RO5126766(CH5126766) Struktur

RO5126766(CH5126766)

Bezeichnung:RO5126766(CH5126766)

CAS-Nr946128-88-7

Englisch Name:RO5126766(CH5126766)

CBNumberCB82712006

SummenformelC21H18FN5O5S

Molgewicht471.46

MOL-Datei946128-88-7.mol

RO5126766(CH5126766) physikalisch-chemischer Eigenschaften

Siedepunkt	690.8±65.0 °C(Predicted)
Dichte	1.495±0.06 g/cm3(Predicted)
storage temp.	Store at -20°C
Löslichkeit	insoluble in H2O; insoluble in EtOH; ≥35.7 mg/mL in DMSO
Aggregatzustand	Powder
pka	6.60±0.50(Predicted)
Farbe	White to yellow

Gefahreninformationscode (GHS)

RO5126766(CH5126766) Chemische Eigenschaften,Einsatz,Produktion Methoden

Definition
ChEBI: CH5126766 is a member of the class of coumarins that is 4-methyl-7-[(pyrimidin-2-yl)oxy]coumarin carrying an additional [2-[(methylaminosulfonyl)amino]-3-fluoropyridin-4-yl]methyl substituent at position 3. It has a role as an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor and an antineoplastic agent. It is an aryloxypyrimidine, a member of coumarins, a member of pyridines, an organofluorine compound and a member of sulfamides.
Biologische Aktivität
ro5126766 (ch5126766) is a first-in-class dual inhibitor of raf/mek [1].the ras/raf/mek/erk signaling pathway is an important signal transduction system and participates in cell differentiation, movement, division and death. activated ras activates raf kinase, which then phosphorylates and activates mek (mek1 and mek2) [1]. the mutations in braf, ras, and nf1 are associated with many human tumors [2].ro5126766 (ch5126766) is a first-in-class dual raf/mek inhibitor. in cell-free kinase assays, ch5126766 effectively inhibited the phosphorylation of mek1 protein by raf and the activation of erk2 protein by mek1 with ic50 values of 0.0082-0.056 and 0.16 μm, respectively. in nci-h460 (kras q61h) human lung large cell carcinoma cell line, ro5126766 induced cell-cycle inhibitor p27kip1 protein expression and caused g1 arrest. in hct116 kras-mutant colorectal cancer cells, ro5126766 ch5126766 completely inhibited the phosphorylation of mek and erk [2].in japanese patients with advanced solid tumors, ro5126766 exhibited the maximum tolerable dose (mtd) of 2.25 mg/day once daily [1]. in a hct116 (g13d kras) mouse xenograft model, ro5126766 (1.5 mg/kg) inhibited perk and erk signaling and exhibited ed50 value of 0.056 mg/kg [2].
Einzelnachweise
[1]. honda k, yamamoto n, nokihara h, et al. phase i and pharmacokinetic/pharmacodynamic study of ro5126766, a first-in-class dual raf/mek inhibitor, in japanese patients with advanced solid tumors. cancer chemother pharmacol, 2013, 72(3): 577-584.
[2]. ishii n, harada n, joseph ew, et al. enhanced inhibition of erk signaling by a novel allosteric mek inhibitor, ch5126766, that suppresses feedback reactivation of raf activity. cancer res, 2013, 73(13): 4050-4060.

RO5126766(CH5126766) Upstream-Materialien And Downstream Produkte

RO5126766(CH5126766) Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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