Ravoxertinib hydrochloride(GDC-0994 RG7842)

Molecular Weight (MW)	477.32
Formula	C21H19Cl2FN6O2
CAS No.	2070009-58-2
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO:> 100 mg/mL
Water: N/A
Ethanol: N/A
Solubility (In vivo)	2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30 mg/mL
Synonyms	RG 7842 HCl; GDC0994; GDC-0994; GDC 0994; RG7842; RG-7842; RG 7842

Molecular Weight (MW)

477.32

Formula

C21H19Cl2FN6O2

CAS No.

2070009-58-2

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO:> 100 mg/mL

Water: N/A

Ethanol: N/A

Solubility (In vivo)

2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30 mg/mL

Synonyms

RG 7842 HCl; GDC0994; GDC-0994; GDC 0994; RG7842; RG-7842; RG 7842

In Vitro	In vitro activity: GDC-0994, also known as ravoxertinib and RG7842, is a potent, orally available ERK1/2 inhibitor with IC50 of 1.1 nM and 0.3 nM, respectively. It has demonstrated anticancer activity. Upon oral administration, GDC-0994 inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways. This prevents ERK-dependent tumor cell proliferation and survival. Kinase Assay: Ravoxertinib (GDC-0994) is an orally bioavailable ERK kinase inhibitor with an IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively. Ravoxertinib (GDC-0994) also inhibits p90RSK with an IC50 of 12 nM. Ravoxertinib (GDC-0994) is highly selective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively. Cell Assay: GDC-0994 potently inhibits phospho-p90RSK in tumor cells.
In Vivo	GDC-0994 (p.o.) results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. In vivo, GDC-0994 (p.o.) inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways, and subsequently prevents ERK-dependent tumor cell proliferation and survival.
Animal model	PK/PD data for Ravoxertinib (GDC-0994) 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.
Formulation & Dosage	Dissolved in 40% PEG400/60% (10% HPβCD); 15, 30, or 100 mg/kg; oral
References	J Med Chem. 2016 Jun 23;59(12):5650-60.

In Vitro

In vitro activity: GDC-0994, also known as ravoxertinib and RG7842, is a potent, orally available ERK1/2 inhibitor with IC50 of 1.1 nM and 0.3 nM, respectively. It has demonstrated anticancer activity. Upon oral administration, GDC-0994 inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways. This prevents ERK-dependent tumor cell proliferation and survival.

Kinase Assay: Ravoxertinib (GDC-0994) is an orally bioavailable ERK kinase inhibitor with an IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively. Ravoxertinib (GDC-0994) also inhibits p90RSK with an IC50 of 12 nM. Ravoxertinib (GDC-0994) is highly selective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively.

Cell Assay: GDC-0994 potently inhibits phospho-p90RSK in tumor cells.

In Vivo

GDC-0994 (p.o.) results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. In vivo, GDC-0994 (p.o.) inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways, and subsequently prevents ERK-dependent tumor cell proliferation and survival.

Animal model

PK/PD data for Ravoxertinib (GDC-0994) 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.

Formulation & Dosage

Dissolved in 40% PEG400/60% (10% HPβCD); 15, 30, or 100 mg/kg; oral

References

J Med Chem. 2016 Jun 23;59(12):5650-60.

CAS NO:	2070009-58-2
规格:	≥98%

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