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

Summary: Study develops potent HDAC6 inhibitor for cone cell preservation in retinal disease models. #RetinalDisease #HDACInhibitors

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}

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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Alireza Dehghani (3)

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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

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 -

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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Abstract