Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy

Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy Publisher Pubmed

Carullo G¹ ; Orsini N^{2, 3} ; Piano I⁴ ; Pozzetti L¹ ; Papa A¹ ; Fontana A¹ ; Napoli D^{2, 3} ; Corsi F⁴ ; Marco BD^{2, 3} ; Galante A⁴ ; Marotta L¹ ; Panzeca G¹ ; Obrien J⁵ ; Sanchez AG⁵ Show All Authors

Carullo G¹
Orsini N^{2, 3}
Piano I⁴
Pozzetti L¹
Papa A¹
Fontana A¹
Napoli D^{2, 3}
Corsi F⁴
Marco BD^{2, 3}
Galante A⁴
Marotta L¹
Panzeca G¹
Obrien J⁵
Sanchez AG⁵
Doherty H⁵
Mahon N⁵
Clarke L⁵
Contri C⁶
Pasquini S⁷
Gorelli B⁸
Saponara S⁸
Valoti M⁸
Vincenzi F⁷
Varani K⁷
Ramunno A⁹
Brogi S⁴
Butini S¹
Gemma S¹
Kennedy BN⁵
Gargini C⁴
Strettoi E²
Campiani G^{1, 10}

Show Affiliations

1. Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
2. Neuroscience Institute, Italian National Research Council (CNR) Area della Ricerca, Via Giuseppe Moruzzi 1, Pisa, 56124, Italy
3. Regional Doctorate School in Neuroscience of Universities of Florence, Pisa, Siena, Florence, CNR Via Giuseppe Moruzzi 1, Pisa, 56124, Italy
4. Department of Pharmacy, Via Bonanno 6, Pisa, 56124, Italy
5. UCD School of Biomolecular and Biomedical Science and UCD Conway Institute, University College Dublin, Dublin, D04 V1W8, Ireland
6. Department of Translational Medicine, University of Ferrara, Via Fossato di Mortara 17−19, Ferrara, 44121, Italy
7. Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Fossato di Mortara 17−19, Ferrara, 44121, Italy
8. Department of Life Sciences, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
9. Department of Pharmacy, University of Salerno, Via G. Paolo II 132, (SA), Fisciano, 84100, Italy
10. Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-7346, Iran

Source: Journal of Medicinal Chemistry Published:2024

Abstract

Inherited retinal diseases, which include retinitis pigmentosa, are a family of genetic disorders characterized by gradual rod-cone degeneration and vision loss, without effective pharmacological treatments. Experimental approaches aim to delay disease progression, supporting cones’ survival, crucial for human vision. Histone deacetylases (HDACs) mediate the activation of epigenetic and nonepigenetic pathways that modulate cone degeneration in RP mouse models. We developed new HDAC inhibitors (5a-p), typified by a tetrahydro-γ-carboline scaffold, characterized by high HDAC6 inhibition potency with balanced physicochemical properties for in vivo studies. Compound 5d (repistat, IC50 HDAC6 = 6.32 nM) increased the levels of acetylated α-tubulin compared to histone H3 in ARPE-19 and 661W cells. 5d promoted vision rescue in the atp6v0e1-/- zebrafish model of photoreceptor dysfunction. A single intravitreal injection of 5d in the rd10 mouse model of RP supported morphological and functional preservation of cone cells and maintenance of the retinal pigment epithelium array. © 2024 American Chemical Society.

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Style	Citing Format
MLA	Carullo G, et al.. "Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy." Journal of Medicinal Chemistry, vol. 67, no. 17, 2024, pp. 14946-14973.
APA	Carullo G, Orsini N, Piano I, Pozzetti L, Papa A, Fontana A, Napoli D, Corsi F, Marco BD, Galante A, Marotta L, Panzeca G, Obrien J, Sanchez AG, Doherty H, Mahon N, Clarke L, Contri C, Pasquini S, ... Campiani G (2024). Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy. Journal of Medicinal Chemistry, 67(17), 14946-14973.
Chicago	Carullo G, Orsini N, Piano I, Pozzetti L, Papa A, Fontana A, Napoli D, et al.. "Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy." Journal of Medicinal Chemistry 67, no. 17 (2024): 14946-14973.
Harvard	Carullo G et al. (2024) 'Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy', Journal of Medicinal Chemistry, 67(17), pp. 14946-14973.
Vancouver	Carullo G, Orsini N, Piano I, Pozzetti L, Papa A, Fontana A, et al.. Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy. Journal of Medicinal Chemistry. 2024;67(17):14946-14973.
BibTex	@article{ author = {Carullo G and Orsini N and Piano I and Pozzetti L and Papa A and Fontana A and Napoli D and Corsi F and Marco BD and Galante A and Marotta L and Panzeca G and Obrien J and Sanchez AG and Doherty H and Mahon N and Clarke L and Contri C and Pasquini S and Gorelli B and Saponara S and Valoti M and Vincenzi F and Varani K and Ramunno A and Brogi S and Butini S and Gemma S and Kennedy BN and Gargini C and Strettoi E and Campiani G}, title = {Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy}, journal = {Journal of Medicinal Chemistry}, volume = {67}, number = {17}, pages = {14946-14973}, year = {2024} }
RIS	TY - JOUR AU - Carullo G AU - Orsini N AU - Piano I AU - Pozzetti L AU - Papa A AU - Fontana A AU - Napoli D AU - Corsi F AU - Marco BD AU - Galante A AU - Marotta L AU - Panzeca G AU - Obrien J AU - Sanchez AG AU - Doherty H AU - Mahon N AU - Clarke L AU - Contri C AU - Pasquini S AU - Gorelli B AU - Saponara S AU - Valoti M AU - Vincenzi F AU - Varani K AU - Ramunno A AU - Brogi S AU - Butini S AU - Gemma S AU - Kennedy BN AU - Gargini C AU - Strettoi E AU - Campiani G TI - Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy JO - Journal of Medicinal Chemistry VL - 67 IS - 17 SP - 14946 EP - 14973 PY - 2024 ER -

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