Art. -Nr.: HY-112089

Naporafenib

(Synonyms: LXH254)

6 Cited Publications

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Based on 6 publication(s) in Google Scholar

Naporafenib (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.

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Reinheit: 99.92%
CAS. Nr.: 1800398-38-2
Formel: C₂₅H₂₅F₃N₄O₄
Molecular Weight:502.49

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months

Naporafenib Chemical Structure

CAS. Nr.: 1800398-38-2

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (6)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Naporafenib (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^[1]^[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)

Alle Raf Isoform-spezifische Produkte anzeigen :

Alle p38 MAPK Isoform-spezifische Produkte anzeigen :

Alle Bcr-Abl Isoform-spezifische Produkte anzeigen :

Abl
Bcr-Abl

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	0.24 μM Compound: 14, LXH254	Antiproliferative activity against human A-375 cells Antiproliferative activity against human A-375 cells	[PMID: 32910655]
Calu-6	EC₅₀	0.28 μM Compound: 15; LXH254	Antiproliferative activity against human Calu6 cells harboring KRAS Q61K mutant assessed as reduction in cell viability after 72 hrs by CellTiter-Glo assay Antiproliferative activity against human Calu6 cells harboring KRAS Q61K mutant assessed as reduction in cell viability after 72 hrs by CellTiter-Glo assay	[PMID: 31059256]
NCI-H358	GI₅₀	3 μM Compound: LXH254	Cytotoxicity against human NCI-H358 cells assessed as inhibition of growth measured after 72 hrs by CellTiter-Glo luciferase assay Cytotoxicity against human NCI-H358 cells assessed as inhibition of growth measured after 72 hrs by CellTiter-Glo luciferase assay	[PMID: 34906761]
NCI-H358	GI₅₀	3 μM Compound: LXH254	Growth inhibition of human H358 cells expressing KRAS G21C mutant measured after 3 days by Cell-titer Glo assay Growth inhibition of human H358 cells expressing KRAS G21C mutant measured after 3 days by Cell-titer Glo assay	[PMID: 35276360]

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^[1].
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^[2].
Naporafenib shows more sensitivity when cells lack ARAF^[2].

MedChemExpress (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(BRAF^V600E), and HCT116 (KRAS^G13D)
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 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^[1].
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^[2].

MedChemExpress (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

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS. Nr. 1800398-38-2
Appearance Solid
Molecular Weight 502.49
Formel C₂₅H₂₅F₃N₄O₄
Color Off-white to light yellow
SMILES

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

LXH254
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Publications (6)

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Journal Impact Factor

PLoS One

2026 Apr 24;21(4):e0347843.
Biomed Chromatogr

A validated LC-MS/MS method for the determination of RAF inhibitor LXH254: Application to pharmacokinetic study in rat. [Abstract]

2021 Feb;35(2):e4968. PMID: 32881002

Naporafenib purchased from MedChemExpress. Usage Cited in: Biomed Chromatogr. 2021 Feb;35(2):e4968. [Abstract]

Plasma concentration-time profiles of Naporafenib (LXH254) in rat plasma after intravenous (2 mg/kg) administration.

Naporafenib purchased from MedChemExpress. Usage Cited in: Biomed Chromatogr. 2021 Feb;35(2):e4968. [Abstract]

Pharmacokinetic parameters of Naporafenib (LXH254) in rats after intravenous administration
Note. Data are expressed as mean ± standard deviation (n = 6). AUC, area under the plasma concentration–time curve; CL, clearance; MRT, mean residence time.

Naporafenib purchased from MedChemExpress. Usage Cited in: Biomed Chromatogr. 2021 Feb;35(2):e4968. [Abstract]

Plasma concentration-time profiles of Naporafenib (LXH254) in rat plasma after oral (2, 5, and 15 mg/kg) administrations.

Naporafenib purchased from MedChemExpress. Usage Cited in: Biomed Chromatogr. 2021 Feb;35(2):e4968. [Abstract]

Pharmacokinetic parameters of Naporafenib (LXH254) in rats after oral administration
Note. Data are expressed as mean ± standard deviation (n = 6). AUC, area under the plasma concentration–time curve; CL, clearance; MRT, mean residence time.
Patent

US20240239801A1.

Naporafenib purchased from MedChemExpress. Usage Cited in: Patent. US20240239801A1.

Naporafenib (LXH254) exhibited an IC₅₀ of >20 nM for ARAF kinase.
Patent

US20240140945A1.
bioRxiv

2024 July 12.
Research Square Print

October 27th, 2022.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (199.01 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 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

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 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

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

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

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

Protocol 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

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.9901 mL	9.9504 mL	19.9009 mL	49.7522 mL
	5 mM	0.3980 mL	1.9901 mL	3.9802 mL	9.9504 mL
	10 mM	0.1990 mL	0.9950 mL	1.9901 mL	4.9752 mL
	15 mM	0.1327 mL	0.6634 mL	1.3267 mL	3.3168 mL
	20 mM	0.0995 mL	0.4975 mL	0.9950 mL	2.4876 mL
	25 mM	0.0796 mL	0.3980 mL	0.7960 mL	1.9901 mL
	30 mM	0.0663 mL	0.3317 mL	0.6634 mL	1.6584 mL
	40 mM	0.0498 mL	0.2488 mL	0.4975 mL	1.2438 mL
	50 mM	0.0398 mL	0.1990 mL	0.3980 mL	0.9950 mL
	60 mM	0.0332 mL	0.1658 mL	0.3317 mL	0.8292 mL
	80 mM	0.0249 mL	0.1244 mL	0.2488 mL	0.6219 mL
	100 mM	0.0199 mL	0.0995 mL	0.1990 mL	0.4975 mL

Keywords

Naporafenib

6 Cited Publications

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Naporafenib

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Publications Citing Use of MedChemExpress (MCE) Naporafenib

Alle Raf Isoform-spezifische Produkte anzeigen

Alle p38 MAPK Isoform-spezifische Produkte anzeigen

Alle Bcr-Abl Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (6)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Naporafenib Related Classifications

HY-112089 Related Classifications