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. 2024 Jun 1;35(6):809-811.
doi: 10.1681/ASN.0000000000000327. Epub 2024 Feb 7.

Small Molecule Allosteric Inhibitor of HIPK2 as a Novel Therapy against Kidney Fibrosis

Kyung Lee  1   2 , Robert Drakas  2   3 , John C He  1   2
Affiliations

Small Molecule Allosteric Inhibitor of HIPK2 as a Novel Therapy against Kidney Fibrosis

Kyung Lee et al. J Am Soc Nephrol. .
No abstract available

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Conflict of interest statement

R. Drakas reports employment with ShangPharma Innovation Inc. and Rila Therapeutics and advisory or leadership roles for Azkarra Therapeutics, Blue Oak Therapeutics, Evrys Bio, Mediar Therapeutics, Rila Therapeutics Inc, and ShangPharma Innovation. J.C. He reports consultancy for Ono Pharmaceutical Co, Ltd, Renalytix AI, and Yingli Pharmaceutical; ownership interest in Renalytix AI, Rila Therapeutics, and Yingli Pharmaceutical; research funding from Shangpharma Innovation; honoraria from Ono Pharmaceutical Co, Ltd, Renalytix AI, and Yingli Pharmaceutical; advisory or leadership roles as Board member of Chinese American Society of Nephrology and International Chinese Society of Nephrology, Associate Editor for Kidney Disease, and Section Editor for Nephron; and role on the Editorial Boards for American Journal of Physiology, Diabetes, JASN, and Kidney International. J.C. He is funded by NIH/NIDDK. K. Lee reports ownership interest in Rila Therapeutics Inc. K. Lee is funded by NIH/NIDDK.

Figures

Figure 1
Figure 1
One of the Seven Rila Lakes, Babreka (“The kidney”). Image from Wikipedia Commons.
Figure 2
Figure 2
Efficacy of HIPK2 inhibitor against kidney fibrosis. While TGF-β or HIPK2 are key promoters of kidney fibrosis, because of their pleiotropic functions, full blockade of their functions may lead to adverse side effects. As HIPK2 is typically increased in disease settings to potentiate Smad3-mediated transcription, allosteric inhibition of HIPK2-Smad3 interaction by RLA-23174 is sufficient to markedly reduce kidney fibrosis, without incurring potential systemic toxicities associated with TGF-β or HIPK2 inhibition. HIPK2, homeodomain-interacting protein kinase 2; TGF, transforming growth factor.
See this image and copyright information in PMC

References

    1. Gu YY, Liu XS, Huang XR, Yu XQ, Lan HY. Diverse role of TGF-β in kidney disease. Front Cell Dev Biol. 2020;8:123. doi:10.3389/fcell.2020.00123 - DOI - PMC - PubMed
    1. Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, Driscoll JJ. Novel therapies emerging in oncology to target the TGF-β pathway. J Hematol Oncol. 2021;14(1):55. doi:10.1186/s13045-021-01053-x - DOI - PMC - PubMed
    1. Jin Y Ratnam K Chuang PY, et al. . A systems approach identifies HIPK2 as a key regulator of kidney fibrosis. Nat Med. 2012;18(4):580–588. doi:10.1038/nm.2685 - DOI - PMC - PubMed
    1. Cozza G, Zanin S, Determann R, Ruzzene M, Kunick C, Pinna LA. Synthesis and properties of a selective inhibitor of homeodomain-interacting protein kinase 2 (HIPK2). PLoS One. 2014;9:e89176. doi:10.1371/journal.pone.0089176 - DOI - PMC - PubMed
    1. Miduturu CV Deng X Kwiatkowski N, et al. . High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors. Chem Biol. 2011;18(7):868–879. doi:10.1016/j.chembiol.2011.05.010 - DOI - PMC - PubMed

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