Entrectinib(NMS-E 628 RXDX101 ROZLYTREK)

Molecular Weight (MW)	560.64
Formula	C31H34F2N6O2
CAS No.	1108743-60-7
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 100 mg/mL (178.4 mM)
Water: <1 mg/mL
Ethanol: 100 mg/mL (178.4 mM)
Other info	Chemical Name: N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide SMILES Code: O=C(NC1=NNC2=C1C=C(CC3=CC(F)=CC(F)=C3)C=C2)C4=CC=C(N5CCN(C)CC5)C=C4NC6CCOCC6
Synonyms	Entrectinib, RXDX-101, NMS-E628; RXDX101; RXDX 101; RXDX-101; NMS E628; NMS-E-628; trade nameROZLYTREK

Molecular Weight (MW)

560.64

Formula

C31H34F2N6O2

CAS No.

1108743-60-7

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 100 mg/mL (178.4 mM)

Water: <1 mg/mL

Ethanol: 100 mg/mL (178.4 mM)

Other info

Chemical Name: N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide
SMILES Code: O=C(NC1=NNC2=C1C=C(CC3=CC(F)=CC(F)=C3)C=C2)C4=CC=C(N5CCN(C)CC5)C=C4NC6CCOCC6

Synonyms

Entrectinib, RXDX-101, NMS-E628; RXDX101; RXDX 101; RXDX-101; NMS E628; NMS-E-628; trade nameROZLYTREK

In Vitro	In vitro activity: Entrectinib selectively blocks proliferation of ALK-dependent cell lines and potently inhibits ALK‐dependent signaling. Entrectinib also highly inhibits cell growth of the NSCLC cell line NCI‐H2228 bearing the EML4-ALK rearrangement. Kinase Assay: Entrectinib is a potent and orally available Trk, ROS1, and ALK inhibitor; inhibits TrkA, TrkB, TrkC, ROS1 and ALK with IC50 values of 1, 3, 5, 12 and 7 nM, respectively. Cell Assay: NLF, NLF-TrkB, SY5Y or SY5Y-TrkB cells are plated in 96 well plates, and they are exposed to drug at different concentrations (1, 5, 10, 20, 30, 50 and 100 nM of entrectinib, 1.5 μM Irino and 50 μM TMZ, respectively) for one hr followed by addition of 100 ng/mL of BDNF. Plates are harvested at 24, 48, and 72 hr following addition of drug. The plates are processed and cell viability is analyzed using a standard SRB assay protocol.
In Vivo	In mice bearing Karpas-299 and SR-786 xenografts, Entrectinib (p.o.) induces complete tumor regression. In NPM-ALK transgenic mice, Entrectinib induces complete regression of tumor masses observed in the thymus and in lymph nodes. In the NB xenograft model, Entrectinib cotreatment enhanced the efficacy of conventional chemotherapy.
Animal model	Mice bearing Karpas-299 and SR-786 xenograft models
Formulation & Dosage	p.o. and i.v.; Entrectinib is reconstituted in 0.5% methylcellulose containing 1% Tween 80 at a final dosing volume of 10 mL/kg (e.g., 0.2 mL for a 20 gm mouse). Treatment with entrectinib, Irino and TMZ started about 15–17 days after tumor inoculation when the average tumor size is 0.2 cm3. Mice are sacrificed when tumor volume reached 3 cm3.
References	Expert Opin Investig Drugs. 2015;24(11):1493-500; Cancer Res 2013;73(8 Suppl): Abstract nr 2092. doi:10.1158/1538-7445.AM2013-2092.

In Vitro

In vitro activity: Entrectinib selectively blocks proliferation of ALK-dependent cell lines and potently inhibits ALK‐dependent signaling. Entrectinib also highly inhibits cell growth of the NSCLC cell line NCI‐H2228 bearing the EML4-ALK rearrangement.

Kinase Assay: Entrectinib is a potent and orally available Trk, ROS1, and ALK inhibitor; inhibits TrkA, TrkB, TrkC, ROS1 and ALK with IC50 values of 1, 3, 5, 12 and 7 nM, respectively.

Cell Assay: NLF, NLF-TrkB, SY5Y or SY5Y-TrkB cells are plated in 96 well plates, and they are exposed to drug at different concentrations (1, 5, 10, 20, 30, 50 and 100 nM of entrectinib, 1.5 μM Irino and 50 μM TMZ, respectively) for one hr followed by addition of 100 ng/mL of BDNF. Plates are harvested at 24, 48, and 72 hr following addition of drug. The plates are processed and cell viability is analyzed using a standard SRB assay protocol.

In Vivo

In mice bearing Karpas-299 and SR-786 xenografts, Entrectinib (p.o.) induces complete tumor regression. In NPM-ALK transgenic mice, Entrectinib induces complete regression of tumor masses observed in the thymus and in lymph nodes. In the NB xenograft model, Entrectinib cotreatment enhanced the efficacy of conventional chemotherapy.

Animal model

Mice bearing Karpas-299 and SR-786 xenograft models

Formulation & Dosage

p.o. and i.v.; Entrectinib is reconstituted in 0.5% methylcellulose containing 1% Tween 80 at a final dosing volume of 10 mL/kg (e.g., 0.2 mL for a 20 gm mouse). Treatment with entrectinib, Irino and TMZ started about 15–17 days after tumor inoculation when the average tumor size is 0.2 cm3. Mice are sacrificed when tumor volume reached 3 cm3.

References

Expert Opin Investig Drugs. 2015;24(11):1493-500; Cancer Res 2013;73(8 Suppl): Abstract nr 2092. doi:10.1158/1538-7445.AM2013-2092.

CAS NO:	1108743-60-7
规格:	≥98%

包装	价格(元)
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议
1g	电议