para-Aminoblebbistatin

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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
  • 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
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[edit]

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[edit]

  1. ^ 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.
  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. ^ 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.
  5. ^ 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.
  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.