MK 2461
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]sulfam
CAS: 917879-39-1
Molecular Formula: C24H25N5O5S
MK 2461 - Names and Identifiers
| 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]sulfam |
| Synonyms | MK2461 CS-528 MK 2461 MK-2461 Mk-2461 . 9-[[[(2R)-1,4-DIOXAN-2-YL]METHYL-METHYLSULFAMOYL]AMINO]-2-(1-METHYLPYRAZOL-4-YL)-11-OXOBENZO[1,2]CYCLOHEPTA[2,4-B]PYRIDINE 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]sulfam 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 Sulfamide, 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]- |
| CAS | 917879-39-1 |
MK 2461 - Physico-chemical Properties
| Molecular Formula | C24H25N5O5S |
| Molar Mass | 495.55 |
| Density | 1.45±0.1 g/cm3(Predicted) |
| Melting Point | 192-193 °C |
| Boling Point | 732.4±70.0 °C(Predicted) |
| pKa | 6.81±0.20(Predicted) |
| Storage Condition | -20℃ |
| In vitro study | MK-2461 can effectively inhibit FGFR1, FGFR2, FGFR3, KDR, TrkA, TrkB and Flt4,IC50 of 65 nM, 39 nM, 50 nM, 44 nM, 46 nM, 61 nM, and 78 nM. Compared with wild-type c-Met, it MK-2461 more effectively inhibit the proto-oncogene c-Met mutants N1100Y, Y1230C, Y1230H, Y1235D, and M1250Tn1100y, IC 50 at 1.5 nM and 1.5 nM respectively, 1.0 nM, 0.5 nM, and 0.4 nM. MK-2461 binds more strongly to phosphorylated c-met. MK-2461 potent inhibition of ATP-induced c-Met autophosphorylation occurs in the carboxy-terminal docking domain, rather than the activation loop. In contrast, MK-2461 inhibited FGFR2 (Y653/Y654) and PDGFR-α in Kato III cells and h1703 cells (Y849) activation of cyclic phosphate activation, IC 50 are <0.3 μm. MK-2461 inhibited hepatocyte growth factor-induced mitogen in 4MBr-5 cells, with IC 50 at 204nM, and hepatocyte growth factor-induced migration in HPAF II cells, with IC 50 at 404 nM, and hepatocyte growth factor-induced branching tube type formation of MDCK Cells. In addition, MK-2461 effectively inhibited IL-3-independent proliferation in 32D cells mutated by Tpr-Met or Tpr-Met(y362c) with an IC 50 of ~ 100nm. MK-2461 significantly inhibited the proliferation of a broad spectrum of tumor cell lines, especially for cancer cells with high expression of MET and fgfr2. |
| In vivo study | MK-2461 treatment significantly inhibited c-Met(y1349) phosphorylation in GTL-16 tumors, IC 50~1 μm. The oral MK-2461 dose is 10 mg/kg, 50 mg/kg, 100 mg/kg twice daily, or 200 mg/kg once daily. Oral treatment effectively inhibited tumor growth in the GTL-16-transplanted mouse model by 62%,77%,75%, and 90%, respectively. Similarly, MK-2461 treatment of NI H3T 3 tumor cells containing c-Met mononucleotide mutations T3936C and T3997C at a dose of 134 mg/kg twice daily resulted in 78% and 62% inhibition, respectively. |
MK 2461 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.018 ml | 10.09 ml | 20.18 ml |
| 5 mM | 0.404 ml | 2.018 ml | 4.036 ml |
| 10 mM | 0.202 ml | 1.009 ml | 2.018 ml |
| 5 mM | 0.04 ml | 0.202 ml | 0.404 ml |
Last Update：2024-01-02 23:10:35
MK 2461 - Reference Information
| biological activity | MK-2461 is a potent, multi-target inhibitor that acts on c-Met(WT/mutants),IC50 is 0.4-2.5 nM, the effect of Ron, and Flt1 is slightly weaker; The effect of c-Met on FGFR1, FGFR2, FGFR3, PDGFR, KDR, Flt3, Flt4, trkA and TrkB selectivity is 8 to 30 times higher. Phase 1/2. MK-2461 is a potent, multi-target inhibitor, acting on c-Met(WT/mutants) with IC50 of 0.4-2.5 nM, with slightly weaker effects on Ron and Flt1; the selectivity for c-Met is 8 to 30 times higher than for FGFR1, FGFR2, FGFR3, PDGFR β, KDR, Flt3, Flt4, TrkA and TrkB. Phase 1/2. |
| characteristic | unlike other known ATP competitive tyrosine kinase inhibitors, MK-2461 preferentially binds to c-Met of activation. Most other inhibitors have no binding preference or preference for binding to an unactivated kinase. |
| Target | Value |
| c-Met (M1250T) | 0.4 nM |
| c-Met (Y1235D) | 0.5 nM |
| c-Met (Y1230H) | 1.0 nM |
| c-Met (N1100) | 1.5 nM |
| c-Met (Y1230C) | 1.5 nM |
Last Update：2024-04-09 19:05:17
Supplier List
Product 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]sulfam Visit Supplier Webpage Request for quotation
CAS: 917879-39-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 917879-39-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
Product 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]sulfam Visit Supplier Webpage Request for quotation
CAS: 917879-39-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 917879-39-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
View History