| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
ERK5 (IC50 = 87 nM); LRRK2[G2019S] (IC50 = 26 nM)
XMD8-85 targets extracellular signal-regulated kinase 5 (ERK5/MAPK7), a member of the mitogen-activated protein kinase (MAPK) family involved in cellular proliferation, differentiation, and survival. It acts as a selective ERK5 inhibitor with an IC50 of 87 nM in enzyme assays. The compound also inhibits the leucine-rich repeat kinase 2 (LRRK2) mutant LRRK2G2019S with an IC50 of 26 nM, and has activity against tyrosine non-receptor kinase 2 (TNK2, IC50=959 nM). Additionally, XMD8-85 inhibits Brd4/BET family bromodomains. |
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| ln Vitro |
Compound 5, ERK5-IN-1, has an EC50 of 0.19±0.04 μM and prevents ERK5 autophosphorylation in cells stimulated by epidermal growth factor (EGF)[1].
In vitro, XMD8-85 potently inhibits ERK5 kinase activity with an IC50 of 87 nM in an enzyme assay. It inhibits EGF-induced ERK5 autophosphorylation in HeLa cells with an EC50 of 0.19 μM. XMD8-85 also inhibits the LRRK2G2019S mutant with an IC50 of 26 nM and TNK2 with an IC50 of 959 nM. The compound modulates ERK5-mediated signaling pathways involved in cell proliferation and survival. |
| ln Vivo |
In vivo activity data for XMD8-85 are limited in publicly available literature. The compound has been studied in cancer models to evaluate its antitumor efficacy. As an ERK5 inhibitor, XMD8-85 may modulate tumor growth and metastasis. Further in vivo studies are needed to fully characterize its pharmacological effects and therapeutic potential.
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| Enzyme Assay |
The in vitro kinase inhibition assay for XMD8-85 involves measuring its inhibitory effect on ERK5 kinase activity. Kinase activity is determined in an assay volume of 40 μL in kinase buffer (50 mM Tris-HCl, pH 7.5, 0.1 mM EGTA, 1 mM 2-mercaptoethanol) containing 200 ng of pure active ERK5 and the indicated amount of inhibitor. The reaction is started by adding 10 mM magnesium acetate, 50 μM [γ-32P]-ATP (500 cpm/pmol), and 250 μM PIMtide (ARKKRRHPSGPPTA) as substrates. Assays are carried out for 20 min at 30°C, terminated by applying the reaction mixture onto p81 paper, and the incorporated radioactivity is measured. The IC50 is calculated from dose-response curves.
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| Cell Assay |
In vitro cellular assays for XMD8-85 involve treating cancer cell lines (e.g., HeLa cells) with varying concentrations of the compound. ERK5 autophosphorylation is measured by Western blotting using phospho-specific antibodies. Cell proliferation is assessed using MTT or colony formation assays. Apoptosis is detected by flow cytometry using Annexin V/PI staining. The compound's effects on ERK5-mediated signaling pathways and cell viability are evaluated.
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| Animal Protocol |
In vivo animal experiments for XMD8-85 would typically use mouse xenograft models of human cancers. Tumor-bearing mice would be administered XMD8-85 via oral or intraperitoneal routes at various doses. Tumor volume would be measured regularly. ERK5 inhibition and downstream signaling would be assessed in tumor tissues. However, specific in vivo protocols for XMD8-85 are not extensively documented in public literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of XMD8-85 have not been extensively characterized in publicly available literature. The compound has a molecular weight of 459.54 (C25H29N7O2). As a small molecule kinase inhibitor, it is expected to have reasonable bioavailability and tissue distribution. Specific PK parameters including half-life, Cmax, and metabolic pathways are not well documented.
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| Toxicity/Toxicokinetics |
XMD8-85 has been used as a research tool in preclinical studies. As a kinase inhibitor, potential adverse effects may include off-target kinase inhibition. The compound's selectivity profile suggests a manageable safety profile. Complete toxicology studies including acute, repeated-dose, and genotoxicity assessments would be required for therapeutic development.
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| References | |
| Additional Infomation |
2-[2-methoxy-4-(4-methyl-1-piperazinyl)anilino]-5,11-dimethyl-6-pyrimidino[4,5-b][1,4]benzodiazepine is a member of the piperazine class of compounds.
XMD8-85 (CAS#: 1234479-76-5) is a selective and potent inhibitor of ERK5 (IC50=87 nM) also known as ERK5-IN-1. It also inhibits the LRRK2G2019S mutant (IC50=26 nM) and TNK2 (IC50=959 nM), and inhibits Brd4/BET bromodomains. XMD8-85 inhibits EGF-induced ERK5 autophosphorylation in HeLa cells (EC50=0.19 μM). The compound is not approved for clinical use and remains a research tool for studying ERK5 biology. |
| Molecular Formula |
C25H29N7O2
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|---|---|
| Molecular Weight |
459.55
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| Exact Mass |
459.238
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| Elemental Analysis |
C, 65.34; H, 6.36; N, 21.34; O, 6.96
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| CAS # |
1234479-76-5
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| Related CAS # |
1234479-76-5
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| PubChem CID |
46844147
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.962
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
34
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| Complexity |
703
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])[H])C1=C(C([H])=C([H])C(=C1[H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])N([H])C1=NC([H])=C2C(=N1)N(C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1C(N2C([H])([H])[H])=O
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| InChi Key |
DDTPGANIPBKTNU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H29N7O2/c1-29-11-13-32(14-12-29)17-9-10-19(22(15-17)34-4)27-25-26-16-21-23(28-25)30(2)20-8-6-5-7-18(20)24(33)31(21)3/h5-10,15-16H,11-14H2,1-4H3,(H,26,27,28)
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| Chemical Name |
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one
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| Synonyms |
ERK5 IN 1; ERK5-IN-1; ERK5IN1; XMD 8-85; XMD8-85; XMD-8-85; XMD 885; XMD-885; XMD885
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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 |
| 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) |
DMSO: ~92 mg/mL (~200.2 mM)
Ethanol: ~11 mg/mL (~23.9 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (5.98 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 27.5 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: ≥ 2.75 mg/mL (5.98 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 27.5 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: ≥ 2.75 mg/mL (5.98 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 | 2.1760 mL | 10.8802 mL | 21.7604 mL | |
| 5 mM | 0.4352 mL | 2.1760 mL | 4.3521 mL | |
| 10 mM | 0.2176 mL | 1.0880 mL | 2.1760 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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