FSD-C10: A more promising novel ROCK inhibitor than Fasudil for treatment of CNS autoimmunity
Authors: Guang-Xian Zhang
Wan-Fang Yang
Ling Feng
Yan-Le Xin
Qing Wang
Cun-Gen Ma
Chun-Yun Liu
Yan-Hua Li
Zhi Chai
Xin-Wang Yang
Wei-Jia Jiang
Bao-Guo Xiao
Jie-Zhong Yu
Journal: Bioscience reports (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FSD-C10; Fasudil; Rho kinase; Rho kinase inhibitor.
Affiliations: Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong 037009, China., "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan 030619, China., Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A., Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, China  ., Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong 037009, China "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan 030619, China  .

Abstract:  Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that regulates cell survival, death, adhesion, migration, neurite outgrowth and retraction and influences the generation and development of several neurological disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study, we present chemical synthesis and structure of FSD-C10, as well as the relationship between compound concentration and ROCK inhibition. We compared the inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite outgrowth and dendritic formation, neurotrophic factors and vasodilation between Fasudil and FSD-C10. The results demonstrated that FSD-C10, like Fasudil, induced neurite outgrowth of neurons and dendritic formation of BV-2 microglia and enhanced the production of neurotrophic factor brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3). However, the cell cytotoxicity and vasodilation of FSD-C10 were relatively small compared with Fasudil. Although Fasudil inhibited both ROCK I and ROCK II, FSD-C10 more selectively suppressed ROCK II, but not ROCK I, which may be related to vasodilation insensitivity and animal mortality. Thus, FSD-C10 may be a safer and more promising novel ROCK inhibitor than Fasudil for the treatment of several neurological disorders. 

Retracted: No

PubPeer comments:
 Figure 5c contains part of the cells treated with PBS in both Fasudil and FSD-C10 images: ![file] Figure 6a and d use the same beta-actin bands: ![file] , 
 2020-03-25 Dear ladies and gentlemen: In Fig. 5c, the two photos in the first column on the left should be the same originally, because they are PBS controls and there is no drug in both. In order to align with the photos on the left side, we took photos in the following order: fasudil PBS 5 15 75 200, then fsd-c10 PBS 5 15 75 200. When we took fsd-c10 picture again, therefore the rotation was possible (because we used a single round culture dish and remove it by hand under microscope). Now, we used a single photo instead of two photos that should be the same. This substitution does not affect the results at all. In Fig. 6a and d, we stained three protein bands on one membrane. Based on such experimental conditions, and used the same internal parameter GAPDH (it is indeed the same internal parameter). In order to match the histogram on the right side, we display the corresponding bands respectively. Now, let s combine the strips into a row, using the unified internal parameter. This arrangement does not affect the results, because these bands are representative bands, which were originally included in the quantitative analysis. Above replacement not affect the result and does not need to change the text, but we have to apologize again for our carelessness. Finally, we sincerely thank you for your serious spirit and scientific attitude. We will learn from this lesson, carefully mapping all figures, so that readers can understand them more easily. Finally, we would like to apologize for our carelessness and carelessness, and for the confusion we have added to you. Thank you again! Sincerely, Bao-Guo Xiao Cun-Gun Ma , 
 Dear authors, thank you for your answers to the concerns raised in comment #1 (raised by another commenter), which are satisfactory. However, there also appears to be an additional overlap in Figure 5C, marked below with blue boxes, where two different photos appear to overlap. Those photos represent different experiments, and the photos are rotated 180 degrees. Could you please check? ![file] , 
 Figure 6: * Green boxes: Two lanes in the b-actin panel of Figure 6C look similar to two lanes in the b-actin panel of Figure 6A and 6D. Because of the shift in lanes, the lanes do not represent the same samples. ![file] , 
 #1 I gave a reasonable reply to this question 2-3 years ago. Bao-Guo Xiao , 
 #5 #5 #5 I gave a reasonable reply to this question 2-3 years ago. Bao-Guo Xiao ,