MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 406833 | Name: MK-4101
Featured New

Description:

WARNING: This product is for research use only, not for human or veterinary use.

MK-4101 is a potent and selective inhibitor of the Hedgehog Pathway. MK-401 Is Highly Active against Medulloblastoma and Basal Cell Carcinoma. MK-4101 showed anti-tumor activity through the inhibition of proliferation and induction of extensive apoptosis in tumor cells. MK-4101 was highly efficacious against primary medulloblastoma and BCC developing in the cerebellum and skin of Ptch1(+/-) mice. MK-4101 targets the Hh pathway in tumor cells, showing the maximum inhibitory effect on Gli1 MK-4101 also induced deregulation of cell cycle and block of DNA replication in tumors.

Chemical Structure

MK-4101
MK-4101
CAS#935273-79-3

Theoretical Analysis

MedKoo Cat#: 406833

Name: MK-4101

CAS#: 935273-79-3

Chemical Formula: C24H24F5N5O

Exact Mass: 493.1901

Molecular Weight: 493.48

Elemental Analysis: C, 58.41; H, 4.90; F, 19.25; N, 14.19; O, 3.24

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 1,950.00 Ready to ship
1g USD 2,950.00 2 weeks
2g USD 5,250.00 2 weeks
5g USD 7,650.00 2 weeks
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
MK-4101; MK 4101; MK4101.
IUPAC/Chemical Name
5-(3,3-Difluorocyclobutyl)-3-[4-[4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl]-1,2,4-oxadiazole
InChi Key
HKJOIWLYDJCTQR-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H24F5N5O/c1-34-17(15-4-2-3-5-16(15)24(27,28)29)31-32-20(34)22-9-6-21(7-10-22,8-11-22)19-30-18(35-33-19)14-12-23(25,26)13-14/h2-5,14H,6-13H2,1H3
SMILES Code
FC(C1=CC=CC=C1C2=NN=C(C34CCC(C5=NOC(C6CC(F)(F)C6)=N5)(CC4)CC3)N2C)(F)F
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
MK-4101 is a Smoothened (SMO) antagonist (IC50 of 1.1 µM for 293 cells ) and also a potent inhibitor of the hedgehog pathway (IC50 of 1.5 µM for mouse cells; IC50 of 1 µM for KYSE180 oesophageal cancer cells).
In vitro activity:
To further dissect the mechanism of tumor growth inhibition by MK-4101 and confirm microarray data, medulloblastoma and BCC single-cell suspensions were treated with a saturating dose MK-4101 (10 μmol/L) to maximize effects. Cell cycle was analyzed by FACS monitoring EdU incorporation. Medulloblastoma cells treated with MK-4101 for 60 hours showed cell-cycle arrest with a nearly complete disappearance of the S-phase subpopulation, a prominent increase of the G1 population and, to a minor extent, of the G2 population, indicative of a cell-cycle block in these two phases (Fig. 6A). Moreover, an increase in the sub-G1 population was observed, indicative of underlying cell death. BCC cells treated with MK-4101 for 72 hours showed similar, although less pronounced effect (Fig. 6B), probably due to the lower growth rate of BCC compared with medulloblastoma cells. The cell-cycle blocks in G1–S and G2–M phases were confirmed by a remarkable decrease in cyclin D1 protein and accumulation of cyclin B1 protein, detected by Western blot analysis after MK-4101 treatment both in medulloblastoma and BCC tumor cells (Fig. 6C and D). Altogether, these results confirmed that MK-4101 inhibits medulloblastoma and BCC tumor growth by arresting cell cycle and inducing apoptosis. Reference: Mol Cancer Ther. 2016 Jun;15(6):1177-89. https://pubmed.ncbi.nlm.nih.gov/26960983/
In vivo activity:
To further investigate the efficacy of MK-4101, primary medulloblastomas from neonatally irradiated Ptch1+/− mice, a highly penetrant model with 80% of mice developing full-blown medulloblastoma by 20 weeks of age were focused on. Quantification of tumor size in a subset of P1-irradiated Ptch1+/− mice (n = 5) of 8 weeks of age show an incidence of preneoplastic lesion of 80% (4/5) and an average size of 0.28 mm2 (range 0.053–0.75 mm2). It was therefore asked whether treatment with MK-4101 (80 mg/kg twice a day) at this stage could prevent medulloblastoma formation and improve mouse survival. By the end of the treatment (17 weeks of age), none (0/24) of the MK-4101–treated mice had developed medulloblastoma-related lethargy, compared with over 50% (13/23) of the vehicle-treated mice (Fig. 3A), demonstrating that MK-4101 treatment significantly improved survival (P = 0.0002). A significant brain weight decrease of 17% was detected in MK-4101–treated animals as compared with vehicle-treated mice (0.501 vs. 0.604 g; P = 0.0004, Fig. 3B), reflecting the absence of tumor masses in the brains of MK-4101–treated animals. Moreover, highly significant differences in medulloblastoma incidence (P < 0.0001), between vehicle- (13/23) and MK-4101–treated mice (0/24), were revealed by histologic examination (Fig. 3C–E). Only four of MK-4101–treated mice (17%) presented small ectopic foci of abortive tumor cells on the cerebellar surface (Fig. 3E). Collectively, these data showed that treatment with MK-4101 efficaciously eliminates both early and more progressed medulloblastoma stages. Reference: Mol Cancer Ther. 2016 Jun;15(6):1177-89. https://pubmed.ncbi.nlm.nih.gov/26960983/
Solvent mg/mL mM comments
Solubility
DMSO 59.0 119.56
Ethanol 64.0 129.69
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 493.48 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Filocamo G, Brunetti M, Colaceci F, Sasso R, Tanori M, Pasquali E, Alfonsi R, Mancuso M, Saran A, Lahm A, Di Marcotullio L, Steinkühler C, Pazzaglia S. 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. doi: 10.1158/1535-7163.MCT-15-0371. Epub 2016 Mar 9. PMID: 26960983.
In vitro protocol:
1. Filocamo G, Brunetti M, Colaceci F, Sasso R, Tanori M, Pasquali E, Alfonsi R, Mancuso M, Saran A, Lahm A, Di Marcotullio L, Steinkühler C, Pazzaglia S. 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. doi: 10.1158/1535-7163.MCT-15-0371. Epub 2016 Mar 9. PMID: 26960983.
In vivo protocol:
1. Filocamo G, Brunetti M, Colaceci F, Sasso R, Tanori M, Pasquali E, Alfonsi R, Mancuso M, Saran A, Lahm A, Di Marcotullio L, Steinkühler C, Pazzaglia S. 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. doi: 10.1158/1535-7163.MCT-15-0371. Epub 2016 Mar 9. PMID: 26960983.
1: Filocamo G, Brunetti M, Colaceci F, Sasso R, Tanori M, Pasquali E, Alfonsi R, Mancuso M, Saran A, Lahm A, Di Marcotullio L, Steinkühler C, Pazzaglia S. 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. doi: 10.1158/1535-7163.MCT-15-0371. Epub 2016 Mar 9. PubMed PMID: 26960983.