para-Aminoblebbistatin

*para*-Aminoblebbistatin
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
CAS Number	2097734-03-5 [ChemSpider];
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL4164044;
ChemSpider	81407800;
PubChem CID	129626534;
CompTox Dashboard (EPA)	DTXSID101336358 ;
	InChI 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;
	SMILES CC1=CC2=C(C=C1)N=C3C(C2=O)(CCN3C4=CC=C(C=C4)N)O;
Properties
Chemical formula	C18H17N3O2
Molar mass	307.353 g·mol−1
Appearance	Yellow solid
Solubility in water	~ 400 μM
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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.

[Várkuti_2016-1] 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.

[Roman_2018-4] 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.

[:0-5] ^ ^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.

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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
CAS Number	2097734-03-5^{N[ChemSpider]}
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL4164044
ChemSpider	81407800
PubChem CID	129626534
CompTox Dashboard (EPA)	DTXSID101336358
InChI 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
SMILES CC1=CC2=C(C=C1)N=C3C(C2=O)(CCN3C4=CC=C(C=C4)N)O
Properties
Chemical formula	C₁₈H₁₇N₃O₂
Molar mass	307.353 g·mol⁻¹
Appearance	Yellow solid
Solubility in water	~ 400 μM
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references