T0901317 293754-55-9

Молекулярный вес: 481,33 T0901317 является сильным и селективным агонистом как для LXR, так и для FXR с EC50 ~ 50 нМ и 5 мкМ соответственно. \ N Биологическая активность

Description	T0901317 is a potent and selective agonist for both LXR and FXR, with EC50 of ~50 nM and 5 μM, respectively.
Targets	LXR [1]	FXR [2]
IC50	50 nM(EC50)	5 μM(EC50)
In vitro	T0901317 acts through LXR and in concert with its RXR heterodimerization partner induces the expression of the ABCA1 reverse cholesterol transporter. T0901317 upregulates expression of the ABCA1 gene associated with cholesterol efflux regulation and HDL metabolism.[1] T0901317 displays an EC50 of ~ 5 μM for activation of bile acid farnesoid X receptors (FXRs), 10-fold more potent than natural FXR ligand chenodeoxycholic acid. [2] T0901317, is also a high-affinity ligand for the xenobiotic receptor pregnane X receptor (PXR). T0901317 binds and activates PXR with the same nanomolar potency with which it stimulates LXR activity. T0901317 induces expression not only of LXR target genes, but also of PXR target genes in cells and animals, including the scavenger receptor CD36. [3] T0901317 decreases amyloid-β production in primary neurons in vitro. [4] T0901317 is found to directly bind to RORα and RORγ with high affinity (Ki = 132 and 51 nM, respectively), resulting in the modulation of the receptor's ability to interact with transcriptional cofactor proteins. T0901317 represses RORα/γ-dependent transactivation of ROR-responsive reporter genes and in HepG2 cells reduces recruitment of steroid receptor coactivator-2 by RORα at an endogenous ROR target gene (G6Pase). [5]
In vivo	T0901317 treatment of 11-week-old APP23 mice for 6 days shows a significant increase in ABCA1 expression and a decrease in the ratio of soluble APP (sAPP)β- to sAPPα-cleavage products. Most importantly, the treatment causes a statistically significant reduction in the levels of soluble Aβ40 and of Aβ42 in the brain these mice. [4]
Features

Протокол (только для справки) Конверсия различных модельных животных на основе BSA (значение на основе данных из проекта руководящих принципов FDA)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

Например, чтобы изменить дозу ресвератрола, используемую для мыши (22,4 мг / кг), на дозу, основанную на BSA для крысы, умножьте 22,4 мг / кг на коэффициент Km для мыши, а затем разделите на коэффициент Km для крыса. Этот расчет дает эквивалентную дозу ресвератрола для крыс 11,2 мг / кг.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

Ссылки [1] Repa JJ, et al. Наука, 2000, 289 (5484), 1524-1529. [2] Houck KA, et al. Мол Генет Метаб, 2004, 83 (1-2), 184-187. [3] Mitro N, et al. FEBS Lett, 2007, 581 (9), 1721-1726. [4] Колдамова Р.П. и др. J Biol Chem, 2005, 280 (6), 4079-4088. [5] Кумар Н. и др. Мол Pharmacol, 2010, 77 (2), 228-236. Химическая информация

Molecular Weight (MW)	481.33
Formula	C17H12F9NO3S
CAS No.	293754-55-9

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms

Solubility (25°C) *	In vitro	DMSO	96 mg/mL (199.44 mM)
		Water	<1 mg/mL (
		Ethanol	96 mg/mL (199.44 mM)

Chemical Name	Benzenesulfonamide, N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-

Калькулятор молярности Калькулятор разведения Калькулятор молекулярной массы

Группа Продуктов : Другие > Ингибитор X-рецепторов печени