1. Protein Tyrosine Kinase/RTK
  2. FAK

Defactinib (Synonyms: VS-6063; PF-04554878)

Cat. No.: HY-12289 Purity: 99.94%
Data Sheet SDS Handling Instructions

Defactinib is a novel FAK inhibitor, which inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner.

For research use only. We do not sell to patients.
Defactinib Chemical Structure

Defactinib Chemical Structure

CAS No. : 1073154-85-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO $79 In-stock
5 mg $70 In-stock
10 mg $90 In-stock
50 mg $250 In-stock
100 mg $350 In-stock
200 mg $600 In-stock
500 mg   Get quote  
1 g   Get quote  

* Please select Quantity before adding items.

Other Forms of Defactinib:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Defactinib is a novel FAK inhibitor, which inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner.

IC50 & Target

FAK[1]

In Vitro

VS-6063 inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. The combination of VS-6063 and Paclitaxel markedly decreases proliferation and increases apoptosis, which results in 92.7% to 97.9% reductions in tumor weight. RPPA data shows that VS-6063 reduces levels of AKT and YB-1 in taxane-resistant cell lines. The expression of pFAK (Tyr397) is statistically significantly inhibited by VS-6063 in a dose-dependent manner in all cell lines. VS-6063 inhibits pFAK (Tyr397) expression within 3 hours, with a gradual return of expression by 48 hours[1].

In Vivo

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 VS-6063 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) VS-6063 25 mg/kg orally twice daily; 3) PTX intraperitoneally weekly; and 4) both VS-6063 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)[1].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02913716 Verastem, Inc. Healthy Subjects August 2015 Phase 1
NCT01943292 Verastem, Inc. Non Hematologic Cancers September 2, 2013 Phase 1
NCT02758587 NHS Greater Glasgow and Clyde|University of Glasgow|Cancer Research UK|Merck Sharp & Dohme Corp.|Verastem, Inc.|University of Edinburgh|University of Southampton|University of Leicester|Queen's University, Belfast Carcinoma, Non-small-cell Lung|Mesothelioma|Pancreatic Neoplasms July 4, 2017 Phase 1|Phase 2
NCT01870609 Verastem, Inc. Malignant Pleural Mesothelioma September 2013 Phase 2
NCT02546531 Washington University School of Medicine Advanced Solid Tumors|Solid Tumors|Pancreatic Cancer February 3, 2016 Phase 1
NCT01951690 Verastem, Inc. Non Small Cell Lung Cancer|Lung Cancer September 2013 Phase 2
NCT01778803 Verastem, Inc. Ovarian Cancer February 26, 2013 Phase 1
NCT02465060 National Cancer Institute (NCI) Advanced Malignant Solid Neoplasm|Bladder Carcinoma|Breast Carcinoma|Cervical Carcinoma|Colon Carcinoma|Colorectal Carcinoma|Endometrial Carcinoma|Esophageal Carcinoma|Gastric Carcinoma|Glioma|Head and Neck Carcinoma|Kidney Carcinoma|Liver and Intrahepatic Bile Duct Carcinoma|Lung Carcinoma|Lymphoma|Malignant Uterine Neoplasm|Melanoma|Ovarian Carcinoma|Pancreatic Carcinoma|Plasma Cell Myeloma|Prostate Carcinoma|Rectal Carcinoma|Recurrent Bladder Carcinoma|Recurrent Breast Carcinoma|Recurrent Cer August 12, 2015 Phase 2
NCT00787033 Verastem, Inc. Cancer December 2008 Phase 1
NCT02004028 Verastem, Inc. Malignant Pleural Mesothelioma December 2013 Phase 2
NCT02372227 Verastem, Inc. Relapsed Malignant Mesothelioma January 2015 Phase 1
NCT02943317 Verastem, Inc. Epithelial Ovarian Cancer October 2016 Phase 1
View MoreCollapse
References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.9589 mL 9.7945 mL 19.5890 mL
5 mM 0.3918 mL 1.9589 mL 3.9178 mL
10 mM 0.1959 mL 0.9795 mL 1.9589 mL
Animal Administration
[1]

Defactinib is prepared in phosphate-buffered saline[1].

Mice[1]
To determine the antitumor effects of VS-6063, SKOV3ip1, SKOV3-TR, HeyA8, and HeyA8-MDR cells are injected intraperitoneally. One week after tumor cell injection, mice are randomly assigned to 4 groups of 10 mice (control, PTX alone, VS-6063 alone, and PTX with VS-6063); treatment is initiated at 3-4 weeks following injection. PTX at 2 mg/kg (SKOV3ip1 and SKOV3-TR) or 2.5 mg/kg (HeyA8 and HeyA8-MDR) is given intraperitoneally weekly; VS-6063 at 25 mg/kg is given orally twice every day. Control mice received HBSS intraperitoneally once a week and vehicle orally twice every day. Mice are monitored daily for adverse effects of therapy and are killed on day 35 (SKOV3ip1 or SKOV3-TR), day 28 (HeyA8 or HeyA8-MDR), or when any of the mice seemed moribund. Total body weight, tumor incidence and mass, and the number of tumor nodules are recorded. Tumors are either fixed in formalin or embedded in paraffin or snap frozen in optimal cutting temperature (OCT) compound in liquid nitrogen. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

510.49

Formula

C₂₀H₂₁F₃N₈O₃S

CAS No.

1073154-85-4

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 39 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.94%

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
Defactinib
Cat. No.:
HY-12289
Quantity: