Para-Aminoblebbistatin

Last updated
para-Aminoblebbistatin
Active enantiomer of para-aminoblebbistatin.png
Names
IUPAC name
(3aS)-3a-Hydroxy-6-methyl-1-(4-aminophenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one
Other names
  • p-Aminoblebbistatin
  • p-Aminoblebb
  • (S)-4'-Aminoblebbistatin
  • pAB
  • Optopharma1
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
  • InChI=1S/C18H17N3O2/c1-11-2-7-15-14(10-11)16(22)18(23)8-9-21(17(18)20-15)13-5-3-12(19)4-6-13/h2-7,10,23H,8-9,19H2,1H3/t18-/m1/s1
    Key: LYWLZINJPRNWFF-GOSISDBHSA-N
  • CC1=CC2=C(C=C1)N=C3C(C2=O)(CCN3C4=CC=C(C=C4)N)O
Properties
C18H17N3O2
Molar mass 307.353 g·mol−1
AppearanceYellow 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

SpeciesMyosin typeIC50
RabbitSkeletal muscle myosin S11.3 μM, [1] 9.22 μM, [4] 0.98 μM [5]
Dictyostelium discoideum Myosin II motor domain6.6 μM, [1] 8.5 μM [5]
Humanslow-twitch skeletal muscle fibre (force)10 μM [6]
Pig (left ventricle)cardiac myosin5.3 μM [5]
Chicken (gizzard)smooth muscle myosin S113 μM [5]
Human (expressed in Sf9 cells)non-muscle myosin 2A / B / C motor domains9 / 20 / 7.2 μM [5]
Drosophila melanogaster bodywall muscle fiber8.5 μM [5]

References

  1. 1 2 3 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.
  2. ↑ 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.
  3. ↑ 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.
  4. 1 2 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.
  5. 1 2 3 4 5 6 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.
  6. ↑ 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.