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Purity: ≥98%
MK-4101 is a novel, potent and selective SMO inhibitor/antagonist of the Hedgehog (Hh) signaling pathway. MK-401 has the potential for the treatment of medulloblastoma and BCC (Basal Cell Carcinoma) as it is highly active against these cells. MK-4101 inhibits Hh signaling both in a reporter gene assay in an engineered mouse cell line (Gli Luc) with IC50 of 1.5 µM and in human KYSE180 oesophageal cancer cells with an IC50 of 1 µM. Furthermore, MK-4101 displaced a fluorescently-labeled cyclopamine derivative from 293 cells expressing recombinant human SMO with an IC50 of 1.1 µM. MK-4101 arrests cells in G1 and G2 phases. Beside antitumor activity on transplanted tumors, MK-4101 was highly efficacious against primary medulloblastoma and BCC developing in the cerebellum and skin of Ptch1(+/-) mice.
| ln Vitro |
MK-4101 suppresses Hh signaling in human KYSE180 oesophageal cancer cells at an IC50 of 1 µM and in a reporter gene test using an engineered mouse cell line with an IC50 of 1.5 µM. With an IC50 of 1.1 µM, MK-4101 clears 293 cells expressing recombinant human SMO, suggesting that the molecule binds to SMO. It also displaces a fluorescently-labeled cyclopamine derivative. With an IC50 of 0.3 µM, MK4101 also prevents the growth of medulloblastoma cells obtained from neonatally irradiated Ptch1-/+ mice in vitro[1]. Treatment of MK -4101 (10 µM; 60 hours, 72 hours; medulloblastoma or BCC cells) results in cell cycle arrest with almost no S phase subpopulation remaining, a significant rise in the G1 population, and a little increase in the G2 population[1]. Treatment with MK-4101 (10 µM; medulloblastoma or BCC cells) dramatically decreases the accumulation of cyclin B1 protein and the cyclin D1 protein[1].
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| ln Vivo |
Tumor growth inhibition is shown at 40 and 80 mg/kg of MK-4101 (oral administration; 3.5 weeks; CD1 nude female mice) and tumor regression is observed at the highest dose (80 mg/kg). Gli1 mRNA is dose-dependently down-regulated in response to MK-4101 therapy; 80 mg/kg produces the greatest tumor inhibition and hedgehog pathway down-regulation[1].
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| Cell Assay |
Cell Cycle Analysis[1]
Cell Types: Medulloblastoma or BCC cells Tested Concentrations: 10 µM Incubation Duration: 60 hrs (hours), 72 hrs (hours) Experimental Results: demonstrated cell cycle arrest. Western Blot Analysis[1] Cell Types: Medulloblastoma or BCC cells Tested Concentrations: 10 µM Incubation Duration: Experimental Results: Significant reduction of cyclin D1 protein and accumulation of cyclin B1 protein. |
| Animal Protocol |
Animal/Disease Models: 5-weeks old CD1 nude female mice with medulloblastoma /BCC cells[1]
Doses: 40 or 80 mg/kg one time/day, 80 mg/kg twice a day Route of Administration: Oral administration; for 3.5 weeks Experimental Results: demonstrated tumor growth inhibition (40 and 80 mg/kg ) and tumor regression at the highest dose (80 mg/kg). |
| References |
[1]. Filocamo G et al. MK-4101, a Potent Inhibitor of the Hedgehog Pathway, Is Highly Active against Medulloblastoma and Basal Cell Carcinoma. Mol Cancer Ther. 2016 Jun;15(6):1177-89.
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| Molecular Formula |
C24H24F5N5O
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| Molecular Weight |
493.47
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| CAS # |
935273-79-3
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| Related CAS # |
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| SMILES |
FC(C1=CC=CC=C1C2=NN=C(C34CCC(C5=NOC(C6CC(F)(F)C6)=N5)(CC4)CC3)N2C)(F)F
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| Synonyms |
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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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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0265 mL | 10.1323 mL | 20.2647 mL | |
| 5 mM | 0.4053 mL | 2.0265 mL | 4.0529 mL | |
| 10 mM | 0.2026 mL | 1.0132 mL | 2.0265 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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