Pralsetinib (Blu667)
(Synonyms: 普拉替尼; BLU-667) 目录号 : GC31780
Pralsetinib (Blu667)是转染重排（RET）激酶抑制剂，用于治疗特定的RET基因变异阳性肿瘤。
Cas No.:2097132-94-8
Sample solution is provided at 25 µL, 10mM.
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Pralsetinib (Blu667) is a selective inhibitor of the rearranged during transfection (RET) kinase, indicated for the treatment of certain RET-altered positive tumors[1-2]. By selectively inhibiting RET fusions and mutations, Pralsetinib blocks downstream signaling pathways such as MAPK and PI3K-AKT, thereby suppressing tumor cell proliferation and inducing apoptosis[3-4].
In vitro, treatment of RET-altered thyroid cancer and non-small cell lung cancer cells (TPC1, LC-2/ad, TT, and MZCRC1) with Pralsetinib (2-5µM) significantly inhibited cell proliferation and induced cell death[5]. In T47D and MCF7 breast cancer cells expressing transcriptionally active ESR1 fusion proteins or ERα ligand-binding domain point mutations (Y537S, D538G), Pralsetinib (100-500nM) markedly suppressed cell growth[6].
In vivo, daily oral administration of Pralsetinib (10-30mg/kg) in female athymic nude mice intracranially inoculated with MDA-MB-231-BrM triple-negative breast cancer cells. Pralsetinib significantly inhibited intracranial tumor growth[7]. In a C57BL/6 mouse model bearing orthotopic lung adenocarcinoma tumors derived from Trim24-Ret cell lines, daily oral treatment with Pralsetinib (20mg/kg) for 8 weeks induced significant tumor shrinkage, although acquired resistance emerged after 3 weeks of treatment[8].
References:
[1] Markham A. Pralsetinib: First Approval. Drugs. 2020 Nov;80(17):1865-1870.
[2] Nguyen L, Monestime S. Pralsetinib: Treatment of metastatic RET fusion-positive non-small cell lung cancer. Am J Health Syst Pharm. 2022 Mar 21;79(7):527-533
[3] Syed YY. Pralsetinib: A Review in Advanced RET Fusion-Positive NSCLC. Drugs. 2022 May;82(7):811-816.
[4] Griesinger F, Curigliano G, Thomas M, et al. Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial. Ann Oncol. 2022 Nov;33(11):1168-1178.
[5] Hu X, Liu X, Khatri U, et al. The heterogeneous transition state of resistance to RET kinase inhibitors converges on ERK1/2-driven Aurora A/B kinases. Drug Resist Updat. 2023 May;68:100958.
[6] Gou X, Kim BJ, Anurag M, et al. Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer. Cancer Res. 2023 Oct 2;83(19):3237-3251.
[7] Regua AT, Bindal S, Najjar M, et al. RET Receptor Tyrosine Kinase Promotes Breast Cancer Metastasis to the Brain and RET Inhibitors Pralsetinib and Selpercatinib Suppress Breast Cancer Brain Metastases. bioRxiv [Preprint]. 2025 Oct 8:2025.10.07.680986.
[8] Hinz TK, Le AT, Doan T, et al. Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma. bioRxiv [Preprint]. 2025 Jun 7:2025.06.04.657911.
Pralsetinib (Blu667)是转染重排（RET）激酶抑制剂，用于治疗特定的RET基因变异阳性肿瘤[1-2]。Pralsetinib通过选择性抑制RET融合和突变，阻断下游MAPK、PI3K-AKT等信号通路，从而抑制肿瘤细胞增殖并诱导其凋亡[3-4]。
在体外，Pralsetinib（2-5μM）处理RET基因改变的TPC1、LC-2/ad、TT和MZCRC1甲状腺癌和非小细胞肺癌细胞，Pralsetinib显著抑制细胞增殖并诱导细胞死亡[5]。Pralsetinib（100-500nM）处理表达转录活性ESR1融合蛋白或ERα配体结合域点突变（Y537S、D538G）的T47D和MCF7乳腺癌细胞，Pralsetinib显著抑制细胞生长[6]。
在体内，Pralsetinib（10-30mg/kg；每日一次口服给药）处理经颅内接种MDA-MB-231-BrM三阴性乳腺癌细胞的雌性无胸腺裸鼠，显著抑制脑内肿瘤生长[7]。Pralsetinib（20mg/kg；每日一次口服给药）处理Trim24-Ret细胞系肺腺癌原位移植瘤的C57BL/6小鼠8周，Pralsetinib显著诱导肿瘤缩小，但治疗3周后出现获得性耐药[8]。
| Cell experiment [1]: | |
Cell lines | T47D and MCF7 ERα+ breast cancer cells (human breast cancer cell lines) |
Preparation Method | T47D and MCF7 cells stably expressing ESR1 fusion proteins or ESR1 LBD point mutants (Y537S, D538G) were maintained in hormone-deprived CSS media. Cells were treated with Pralsetinib at clinically relevant concentrations (100-500nM) for 48 hours to 2 weeks. |
Reaction Conditions | 100-500nM; 48h to 2 weeks. |
Applications | Pralsetinib significantly inhibited cell growth of ESR1 fusion-driven breast cancer cells, with IC50 values of ~100-120nM. Pralsetinib treatment potently inhibited RET phosphorylation (p-RET Y905) and downstream signaling pathways including ERK (p-ERK T202/Y204) and STAT3 (p-STAT3 Y705). Pralsetinib also induced apoptosis. |
| Animal experiment [2]: | |
Animal models | Female athymic nude mice (nu/nu) |
Preparation Method | Mice were intracardially or intracranially inoculated with luciferase-expressing MDA-MB-231-BrM breast cancer cells. Mice received daily oral administration of Pralsetinib (10-30mg/kg; for 2 weeks) starting one day after tumor cell inoculation. For the treatment model, Pralsetinib administration began 10-14 days post-inoculation after brain metastases were established. Mice were monitored by bioluminescent imaging twice weekly. |
Dosage form | 10-30mg/kg; oral gavage; daily for 2 weeks. |
Applications | Pralsetinib treatment significantly reduced brain metastasis burden by 67% in the preventative model when administered early (30mg/kg). In the intracranial model, Pralsetinib (10mg/kg) significantly suppressed established brain tumor growth and enhanced tumor cell apoptosis. |
References: | |
| Cas No. | 2097132-94-8 | SDF | |
| 别名 | 普拉替尼; BLU-667 | ||
| Canonical SMILES | O=C([C@@]1(OC)CC[C@@H](C2=NC(NC3=NNC(C)=C3)=CC(C)=N2)CC1)N[C@H](C4=CC=C(N5N=CC(F)=C5)N=C4)C | ||
| 分子式 | C27H32FN9O2 | 分子量 | 533.6 |
| 溶解度 | DMSO : ≥ 100 mg/mL (187.41 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at 4°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8741 mL | 9.3703 mL | 18.7406 mL |
| 5 mM | 374.8 μL | 1.8741 mL | 3.7481 mL |
| 10 mM | 187.4 μL | 937 μL | 1.8741 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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