LXH254|cas:1800398-38-2|西域试剂

LXH254,99.95%

产品编号：Bellancom-112089| CAS NO：1800398-38-2| 分子式：C₂₅H₂₅F₃N₄O₄| 分子量：502.49

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-112089	￥1500.00	杭州北京（现货）
Bellancom-112089	￥2350.00	杭州北京（现货）
Bellancom-112089	￥4600.00	杭州北京（现货）
Bellancom-112089	￥7200.00	杭州北京（现货）

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LXH254

产品介绍

LXH254 是一种有效的、具有口服活性的 II 型 BRAF 和 CRAF 抑制剂，对 CRAF 和 BRAF的 IC₅₀ 值分别为 0.072 和 0.21 nM。

生物活性

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.

体外研究

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.
LXH254 (0-10 µM, 1 h) inhibits both monomeric and dimeric RAF and promotes RAF dimer formation.
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.
LXH254 shows more sensitivity when cells lack ARAF.

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

Western Blot Analysis

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

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.

体内研究
(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.
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.

西域 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
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.

体内研究

西域 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
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.

体内研究

西域 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
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.

性状

Solid

溶解性数据

In Vitro:

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

配制储备液

浓度溶剂体积质量	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

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (4.98 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (4.98 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (4.98 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (4.98 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.98 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (4.98 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
4.

请依序添加每种溶剂： 5% DMSO 40% PEG300 5% Tween-80 50% saline
Solubility: 2.5 mg/mL (4.98 mM); Suspended solution; Need ultrasonic