Department of Chemistry, Conju-Probe, San Diego, California, USA.
Bharath University, Chennai, Tamil Nadu, 600126, India.
Curr Med Chem. 2024;31(30):4757-4762. doi: 10.2174/0109298673251030231004052822.
Mantle Cell Lymphoma (MCL) is an aggressive subtype of Non-hodgkin's Lymphoma (NHL). Bruton Tyrosine Kinase (BTK) is a non-receptor tyrosine kinase, and is one of the therapeutic targets for B-cell-driven malignancies. Approved covalent BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib are associated with treatment limitations due to off-target side effects and the development of C481 substitution resistance mutations. Pirtobrutinib was approved by the US FDA on January 27, 2023, for the treatment of relapsed or refractory mantle cell lymphoma, including the resistance to covalent BTK inhibitors. In this perspective, physicochemical properties, synthesis, dosage and administration, mechanism of action, pharmacodynamics, pharmacokinetics, drug interactions, and treatment-emergent adverse events of pirtobrutinib are discussed.
套细胞淋巴瘤（MCL）是一种侵袭性非霍奇金淋巴瘤（NHL）亚型。布鲁顿酪氨酸激酶（BTK）是一种非受体酪氨酸激酶，是 B 细胞驱动的恶性肿瘤的治疗靶点之一。已批准的共价 BTK 抑制剂，如伊布替尼、阿卡替尼和泽布替尼，由于脱靶副作用和 C481 取代耐药突变的发展，存在治疗局限性。培托鲁替尼于 2023 年 1 月 27 日被美国 FDA 批准用于治疗复发或难治性套细胞淋巴瘤，包括对共价 BTK 抑制剂的耐药性。在这篇观点文章中，讨论了培托鲁替尼的理化性质、合成、剂量和给药、作用机制、药效学、药代动力学、药物相互作用和治疗中出现的不良事件。
