| Identification | Back Directory | [Name]
SAR-439859 | [CAS]
2114339-57-8 | [Synonyms]
SAR-439859
(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carboxylic acid
5H-Benzocycloheptene-3-carboxylic acid, 8-(2,4-dichlorophenyl)-9-[4-[[(3S)-1-(3-fluoropropyl)-3-pyrrolidinyl]oxy]phenyl]-6,7-dihydro- | [Molecular Formula]
C31H30Cl2FNO3 | [MOL File]
2114339-57-8.mol | [Molecular Weight]
554.48 |
| Chemical Properties | Back Directory | [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) | [form ]
Solid | [pka]
4.18±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [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 (Vss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species. It is noticed that T1/2 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.
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| 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/h?kg), low to moderate volume of distribution (Vss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species.
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| [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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| Company Name: |
BOC Sciences
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| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
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