus expression system
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): Cn1cc(-c2cnc3nnn(Cc4cc5cccnc5cc4F)c3n2)cn1
InChIKey: JLNMOXLBPUEIPE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human c-Met M1250T mutant expressed in mouse 3T3 cells assessed as reduction in cellular c-Met phosphorylation incubated for 1 hr followed by 20 mins stimulation with HGF by ELISA
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 360.36, ALogP 2.36, HBA 8, HBD 0, PSA 87.2, QED 0.49
Compound (SMILES): COc1cccc(OC)c1S(=O)(=O)Nc1noc2cc(Cn3cccn3)cc(OC)c12
InChIKey: VNSQFPFWUAZOTQ-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WYB5
Assay: Kat6B Assay 2: A. Compound preparation    1. Prepare 10 mM stock solutions in 100% DMSO from solid material    2. Serial dilute 10 mM, 1 mM or 0.1 mM compound stocks 3-fold in 100% DMSO for 11-point dose responseB. Reagent preparation    1. Prepare 1× assay buffer containing 10 mM Tris HCL pH 8.0, 2.5 mM NaCl, 0.5 mM EDTA, 0.005% BSG and 0.02% Tween-20    2. Dilute Histone peptide (CPC Scientific) and AcCoA (Sigma) together in assay buffer to 2×.    3. Dilute KAT enzyme in assay buffer to 2×.C. Enzyme reaction    1. Final reaction conditions for each KAT assay in a 20 ul assay reaction volume:  KAT6B 25 nM, 25 uM AcCoA, 2 uM H3 1-21 peptide, 60-minute reaction     2. Add 0.5 ul of diluted compound to the assay plate (384-well V-bottom polypropylene plates) or 0.5 ul of DMSO for control wells.    3. Add 10 ul of 2× Histone peptide/2×AcCoA mix to the assay plate.    4. Add 10 ul of 2× enzyme to the assay plate.    5. Stop the reaction after the indicated time with the addition of 2 ul of 5% formic acid    6. Each reaction was analyzed using self-assembled monolayer desorption/ionization time-of-flight mass spectrometry (Mrksich, Milan (2008) Mass Spectrometry of Self-Assembled Monolayers: A New Tool for Molecular Surface Science ACS Nano 2008 2 (1), 7-18; SAMDI Tech, Inc. (Chicago, Ill.)).    7. Area under the curve (AUC) for both substrate and product peaks was determined for KAT5 at M.W. 2561 [Substrate+H]+ and 2603 [Product+H]+ with a +/−1 Da tolerance, respectively    8. Area under the curve (AUC) for both substrate and product peaks was determined for KAT6a, KAT6B, KAT7 and KAT8 at M.W. 2723 [Substrate+H]+ and 2765 [Product+H]+ with a +/−1 Da tolerance, respectively. 9. Percent conversion to product was calculated by: AUCProduct/(AUCsubstrate+AUCProduct).D. Data analysis    1. IC50 values were determined by fitting the % conversion at each inhibitor concentration to the 4-parameter IC50 equation using Pfizer proprietary curve fitting software.    2. Ki values were determined by fitting the % conversion at each inhibitor concentration to the Morrison equation for tightbinding competitive inhibitors using Pfizer proprietary curve fitting software.
