BiochemProbe — Life Science Research Reagents

Defactinib free base · Synonyms: VS-6063 | PF-04554878

Defactinib is a novel FAK inhibitor.

For research use only. Not for human or veterinary use.

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Defactinib structure

CAS No.: 1073154-85-4

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
1 g USD 560.00 BP-02315-1g In stock Get quote
2 g USD 890.00 BP-02315-2g In stock Get quote
3 g USD 1,075.00 BP-02315-3g In stock Get quote
5 g USD 1,430.00 BP-02315-5g In stock Get quote
10 g USD 2,290.00 BP-02315-10g In stock Get quote
25 g USD 4,590.00 BP-02315-25g In stock Get quote

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Description

Defactinib (VS-6063; PF-04554878) is a novel FAK inhibitor with potential antiangiogenic and antineoplastic activities.

Biological activity

In Vitro Defactinib (VS-6063) inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. RPPA data shows that Defactinib reduces levels of AKT and YB-1 in taxane-resistant cell lines. The expression of pFAK (Tyr397) is statistically significantly inhibited by Defactinib in a dose-dependent manner in all cell lines. Defactinib inhibits pFAK (Tyr397) expression within 3 hours, with a gradual return of expression by 48 hours. In Vivo Defactinib (VS-6063) doses of 25 mg/kg twice a day or greater statistically significantly inhibits pFAK (Tyr397) at 3 hours, with return of expression noted by 24 hours. Therefore, administration of Defactinib at 25 mg/kg twice a day is selected as the dosing schedule for subsequent therapy experiments. For therapy experiments, female nude mice bearing HeyA8 tumors in the peritoneal cavity are randomly divided into 4 groups (n=10 per group): 1) vehicle orally twice daily and phosphate-buffered saline intraperitoneally weekly (control); 2) Defactinib 25 mg/kg orally twice daily; 3) PTX intraperitoneally weekly; and 4) both VDefactinib 25 mg/kg orally twice daily and PTX intraperitoneally weekly. There is an 87.4% reduction in tumor weight by PTX monotherapy in the HeyA8 model, and combination therapy resulted in the greatest tumor weight reduction, with a 97.9% reduction (P=0.05 compared with PTX). In the SKOV3ip1 model, a 92.7% tumor weight reduction is observed in the combination group compared with PTX (P<0.001).

Identifiers

SMILES
CNC(=O)C1=CC=C(NC2=NC=C(C(NCC3=NC=CN=C3N(C)S(C)(=O)=O)=N2)C(F)(F)F)C=C1
InChIKey
FWLMVFUGMHIOAA-UHFFFAOYSA-N

Specifications

MW (average)
510.4930
Formula
C20H21F3N8O3S
CAS No.
1073154-85-4
Physical state
Solid
Color
White to off-white
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

References

[1]. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95.