NMac1

NMac1 (Nm23 activator 1) is a natural compound, cassumunene, derived from Zingiber cassumunar Roxb. and traditionally used as an anti-inflammatory agent in East Asia. NMac1 exhibits anti-metastatic potential by directly interacting with the C-terminal of Nm23-H1, activating its NDP kinase (NDPK) enzymatic activity in vitro. NMac1 inhibits breast cancer metastasis in vivo.
In vitro, NMac1 is a potent activator of NDPK protein, activating NDPK activity of recombinant Nm23-H1 in a dose-dependent manner with an EC50 of 10.7 μM.
The morphological changes observed in MDA-MB-231 cells after treatment with NMac1 (25 μM) included substantial changes in the original height mesenchymal type (with a large number of folds) to a non-metastatic form with reduced folds and increased cell coverage.
NMac1 significantly reduced invasion and migration of MDA-MB-231 cells in a dose-dependent manner without affecting their proliferation. ^[1]
In vivo, In NOD/SCID mice injected in situ with MDA-MB-231-LUS-D3H2LN cells, treatment with NMac1 (10 mg/Kg, 3 weeks) significantly inhibited breast cancer metastasis without affecting primary tumor size. ^[1]

References:
[1]. Lee JJ, et al. Small molecule activator of Nm23/NDPK as an inhibitor of metastasis. Sci Rep. 2018 Jul 19;8(1):10909.
[2]. Kim, B., Lee, JJ., Shin, J.S. et al. Nm23-H1 activator phenylbutenoid dimer exerts cytotoxic effects on metastatic breast cancer cells by inducing mitochondrial dysfunction only under glucose starvation. Sci Rep 11, 23549 (2021).

NMac1 (Nm23 activator 1) 是一种天然产物 cassumunene，从姜科植物 Zingiber cassumunar Roxb.中提取，在东亚传统上用作抗炎剂。NMac1 通过与 Nm23-H1 的 C 端直接相互作用，在体外激活其 NDP 激酶（NDPK）酶活性，具有抗转移潜力，并在体内实验中抑制乳腺癌转移。
在体外，NMac1 是 NDPK 蛋白的有效激活剂，以剂量依赖性方式激活重组 Nm23-H1 的 NDPK 活性，EC50 为 10.7 μM。
NMac1（25 μM） 处理后在 MDA-MB-231 细胞中观察到的形态变化包括原始高度间充质型（具有大量褶皱）的实质性改变，转变为具有减少褶皱和细胞覆盖面积增加的非转移性形态。
NMac1 以剂量依赖性方式显着降低 MDA-MB-231 细胞的侵袭和迁移，而不影响其增殖。^[1]
在体内，在原位注射 MDA-MB-231-Luc-D3H2LN 细胞 NOD/SCID 小鼠中，NMac1（10 mg/Kg，3周）处理可以显著抑制乳腺癌转移，而不影响原发肿瘤大小。^[1]