Pralsetinib (BLU-667)

目录号：S8716 批次号：S871602

化学数据

	别名	CS 3009, Gavreto	储存条件 (自收到货起)	3年 -20°C 粉状
	化学式	C₂₇H₃₂FN₉O₂
	分子量	533.60	CAS号	2097132-94-8
Solubility (25°C)*	体外	DMSO	100 mg/mL (187.4 mM)
		Ethanol	10 mg/mL (18.74 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

制备储备液

生物活性

产品描述

Pralsetinib (BLU-667, CS 3009, Gavreto) 是一种高效的、选择性RET (c-RET)抑制剂，对WT RET (c-RET)的IC50值为0.4 nM。它对一些常见的RET (c-RET)致癌突变同样具有有效的抑制作用，IC50~0.4 nM。

靶点

RET V804L ^[1] (Cell-free assay )	WT RET ^[1] (Cell-free assay)	RET V804M ^[1] (Cell-free assay)	RET M918T ^[1] (Cell-free asssay)	CCDC6-RET ^[1] (Cell-free assay)	View More
0.3 nM	0.4 nM	0.4 nM	0.4 nM	0.4 nM	View More

体外研究

在包含371种激酶的激酶库中，BLU-667对RET的选择性比对其中96%的激酶选择性高至少100倍。在含有RET突变的癌细胞中，BLU-667可特异地抑制RET信号、BLU-667比其他多激酶抑制剂更有效地抑制含RET突变的细胞系增殖^[1]。

体内研究

在体内，BLU-667可有效地抑制受多种RET突变和融合驱动的NSCLC和甲状腺癌异种移植瘤，而不抑制VEGFR2。BLU-667在体内实验中耐受性良好^[1]。

激酶实验	Human Kinase Selectivity
BLU-667 was screened at 300 nmol/L for inhibitory activity across a panel of 371 kinases. The 23 kinases inhibited >50% at 300 nmol/L were selected for full 10 point concentration-response curves with BLU-667 (1 μmol/L maximum concentration) at 200 μmol/L ATP to generate biochemical IC50 (Reaction Biology Corp) using 33P-ATP (10 mCi/mL) to initiate the reaction, followed by the detection of kinase activity by a filter-binding method.
细胞实验	细胞系	LC2/ad细胞,　MZ-CRC-1细胞和TT细胞
浓度	0-1 μM
处理时间	90分钟
方法	--
动物实验	动物模型	PDX肿瘤模型 (BALB/c裸小鼠)
剂量	3, 10, 30 mg/kg（一天两次）或 60 mg/kg（一天一次）
给药处理	--

参考文献

[1] Subbiah V, et al. Cancer Discov. 2018, 8(7):836-849.

Pralsetinib (BLU-667)在文献中得到引用

Loss of tumor suppressor TMEM127 drives RET-mediated transformation through disrupted membrane dynamics [ Elife, 2024, 12RP89100]	PubMed: 38687678
Novel therapeutic strategies targeting bypass pathways and mitochondrial dysfunction to combat resistance to RET inhibitors in NSCLC [ Biochim Biophys Acta Mol Basis Dis, 2024, 1870(6):167249]	PubMed: 38768929
Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+ CD8+ T cells in HCC via blocking VEGFR2 [ Cancer Sci, 2023, 114(4):1284-1296]	PubMed: 36609997
Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+ CD8+ T cells in HCC via blocking VEGFR2 [ Cancer Sci, 2023, 114(4):1284-1296]	PubMed: 36609997
Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+ CD8+ T cells in HCC via blocking VEGFR2 [ Cancer Sci, 2023, 114(4):1284-1296]	PubMed: 36609997
Loss of Tumour Suppressor TMEM127 Drives RET-mediated Transformation Through Disrupted Membrane Dynamics [ bioRxiv, 2023, 2023.06.28.546955]	PubMed: 37425958
Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis [ Cancer Res, 2022, 82(20):3751-3762]	PubMed: 36166639
The kinase PLK1 promotes the development of Kras/Tp53-mutant lung adenocarcinoma through transcriptional activation of the receptor RET [ Sci Signal, 2022, 15(754):eabj4009]	PubMed: 36194647
Targeting RET Kinase in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 18(8):1176-1188]	PubMed: 32461304
Elucidating the Mechanism of RET Kinase Activity in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 1176-1188]	PubMed: None

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如果需要长期保存，请于零下二十度低温保存。禁止用于人体及治疗！

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