RhoA is a ubiquitously expressed cytoplasmic protein that belongs to the family of small GTPases. RhoA acts as a molecular switch that is activated in response to binding of chemokines, cytokines, and growth factors, and via mDia and the ROCK signaling cascade regulates the activation of cytoskeletal proteins, and other factors[3].Rhosin hydrochloride is a potent, specific RhoA subfamily Rho GTPases inhibitor. Rhosin hydrochloride specifically binds to RhoA to inhibit RhoA-GEF interaction with a Kd of ~ 0.4 uM, and does not interact with Cdc42 or Rac1, nor the GEF, LARG. Rhosin hydrochloride induces cell apoptosis[4]. In cells, Rhosin specifically inhibited RhoA activity and RhoA-mediated cellular function without affecting Cdc42 or Rac1 signaling activities. By suppressing RhoA or RhoC activity, Rhosin could inhibit mammary sphere formation by breast cancer cells, suppress invasion of mammary epithelial cells, and induce neurite outgrowth of PC12 cells in synergy with NGF. Rhosin HCL dose-dependently reduces RhoA and p-MLC1 activities of MCF7 cell-derived mammospheres with an EC50 ~30-50 μM, and causes decreased size and reduced number of mammospheres in MCF7 cells[5]. Rhosin HCL promotes stress resiliency through enhancing D1-MSN plasticity and reducing hyperexcitability. Rhosin hydrochloride dose-dependently reduces RhoA and p-MLC1 activities of MCF7 cell-derived mammospheres with an EC50 ~30-50 μM, and causes decreased size and reduced number of mammospheres in MCF7 cells. Rhosin (40 mg/kg; i.p.) treatment prevents social avoidance caused by social defeat stress. Rhosin also blocks sucrose preference deficits induced by defeat in C57Bl6/J (Jackson) mice. Rhosin (30 µM; bilateral, intra- Nucleus Accumbens (NAc) infusions) attenuates stress-induced social avoidance. Rhosin blocks stress-induced hyperexcitability in NAc dopamine 1 receptor medium spiny neurons (D1-MSNs). Rhosin prevents decreased excitatory transmission on NAc D1-MSNs. Rhosin enhances spine density in defeat mice[6].
Rhosin HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Rat bone marrow mesenchymal stem cells
20 µM
14 days
To investigate the effect of Rhosin on the proliferation and osteogenic differentiation of BMSC under dynamic culture conditions. Results showed that Rhosin inhibited the proliferation and osteogenic differentiation of BMSC.
Bioeng Transl Med. 2023 Mar 17;8(3):e10509.
Human lung microvascular endothelial cells (HLMVEC)
30 µM
2 hours
To investigate the inhibitory effect of Rhosin on 2-ClHA-induced endothelial barrier dysfunction. Results showed that Rhosin pretreatment significantly inhibited the barrier dysfunction caused by 2-ClHA.
Redox Biol. 2025 May;82:103596.
HEK293 cells
5 µM, 10 µM, 15 µM, 30 µM
2 hours
To investigate the effect of Rhosin on F/G-actin ratio in GNE mutant cells. Results showed that treatment with 10µM Rhosin restored the F/G-actin ratio in GNE mutant cells.
Front Cell Dev Biol. 2021 Mar 18;9:603742.
Human platelets
20 µM
2 min
Blocked the phosphorylation of the myosin light chain (p-MLC)
Int J Mol Sci. 2023 Feb 19;24(4):4167.
4T1 cells
1-50 µM
3 days
Rhosin inhibited RhoA and RhoC activation, and suppressed YAP nuclear localization, but did not affect ERK1/2, Akt, or NF-κB activation.
Biomedicines. 2021 Jan 4;9(1):35.
B16BL6 cells
1-50 µM
3 days
Rhosin inhibited RhoA and RhoC activation, and suppressed YAP nuclear localization, but did not affect ERK1/2, Akt, or NF-κB activation.
Biomedicines. 2021 Jan 4;9(1):35.
PC-3 cells
30 µM
RhoA inhibitor Rhosin diminished CRMP4a shRNA-induced increase of cancer cell migration
Cancer Biol Ther. 2018;19(12):1193-1203.
Rhosin HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice and Balb/c mice
B16BL6 and 4T1 lung metastasis model
Intraperitoneal injection
10 mg/kg or 30 mg/kg
Daily for 14 days
Rhosin reduced the number of lung metastatic nodules in B16BL6 and 4T1 cells in a dose-dependent manner.
Biomedicines. 2021 Jan 4;9(1):35.
Mice
Chronic social defeat stress model
Intraperitoneal injection
40 mg/kg
Once daily for 7 days
To evaluate the effects of Rhosin on behavioral and physiological changes induced by chronic social defeat stress, it was found that Rhosin prevented social avoidance and reduced sucrose preference caused by CSDS, and enhanced spine density in D1-MSNs.
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