| |
| Names | |
|---|---|
|
IUPAC name
(3aS)-3a-Hydroxy-6-methyl-1-(4-aminophenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one
| |
Other names
| |
| Identifiers | |
3D model (
JSmol)
|
|
| ChEMBL | |
| ChemSpider | |
PubChem
CID
|
|
| |
| |
| Properties | |
| C18H17N3O2 | |
| Molar mass | 307.353 g·mol−1 |
| Appearance | Yellow solid |
| ~ 400 μM | |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
| |
para-Aminoblebbistatin is a water-soluble, non-fluorescent, photostable myosin II inhibitor, developed from blebbistatin. [1] Among the several blebbistatin derivatives it is one of the most promising for research applications. [2] [3] Furthermore, it has a favourable overall profile considering inhibitory properties and ADME calculations. [4]
Myosin specificity
| Species | Myosin type | IC50 |
|---|---|---|
| Rabbit | Skeletal muscle myosin S1 | 1.3 μM, [1] 9.22 μM, [4] 0.98 μM [5] |
| Dictyostelium discoideum | Myosin II motor domain | 6.6 μM, [1] 8.5 μM [5] |
| Human | slow-twitch skeletal muscle fibre (force) | 10 μM [6] |
| Pig (left ventricle) | cardiac myosin | 5.3 μM [5] |
| Chicken (gizzard) | smooth muscle myosin S1 | 13 μM [5] |
| Human (expressed in Sf9 cells) | non-muscle myosin 2A / B / C motor domains | 9 / 20 / 7.2 μM [5] |
| Drosophila melanogaster | bodywall muscle fiber | 8.5 μM [5] |
References
- ^ a b c Várkuti BH, Képiró M, Horváth IÁ, Végner L, Ráti S, Zsigmond Á, et al. (May 2016). "A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative". Scientific Reports. 6: 26141. Bibcode: 2016NatSR...626141V. doi: 10.1038/srep26141. PMC 4886532. PMID 27241904.
- ^ Roman BI, Verhasselt S, Stevens CV (November 2018). "Medicinal Chemistry and Use of Myosin II Inhibitor ( S)-Blebbistatin and Its Derivatives". Journal of Medicinal Chemistry. 61 (21): 9410–9428. doi: 10.1021/acs.jmedchem.8b00503. PMID 29878759.
- ^ Rauscher AÁ, Gyimesi M, Kovács M, Málnási-Csizmadia A (September 2018). "Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential". Trends in Biochemical Sciences. 43 (9): 700–713. doi: 10.1016/j.tibs.2018.06.006. PMID 30057142.
- ^ a b Roman BI, Guedes RC, Stevens CV, García-Sosa AT (2018). "Recovering Actives in Multi-Antitarget and Target Design of Analogs of the Myosin II Inhibitor Blebbistatin". Frontiers in Chemistry. 6: 179. Bibcode: 2018FrCh....6..179R. doi: 10.3389/fchem.2018.00179. PMC 5976736. PMID 29881723.
- ^ a b c d e f in press: Gyimesi M, et al. (2020). "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.
- ^ López-Dávila AJ, Chalovich JM, Zittrich S, Piep B, Matinmehr F, Málnási-Csizmadia A, et al. (2020-03-24). "Cycling Cross-Bridges Contribute to Thin Filament Activation in Human Slow-Twitch Fibers". Frontiers in Physiology. 11: 144. doi: 10.3389/fphys.2020.00144. PMC 7105683. PMID 32265723.
|
| |
| Names | |
|---|---|
|
IUPAC name
(3aS)-3a-Hydroxy-6-methyl-1-(4-aminophenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one
| |
Other names
| |
| Identifiers | |
3D model (
JSmol)
|
|
| ChEMBL | |
| ChemSpider | |
PubChem
CID
|
|
| |
| |
| Properties | |
| C18H17N3O2 | |
| Molar mass | 307.353 g·mol−1 |
| Appearance | Yellow solid |
| ~ 400 μM | |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
| |
para-Aminoblebbistatin is a water-soluble, non-fluorescent, photostable myosin II inhibitor, developed from blebbistatin. [1] Among the several blebbistatin derivatives it is one of the most promising for research applications. [2] [3] Furthermore, it has a favourable overall profile considering inhibitory properties and ADME calculations. [4]
Myosin specificity
| Species | Myosin type | IC50 |
|---|---|---|
| Rabbit | Skeletal muscle myosin S1 | 1.3 μM, [1] 9.22 μM, [4] 0.98 μM [5] |
| Dictyostelium discoideum | Myosin II motor domain | 6.6 μM, [1] 8.5 μM [5] |
| Human | slow-twitch skeletal muscle fibre (force) | 10 μM [6] |
| Pig (left ventricle) | cardiac myosin | 5.3 μM [5] |
| Chicken (gizzard) | smooth muscle myosin S1 | 13 μM [5] |
| Human (expressed in Sf9 cells) | non-muscle myosin 2A / B / C motor domains | 9 / 20 / 7.2 μM [5] |
| Drosophila melanogaster | bodywall muscle fiber | 8.5 μM [5] |
References
- ^ a b c Várkuti BH, Képiró M, Horváth IÁ, Végner L, Ráti S, Zsigmond Á, et al. (May 2016). "A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative". Scientific Reports. 6: 26141. Bibcode: 2016NatSR...626141V. doi: 10.1038/srep26141. PMC 4886532. PMID 27241904.
- ^ Roman BI, Verhasselt S, Stevens CV (November 2018). "Medicinal Chemistry and Use of Myosin II Inhibitor ( S)-Blebbistatin and Its Derivatives". Journal of Medicinal Chemistry. 61 (21): 9410–9428. doi: 10.1021/acs.jmedchem.8b00503. PMID 29878759.
- ^ Rauscher AÁ, Gyimesi M, Kovács M, Málnási-Csizmadia A (September 2018). "Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential". Trends in Biochemical Sciences. 43 (9): 700–713. doi: 10.1016/j.tibs.2018.06.006. PMID 30057142.
- ^ a b Roman BI, Guedes RC, Stevens CV, García-Sosa AT (2018). "Recovering Actives in Multi-Antitarget and Target Design of Analogs of the Myosin II Inhibitor Blebbistatin". Frontiers in Chemistry. 6: 179. Bibcode: 2018FrCh....6..179R. doi: 10.3389/fchem.2018.00179. PMC 5976736. PMID 29881723.
- ^ a b c d e f in press: Gyimesi M, et al. (2020). "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.
- ^ López-Dávila AJ, Chalovich JM, Zittrich S, Piep B, Matinmehr F, Málnási-Csizmadia A, et al. (2020-03-24). "Cycling Cross-Bridges Contribute to Thin Filament Activation in Human Slow-Twitch Fibers". Frontiers in Physiology. 11: 144. doi: 10.3389/fphys.2020.00144. PMC 7105683. PMID 32265723.