Para-Aminoblebbistatin Explained
para-Aminoblebbistatin is a water-soluble, non-fluorescent, photostable myosin II inhibitor, developed from blebbistatin. Among the several blebbistatin derivatives it is one of the most promising for research applications.[1] [2] Furthermore, it has a favourable overall profile considering inhibitory properties and ADME calculations.[3]
Myosin specificity
| Species | Myosin type | IC50 |
|---|
| Rabbit | Skeletal muscle myosin S1 | 1.3 μM,[4] 9.22 μM, 0.98 μM[5] |
| Dictyostelium discoideum | Myosin II motor domain | 6.6 μM, 8.5 μM |
| Human | slow-twitch skeletal muscle fibre (force) | 10 μM[6] |
| Pig (left ventricle) | cardiac myosin | 5.3 μM |
| Chicken (gizzard) | smooth muscle myosin S1 | 13 μM |
| Human (expressed in Sf9 cells) | non-muscle myosin 2A / B / C motor domains | 9 / 20 / 7.2 μM |
| Drosophila melanogaster | bodywall muscle fiber | 8.5 μM | |
Notes and References
- Roman BI, Verhasselt S, Stevens CV . Medicinal Chemistry and Use of Myosin II Inhibitor (S)-Blebbistatin and Its Derivatives . Journal of Medicinal Chemistry . 61 . 21 . 9410–9428 . November 2018 . 29878759 . 10.1021/acs.jmedchem.8b00503 .
- Rauscher AÁ, Gyimesi M, Kovács M, Málnási-Csizmadia A . Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential . Trends in Biochemical Sciences . 43 . 9 . 700–713 . September 2018 . 30057142 . 10.1016/j.tibs.2018.06.006 .
- Roman BI, Guedes RC, Stevens CV, García-Sosa AT . Recovering Actives in Multi-Antitarget and Target Design of Analogs of the Myosin II Inhibitor Blebbistatin . Frontiers in Chemistry . 6 . 179 . 2018 . 29881723 . 5976736 . 10.3389/fchem.2018.00179 . 2018FrCh....6..179R . free .
- Várkuti BH, Képiró M, Horváth IÁ, Végner L, Ráti S, Zsigmond Á, Hegyi G, Lenkei Z, Varga M, Málnási-Csizmadia A . 6 . A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative . Scientific Reports . 6 . 26141 . May 2016 . 27241904 . 4886532 . 10.1038/srep26141 . 2016NatSR...626141V .
- in press: Gyimesi M, etal . Improved inhibitory and ADMET properties of blebbistatin derivatives indicate that blebbistatin scaffold is ideal for drug development targeting myosin-2 . Journal of Pharmacology and Experimental Therapeutics . 2020 .
- López-Dávila AJ, Chalovich JM, Zittrich S, Piep B, Matinmehr F, Málnási-Csizmadia A, Rauscher AÁ, Kraft T, Brenner B, Stehle R . 6 . Cycling Cross-Bridges Contribute to Thin Filament Activation in Human Slow-Twitch Fibers . Frontiers in Physiology . 11 . 144 . 2020-03-24 . 32265723 . 7105683 . 10.3389/fphys.2020.00144 . free .
