| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| 500mg |
| Targets |
iMDK targets PI3K (phosphoinositide 3-kinase), a key enzyme in the PI3K/AKT/mTOR signaling pathway that regulates cell growth, proliferation, and survival. It also inhibits the growth factor MDK (midkine), a heparin-binding growth factor implicated in cancer, angiogenesis, and inflammatory diseases. By inhibiting both PI3K and MDK, iMDK disrupts multiple cancer-promoting pathways.
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| ln Vitro |
After treatment for 72 hours, iMDK (50–500 nM) reduced AKT phosphorylation in H441 lung glands in a dose-dependent manner. By contrast, p-ERK is added by iMDK Turkey[1]. [1]
In vitro, iMDK is a potent PI3K inhibitor that inhibits the growth factor MDK (midkine). It suppresses NSCLC cooperatively with a MEK inhibitor without harming normal cells. The compound's ability to target both PI3K and MDK makes it valuable for studying cancer biology and for developing combination therapies. However, specific IC50 values have not been detailed in the available literature. |
| ln Vivo |
Combined treatment with iMDK ((9 mg/kg/day; i.p. 100 ul) and PD0325901 (5 mg/kg; lung) substantially suppressed lung tumor growth in xenograft animals [1].
In vivo, iMDK suppresses NSCLC cooperatively with a MEK inhibitor without harming mice. This combination strategy may have therapeutic potential for KRAS-mutant NSCLC and squamous NSCLC. However, specific in vivo efficacy data and dosing details have not been extensively detailed in the available literature. Further preclinical studies would be required. |
| Enzyme Assay |
For in vitro kinase assays, recombinant PI3K isoforms are incubated with a lipid substrate and ATP in assay buffer. The test compound is added at various concentrations (0.1-1000 nM). Kinase activity is measured using radioactive or luminescent assays. IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: H441 (lung adenocarcinoma; KRASG12V), H2009 (non-small cell carcinoma; KRASG12A), A549 (lung cancer; KRASG12S), and H520 (lung squamous cell carcinoma; KRASWT) Tested Concentrations: iMDK (2.5 μM) and PD0325901 (0.5 μM) for H441 and H2009 cells iMDK (0.125 μM) and PD0325901 (0.25 μM) for H520 cells iMDK (0.25 μM) and PD0325901 (0.125 μM) for A549 cells Incubation Duration: 72 hrs (hours) Experimental Results: iMDK alone does not inhibit cells In terms of the viability of A549 cells, the combined treatment of iMDK and PD0325901 Dramatically inhibited the viability of A549 cells compared with single treatment of PD0325901. Western Blot Analysis[1] Cell Types: H441 Lung Adenocarcinoma Cell Tested Concentrations: 0-500 nM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of AKT phosphorylation in a dose-dependent manner. Increased ERK1/2 phosphorylation. For cell proliferation assays, NSCLC cell lines (including KRAS-mutant and squamous NSCLC) are seeded in 96-well plates and treated with iMDK at concentrations ranging from 0.01-10 µM, alone or in combination with MEK inhibitors. Cell viability is assessed using MTT or CellTiter-Glo assays. IC50 values are calculated from dose-response curves. |
| Animal Protocol |
Animal/Disease Models: Female Carrier H441 human lung cancer xenograft BALB/c nude mice (6 weeks old) [1]
Doses: iMDK (9 mg/kg) and PD0325901 (5 mg/kg) Route of Administration: daily intraperitoneal (ip) injection of 100 μL iMDK and/ Or take PD0325901 orally five times a week (days 1, 2, 3, 4, 5, 7, 8, 9, 10, 11) Experimental Results: After combined treatment with iMDK and PD0325901, the tumor volume derived from H441 lung adenocarcinoma cells was Dramatically diminished The reduction was compared with a single compound in a xenograft mouse model. For in vivo efficacy studies, immunodeficient mice would be implanted with NSCLC xenografts. When tumors reach a predetermined size, mice would be randomized and treated with iMDK alone or in combination with MEK inhibitors via appropriate routes at doses determined from pharmacokinetic studies. Tumor volumes would be measured twice weekly. |
| ADME/Pharmacokinetics |
iMDK is soluble in DMSO. Storage is recommended at -20°C for long-term stability. Further detailed PK parameters including half-life, oral bioavailability, and tissue distribution would be required for in vivo studies. The compound is for research use only and is not intended for human or veterinary use.
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| Toxicity/Toxicokinetics |
Toxicological data for iMDK have not been extensively reported. In studies, iMDK suppresses NSCLC without harming normal cells and mice. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed.
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| References | |
| Additional Infomation |
iMDK is a potent PI3K inhibitor that also inhibits the growth factor MDK (midkine). It suppresses NSCLC cooperatively with a MEK inhibitor without harming normal cells and mice. iMDK is a research tool for studying PI3K signaling and midkine biology in cancer and is not approved for clinical use.
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| Molecular Formula |
C21H13FN2O2S
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|---|---|
| Molecular Weight |
376.403527021408
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| Exact Mass |
376.068
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| CAS # |
881970-80-5
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| Related CAS # |
iMDK quarterhydrate
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| PubChem CID |
15991416
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.711
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| LogP |
6.14
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
607
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C=C(C(=O)O2)C3=CN4C=C(SC4=N3)CC5=CC=C(C=C5)F
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| InChi Key |
IWFKQTWYILKFGE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H13FN2O2S/c22-15-7-5-13(6-8-15)9-16-11-24-12-18(23-21(24)27-16)17-10-14-3-1-2-4-19(14)26-20(17)25/h1-8,10-12H,9H2
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| Chemical Name |
3-[2-[(4-fluorophenyl)methyl]imidazo[2,1-b][1,3]thiazol-6-yl]chromen-2-one
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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 (~8.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (13.28 mM) in 15% Cremophor EL 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6567 mL | 13.2837 mL | 26.5675 mL | |
| 5 mM | 0.5313 mL | 2.6567 mL | 5.3135 mL | |
| 10 mM | 0.2657 mL | 1.3284 mL | 2.6567 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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