para-Nitroblebbistatin

para-Nitroblebbistatin is a non-phototoxic, photostable myosin inhibitor with low fluorescence.[2] Its myosin inhibitory properties are very similar to those of blebbistatin.[3][4]

para-Nitroblebbistatin
Names
IUPAC name
(3aS)-3a-Hydroxy-6-methyl-1-(4-nitrophenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one
Other names
p-Nitroblebbistatin
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
  • InChI=1S/C18H15N3O4/c1-11-2-7-15-14(10-11)16(22)18(23)8-9-20(17(18)19-15)12-3-5-13(6-4-12)21(24)25/h2-7,10,23H,8-9H2,1H3/t18-/m1/s1
    Key: KAUXNLHXGQGFOS-GOSISDBHSA-N
  • CC1=CC2=C(C=C1)N=C3C(C2=O)(CCN3C4=CC=C(C=C4)[N+](=O)[O-])O
Properties
C18H15N3O4
Molar mass 337.335 g·mol−1
Appearance Yellow solid
~ 5 μM
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Myosin specificity
Species Myosin type IC50
Rabbit Skeletal muscle myosin S1 0.4 μM,[2] 0.1 μM[5][6]
Dictyostelium discoideum Myosin II motor domain 2.3 μM,[2] 9 μM[6]
Human β-Cardiac myosin subfragment 1  13 μM[7]
Chicken Heavy meromyosin fragment of skeletal muscle myosin  0.4 μM[7]
Pig (left ventricle) cardiac myosin 3.9 μM[6]
Chicken (gizzard) smooth muscle myosin S1 5.6 μM[6]
Human (expressed in Sf9 cells) non-muscle myosin 2A / B / C motor domains 18 / 14 / 5 μM[6]

Applications

para-Nitroblebbistatin has been successfully used in fluorescent imaging experiments involving myosin IIA-GFP expressing live dendritic cells[8] and synaptophysin-pHluorin expressing live neurons.[9]

References
  1. "para-Nitroblebbistatin | Targetmol". www.targetmol.com.
  2. Képiró, Miklós; Várkuti, Boglárka H.; Végner, László; Vörös, Gergely; Hegyi, György; Varga, Máté; Málnási-Csizmadia, András (2014-07-28). "para-Nitroblebbistatin, the non-cytotoxic and photostable myosin II inhibitor". Angewandte Chemie International Edition in English. 53 (31): 8211–8215. doi:10.1002/anie.201403540. ISSN 1521-3773. PMID 24954740.
  3. Rauscher, Anna Á.; Gyimesi, Máté; Kovács, Mihály; Málnási-Csizmadia, András (July 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. ISSN 0968-0004. PMID 30057142. S2CID 51864413.
  4. Roman, Bart I.; Verhasselt, Sigrid; Stevens, Christian V. (2018-06-21). "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. ISSN 0022-2623. PMID 29878759. S2CID 46966833.
  5. Várkuti, Boglárka H.; Képiró, Miklós; Horváth, István Ádám; Végner, László; Ráti, Szilvia; Zsigmond, Áron; Hegyi, György; Lenkei, Zsolt; Varga, Máté (2016-05-31). "A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative". Scientific Reports. 6: 26141. Bibcode:2016NatSR...626141V. doi:10.1038/srep26141. ISSN 2045-2322. PMC 4886532. PMID 27241904.
  6. in press: Gyimesi et al Improved inhibitory and ADMET properties of blebbistatin derivatives indicate that blebbistatin scaffold is ideal for drug development targeting myosin-2 in Journal of Pharmacology and Experimental Therapies (2020)
  7. Tang, Wanjian; Blair, Cheavar A.; Walton, Shane D.; Málnási-Csizmadia, András; Campbell, Kenneth S.; Yengo, Christopher M. (2016). "Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels". Frontiers in Physiology. 7: 659. doi:10.3389/fphys.2016.00659. ISSN 1664-042X. PMC 5220080. PMID 28119616.
  8. Chabaud, Mélanie; Heuzé, Mélina L.; Bretou, Marine; Vargas, Pablo; Maiuri, Paolo; Solanes, Paola; Maurin, Mathieu; Terriac, Emmanuel; Le Berre, Maël (2015-06-25). "Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells". Nature Communications. 6: 7526. Bibcode:2015NatCo...6.7526C. doi:10.1038/ncomms8526. ISSN 2041-1723. PMC 4491822. PMID 26109323.
  9. Soykan, Tolga; Kaempf, Natalie; Sakaba, Takeshi; Vollweiter, Dennis; Goerdeler, Felix; Puchkov, Dmytro; Kononenko, Natalia L.; Haucke, Volker (2017). "Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly". Neuron. 93 (4): 854–866.e4. doi:10.1016/j.neuron.2017.02.011. PMID 28231467.
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