Tanaproget

Modify Date: 2024-01-30 22:19:53

Tanaproget structure	Common Name	Tanaproget
	CAS Number	304853-42-7	Molecular Weight	297.37500
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₁₆H₁₅N₃OS	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of Tanaproget

Tanaproget(NSP989) is a novel nonsteroidal progesterone receptor agonist which can bind to the PR from various species with a higher relative affinity than reference steroidal progestins.IC50 value: 0.1 nM (EC50, induce alkaline phosphatase activity) [1]Target: progesterone receptorTanaproget represents a potential first-in-class nonsteroidal PR agonist for contraception with improved safety and side effect profiles versus currently available steroidal oral contraceptives.in vitro: In T47D cells, TNPR induces alkaline phosphatase activity with an EC(50) value of 0.1 nm, comparable with potent steroidal progestins such as medroxyprogesterone acetate (MPA) and trimegestone (TMG), albeit with a reduced efficacy ( approximately 60%). In a mammalian two-hybrid assay to measure PR agonist-induced interaction between steroid receptor co-activator-1 and PR, TNPR showed similar potency (EC(50) value of 0.02 nm) and efficacy to MPA and TMG [1].in vivo: TNPR effectively down-regulated MMP expression in vitro and induced significant reduction of lesions in mice with disease established by tissues from endometriosis patients [2]. The maximum concentration (C(max)) of tanaproget occurred approximately 2 to 3 h after administration. The elimination half-life (t(1/2)) ranged from 12 to 30 h, and the oral clearance was approximately 70 L/h. The pharmacokinetics of tanaproget was not noticeably altered with a high-fat meal [3].Toxicity: All doses of tanaproget decreased cervical mucus scores (using a modified Insler method), indicating poor production and poor quality of cervical mucus. The most frequent treatment-emergent adverse events were vaginal bleeding/spotting, abdominal cramping and vomiting; their incidence was not dose related and most events were mild [3].

Name	5-(4,4-dimethyl-2-sulfanylidene-1H-3,1-benzoxazin-6-yl)-1-methylpyrrole-2-carbonitrile
Synonym	More Synonyms

Description	Tanaproget(NSP989) is a novel nonsteroidal progesterone receptor agonist which can bind to the PR from various species with a higher relative affinity than reference steroidal progestins.IC50 value: 0.1 nM (EC50, induce alkaline phosphatase activity) [1]Target: progesterone receptorTanaproget represents a potential first-in-class nonsteroidal PR agonist for contraception with improved safety and side effect profiles versus currently available steroidal oral contraceptives.in vitro: In T47D cells, TNPR induces alkaline phosphatase activity with an EC(50) value of 0.1 nm, comparable with potent steroidal progestins such as medroxyprogesterone acetate (MPA) and trimegestone (TMG), albeit with a reduced efficacy ( approximately 60%). In a mammalian two-hybrid assay to measure PR agonist-induced interaction between steroid receptor co-activator-1 and PR, TNPR showed similar potency (EC(50) value of 0.02 nm) and efficacy to MPA and TMG [1].in vivo: TNPR effectively down-regulated MMP expression in vitro and induced significant reduction of lesions in mice with disease established by tissues from endometriosis patients [2]. The maximum concentration (C(max)) of tanaproget occurred approximately 2 to 3 h after administration. The elimination half-life (t(1/2)) ranged from 12 to 30 h, and the oral clearance was approximately 70 L/h. The pharmacokinetics of tanaproget was not noticeably altered with a high-fat meal [3].Toxicity: All doses of tanaproget decreased cervical mucus scores (using a modified Insler method), indicating poor production and poor quality of cervical mucus. The most frequent treatment-emergent adverse events were vaginal bleeding/spotting, abdominal cramping and vomiting; their incidence was not dose related and most events were mild [3].
Related Catalog	Signaling Pathways >> Others >> Progesterone Receptor Research Areas >> Endocrinology
References	[1]. Bruner-Tran KL, et al. Down-regulation of endometrial matrix metalloproteinase-3 and -7 expression in vitro and therapeutic regression of experimental endometriosis in vivo by a novel nonsteroidal progesterone receptor agonist, tanaproget. J Clin Endocrin [2]. Zhang Z, et al. Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget. J Biol Chem. 2005 Aug 5;280(31):28468-75. [3]. Bapst JL, et al. Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women. Contraception. 2006 Nov;74(5):414-8.

Description

Related Catalog

Signaling Pathways >> Others >> Progesterone Receptor

Research Areas >> Endocrinology

References

[1]. Bruner-Tran KL, et al. Down-regulation of endometrial matrix metalloproteinase-3 and -7 expression in vitro and therapeutic regression of experimental endometriosis in vivo by a novel nonsteroidal progesterone receptor agonist, tanaproget. J Clin Endocrin

[2]. Zhang Z, et al. Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget. J Biol Chem. 2005 Aug 5;280(31):28468-75.

[3]. Bapst JL, et al. Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women. Contraception. 2006 Nov;74(5):414-8.