1. MAPK/ERK Pathway
  2. Raf

PLX8394 

Cat. No.: HY-18972 Purity: 98.44%
Data Sheet SDS Handling Instructions

PLX8394 is a potent and selective Raf inhibitor, with IC50 of appr 5 nM for BRAFV600E.

For research use only. We do not sell to patients.
PLX8394 Chemical Structure

PLX8394 Chemical Structure

CAS No. : 1393466-87-9

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $107 In-stock
5 mg $90 In-stock
10 mg $150 In-stock
50 mg $490 In-stock
100 mg $790 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

PLX8394 is a potent and selective Raf inhibitor, with IC50 of appr 5 nM for BRAFV600E.

IC50 & Target

IC50: appr 5 nM (BRAFV600E)[1]

In Vitro

PLX8394 potently inhibits phosphorylation of ERK1/2 in PRT #3 and PRT #4 cells at >25 nM and in addition to parental cells at 10 nM. PLX8394 effectively reduces cyclin D3 and cyclin D1, phosphorylation of retinoblastoma protein, and expression of cyclin A2 in parental cells and PRT #3 and PRT #4 cells. PLX8394 inhibits ERK1/2 phosphorylation and the growth of vemurafenib-resistant cells harboring either a BRAF V600K/L505H double mutation or an transposon-induced, N-terminal truncated form of BRAF[1]. PLX8394 significantly impairs tumor cell growth and suppresses MAPK signaling in LA cell lines expressing either endogenous V600E or non-V600 mutant forms of BRAF[2].

In Vivo

PLX8394 (150 mg/kg/d) substantially suppresses tumor growth, MAPK pathway signaling and tumor cell proliferation in these H1755 xenograft tumors without overt toxicity in mice. PLX8394 combines with erlotinib yields plasma erlotinib concentrations of >1 μM[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02428712 Plexxikon Advanced Unresectable Solid Tumors April 2015 Phase 1|Phase 2
NCT02012231 Plexxikon Melanoma|Thyroid Cancer|Colorectal Cancer|Non-small Cell Lung Cancer|Cholangiocarcinoma|Histiocytosis|Hairy Cell Leukemia February 2014 Phase 1|Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.8432 mL 9.2161 mL 18.4322 mL
5 mM 0.3686 mL 1.8432 mL 3.6864 mL
10 mM 0.1843 mL 0.9216 mL 1.8432 mL
Cell Assay
[1]

PLX8394 is dissolved in DMSO.

For MTT assays, 2×103 cells are seeded in triplicate in 96 wells in their regular culture medium (containing PLX4720 for PRT lines). Next day, cells are washed twice with PBS and then the medium is replenished containing the indicated RAF inhibitor. Medium is changed 48 hours later and after a further 48 hours, 10 μL of 5 mg/mL MTT reagent is added to wells, and incubated for three hours. Formazan crystals are then solubilized overnight with a 1:10 dilution of 0.1 M glycine (pH 10.5) in DMSO. Wells are then analyzed at 450 nM in a Multiskan® Spectrum spectrophotometer. Results depicted are normalized to DMSO conditions and are a composite of three independent experiments. Error bars shown are representative of the standard error of mean (SEM). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

PLX8394 is dissolved in PEG 400 [20% (vol/vol)], TPGS [5% (vol/vol)], and water [75% (vol/vol)].

H1755 tumor xenografts are generated by injection of 5×106 cells in a 50/50 mixture for matrigel and PBS into 6- to 8-wk-old female NOD/SCID mice. Mice are randomized to treatment groups once tumors reach an average size of 150 mm3. H1755 cells are s.c. implanted and allowed to grow to appr 200 mm3 (4 wk after implantation). Mice are then treated with vehicle, vemurafenib, or PLX8394 for 15 d. The vehicle for daily oral gavage is PEG 400 [20% (vol/vol)], tocopheryl polyethylene glycol succinate (TPGS) [5% (vol/vol)], water [75% (vol/vol)]. PLX8394 is dissolved in PEG 400 [20% (vol/vol)], TPGS [5% (vol/vol)], and water [75% (vol/vol)] and vortexed continuously throughout the dosing period. PLX8394 is given daily by oral gavage at a dose of 150 mg/kg/d. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

542.53

Formula

C₂₅H₂₁F₃N₆O₃S

CAS No.

1393466-87-9

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.

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Product Name:
PLX8394
Cat. No.:
HY-18972
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