LXH254 free base · Synonyms: Naporafenib

LXH254 is a potent B/C RAF inhibitor extracted from patent WO2018051306A1, Compound A.

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

Target Raf p38 MAPK Bcr-Abl

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

LXH254 structure

CAS No.: 1800398-38-2

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
100 mg	USD 580.00	BP-02136-100mg	In stock	Get quote
250 mg	USD 1,150.00	BP-02136-250mg	In stock	Get quote
500 mg	USD 1,800.00	BP-02136-500mg	In stock	Get quote
1 g	USD 2,900.00	BP-02136-1g	In stock	Get quote
2 g	Inquire	BP-02136-2g	In stock	Inquire

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Description

LXH254 is a potent B/C RAF inhibitor extracted from patent WO2018051306A1, Compound A.

Biological activity

In Vitro Naporafenib (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, Naporafenib is also referred to as a c-RAF (or CRAF) inhibitor or a C-RAF/c-Raf kinase inhibitor. In cell-based assays, Naporafenib has demonstrated anti-proliferative activity in cell lines that contain a variety of mutations that activate MAPK signaling. Moreover, Naporafenib 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. Naporafenib (0-10 µM, 1 h) inhibits both monomeric and dimeric RAF and promotes RAF dimer formation[2]. Naporafenib 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. Naporafenib shows more sensitivity when cells lack ARAF. In Vivo Treatment with Naporafenib (Compound A) generates tumor regression in several KRAS-mutant models including the NSCLC-derived Calu-6 (KRAS Q61K) and NCI-H358 (KRAS G12C). Naporafenib 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. Naporafenib 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 Naporafenib.

Identifiers

SMILES: CC1=CC=C(NC(=O)C2=CC(=NC=C2)C(F)(F)F)C=C1C1=CC(OCCO)=NC(=C1)N1CCOCC1
InChIKey: UEPXBTCUIIGYCY-UHFFFAOYSA-N

Specifications

MW (average): 502.4856
Formula: C₂₅H₂₅F₃N₄O₄
CAS No.: 1800398-38-2
Physical state: Solid
Color: Off-white to light yellow
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

Documents

References

[1]. CAPONIGRO, Giordano, et al. THERAPEUTIC COMBINATIONS COMPRISING A RAF INHIBITOR AND A ERK INHIBITOR. WO 2018051306 A1 20180322

[2]. Kelli-Ann Monaco, et al. LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors. Clin Cancer Res. 2021 Apr 1;27(7):2061-2073.

Same target

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Same research area

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