| Description | PCLX-001 is a small-molecule compound that acts as an orally active inhibitor of N-myristoyltransferase (NMT), specifically targeting NMT1 and NMT2 with IC50 values of 5 nM and 8 nM, respectively. This compound demonstrates anti-tumor effects and effectively inhibits the early signaling of B-cell receptor (BCR). Consequently, PCLX-001 is a valuable tool for researching B-cell malignancies [1] [2]. |
| In vitro | 我们发现，包括B细胞淋巴瘤在内的血液癌细胞系对强效的全NMT抑制剂PCLX-001表现出显著敏感性。PCLX-001处理影响了淋巴瘤细胞蛋白的全局肉豆蔻酰化作用，并且抑制了对存活至关重要的早期B细胞受体（BCR）信号事件。除了抑制Src家族激酶的肉豆蔻酰化外，PCLX-001还促进了这些激酶的降解，并且意外地也促进了包括c-Myc、NFκB和P-ERK在内的多种非肉豆蔻酰化的BCR效应器的降解，导致体外和异种移植模型中癌细胞的死亡。[2] |
| In vivo | 在体外实验中，将PCLX-001处理培养的乳腺癌细胞，能显著降低细胞活性。通过每日口服PCLX-001给免疫缺陷小鼠（这些小鼠携带有人类MDA-MB-231乳腺癌异种移植瘤），能在体内显著产生剂量依赖的肿瘤生长抑制效果。[4] |
| Target activity | NMT1:5 nM, NMT2:8 nM |
| molecular weight | 537.51 |
| Molecular formula | C24H30Cl2N6O2S |
| CAS | 1215011-08-7 |
| Storage | store at low temperature,keep away from direct sunlight|Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 5.38 mg/mL (10 mM) |
| References | 1. Weickert M, et al. Initial characterization and toxicology of an nmt inhibitor in development for hematologic malignancies. Blood. 2019;134: 3362. 2. Beauchamp E, et al. Targeting N-myristoylation for therapy of B-cell lymphomas. Nat Commun. 2020;11(1):5348. 3. Sangha R, et al. Novel, First-in-Human, Oral PCLX-001 Treatment in a Patient with Relapsed Diffuse Large B-Cell Lymphoma. Curr Oncol. 2022;29(3):1939-1946. 4. Mackey JR, et al. N-myristoyltransferase proteins in breast cancer: prognostic relevance and validation as a new drug target. Breast Cancer Res Treat. 2021;186(1):79-87. |