《The influence of hypoxia and energy depletion on the response of endothelial cells to the vascular disrupting agent combretastatin A-4-phosphate》 was published in Scientific Reports in 2020. These research results belong to Holmes, Toby; Brown, Andrew W.; Suggitt, Marie; Shaw, Lucy A.; Simpson, Lucy; Harrity, Joseph P. A.; Tozer, Gillian M.; Kanthou, Chryso. Formula: C9H11BrO3 The article mentions the following:
Combretastatin A-4 phosphate (CA4P) is a microtubule-disrupting tumor-selective vascular disrupting agent (VDA). While hypoxia renders tumors resistant to many conventional therapies, little is known about its influence on VDA activity. Here, we found that active RhoA and ROCK effector phospho-myosin light chain (pMLC) were downregulated in endothelial cells by severe hypoxia. CA4P failed to activate RhoA/ROCK/pMLC but its activity was restored upon reoxygenation. Hypoxia also inhibited CA4P-mediated actinomyosin contractility, VE-cadherin junction disruption and permeability rise. Glucose withdrawal downregulated pMLC, and coupled with hypoxia, reduced pMLC faster and more profoundly than hypoxia alone. Concurrent inhibition of glycolysis (2-deoxy-D-glucose, 2DG) and mitochondrial respiration (rotenone) caused profound actin filament loss, blocked RhoA/ROCK signalling and rendered microtubules CA4P-resistant. Withdrawal of the metabolism inhibitors restored the cytoskeleton and CA4P activity. The AMP-activated kinase AMPK was investigated as a potential mediator of pMLC downregulation. Pharmacol. AMPK activators that generate AMP, unlike allosteric activators, downregulated pMLC but only when combined with 2DG and/or rotenone. Altogether, our results suggest that Rho/ROCK and actinomyosin contractility are regulated by AMP/ATP levels independently of AMPK, and point to hypoxia/energy depletion as potential modifiers of CA4P response. In the experiment, the researchers used 1-Bromo-3,4,5-trimethoxybenzene(cas: 2675-79-8Formula: C9H11BrO3)
1-Bromo-3,4,5-trimethoxybenzene(cas: 2675-79-8) is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff.Formula: C9H11BrO31-Bromo-3,4,5-trimethoxybenzene can be used to synthesize N,N′-diarylated indolo[3,2-b]carbazole derivatives, which can find applications in electrophotography.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary