1. MAPK/ERK Pathway
    Protein Tyrosine Kinase/RTK
  2. Raf
    p38 MAPK
    Bcr-Abl
  3. LXH254

LXH254 

Cat. No.: HY-112089 Purity: 99.95%
Handling Instructions

LXH254 is a potent, selective, orally active, type II BRAF and CRAF inhibitor, with IC50 values of 0.072 and 0.21 nM against CRAF and BRAF, respectively.

For research use only. We do not sell to patients.

LXH254 Chemical Structure

LXH254 Chemical Structure

CAS No. : 1800398-38-2

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Solution
10 mM * 1 mL in DMSO USD 276 In-stock
Estimated Time of Arrival: December 31
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10 mM * 1 mL
ready for reconstitution
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Estimated Time of Arrival: December 31
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5 mg USD 250 In-stock
Estimated Time of Arrival: December 31
10 mg USD 390 In-stock
Estimated Time of Arrival: December 31
25 mg USD 680 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1200 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 1 publication(s) in Google Scholar

Top Publications Citing Use of Products

1 Publications Citing Use of MCE LXH254

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Description

LXH254 is a potent, selective, orally active, type II BRAF and CRAF inhibitor, with IC50 values of 0.072 and 0.21 nM against CRAF and BRAF, respectively[2].

IC50 & Target[1]

CRAF

0.072 nM (IC50)

Braf

0.21 nM (IC50)

ARAF

6.4 nM (IC50)

p38α

2.1 μM (IC50)

Abl1

4.9 μM (IC50)

In Vitro

LXH254 (Compound A) is an adenosine triphosphate (ATP)-competitive inhibitor of BRAF (also referred to herein as b-RAF or b-Raf) and CRAF (also referred to herein as c-RAF or c- Raf) protein kinases. Throughout the present disclosure, LXH254 is also referred to as a c-RAF (or CRAF) inhibitor or a C-RAF/c-Raf kinase inhibitor. In cell-based assays, LXH254 has demonstrated anti-proliferative activity in cell lines that contain a variety of mutations that activate MAPK signaling. Moreover, LXH254 is a Type 2 ATP -competitive inhibitor of both B-Raf and C-Raf that keeps the kinase pocket in an inactive conformation, thereby reducing the paradoxical activation seen with many B-Raf inhibitors, and blocking mutant RAS-driven signaling and cell proliferation[1].
LXH254 (0-10 µM, 1 h) inhibits both monomeric and dimeric RAF and promotes RAF dimer formation[2].
LXH254 has reduced ability to suppress MAPK signaling driven by ARAF and further that the contribution of ARAF to MAPK signaling increases in the absence of CRAF expression[2].
LXH254 shows more sensitivity when cells lack ARAF[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[2]

Cell Line: HCT116, MEL-JUSO, Mia PaCa-2, A375(BRAFV600E), and HCT116 (KRASG13D)
Concentration: 0-10 µM
Incubation Time: 1 h
Result: Promoted B/CRAF heterodimer formation. Displayed similar inhibition of monomeric BRAFV600 and wild-type dimeric RAF (IC50 for p-ERK levels of 59 and 78 nmol/L in A-375 and HCT 116 cells, respectively).

Cell Proliferation Assay[2]

Cell Line: Two NRAS-mutant melanoma cell lines (MEL-JUSO and SK-MEL-30), three KRAS-mutant cell lines (COR-L23, MIA PaCa-2, and HCT116), and derived variants lacking expression of either ARAF, BRAF, or CRAF.
Concentration: 0-10 µM
Incubation Time: 24 h
Result: The sensitivity was increased relative to parental cell lines in all models tested by loss of ARAF expression.
In Vivo

Treatment with LXH254 (Compound A) generates tumor regression in several KRAS-mutant models including the NSCLC-derived Calu-6 (KRAS Q61K) and NCI-H358 (KRAS G12C). LXH254 exhibits efficacy in numerous MAPK-driven human cancer cell lines and in xenograft tumors representing model tumors harboring human lesions in KRAS, NRAS and BRAF oncogenes[1].
LXH254 shows significant antitumor activity in models harboring BRAF mutations either alone or coincident with either activated NRAS or KRAS, and RAS mutants lacking ARAF are more sensitive to LXH254[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Outbred athymic (nu/nu) female mice and SCID Beige mice; BRAF-, NRAS-, and KRAS-mutant xenograft models, as well as a RAS/RAF wild-type model[2]
Dosage: 100 mg/kg
Administration: Orally, daily
Result: Significantly decreased tumor volume in models harboring BRAF mutations either alone or coincident with either activated NRAS or KRAS, slightly decreased tumor volume in KRAS model.
Clinical Trial
Molecular Weight

502.49

Formula

C25H25F3N4O4

CAS No.
SMILES

CC1=CC=C(NC(C2=CC(C(F)(F)F)=NC=C2)=O)C=C1C3=CC(N4CCOCC4)=NC(OCCO)=C3

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (199.01 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.9901 mL 9.9504 mL 19.9009 mL
5 mM 0.3980 mL 1.9901 mL 3.9802 mL
10 mM 0.1990 mL 0.9950 mL 1.9901 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (4.98 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (4.98 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (4.98 mM); Clear solution

  • 4.

    Add each solvent one by one:  5% DMSO    40% PEG300    5% Tween-80    50% saline

    Solubility: 2.5 mg/mL (4.98 mM); Suspended solution; Need ultrasonic

*All of the co-solvents are available by MCE.
References

Purity: 99.95%

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Product Name:
LXH254
Cat. No.:
HY-112089
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