WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 525682
Description: MK-2461 is a novel ATP-competitive multitargeted inhibitor of activated c-Met. MK-2461 inhibited in vitro phosphorylation of a peptide substrate recognized by wild-type or oncogenic c-Met kinases (N1100Y, Y1230C, Y1230H, Y1235D, and M1250T) with IC50 values of 0.4 to 2.5 nmol/L. In tumor cells, MK-2461 effectively suppressed constitutive or ligand-induced phosphorylation of the juxtamembrane domain and COOH-terminal docking site of c-Met, and its downstream signaling to the phosphoinositide 3-kinaseÂ–AKT and RasÂ–extracellular signal-regulated kinase pathways, without inhibiting autophosphorylation of the c-Met activation loop. In cell culture, MK-2461 inhibited hepatocyte growth factor/c-MetÂ–dependent mitogenesis, migration, cell scatter, and tubulogenesis. In a murine xenograft model of c-MetÂ–dependent gastric cancer, a well-tolerated oral regimen of MK-2461 administered at 100 mg/kg twice daily effectively suppressed c-Met signaling and tumor growth. (Cancer Res; 2010, 70(4):1524Â–33)
MedKoo Cat#: 525682
Chemical Formula: C24H25N5O5S
Exact Mass: 495.15764
Molecular Weight: 495.554
Elemental Analysis: C, 58.17; H, 5.09; N, 14.13; O, 16.14; S, 6.47
Synonym: MK2461; MK 2461; MK-2461
IUPAC/Chemical Name: N-((2R)-1,4-Dioxan-2-ylmethyl)-N-methyl-N'-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]sulfamide
InChi Key: JGEBLDKNWBUGRZ-HXUWFJFHSA-N
InChi Code: InChI=1S/C24H25N5O5S/c1-28-13-18(12-26-28)17-9-22-23(25-11-17)6-4-16-3-5-19(10-21(16)24(22)30)27-35(31,32)29(2)14-20-15-33-7-8-34-20/h3-6,9-13,20,27H,7-8,14-15H2,1-2H3/t20-/m1/s1
SMILES Code: O=S(NC1=CC=C2C(C(C3=CC(C4=CN(C)N=C4)=CN=C3C=C2)=O)=C1)(N(C[C@H]5OCCOC5)C)=O
Appearance: Solid powder
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, not in water
Shelf Life: >5 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
The following data is based on the product molecular weight 495.554 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.
|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|
1. Pan, Bo-Sheng; Chan, Grace K. Y.; Chenard, Melissa; Chi, An; Davis, Lenora J.; Deshmukh, Sujal V.; Gibbs, Jackson B.; Gil, Susana; Hang, Gaozhen; Hatch, Harold; Jewell, James P.; Kariv, Ilona; Katz, Jason D.; Kunii, Kaiko; Lu, Wei; Lutterbach, Bart A.; Paweletz, Cloud P.; Qu, Xianlu; Reilly, John F.; Szewczak, Alexander A.; Zeng, Qinwen; Kohl, Nancy E.; Dinsmore, Christopher J. MK-2461, a Novel Multitargeted Kinase Inhibitor, Preferentially Inhibits the Activated c-Met Receptor. Cancer Research (2010), 70(4), 1524-1533.
2. Burgess, Theresa L.; Coxon, Angela; Dussault, Isabelle; Kaplan-Lefko, Paula; Polverino, Anthony J.; Beaupre, Darrin. Combinations VEGF(R) inhibitors and hepatocyte growth factor (c-met) inhibitors for the treatment of cancer. PCT Int. Appl. (2009), 83pp. CODEN: PIXXD2 WO 2009140549
3. Tomillero A; Moral M A Gateways to clinical trials. Methods and findings in experimental and clinical pharmacology (2009), 31(1), 47-57.
Phase I study of MK-2461: Fourteen patients (10 M/ 4 F), mean age 54 (range 19-76), have received 31 cycles (range 1-6). Dose levels tested include 60mg daily, 60mg BID, 120mg BID, and 180 mg BID. Toxicity data are available for 11 patients treated at the 60mg daily-120mg BID dosing cohorts. Ten patients (91%) have not experienced > Grade 1 drug-related toxicity. Dose limiting toxicity has not been reached and no objective antitumor responses have been observed. One patient with mucinous carcinoma of the appendix had stable disease for 6 cycles. Common drug related toxicities are outlined in the table below. Four patients experienced serious adverse experiences that were considered not related to MK-2461. PK analysis revealed a rapid Tmax (1-3 hr) across all dosing cohorts with a terminal half life of 6.3 hr following the final day of dosing for the QD dosing cohort. Conclusions: Twice daily administration of MK-2461 at the doses tested is well tolerated. Terminal t1/2 suggests acceptable drug plasma concentrations expected at BID dosing. Dose escalation continues. (source: J Clin Oncol 26: 2008 (May 20 suppl; abstr 14657)
Phase I study of MK-2461: