2. Academic Validation
  3. Inhibition of ABCG2 prevents phototoxicity in a mouse model of erythropoietic protoporphyria

Inhibition of ABCG2 prevents phototoxicity in a mouse model of erythropoietic protoporphyria

  • Nat Commun. 2024 Dec 4;15(1):10557. doi: 10.1038/s41467-024-54969-6.
Junjie Zhu 1,  Fu-Ying Qin 1,  Saifei Lei 1,  Ruizhi Gu 1,  Qian Qi 1,  Jie Lu 1,  Karl E Anderson 2,  Peter Wipf 3,  Xiaochao Ma 4
Affiliations

Affiliations

  • 1 Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
  • 2 Porphyria Laboratory & Center, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • 3 Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
  • 4 Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA. mxiaocha@pitt.edu.
PMID: 39632884 DOI: 10.1038/s41467-024-54969-6
Abstract

Erythropoietic protoporphyria (EPP) is a genetic disease characterized by protoporphyrin IX-mediated painful phototoxicity. Currently, options for the management of EPP-associated phototoxicity are limited and no oral medication is available. Here, we investigated a novel therapy against EPP-associated phototoxicity by targeting the ATP-binding cassette subfamily G member 2 (ABCG2), the efflux transporter of protoporphyrin IX. Oral ABCG2 inhibitors were developed, and they successfully prevented EPP-associated phototoxicity in a genetically engineered EPP mouse model. Mechanistically, ABCG2 inhibitors suppress protoporphyrin IX release from erythroid cells and reduce the systemic exposure to protoporphyrin IX in EPP. In summary, our work establishes a novel strategy for EPP therapy by targeting ABCG2 and provides oral ABCG2 inhibitors that can effectively prevent protoporphyrin IX-mediated phototoxicity in mice.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z