TM6008 is a prolyl hydroxylase (PHD) inhibitor that protects against cell death after hypoxia. TM6008 suppresses the activity of PHDs, inducing continuous HIF-1α activation. Immunoblotting revealed that TM6008 increased the expression of HIF-1α, HIF-2α and vascular endothelial growth factor in myocarditis.
In vivo, TM6008 improved left ventricular ejection fraction significantly on the 21st day of EAM. Though TM6008 did not affect the severity of myocardial cell infiltration, it tended to reduce cardiac fibrosis. Immunohistochemistry showed that CD31-positive blood vessels were preserved in the TM6008 group compared to the control group. Immunoblotting revealed that TM6008 increased the expression of HIF-1α, HIF-2α and vascular endothelial growth factor in myocarditis. Oral administration of TM6008 protected neurons in a model of cerebrovascular disease.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Neovascularization induced by hypoxia inducible transcription factor is associated with the improvement of cardiac dysfunction in experimental autoimmune myocarditis.
Tada Y, et al. Expert Opin Investig Drugs. 2014 Feb;23(2):149-62. PMID: 24205804.
A novel prolyl hydroxylase inhibitor protects against cell death after hypoxia.
Kontani S, et al. Neurochem Res. 2013 Dec;38(12):2588-94. PMID: 24132642.
[Novel neuroprotective agents: a HIF activator and an Akt activator].
Takizawa S, et al. Rinsho Shinkeigaku. 2012;52(11):911-2. PMID: 23196464.
Inhibition of prolyl hydroxylase domain-containing protein suppressed lipopolysaccharide-induced TNF-alpha expression.
Takeda K, et al. Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2132-7. PMID: 19762779.
A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia.
Nangaku M, et al. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2548-54. PMID: 17932321.
Dithiothreitol (DTT) is the common name for a small-molecule redox reagent known as Cleland's reagent; as a reducing or "deprotecting" agent for thiolated DNA.
SAR7334 is a novel, highly potent and bioavailable inhibitor of TRPC6 channels.
FICZ is a potent aryl hydrogen receptor (AhR) agonist.
NAD+ is a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage.
STING-Inducer-1 (ML RR-S2 CDA) is an inducer of STING (stimulator of interferon genes).
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