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Purity: ≥98%
XMD17-109 (XMD-17-109), a pyrimido-diazepinone analog, is a novel, potent, specific, cell-permeable and ATP-competitive inhibitor of ERK-5 with important biological/anticancer activity. In HEK293 cells, it has an EC50 of 4.2 μM and inhibits ERK-5. In cellular assays, XMD17-109 is able to prevent ERK5 from becoming autophosphorylated. The pharmacokinetic characteristics of XMD17-109 when administered to mice orally and intravenously are as follows: the oral bioavailability is 90%, the oral clearance is 15745 h*ng/mL, the plasma clearance is 8.64 mL/min/Kg, and the T1/2 is 8.2 h.
| Targets |
ERK5 (IC50 = 162 nM); LRRK2[G2019S] (IC50 = 339 nM)
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| ln Vitro |
XMD17-109 (Compound 26) blocks pidermal growth factor-induced ERK5 autophosphorylation in cells with an EC50 of 0.09 ± 0.03 μM and inhibits ERK5 biochemically with an IC50 of 0.162 0.006 M. Additionally, XMD17-109 blocks LRRK2[G2019S] with an IC50 value of 339 nM[1]. By significantly dose-dependently reducing the mobility shifted phosphorylated ERK5 bands from sorbitol stimulated cells, XMD17-109 demonstrates low nanomolar cellular activity. At 30 M and an EC50 of 4.2 μM, XMD17-109 completely blocks ERK5-mediated AP1 transcriptional activity[2].
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| ln Vivo |
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| Enzyme Assay |
In kinase buffer (50 mM Tris-HCl, pH 7.5, 0.1 mM EGTA, 1 mM 2-mercaptoethanol) with 200 ng of pure active ERK5 and the specified amount of inhibitor, kinase activity was assessed in an assay volume of 40 μL. 10 mM magnesium acetate, 50 μM [γ-32P]-ATP (500 cpm/pmol), and 250 μM PIMtide (ARKKRRHPSGPPTA) were added as substrates to begin the reaction. Assays were conducted for 20 min at 30 °C, followed by the application of the reaction mixture onto p81 paper and the measurement of the incorporated radioactivity as previously described.
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| Cell Assay |
HeLa cells are maintained in 10% FBS, 2 mM l-glutamine, 50 U/mL penicillin G, and 50 μg/mL streptomycin-supplemented DMEM. Before use HeLa cells are serum starved for 16 h in DMEM supplemented with 2 mM l-glutamine, 50 U/mL penicillin G, and 50 μg/mL streptomycin. After that, HeLa cells are exposed to ERK5-IN-1 at the indicated concentrations for 1 hour before being stimulated with 0.5mol/L sorbitol for 30 minutes. Triton lysis buffer, which contains 20 μg of protein per well and contains 50 mM Tris-HCl, pH 7.5, 1 mM EGTA, 1 mM EDTA, 1 mM sodium orthovanadate, 50 mM sodium fluoride, and 1 mM sodium pyrophosphate, as well as 0.27 mol/L sucrose and 1 M microcystin-LR, is used to lyse cells. Standard procedures are used to run samples on 8% polyacrylamide gels. Proteins are transferred onto nitrocellulose membranes, and specific proteins are found using immunoblotting.
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| References |
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| Molecular Formula |
C36H46N8O3
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| Molecular Weight |
638.81
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| Exact Mass |
638.37
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| Elemental Analysis |
C, 67.69; H, 7.26; N, 17.54; O, 7.51
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| CAS # |
1435488-37-1
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| Appearance |
White to beige solid powder
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| SMILES |
CCOC1=C(C=CC(=C1)C(=O)N2CCC(CC2)N3CCN(CC3)C)NC4=NC=C5C(=N4)N(C6=CC=CC=C6C(=O)N5C)C7CCCC7
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| InChi Key |
XVBGRTMNFNMINE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C36H46N8O3/c1-4-47-32-23-25(34(45)43-17-15-26(16-18-43)42-21-19-40(2)20-22-42)13-14-29(32)38-36-37-24-31-33(39-36)44(27-9-5-6-10-27)30-12-8-7-11-28(30)35(46)41(31)3/h7-8,11-14,23-24,26-27H,4-6,9-10,15-22H2,1-3H3,(H,37,38,39)
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| Chemical Name |
11-cyclopentyl-2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5654 mL | 7.8271 mL | 15.6541 mL | |
| 5 mM | 0.3131 mL | 1.5654 mL | 3.1308 mL | |
| 10 mM | 0.1565 mL | 0.7827 mL | 1.5654 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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