Agerafenib(CEP-32496 RXDX-105 AC013773)

Molecular Weight (MW)	517.46
Formula	C24H22F3N5O5
CAS No.	1188910-76-0
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 9 mg/mL (17.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)	15% Captisol: 15 mg/mL
Synonyms	Agerafenib; CEP32496; CEP 32496; RXDX 105; RXDX105; AC013773; RXDX-105; CEP-32496; AC 013773; AC-013773.

Molecular Weight (MW)

517.46

Formula

C24H22F3N5O5

CAS No.

1188910-76-0

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 9 mg/mL (17.4 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In vivo)

15% Captisol: 15 mg/mL

Synonyms

Agerafenib; CEP32496; CEP 32496; RXDX 105; RXDX105; AC013773; RXDX-105; CEP-32496; AC 013773; AC-013773.

In Vitro	In vitro activity: CEP-32496 inhibits A375 cell (BRAFV600E) proliferation with EC50 of 78 nM. CEP-32496 exhibits more sensitive cytotoxicity for tumor cell lines (A375, SK-MEL-28, Colo-205, Colo-679, and HT-144) expressing mutant BRAF than those expressing wild-type BRAF (HCT116, Hs578T, LNCaP, DU145, and PC-3). CEP-32496 inhibits mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) in human melanoma (A375) and colorectal cancer (Colo-205) cell lines with IC50 of 78 nM and 60 nM, respectively. Kinase Assay: CEP-32496 inhibits A375 cell (BRAFV600E) proliferation with EC50 of 78 nM. CEP-32496 exhibits more sensitive cytotoxicity for tumor cell lines (A375, SK-MEL-28, Colo-205, Colo-679, and HT-144) expressing mutant BRAF than those expressing wild-type BRAF (HCT116, Hs578T, LNCaP, DU145, and PC-3). CEP-32496 inhibits mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) in human melanoma (A375) and colorectal cancer (Colo-205) cell lines with IC50 of 78 nM and 60 nM, respectively. Cell Assay: A375 Cells are seeded at 104 cells per well in DMEM with 10% fetal calf serum and allowed to attach. The cells are washed with PBS and switched to DMEM with 0.5% of serum and incubated overnight. CEP-32496 is then added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h. At the end of incubation, a Cell Titer Blue is added per instructions, and incubation is continued for 3 hours. Remaining viable cells are quantified by measuring the strength of the fluorescence signal using SoftMax Pro (excitation at 560 nm and emission at 590 nm). IC50 values are derived using a 9-point curve fitted with Igor Pro and are presented as mean values from experiments performed in duplicate. Variability between individual values is less than 2-fold.
In Vivo	CEP-32496 exhibits good stability in mouse, dog, monkey, and human liver microsomal preparations with measured intrinsic clearance values of<23 2='' mg='' and=''>60 min in all assays. CEP-32496 (30 mg/kg, orally, BID) exhibits tumor stasis and a 40% incidence of partial tumor regressions (PRs) in Colo-205 xenograft mouse model, whereas the 100 mg/kg dose group exhibits both tumor stasis and an 80% incidence of PRs. CEP-32496 (30 mg/kg, orally, BID) leads to a 50% and 75% inhibition of normalized pMEK in tumor lysates at the 2 hours and 6 hours postdose time point, respectively, while a 55 mg/kg dose results in a 75% to 57% inhibition of pMEK at 2 hours through 10 hours post administration in Colo-205 xenograft mouse model. CEP-32496 is orally bioavailable in multiple preclinical species (>95% in rats, dogs, and monkeys). CEP-32496 (100 mg/kg) results in inhibition of pMEK and pERK and sustained tumor stasis and regressions in BRAF(V600E) colon carcinoma xenografts in nude mice.
Animal model	Colo-205 xenograft mouse model
Formulation & Dosage	Dissolved in 22% HPβCD; 100mg/kg; Oral gavage
References	[1] Rowbottom MW, et al. J Med Chem, 2012, 55(3), 1082-1105. [2] James J, et al. Mol Cancer Ther, 2012, 11(4), 930-941.

In Vitro

In vitro activity: CEP-32496 inhibits A375 cell (BRAFV600E) proliferation with EC50 of 78 nM. CEP-32496 exhibits more sensitive cytotoxicity for tumor cell lines (A375, SK-MEL-28, Colo-205, Colo-679, and HT-144) expressing mutant BRAF than those expressing wild-type BRAF (HCT116, Hs578T, LNCaP, DU145, and PC-3). CEP-32496 inhibits mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) in human melanoma (A375) and colorectal cancer (Colo-205) cell lines with IC50 of 78 nM and 60 nM, respectively.

Kinase Assay: CEP-32496 inhibits A375 cell (BRAFV600E) proliferation with EC50 of 78 nM. CEP-32496 exhibits more sensitive cytotoxicity for tumor cell lines (A375, SK-MEL-28, Colo-205, Colo-679, and HT-144) expressing mutant BRAF than those expressing wild-type BRAF (HCT116, Hs578T, LNCaP, DU145, and PC-3). CEP-32496 inhibits mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) in human melanoma (A375) and colorectal cancer (Colo-205) cell lines with IC50 of 78 nM and 60 nM, respectively.

Cell Assay: A375 Cells are seeded at 104 cells per well in DMEM with 10% fetal calf serum and allowed to attach. The cells are washed with PBS and switched to DMEM with 0.5% of serum and incubated overnight. CEP-32496 is then added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h. At the end of incubation, a Cell Titer Blue is added per instructions, and incubation is continued for 3 hours. Remaining viable cells are quantified by measuring the strength of the fluorescence signal using SoftMax Pro (excitation at 560 nm and emission at 590 nm). IC50 values are derived using a 9-point curve fitted with Igor Pro and are presented as mean values from experiments performed in duplicate. Variability between individual values is less than 2-fold.

In Vivo

CEP-32496 exhibits good stability in mouse, dog, monkey, and human liver microsomal preparations with measured intrinsic clearance values of<23 2='' mg='' and=''>60 min in all assays. CEP-32496 (30 mg/kg, orally, BID) exhibits tumor stasis and a 40% incidence of partial tumor regressions (PRs) in Colo-205 xenograft mouse model, whereas the 100 mg/kg dose group exhibits both tumor stasis and an 80% incidence of PRs. CEP-32496 (30 mg/kg, orally, BID) leads to a 50% and 75% inhibition of normalized pMEK in tumor lysates at the 2 hours and 6 hours postdose time point, respectively, while a 55 mg/kg dose results in a 75% to 57% inhibition of pMEK at 2 hours through 10 hours post administration in Colo-205 xenograft mouse model. CEP-32496 is orally bioavailable in multiple preclinical species (>95% in rats, dogs, and monkeys). CEP-32496 (100 mg/kg) results in inhibition of pMEK and pERK and sustained tumor stasis and regressions in BRAF(V600E) colon carcinoma xenografts in nude mice.

Animal model

Colo-205 xenograft mouse model

Formulation & Dosage

Dissolved in 22% HPβCD; 100mg/kg; Oral gavage

References

[1] Rowbottom MW, et al. J Med Chem, 2012, 55(3), 1082-1105. [2] James J, et al. Mol Cancer Ther, 2012, 11(4), 930-941.

CAS NO:	1188910-76-0
规格:	≥98%

包装	价格(元)
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
500mg	电议