Measurement: Ki = 1.38 nM (pChEMBL 8.859999656677246)
Descriptors: MW 444.47, ALogP 2.9, HBA 9, HBD 1, PSA 117.71, QED 0.44
Compound (SMILES): Cc1cc(C(=O)N2CC[C@@H](C)[C@H](c3cc(C(F)F)nc4ncnn34)C2)cc(C)n1
InChIKey: OKZITNMVZCTKEZ-IAQYHMDHSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: IC50 of hPDE5A3 in the PDE screen at 1.0 µM
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 400.43, ALogP 3.34, HBA 6, HBD 0, PSA 76.28, QED 0.67
Compound (SMILES): Cc1[nH]c(/C=C2/C(=O)Nc3ccc(S(=O)(=O)N(C)c4cccc(Cl)c4)cc32)c(C)c1C(=O)N1CCN(C)CC1
InChIKey: FPYJSJDOHRDAMT-XQNSMLJCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met in human U-266 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 568.1, ALogP 3.99, HBA 5, HBD 2, PSA 105.82, QED 0.45
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: Mitogen-activated protein kinase kinase kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P41279
Assay: Inhibition of recombinant Tpl-2 (unknown origin) using peptide as substrate
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): N[C@H]1CC[C@H](S(=O)(=O)N2[C@@H]3CC[C@H]2C[C@@H](NC(=O)c2cc(C4CC4)on2)C3)CC1
InChIKey: JYZQPJRVTADXNE-BSBCAUIJSA-N
Target: Histone-lysine N-methyltransferase SUV39H1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43463
Assay: Inhibition of SUV39H1 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.55, ALogP 1.88, HBA 6, HBD 2, PSA 118.53, QED 0.75
Compound (SMILES): CCN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(/C=C/c4cnc5[nH]ccc5c4OC)c3)cc2C(F)(F)F)CC1
InChIKey: UMBFDGUGXMOMHX-BQYQJAHWSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of EphA2 (unknown origin) ACT labeling site by KiNativ Profiling analysis
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 577.65, ALogP 6.46, HBA 5, HBD 2, PSA 73.49, QED 0.25
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of GST-tagged recombinant EGFR L858R/T790M mutant (668 to 1210 residues) (unknown origin) expressed in Insect cell
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): Cn1cc(-c2cnc3nnn(Cc4cc5cccnc5cc4F)c3n2)cn1
InChIKey: JLNMOXLBPUEIPE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of wild type human c-Met expressed in human T47D cells assessed as reduction in cellular c-Met phosphorylation incubated for 1 hr followed by 20 mins stimulation with HGF by ELISA
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 360.36, ALogP 2.36, HBA 8, HBD 0, PSA 87.2, QED 0.49
Compound (SMILES): COc1cccc(OC)c1S(=O)(=O)Nc1noc2cc(Cn3cccn3)cc(OC)c12
InChIKey: VNSQFPFWUAZOTQ-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Kat6A Assay 1: A. Compound preparation    1. Prepare 10 mM stock solutions in 100% DMSO from solid material    2. Serial dilute 10 mM, 1 mM or 0.1 mM compound stocks 3-fold in 100% DMSO for 11-point dose responseB. Reagent preparation    1. Prepare 1× assay buffer containing 10 mM Tris HCL pH 8.0, 2.5 mM NaCl, 0.5 mM EDTA, 0.005% BSG and 0.02% Tween-20    2. Dilute Histone peptide (CPC Scientific) and AcCoA (Sigma) together in assay buffer to 2×.    3. Dilute KAT enzyme in assay buffer to 2×.C. Enzyme reaction    1. Final reaction conditions for each KAT assay in a 20 ul assay reaction volume:  ii. KAT6A 15 nM, 1 uM AcCoA, 2 uM H3 1-21 peptide, 45-minute reaction 2. Add 0.5 ul of diluted compound to the assay plate (384-well V-bottom polypropylene plates) or 0.5 ul of DMSO for control wells.    3. Add 10 ul of 2× Histone peptide/2×AcCoA mix to the assay plate.    4. Add 10 ul of 2× enzyme to the assay plate.    5. Stop the reaction after the indicated time with the addition of 2 ul of 5% formic acid    6. Each reaction was analyzed using self-assembled monolayer desorption/ionization time-of-flight mass spectrometry (Mrksich, Milan (2008) Mass Spectrometry of Self-Assembled Monolayers: A New Tool for Molecular Surface Science ACS Nano 2008 2 (1), 7-18; SAMDI Tech, Inc. (Chicago, Ill.)).    7. Area under the curve (AUC) for both substrate and product peaks was determined for KAT5 at M.W. 2561 [Substrate+H]+ and 2603 [Product+H]+ with a +/−1 Da tolerance, respectively    8. Area under the curve (AUC) for both substrate and product peaks was determined for KAT6a, KAT6B, KAT7 and KAT8 at M.W. 2723 [Substrate+H]+ and 2765 [Product+H]+ with a +/−1 Da tolerance, respectively. 9. Percent conversion to product was calculated by: AUCProduct/(AUCsubstrate+AUCProduct).D. Data analysis    1. IC50 values were determined by fitting the % conversion at each inhibitor concentration to the 4-parameter IC50 equation using Pfizer proprietary curve fitting software.    2. Ki values were determined by fitting the % conversion at each inhibitor concentration to the Morrison equation for tightbinding competitive inhibitors using Pfizer proprietary curve fitting software.
Measurement: Ki = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 444.47, ALogP 2.9, HBA 9, HBD 1, PSA 117.71, QED 0.44
Compound (SMILES): Cc1cc(C(=O)N2CC[C@@H](C)[C@H](c3cc(C(F)F)nc4ncnn34)C2)cc(C)n1
InChIKey: OKZITNMVZCTKEZ-IAQYHMDHSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: IC50 of hPDE7A1 in the PDE screen at 1.0 µM
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 400.43, ALogP 3.34, HBA 6, HBD 0, PSA 76.28, QED 0.67
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 autophosphorylation in human BT-474 cells measured after 3 hrs by Western blot analysis
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): N[C@H]1CC[C@H](S(=O)(=O)N2[C@@H]3CC[C@H]2C[C@@H](NC(=O)c2cc(C4CC4)on2)C3)CC1
InChIKey: JYZQPJRVTADXNE-BSBCAUIJSA-N
Target: Histone-lysine N-methyltransferase NSD2 (SINGLE PROTEIN), Homo sapiens
UniProt: O96028
Assay: Inhibition of WHSC1 (unknown origin) methyltransferase activity measured
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.55, ALogP 1.88, HBA 6, HBD 2, PSA 118.53, QED 0.75
Compound (SMILES): CCN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(/C=C/c4cnc5[nH]ccc5c4OC)c3)cc2C(F)(F)F)CC1
InChIKey: UMBFDGUGXMOMHX-BQYQJAHWSA-N
Target: Ephrin type-B receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29323
Assay: Inhibition of EphB2 (unknown origin) ACT labeling site by KiNativ Profiling analysis
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 577.65, ALogP 6.46, HBA 5, HBD 2, PSA 73.49, QED 0.25
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of GST-tagged recombinant EGFR T790M mutant (668 to 1210 residues) (unknown origin) expressed in Insect cell
Measurement: IC50 = 319 nM (pChEMBL 6.5)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): Cn1cc(-c2cnc3nnn(Cc4cc5cccnc5cc4F)c3n2)cn1
InChIKey: JLNMOXLBPUEIPE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human c-Met Y1235D mutant expressed in human T47D cells assessed as reduction in cellular c-Met phosphorylation incubated for 1 hr followed by 20 mins stimulation with HGF by ELISA
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 360.36, ALogP 2.36, HBA 8, HBD 0, PSA 87.2, QED 0.49
Compound (SMILES): COc1cccc(OC)c1S(=O)(=O)Nc1noc2cc(Cn3cccn3)cc(OC)c12
InChIKey: VNSQFPFWUAZOTQ-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Kat6A Assay 2: A. Compound preparation    1. Prepare 10 mM stock solutions in 100% DMSO from solid material    2. Serial dilute 10 mM, 1 mM or 0.1 mM compound stocks 3-fold in 100% DMSO for 11-point dose responseB. Reagent preparation    1. Prepare 1× assay buffer containing 10 mM Tris HCL pH 8.0, 2.5 mM NaCl, 0.5 mM EDTA, 0.005% BSG and 0.02% Tween-20    2. Dilute Histone peptide (CPC Scientific) and AcCoA (Sigma) together in assay buffer to 2×.    3. Dilute KAT enzyme in assay buffer to 2×.C. Enzyme reaction    1. Final reaction conditions for each KAT assay in a 20 ul assay reaction volume:  KAT6A 15 nM, 10 uM AcCoA, 2 uM H3 1-21 peptide, 45-minute reaction   2. Add 0.5 ul of diluted compound to the assay plate (384-well V-bottom polypropylene plates) or 0.5 ul of DMSO for control wells.    