1. Protein Tyrosine Kinase/RTK
  2. FAK

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

Cat. No.: HY-12289 Purity: 99.32%
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
Free Sample (0.5-1 mg)   Apply now  
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  

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Other Forms of Defactinib:

    Defactinib purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    Defactinib purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.
    • 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].

    References
    Preparing Stock Solutions
    Concentration Volume 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
    Please refer to the solubility information to select the appropriate solvent.
    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: 99.32%

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