| Identification | Back Directory | [Name]
NSP989 | [CAS]
304853-42-7 | [Synonyms]
NSP989
NSP-989
NSP 989
Tanaproget
NSP-989; NSP 989; NSP989
5-(1,4-dihydro-4,4-dimethyl-2-thioxo-2H-3,1-benzoxazin-6-yl)-1-methyl-1H-Pyrrole-2-carbonitrile
1H-Pyrrole-2-carbonitrile, 5-(1,4-dihydro-4,4-dimethyl-2-thioxo-2H-3,1-benzoxazin-6-yl)-1-methyl-
5-(4,4-dimethyl-2-thioxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile
5-(4,4-Dimethyl-2-thioxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile | [Molecular Formula]
C16H15N3OS | [MDL Number]
MFCD18450396 | [MOL File]
304853-42-7.mol | [Molecular Weight]
297.37 |
| Chemical Properties | Back Directory | [Melting point ]
225-228℃ | [Boiling point ]
441.3±55.0 °C(Predicted) | [density ]
1.26±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
Powder | [pka]
11.84±0.40(Predicted) | [color ]
Light yellow to yellow | [InChI]
1S/C16H15N3OS/c1-16(2)12-8-10(4-6-13(12)18-15(21)20-16)14-7-5-11(9-17)19(14)3/h4-8H,1-3H3,(H,18,21) | [InChIKey]
PYVFWTPEBMRKSR-UHFFFAOYSA-N | [SMILES]
S=C1Nc2c(cc(cc2)c3[n](c(cc3)C#N)C)C(O1)(C)C |
| Hazard Information | Back Directory | [Uses]
Oral contraception; nonsteroidal ligand for the progesterone receptor. | [Biological Activity]
tanaproget is a novel agonist of progesterone receptor with ic50 of 1.7 nm [1].progesterone receptor (pr) is a member of the nuclear receptor superfamily and binding of progesterone causes pr conformational changes, which then changing gene expression. progesterone plays an important role in female reproduction [1].in t47d cells, tanaproget caused alkaline phosphatase activity with ec50 value of 0.1 nm. in a mammalian two-hybrid assay, tanaproget showed 50-fold more potent than progesterone. in stromal cells isolated from endometrial, tanaproget (1 nm) significantly suppressed pro-mmp-3 secretion. also, tanaproget effectively prevented pro-mmp-3 secretion through il-1α-mediated stimulation [2].in endometriosis mice model with human lesions growing on the parietal peritoneum of mice, tanaproget completely regressed human lesions in 58% treated animals. also, the lesions were smaller and fewer compared with the lesions in placebo-treated mice at the end of therapy [2]. in healthy women, the elimination half-life (t(1/2)) of tanaproget ranged from 12 to 30 h. tanaproget reduced cervical mucus scores, which suggesting poor production and quality of cervical mucus [3]. | [in vivo]
Tanaproget (300 μg/kg; gavage/sustained-release capsules; once daily; 14-16 days) significantly reduces the number and size of human endometriotic lesions in the ncr/nude mouse endometriosis model[1].
Tanaproget (0.03 mg/kg; oral; once daily; 4 days) completely inhibits ovulation in the Sprague-Dawley rat ovulation inhibition model and is 30 times more potent than steroidal progestins[2].
| Animal Model: | Human endometriosis xenograft model
in ncr/nude athymic mice (female, 5-week-old, ovariectomized)[1] | | Dosage: | 300μg/kg (2% Tween 80/0.5% methylcellulose)
| | Administration: | Gavage or slow-release capsule, daily for 14–16 days
| | Result: | Reduced the number and size of human endometrial lesions derived from endometriosis patients, with complete regression in 33% of treated mice. |
| Animal Model: | Sprague-Dawley rats (female, 200 g, estrus-synchronized)[2] | | Dosage: | 0.03 mg/kg (corn oil) | | Administration: | Oral gavage, daily for 4 days | | Result: | Completely inhibited ovulation in all treated rats at 0.03 mg/kg, showing 30-fold higher efficacy than medroxyprogesterone acetate (MPA). |
| [target]
progesterone receptor | [References]
[1]. zhang z, olland am, zhu y, et al. molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget. j biol chem, 2005, 280(31): 28468-28475.
[2]. bruner-tran kl, zhang z, eisenberg e, 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 endocrinol metab, 2006, 91(4): 1554-1560.
[3]. bapst jl, ermer jc, ferron gm, et al. pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women. contraception, 2006, 74(5): 414-418. |
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| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
| Company Name: |
SPIRO PHARMA
|
| Telephone: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
InvivoChem
|
| Telephone: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
|