Pirtobrutinib是一种高选择性、非共价、可逆的Bruton's tyrosine kinase (BTK)抑制剂，对BTK和BTKC481S的IC50值分别为3.2nM和1.4nM。
Cas No.:2101700-15-4
Sample solution is provided at 25 µL, 10mM.
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Pirtobrutinib is a highly selective, non-covalent, reversible Bruton's tyrosine kinase (BTK) inhibitor, with IC50 values of 3.2nM and 1.4nM for BTK and BTKC481S, respectively [1]. Pirtobrutinib can effectively inhibit the self-phosphorylation of BTK at the tyrosine 223 (Y223) site and the related downstream signaling pathways, and can reduce the phosphorylation at the upstream tyrosine 551 (Y551) site[2]. Pirtobrutinib has been widely used to inhibit chronic B-cell malignancies and platelet signal transduction and function[3].
In vitro, Pirtobrutinib treatment for 72 hours significantly inhibited the proliferation of TMD8 cells and REC-1 cells, with IC50 values of 6.4nM and 3.1nM, respectively[4]. Treatment with Pirtobrutinib (0.5μM) for 36 hours significantly inhibited the release of p-ERK1/2 and ERK1/2-driven inflammatory cytokines in BCWM.1 cells expressing BTKC481S [5]. Treatment with Pirtobrutinib (1μM) for 24 hours significantly inhibited the overall DNA and RNA synthesis in MEC-1 cells that expressed BTKC481S [6].
References:
[1] Gomez E B, Ebata K, Randeria H S, et al. Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor[J]. Blood, The Journal of the American Society of Hematology, 2023, 142(1): 62-72.
[2] Molica S, Allsup D. Pirtobrutinib in Chronic Lymphocytic Leukemia: Navigating Resistance and the Personalisation of BTK-Targeted Therapy[J]. Cancers, 2025, 17(18): 2974.
[3] Bye A P, Kriek N, Sage T, et al. Pirtobrutinib results in reversible platelet dysfunction compared to ibrutinib and acalabrutinib[J]. Haematologica, 2022, 108(5): 1429.
[4] Keam S J. Pirtobrutinib: First Approval[J]. Drugs, 2023, 83(6).
[5] Munshi M, Liu X, Kofides A, et al. ERK1/2 pro‐survival signalling is suppressed by pirtobrutinib in ibrutinib‐resistant MYD88‐mutated lymphoma cells[J]. British Journal of Haematology, 2024, 205(5): 1866-1872.
[6] Aslan B, Kismali G, Iles L R, et al. Pirtobrutinib inhibits wild-type and mutant Bruton’s tyrosine kinase-mediated signaling in chronic lymphocytic leukemia[J]. Blood cancer journal, 2022, 12(5): 80.
Pirtobrutinib是一种高选择性、非共价、可逆的Bruton's tyrosine kinase (BTK)抑制剂，对BTK和BTKC481S的IC50值分别为3.2nM和1.4nM[1]。Pirtobrutinib能有效抑制BTK在酪氨酸223位点的自身磷酸化及相关的下游信号通路，并能减少上游酪氨酸551位点的磷酸化[2]。Pirtobrutinib已被广泛用于抑制慢性B细胞恶性肿瘤以及血小板信号转导和功能[3]。
在体外，Pirtobrutinib处理72小时显著抑制了TMD8细胞和REC-1细胞的增殖，IC50值分别为6.4nM和3.1nM[4]。使用0.5μM的Pirtobrutinib处理表达BTKC481S的BCWM.1细胞36小时，显著抑制了p-ERK1/2以及ERK1/2驱动的炎症细胞因子的释放[5]。使用1μM的Pirtobrutinib处理表达BTKC481S的MEC-1细胞24小时，显著抑制了细胞总的DNA和RNA合成[6]。
| Cell experiment [1]: | |
Cell lines | TMD8 cells |
Preparation Method | TMD8 cells were cultured at 37°C and 5% CO2 in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS). TMD8 cells were plated at a density of 1.5×104 cells/ml in a 384-well plate with growth medium for 24h, and then were incubated with the different concentrations of Pirtobrutinib (0.01, 0.1, 1, 10, 100, and 1000nM) for 72h, analyzed the cell viability. |
Reaction Conditions | 0.01, 0.1, 1, 10, 100, and 1000nM; 72h |
Applications | Pirtobrutinib treatment significantly inhibited cell viability of TMD8 cells in a concentration-dependent manner. |
References: | |
| Cas No. | 2101700-15-4 | SDF | |
| 别名 | LOXO-305 | ||
| 分子式 | C22H21F4N5O3 | 分子量 | 479.43 |
| 溶解度 | DMSO : 50 mg/mL (104.29 mM; Need ultrasonic) | 储存条件 | 4°C, stored under nitrogen |
| 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0858 mL | 10.4291 mL | 20.8581 mL |
| 5 mM | 417.2 μL | 2.0858 mL | 4.1716 mL |
| 10 mM | 208.6 μL | 1.0429 mL | 2.0858 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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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- Purity: >98.50% Appearance: A solid
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