UH15-38

UH15-38
Clinical data
Other names	HY-158312
Identifiers
	IUPAC name 3-(3-hydroxyphenyl)-1-methyl-7-[3-(4-methylpiperazin-1-yl)anilino]-1,6-naphthyridin-2-one ;
CAS Number	2540881-21-6;
PubChem CID	155288621;
Chemical and physical data
Formula	C26H27N5O2
Molar mass	441.535 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1CCN(CC1)C2=CC=CC(=C2)NC3=NC=C4C=C(C(=O)N(C4=C3)C)C5=CC(=CC=C5)O;
	InChI InChI=1S/C26H27N5O2/c1-29-9-11-31(12-10-29)21-7-4-6-20(15-21)28-25-16-24-19(17-27-25)14-23(26(33)30(24)2)18-5-3-8-22(32)13-18/h3-8,13-17,32H,9-12H2,1-2H3,(H,27,28); Key:DLRROFRAOBFFEP-UHFFFAOYSA-N;

UH15-38 is an experimental RIPK3 inhibitor being studied as a potential treatment for influenza.

Mechanism of action

UH15-38 targets and inhibits receptor-interacting protein kinase 3 (RIPK3), a key enzyme involved in necroptosis, a form of programmed cell death that can lead to excessive inflammation when left unchecked during severe influenza infections. By inhibiting RIPK3, UH15-38 appears to allow the immune system to effectively combat the virus while minimizing excessive cellular death and inflammatory responses, which in turn results in a decrease in lung damage.^[1]^[2]^[3]

Research

In preclinical studies, UH15-38 demonstrated the ability to significantly reduce lung inflammation and injury in mouse models, even when administered up to five days after infection. This may lead to more effective treatments for severe influenza cases, potentially addressing an unmet medical need for patients who seek care several days after initial infection.^[3]^[4]

References

^ Kirkin A (10 April 2024). "Researchers Uncover Novel Compound Able To Prevent Influenza Lung Damage". Inside Precision Medicine.
^ Halford B (10 April 2024). "Compound prevents flu-related lung damage in mice". Chemical & Engineering News.
^ ^a ^b Gautam A, Boyd DF, Nikhar S, Zhang T, Siokas I, Van de Velde LA, et al. (April 2024). "Necroptosis blockade prevents lung injury in severe influenza". Nature. 628 (8009): 835–843. doi:10.1038/s41586-024-07265-8. PMC 11151938. PMID 38600381.
^ Willson J (June 2024). "RIPK3 inhibitor prevents lung damage in severe influenza infection". Nature Reviews. Drug Discovery. 23 (6): 417. doi:10.1038/d41573-024-00072-w. PMID 38658639.

[1] Kirkin A (10 April 2024). "Researchers Uncover Novel Compound Able To Prevent Influenza Lung Damage". Inside Precision Medicine.

[2] Halford B (10 April 2024). "Compound prevents flu-related lung damage in mice". Chemical & Engineering News.

[pmid38600381-3] Gautam A, Boyd DF, Nikhar S, Zhang T, Siokas I, Van de Velde LA, et al. (April 2024). "Necroptosis blockade prevents lung injury in severe influenza". Nature. 628 (8009): 835–843. doi:10.1038/s41586-024-07265-8. PMC 11151938. PMID 38600381.

[pmid38658639-4] Willson J (June 2024). "RIPK3 inhibitor prevents lung damage in severe influenza infection". Nature Reviews. Drug Discovery. 23 (6): 417. doi:10.1038/d41573-024-00072-w. PMID 38658639.

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