Pralsetinib (BLU-667)

製品コードS8716 バッチS871603

印刷

化学情報

Synonyms

CS 3009, Gavreto

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₇H₃₂FN₉O₂

分子量

533.60

CAS No.

2097132-94-8

Solubility (25°C)*

体外

DMSO

100 mg/mL (187.4 mM)

Ethanol

13 mg/mL (24.36 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (9.37mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Pralsetinib (BLU-667, CS 3009, Gavreto)は、WT RETに対してIC50 0.4 nMを示す、非常に強力で選択的なRET (c-RET)阻害剤です。また、RET (M918T)を含む一般的な癌原性RET変異に対しても強力な活性（IC50 0.4 nmol/L）を示します。
in vitro	Pralsetinib (BLU-667) is at least 100-fold more selective for RET over 96% of kinases tested (a panel of 371 kinases). It specifically abrogates RET signaling in RET-altered cancers from diverse lineages. RET pathway inhibition with this compound also more potently inhibits proliferation of RET-altered cell lines relative to multikinase inhibitors.
in vivo	Pralsetinib (BLU-667) potently inhibits growth of NSCLC and thyroid cancer xenografts driven by various RET mutations and fusions without inhibiting VEGFR2 in vivo. It is well tolerated throughout the in vivo studies.

プロトコル(参考用のみ)

キナーゼアッセイ	Human Kinase Selectivity
キナーゼアッセイ	Pralsetinib (BLU-667) is screened at 300 nmol/L for inhibitory activity across a panel of 371 kinases. The 23 kinases inhibited >50% at 300 nmol/L are selected for full 10 point concentration-response curves with this compound (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.
細胞アッセイ	細胞株	LC2/ad cells,　MZ-CRC-1 cells and TT cells
	濃度	0-1 μM
	反応時間	90 minutes
	実験の流れ	--
動物実験	動物モデル	PDX tumor models (BALB/c nude mice)
	投薬量	3, 10, or 30 mg/kg twice daily or 60 mg/kg once daily
	投与方法	--

参考

https://pubmed.ncbi.nlm.nih.gov/29657135/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

AP1-mediated reprogramming of EGFR expression triggers resistance to BLU-667 and LOXO-292 in RET-rearranged tumors [ J Exp Clin Cancer Res, 2025, 44(1):154]	PubMed: 40405293
LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib [ J Pharm Biomed Anal, 2025, 266:117078]	PubMed: 40743983
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
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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。