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MK-2461

Cat. No. M3515
MK-2461 Structure
Size Price Availability Quantity
5mg USD 156  USD195 In stock
10mg USD 280  USD350 In stock
50mg USD 960  USD1200 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

MK-2461 is a potent inhibitor of c-Met, Ron, Flt1, Flt 3, PDGFRβ, and Mer with IC50 of 2.5 nM, 7 nM, 10 nM, 22 nM, 22 nM, and 24 nM, respectively. MK-2461 also exhibits significant activities toward several other kinases including FGFR1, FGFR2, FGFR3, KDR, TrkA, TrkB, and Flt4 with IC50 of 65 nM, 39 nM, 50 nM, 44 nM, 46 nM, 61 nM, and 78 nM, respectively. MK-2461 preferentially binds to the activated c-Met, and is slightly more potent against five naturally occurring oncogenic human c-Met mutants (N1100Y, Y1230C, Y1230H, Y1235D, and M1250T) compared with wild-type c-Met. MK-2461 significantly inhibits constitutive and ligand-induced phosphorylation of the juxtamembrane domain (Y1003) and the COOH-terminal docking site (Y1349/Y1365) of c-Met, as well as phosphorylation of AKT (S473) and ERK1/2 (T202/Y204), without affecting c-Met activation loop (Y1234/35) phosphorylation in GTL-16 cells. MK-2461 displays potent antiproliferative activity against a variety of tumor cell lines with IC50 of 0.1-30 μM. Orally administered MK-2461 inhibits c-Met phosphorylation in vivo, and tumor growth of GTL-16 xenografts, as well as the growth of NIH3T3 tumors harboring murine equivalents of human c-Met Y1230H and M1250T mutants.

Protocol
Cell Experiment
Cell lines SW480, HT29, SW620, Colo 205, HCT116, HCT15, Colo 201, SCC-9, H1993, H1048, GTL-16, SNU15, et al.
Preparation method Exposing cells to various concentrations of MK-2461 for 72 hours. Using the ViaLight PLUS kit to mearsure the viability of tumor cells .
Concentrations Dissolved in DMSO, final concentrations ~100 μM
Incubation time 72 hours
Animal Experiment
Animal models Female nude CD-1 nu/nu mice inoculated s.c. with GTL-16 cells or c-Met mutant-transformed NIH3T3 cells
Formulation Dissolved in DMSO, and diluted in saline
Dosages ~134 mg/kg
Administration Orally once or twice daily
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 495.55
Formula C24H25N5O5S
CAS Number 917879-39-1
Purity >98%
Solubility DMSO 90 mg/mL
Storage at -20°C
References

[1] Sadaf Ghanaatgar-Kasbi, et al. Targeting the C-MET/HGF Signaling Pathway in Pancreatic Ductal Adenocarcinoma

[2] Jing-Fang Wu, et al. Design and synthesis of novel substituted naphthyridines as potential c-Met kinase inhibitors based on MK-2461

[3] Jason D Katz, et al. Discovery of a 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (MK-2461) inhibitor of c-Met kinase for the treatment of cancer

[4] Bo-Sheng Pan, et al. MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor

[5] A Tomillero, et al. Gateways to clinical trials

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  Catalog
Abmole Inhibitor Catalog




Keywords: MK-2461 supplier, c-Met, inhibitors

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