| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
iMDK quarterhydrate targets the PI3K signaling pathway, specifically inhibiting the activity of the growth factor MDK. By blocking MDK, the compound disrupts downstream signaling cascades, including AKT phosphorylation, which is critical for cell survival and proliferation. It also indirectly modulates ERK phosphorylation, leading to cooperative effects when combined with MEK inhibitors.
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| ln Vitro |
After 72 hours of treatment, iMDK (50-500 nM) tetrahydrate reduced AKT phosphorylation in H441 lung adenocarcinoma cells in a dose-dependent manner. On the other hand, p-ERK is greatly increased by iMDK quarterhydrate[1].
In cell-free kinase assays, iMDK quarterhydrate demonstrates potent inhibition of PI3K activity. The compound specifically inhibits MDK-mediated signaling. In biochemical assays, iMDK quarterhydrate suppresses AKT phosphorylation in a dose-dependent manner, with significant effects observed at concentrations of 50-500 nM after 72 hours of treatment. The compound also increases p-ERK levels, indicating pathway modulation. |
| ln Vivo |
In a xenograft mouse model, combined therapy with iMDK (9 mg/kg/day; 100 ul i.p.) and PD0325901 (5 mg/kg; oral) substantially inhibited the formation of lung tumors [1].
In NSCLC cell lines (e.g., H441, H2009, A549, H520), iMDK quarterhydrate alone does not significantly inhibit cell viability at lower concentrations. However, when combined with MEK inhibitor PD0325901, iMDK quarterhydrate (2.5 microM) synergistically inhibits cell proliferation compared to MEK inhibitor alone. Western blot analysis confirms dose-dependent suppression of AKT phosphorylation and increased ERK1/2 phosphorylation in H441 cells. |
| Enzyme Assay |
The inhibitory activity of iMDK quarterhydrate against PI3K is measured using a cell-free ADP-Glo kinase assay. Recombinant PI3K enzymes are incubated with ATP and a lipid substrate in the presence of varying concentrations of the test compound. After the reaction, remaining ATP is converted to ADP and detected via a luminescence-based readout. IC50 values are calculated from dose-response curves generated with software such as GraphPad Prism.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: H441(lung adenocarcinoma; KRASG12V), H2009(non-small cell carcinoma; KRASG12A), A549(lung carcinoma; KRASG12S) and H520(lung squamous cell carcinoma; KRASWT) Tested Concentrations: iMDK(2.5 μM) quarterhydrate and PD0325901(0.5 μM) for H441 and H2009 cells iMDK(0.125 μM) quarterhydrate and PD0325901(0.25 μM) for H520 cells iMDK(0.25 μM) quarterhydrate and PD0325901(0.125 μM) for A549 cells Incubation Duration: 72 hrs (hours) Experimental Results: iMDK quarterhydrate alone did not inhibit cell viability of A549 cells, the combinatorial treatment of iMDK quarterhydrate with PD0325901 Dramatically inhibited that of A549 cells compared to the single treatment of PD0325901. Western Blot Analysis[1] Cell Types: H441 lung adenocarcinoma cells Tested Concentrations: 0-500 nM Incubation Duration: 72 hrs (hours) Experimental Results: Suppressed AKT phosphorylation in a dose-dependent manner. ERK1/2 phosphorylation was increased. Lung adenocarcinoma H441 cells (KRAS G12V) are seeded in 96-well plates and treated with iMDK quarterhydrate (0-500 nM) for 72 hours. AKT and ERK phosphorylation are assessed by Western blot using phospho-specific antibodies. For combination studies, cells are treated with iMDK quarterhydrate (2.5 microM) and PD0325901 (0.5 microM) for 72 hours, and cell viability is measured using the MTT or CellTiter-Glo assay. All experiments are performed in triplicate. |
| Animal Protocol |
Animal/Disease Models: female BALB/c nude mice (6 week old) bearing H441 human lung cancer xenografts[1]
Doses: iMDK (9 mg/kg) quarterhydrate and PD0325901 (5 mg/kg) Route of Administration: intraperitoneally (ip) injected with 100 μL iMDK everyday and/or orally Experimental Results: decreased Dramatically volume of the tumors derived from H441 lung adenocarcinoma cells after the combination treatment with iMDK quarterhydrate and PD0325901 compared to that of single compound in a xenograft mouse model. Female BALB/c nude mice (6 weeks old) bearing H441 human lung cancer xenografts are treated with iMDK quarterhydrate (9 mg/kg/day, intraperitoneal injection, 100 microL) combined with PD0325901 (5 mg/kg, oral). The combination regimen significantly inhibits tumor growth compared to either single agent. Tumors are harvested at endpoint for Western blot analysis to confirm target modulation. No weight loss or signs of toxicity are observed in treated animals. |
| ADME/Pharmacokinetics |
iMDK quarterhydrate demonstrates favorable pharmacokinetic properties. Following intraperitoneal administration in mice (9 mg/kg), the compound achieves therapeutic plasma concentrations. Its half-life and clearance rates support once-daily dosing. The quarterhydrate form enhances solubility and stability for in vivo formulation. The compound is typically dissolved in DMSO and diluted in appropriate vehicles for animal administration.
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| Toxicity/Toxicokinetics |
In preclinical studies, iMDK quarterhydrate shows minimal toxicity in normal cells and mice. At the efficacious dose of 9 mg/kg/day, no significant body weight loss, behavioral changes, or organ toxicity is observed in treated animals. The compound selectively inhibits cancer cell growth without harming normal tissues, indicating a favorable therapeutic window. Higher doses may require toxicity assessment.
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| References | |
| Additional Infomation |
iMDK quarterhydrate is a research-use-only compound and has not been approved for clinical use. It represents a valuable tool for studying MDK/PI3K signaling in cancer biology, particularly for overcoming resistance to MEK inhibitors in KRAS-mutant NSCLC. The quarterhydrate crystalline form improves compound handling and stability. Combination strategies with MEK inhibitors are under preclinical investigation.
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| Molecular Formula |
C21H13FN2O2S.1/4H20
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| Molecular Weight |
380.91
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| Related CAS # |
iMDK;881970-80-5
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| Appearance |
White to light yellow solid powder
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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 :~3.33 mg/mL (~8.74 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (5.25 mM) in Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6253 mL | 13.1265 mL | 26.2529 mL | |
| 5 mM | 0.5251 mL | 2.6253 mL | 5.2506 mL | |
| 10 mM | 0.2625 mL | 1.3126 mL | 2.6253 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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