blebbistatin

Blebbistatin ((±)-Blebbistatin) 是一种非肌肉肌球蛋白 II(NMII)选择性和非肌肉肌球蛋白重链9（MYH9）特异性的抑制剂，可促进角膜内皮细胞 (CEC) 的定向迁移并加速伤口愈合，并保留了细胞连接的完整性和屏障功能。

(-)-Blebbistatin ((S)-(-)-Blebbistatin) 是 blebbistatin 的 S 对映异构体。(-)-Blebbistatin 是一种肌球蛋白 II 抑制剂 (IC50=0.5-5 μM)，具有有效性和选择性。(-)-Blebbistatin 可以用于抑制心肌肌球蛋白、非肌肉肌球蛋白II和骨骼肌肌球蛋白。

(+)-Blebbistatin 是 (–)-Blebbistatin 的非活性对映异构体。 (–)-Blebbistatin 是一种选择性肌球蛋白 II ATPase 抑制剂。

(S)-3'-amino Blebbistatin, retaining the active stereochemistry of the less stable and more phototoxic (–)-blebbistatin, serves as a refined selective cell-permeable inhibitor of non-muscle myosin II ATPases. This compound efficaciously inhibits the Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB across several species with IC50s ranging from 0.5-5 µM, and exhibits minimal inhibition against smooth muscle myosin (IC50= 80 µM). Its primary functions include obstructing apoptosis-related bleb formation, directed cell migration, and cytokinesis in vertebrate cells. (S)-3'-amino Blebbistatin overcomes (–)-blebbistatin’s limitation of rapid degradation under blue light (450-490 nm) exposure, which generates cytotoxic intermediates, thus posing a challenge for fluorescent live cell imaging applications. The introduction of a 3’-amino group to its structure notably reduces fluorescence while maintaining (–)-blebbistatin’s activity, making it a superior alternative for research purposes.

(S)-nitro-Blebbistatin is a more stable form of (-)-blebbistatin , which is a selective cell-permeable inhibitor of non-muscle myosin II ATPases. (-)-Blebbistatin rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB for several species (IC50s = 0.5-5 μM), while poorly inhibiting smooth muscle myosin (IC50 = 80 μM). Through these effects, it blocks apoptosis-related bleb formation, directed cell migration, and cytokinesis in vertebrate cells. However, prolonged exposure to blue light (450-490 nm) results in degradation of blebbistatin to an inactive product via cytotoxic intermediates, which may be problematic for its use in fluorescent live cell imaging applications. The addition of a nitro group stabilizes the molecule to circumvent its degradation by prolonged blue light exposure. (S)-nitro-Blebbistatin has the same stereochemistry as the active (-)-blebbistatin enantiomer.

(R)-nitro-Blebbistatin is a more stable form of (+)-blebbistatin , which is the inactive form of (-)-blebbistatin . Prolonged exposure to blue light (450-490 nm) results in degradation of blebbistatin to an inactive product via cytotoxic intermediates, which may be problematic for its use in fluorescent live cell imaging applications. The addition of a nitro group stabilizes the molecule to circumvent its degradation by prolonged blue light exposure. (R)-nitro-Blebbistatin has the same stereochemistry as the inactive (+)-blebbistatin enantiomer.

(S)-3'-hydroxy-Blebbistatin is a more stable and less phototoxic derivative of (–)-blebbistatin, retaining the latter's properties as a selective, cell-permeable inhibitor of non-muscle myosin II ATPases. Unlike its predecessor, (S)-3'-hydroxy-Blebbistatin exhibits reduced fluorescence, improving its utility in live cell imaging applications by diminishing degradation into cytotoxic intermediates under blue light exposure (450-490 nm). It effectively inhibits the Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB across various species with IC50 values ranging from 0.5-5 µM and shows minimal inhibition against smooth muscle myosin with an IC50 of 80 µM. This compound plays a critical role in preventing apoptosis-related bleb formation, directed cell migration, and cytokinesis in vertebrate cells, mirroring the active (–)-blebbistatin enantiomer in mechanism and efficacy.

para-amino-Blebbistatin is a more water-soluble form of (S)-4'-nitro-blebbistatin , which is a more stable and less phototoxic form of (-)-blebbistatin .1,2,3 (-)-Blebbistatin is a selective cell-permeable inhibitor of non-muscle myosin II ATPases that rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB for several species (IC50s = 0.5-5 μM), while poorly inhibiting smooth muscle myosin (IC50 = 80 μM).2,3,4 Through these effects, it blocks apoptosis-related bleb formation, directed cell migration, and cytokinesis in vertebrate cells. However, prolonged exposure to blue light (450-490 nm) results in degradation of blebbistatin to an inactive product via cytotoxic intermediates, which may be problematic for its use in fluorescent live cell imaging applications.5,6 The addition of a 4'-amino group increases its water solubility, decreases the inherent fluorescence, stabilizes the molecule to circumvent its degradation by prolonged blue light exposure, and decreases its phototoxicity while retaining the in vitro and in vivo activity of blebbistatin.7 para-amino-Blebbistatin has the same stereochemistry as the active (-)-blebbistatin enantiomer. |1. Várkuti, B.H., Képiró, M., Horváth, I.á., et al. A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative. Sci. Rep. 6:26141, (2016).|2. Straight, A.F., Cheung, A., Limouze, J., et al. Dissecting temporal and spatial control of cytokinesis with a myosin II inhibitor. Science 299(5613), 1743-1747 (2003).|3. Kovács, M., Tóth, J., Hetényi, C., et al. Mechanism of blebbistatin inhibition of myosin II. J. Biol. Chem. 279(34), 35557-35563 (2004).|4. Limouze, J., Straight, A.F., Mitchison, T., et al. Specificity of blebbistatin, an inhibitor of myosin II. J. Muscle Res. Cell Motil. 25(4-5), 337-341 (2004).|5. Kolega, J. Phototoxicity and photoinactivation of blebbistatin in UV and visible light. Biochem. Biophys. Res. Commun. 320(3), 1020-1025 (2004).|6. Sakamoto, T., Limouze, J., Combs, C.A., et al. Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light. Biochemistry 44(2), 584-588 (2005).|7. Verhasselt, S., Roman, B.I., Bracke, M.E., et al. Improved synthesis and comparative analysis of the tool properties of new and existing D-ring modified (S)-blebbistatin analogs. Eur. J. Med. Chem. 136, 85-103 (2017).

(R)-(+)-Blebbistatin O-Benzoate is a derivative of Blebbistatin. (R)-(+)-Blebbistatin is a 1-phenyl-2-pyrrolidinone derivative and a selective inhibitor of non-muscle myosin II. It blocks cell blebbing rapidly and reversibly and also disrupts directed cell migration and cytokinesis in vertebrate cell. (R)-(+)-Blebbistatin can also inhibit contraction of the cleavage furrow without disrupting mitosis or contractile ring assembly. (R)-(+)-Blebbistatin is suitable as a negative control for (S)-(-)-Blebblastatin.

para-Nitroblebbistatin 是无细胞毒性、无荧光、光稳定、特异性的肌球蛋白 II (Myosin II) 抑制剂。para-Nitroblebbistatin 可用于肌球蛋白 II 在生理学、发育和细胞生物学中特殊作用的相关研究。