L6H21 | MD-2/TLR4 interaction inhibitor

L6H21 binds to MD-2 (myeloid differentiation protein-2, K_d=33.3 µM) and blocks its interaction with TLR4 (toll-like receptor 4) in LPS-stimulated cells, inhibiting TNFα and IL-6 production.¹ Attenuates disease progression in a high-fat diet (HFD) induced NASH mouse model.² Inhibits obesity-induced cardiomyopathy and fibrosis.³ Reduces ethanol plus LPS-induced liver injury via inhibition of NLRP3 inflammasome activation.⁴ Provides cardioprotective effects⁵ and protects against cognitive impairment and brain pathologies in HFD prediabetic rats⁶. Cell permeable. Active in vivo.

References/Citations:

1. Wang et al. (2015), MD-2 as the target of a novel small molecule, L6H21, in the attenuation of LPS-induced inflammatory response and sepsis; J. Pharmacol., 172 4391
2. Zhang et al. (2018), Inhibition of MD1-dependent inflammation attenuates the progression of non-alcoholic fatty liver disease; Cell. Mol. Med., 22 936
3. Fang et al. (2018), Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis; Biophys. Acta Mol. Basis Dis., 1864 252
4. Kong et al. (2019), Chalcone Derivative L6H21 Reduces EtOH + LPS-Induced Liver Injury Through Inhibition of NLRP3 Inflammasome Activation; Alcohol Clin. Exp. Res., 43 1662
5. Sumneang et al. (2022), Inhibition of myeloid differentiation factor-2 attenuates cardiometabolic impairments via reducing cardiac mitochondrial dysfunction, inflammation, apoptosis and ferroptosis in prediabetic rats; Biophys. Acta Mol. Basis Dis., 1868 166301
6. Oo et al. (2021), L6H21 protects against cognitive impairment and brain pathologies via toll-like receptor 4-myeloid differentiation factor 2 signalling in prediabetic rats; J. Pharmacol., doi:10.1111/bph.15741 Epub ahead of print