YM158 (free base)

Modify Date: 2024-01-10 17:07:16

YM158 (free base) structure	Common Name	YM158 (free base)
	CAS Number	179102-65-9	Molecular Weight	681.22
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₃₂H₃₃ClN₆O₅S₂	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of YM158 (free base)

YM158 free base is a potent and selective LTD4 and TXA2 receptor antagonist with pA2 values of about 8.87 and 8.81, respectively.

Name	YM158 free base
Synonym	More Synonyms

Description	YM158 free base is a potent and selective LTD4 and TXA2 receptor antagonist with pA2 values of about 8.87 and 8.81, respectively.
Related Catalog	Signaling Pathways >> GPCR/G Protein >> Prostaglandin Receptor Research Areas >> Inflammation/Immunology
Target	LTD4:8.87 (pA2) TXA2 Receptor:8.81 (pA2)
In Vitro	YM158 antagonizes leukotriene (LT) D4 and thromboxane (TX) A2 receptors. Functional assays in vitro show that YM158 exhibits competitive dual antagonism of LTD4 and TXA2 receptor-mediated contraction of isolated guinea pig tracheae, with pA2 values of about 8.87 and 8.81, respectively. Its antagonistic activity for the LTD4 receptor is approximately 6.5 times less potent than that of Montelukast, and that for the TXA2 receptor is 2.5 times more potent than that of Seratrodast. YM158 also inhibits PGD2- and PGF2α -induced tracheal contractions. YM158 antagonizes the stable TXA2 analog U46619-induced aggregation of both guinea pig and human platelets and inhibits the LTD4-induced contraction of guinea pig ileum. YM158 produces a concentration-dependent inhibition of guinea pig ileum contraction induced by 1 nM LTD4 with an IC50 value of 0.58 nM[1].
In Vivo	YM158, an orally active dual antagonist for LTD4 and TXA2 receptors, is expected to have a stronger antiasthmatic efficacy in a broader class of asthmatic patients than single antagonistic drugs.The effect of YM158 is examined on these asthmatic responses in mediator-controlled and passively sensitized guinea pigs. Because the inhibitory effects of YM158 on increase in the airway resistance induced by LTD4 or U46619 are shown to be dose-dependent when p.o. administered 1 h before LTD4 or U46619 injection, with ED50 values of 8.6 and 14 mg/kg, respectively, the antagonistic activities of p.o. YM158 for LTD4 and TXA2 receptors are exhibited at the same dose range. Oral YM158 shows significant effects, approximately the same as the combination of Pranlukast and Daltroban on antigen-induced response under various conditions; namely, where LTD4 is predominant, TXA2 is predominant; or where both mediators participated equally. In groups not treated with Indomethacin, administration of Daltroban (10 mg/kg), a combination of Pranlukast (30 mg/kg) and Daltroban (10 mg/kg), or YM158 (30 mg/kg) significantly prolongs the onset time for asthmatic response and significantly suppresses symptoms[2].
Animal Admin	Guinea pigs[2] Male Hartley guinea pigs are used. Effects of YM158 (30 mg/kg, p.o.) , Pranlukast, and Daltroban are measured on the shortening of onset time for asthmatic response. Each compound is administered p.o. to animals without or with 5 mg/kg or 1 mg/kg of Indomethacin[2].
References	[1]. Arakida Y, et al. In vitro pharmacologic profile of YM158, a new dual antagonist for LTD₄ and TXA₂ receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9. [2]. Arakida Y, et al. Effects of lipid mediator antagonists on predominant mediator-controlled asthmatic reactions in passively sensitized guinea pigs. J Pharmacol Exp Ther. 1999 Sep;290(3):1285-91.

Molecular Formula	C₃₂H₃₃ClN₆O₅S₂
Molecular Weight	681.22

YM158 (free base)