3. Add 10 ul of 2× Histone peptide/2×AcCoA mix to the assay plate.    4. Add 10 ul of 2× enzyme to the assay plate.    5. Stop the reaction after the indicated time with the addition of 2 ul of 5% formic acid    6. Each reaction was analyzed using self-assembled monolayer desorption/ionization time-of-flight mass spectrometry (Mrksich, Milan (2008) Mass Spectrometry of Self-Assembled Monolayers: A New Tool for Molecular Surface Science ACS Nano 2008 2 (1), 7-18; SAMDI Tech, Inc. (Chicago, Ill.)).    7. Area under the curve (AUC) for both substrate and product peaks was determined for KAT5 at M.W. 2561 [Substrate+H]+ and 2603 [Product+H]+ with a +/−1 Da tolerance, respectively    8. Area under the curve (AUC) for both substrate and product peaks was determined for KAT6a, KAT6B, KAT7 and KAT8 at M.W. 2723 [Substrate+H]+ and 2765 [Product+H]+ with a +/−1 Da tolerance, respectively. 9. Percent conversion to product was calculated by: AUCProduct/(AUCsubstrate+AUCProduct).D. Data analysis    1. IC50 values were determined by fitting the % conversion at each inhibitor concentration to the 4-parameter IC50 equation using Pfizer proprietary curve fitting software.    2. Ki values were determined by fitting the % conversion at each inhibitor concentration to the Morrison equation for tightbinding competitive inhibitors using Pfizer proprietary curve fitting software.
Measurement: Ki = 0.66 nM (pChEMBL 9.180000305175781)
Descriptors: MW 444.47, ALogP 2.9, HBA 9, HBD 1, PSA 117.71, QED 0.44
Compound (SMILES): Cc1cc(C(=O)N2CC[C@@H](C)[C@H](c3cc(C(F)F)nc4ncnn34)C2)cc(C)n1
InChIKey: OKZITNMVZCTKEZ-IAQYHMDHSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: IC50 of hPDE8A1 in the PDE screen at 1.0 µM
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 400.43, ALogP 3.34, HBA 6, HBD 0, PSA 76.28, QED 0.67
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGF-induced EGFR phosphorylation in human A-431 cells incubated for 3 hrs by Western blot analysis
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): N[C@H]1CC[C@H](S(=O)(=O)N2[C@@H]3CC[C@H]2C[C@@H](NC(=O)c2cc(C4CC4)on2)C3)CC1
InChIKey: JYZQPJRVTADXNE-BSBCAUIJSA-N
Target: Histone-lysine N-methyltransferase SMYD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H7B4
Assay: Inhibition of SMYD3 in human HEK293T cells co-transfected with MAP3K assessed as inhibition of Lys260 methylation of MAP3K2 by Western blot analysis
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 422.55, ALogP 1.88, HBA 6, HBD 2, PSA 118.53, QED 0.75
Compound (SMILES): CCN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(/C=C/c4cnc5[nH]ccc5c4OC)c3)cc2C(F)(F)F)CC1
InChIKey: UMBFDGUGXMOMHX-BQYQJAHWSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
Assay: Inhibition of EphB4 (unknown origin) ACT labeling site by KiNativ Profiling analysis
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 577.65, ALogP 6.46, HBA 5, HBD 2, PSA 73.49, QED 0.25
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged recombinant JAK2 (809 to 1153 residues) (unknown origin) expressed in Insect cell
Measurement: IC50 = 529 nM (pChEMBL 6.28000020980835)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72