Ravoxertinib hydrochloride
Names
Biological Activity
[Description]:
Ravoxertinib hydrochloride (GDC-0994 hydrochloride) is an orally bioavailable inhibitor selective for ERK kinase activity with IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively.
[Related Catalog]:
[Target]
ERK2:3.1 nM (IC50)
ERK1:6.1 nM (IC50)
p-RSK:12 nM (IC50)
[In Vitro]
Ravoxertinib also inhibits p90RSK with IC50 of 12 nM[1]. Ravoxertinib is highly selective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively[2].
[In Vivo]
In CD-1 mice, a 10 mg/kg oral dose of Ravoxertinib is sufficient to achieve the desired target coverage for at least 8 h[1]. Daily, oral dosing of Ravoxertinib results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice[2].
[Animal admin]
Mice[1] PK/PD data for Ravoxertinib in the HCT116 mouse xenograft model. HCT116 tumors are established in nude mice to a tumor volume of 400−600 mm3. Mice are treated with a single oral dose of 22 at 15, 30, or 100 mg/kg versus vehicle control alone (40% PEG400/60% (10% HPβCD)) follow by tumor and plasma collection at 2, 8, 16, and 24 h postdose. Tumor levels of phosphorylated p90RSK (pRSK) relative total p90RSK (tRSK) are measured by quantitative Western blot and are normalized to vehicle control at 2 h postdose (set to 100%). Plasma and tumor concentrations are measured by LC−MS.
[References]
[Related Small Molecules]
SCH772984
|
Ravoxertinib
|
Honokiol
|
Sodium tauroursodeoxycholate
|
LY3214996
|
Ulixertinib (BVD-523)
|
TIC10
|
Astragaloside IV
|
XMD8-92
|
LM22B 10
|
VX-11e
|
FR 180204
|
Mogrol
|
Pluripotin
|
AX 15836
Chemical & Physical Properties
[ Molecular Formula ]:
C21H19Cl2FN6O2
[ Molecular Weight ]:
477.32