ChemicalBook Product Catalog API Hormones and the Endocrine System Estrogen and progestin drugs Sar-439859

Sar-439859

Product NameSar-439859
CAS2114339-57-8
MFC31H30Cl2FNO3
MW554.48
EINECS
MOL File2114339-57-8.mol

Chemical Properties

Boiling point	676.7±55.0 °C(Predicted)
Density	1.297±0.06 g/cm3(Predicted)
solubility	DMSO:100.0(Max Conc. mg/mL);180.35(Max Conc. mM)
pka	4.18±0.20(Predicted)
form	Solid
color	White to off-white

Usage And Synthesis

Uses

SAR439859 (compound 43d) is an orally active, non-steroidal, and selective estrogen receptor degrader (SERD). SAR439859 is an effective ER antagonist with ER degradation activity, an EC50 of 0.2 nM. SAR439859 can show potent anti-tumor effects and limited cross-resistance in ER+ breast cancer.

in vivo

SAR439859 (compound 43d; orally; 2.5-25 mg/kg; twice daily for 30 days) exhibits substantial tumor-growth inhibition and displays tumor regression at the dose of 25 mg/kg/BID^[1].
SAR439859 (3 mg/kg for iv and 10 mg/kg for po) shows a low to moderate clearance in the three animal species tested (0.03-1.92 L/h kg), low to moderate volume of distribution (V_ss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species. It is noticed that T_1/2 was variable across species (1.98 h in mouse, 4.13 h in rat and 9.80 h in dog)^[1].

Animal Model:	Nu/nu mouse with MCF7 tumor xenograft model^[1]
Dosage:	2.5, 5, 12.5, 25 mg/kg
Administration:	Orally; twice daily for 30 days
Result:	Exhibited substantial tumor-growth inhibition and displayed tumor regression at the dose of 25 mg/kg/BID.

Animal Model:	Mouse, rat and dog^[1]
Dosage:	3 mg/kg (iv) and 10 mg/kg (po) (Pharmacokinetic Analysis)
Administration:	Iv or po
Result:	Showed a low to moderate clearance in the three animal species tested (0.03-1.92 L/hkg), low to moderate volume of distribution (V_ss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species.

IC 50

ERα: 0.2 nM (EC₅₀)

References

[1] El-Ahmad Y, et al. Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer. J Med Chem. 2019 Nov 27. DOI:10.1021/acs.jmedchem.9b01293
[2] Monsif Bouaboula, et al. Abstract 943: SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust antitumor efficacy and limited cross-resistance in ER+ breast cancer.

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