AG-045572

• CAT Number: I010616
• CAS Number: 263847-55-8
• Molecular Formula: C30H37NO5
• Molecular Weight: 491.62
• Purity: ≥95%
• Synonyms: 5-[(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)methyl]-N-(2,4,6-trimethoxyphenyl)furan-2-carboxamide
• InChI: InChI=1S/C30H37NO5/c1-18-13-22-23(30(4,5)12-11-29(22,2)3)15-19(18)14-20-9-10-24(36-20)28(32)31-27-25(34-7)16-21(33-6)17-26(27)35-8/h9-10,13,15-17H,11-12,14H2,1-8H3,(H,31,32)
• InChIKey: IPEMCIBPDYCJLO-UHFFFAOYSA-N
• SMILES: CC1=CC2=C(C=C1CC3=CC=C(O3)C(=O)NC4=C(C=C(C=C4OC)OC)OC)C(CCC2(C)C)(C)C

AG-045572 is a GnRH receptor antagonist with Kis of 6.0 nM and 3.8 nM for human and rat GnRH receptor, respectively. AG-045572 is metabolized by CYP3A and ressuppresses testosterone[1].
AG-045572 (10 μM, 40 min, for human liver microsomes; 10 μM, 10 min, for male rat liver microsomes; 1 μM, 10 min, for female rat liver microsomes) is metabolized by CYP3A4 (HY-P74210) in both rats and humans with the Km values were similar in male and female human, female rat liver microsomes, and expressed CYP3A4 and CYP3A5 (0.39, 0.27, 0.28, 0.25, and 0.26 μM, respectively), and the Km in male rat liver microsomes was 1.5 μM, suggesting that in male and female rats AG-045572 is metabolized by different CYP3A isozymes[1].
AG-045572 (10 mg/kg (i.v.) or 20 mg/kg (p.o.), one time) give to intact male rats, it showed medium T1/2, CL and Vss but oral bioavailability was low, in female rats the bioavailability was much higher (24%), in castrated male rats the pharmacokinetics was similar to that in female rats[1].
AG-045572 (40 mg/kg, i.m. twice a day for 3 days) pretreated of intact male rats resulted in a change of its pharmacokinetics, the parameters became similar to those in female and castrated male rats[1].
Pharmacokinetic Parameters of AG-045572 in Rats after Administration at 10 mg/kg i.v. and 20 mg/kg p.o.[1]
大鼠静脉注射10 mg/kg和口服20 mg/kg剂量后AG-045572的药代动力学参数[1]

Animals
t1/2 (h)
CL (L/h/kg)
Vss (L/kg)
Cmax (μM)
Tmax (h)
Fp.o. (%)

Male
1.4 ± 0.1
2.2 ± 0.5
2.1 ± 0.1
0.61 ± 0.21
1
8

Female
1.7 ± 0.1
1.5 ± 0.1
2.7 ± 0.4
2.31 ± 0.57
1
24

Castrated male
1.7 ± 0.4
1.5 ± 0.3
3.7 ± 1.5
1.98 ± 0.51
1
23

Pretreated male
1.9 ± 0.2
1.5 ± 0.2
2.0 ± 0.6
1.89 ± 0.41
1
27

Reference

[1]. Iatsimirskaia EA, et al. Effect of testosterone suppression on the pharmacokinetics of a potent gnRH receptor antagonist. Pharm Res. 2002 Feb;19(2):202-8.
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