EOS789 (at different concentrations) inhibited phosphate uptake by brush border membrane vesicles in normal rats, with an IC50 of 3.1 μmol/l[1]. EOS789 (0.3–3.0 μM; 24 hours) dose-dependently inhibited the upregulation of collagen 1A1, collagen 3A1, and α-smooth muscle actin mRNA in hMes 130hT-9 human mesangial cells induced by high phosphate[2].

EOS789 (0.050–0.50%; orally; daily; 3 days) dose-dependently increased fecal phosphorus excretion, decreased urinary phosphorus excretion, and reduced serum phosphorus levels in normal male Wistar rats, demonstrating its inhibitory effect on intestinal phosphate absorption [1]. EOS789 (0.015–1.0%; orally; daily; 14 days) dose-dependently reduced serum phosphate, FGF-23, and intact PTH levels in adenine-induced hyperphosphatemic male Wistar rats, increased fecal phosphorus excretion, and reduced urinary phosphorus excretion, with efficacy higher than equivalent doses of NaPi-IIb selective inhibitors [1]. EOS789 (0.3%; orally; free access; day 21–116) sustainedly inhibited serum phosphate, FGF-23, and intact PTH levels in male Fisher rats with chronic anti-Thy1.1 nephritis, improved aortic calcification, reduced serum creatinine, and improved renal histopathology and fibrosis gene expression [1]. EOS789 (0.3%; feed addition; free access; 5 weeks) significantly improved hyperphosphatemia, improved renal function, and reduced glomerular crescent formation in anti-GBM-induced glomerulonephritis rats, significantly reducing serum creatinine to 1.31 mg/dL and glomerular crescent formation rate to 66.1% of total glomeruli [2].

Real-time quantitative PCR[2]
Cell Types: hMes 130hT-9 immortalized human mesangial cells
Tested Concentrations: 0.3 μM, 1.0 μM, 3.0 μM
Incubation Duration: 24 hours
Experimental Results: The relative expression of collagen IA1 was significantly reduced at 1.0 μM and 3.0 μM concentrations. The relative expression of collagen IIIA1 was significantly reduced at 1.0 μM and 3.0 μM concentrations. The relative expression of α-smooth muscle actin was significantly reduced at 3.0 μM concentration. It showed dose-dependent inhibition of all three fibrosis marker genes.

Animal/Disease Models:Crlj:WI (Wistar) (male) [1]
Doses: 0.050%, 0.15%, 0.50%
Route of Administration: Oral; Daily; 3 days
Experimental Results: Fecal excretion of 33P increased from approximately 45% to approximately 55%. Urinary excretion of 33P decreased from approximately 4.5% to approximately 3%. Serum 33P radioactivity decreased from approximately 3900 dpm/mL to approximately 3500 dpm/mL. Fecal excretion of 33P increased to approximately 60%. Urinary excretion of 33P decreased to approximately 2.2%. Serum 33P radioactivity decreased to approximately 3200 dpm/mL. Fecal excretion of 33P increased to approximately 70%. Urinary excretion of 33P decreased to approximately 1.2%. Serum 33P radioactivity decreased to approximately 2700 dpm/mL.

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Animal/Disease Models:Crlj:WI (Wistar) (male, adenine-induced hyperphosphatemia) [1]
Doses: 0.015%, 0.05%, 0.15%, 0.50%, 1.0%
Route of Administration: Oral; daily; 14 days
Experimental Results: Serum phosphate decreased from 9.7 mg/dl to approximately 7.5 mg/dl. Serum FGF-23 decreased from approximately 10,000 pg/mL to approximately 1,500 pg/mL. Serum intact PTH decreased from approximately 700 pg/mL to approximately 450 pg/mL. Serum phosphate decreased to approximately 6.8 mg/dl. Serum FGF-23 decreased to approximately 1,200 pg/mL. Serum intact parathyroid hormone (PTH) levels decreased to approximately 350 pg/mL. Serum fibroblast growth factor 23 (FGF-23) levels decreased to approximately 800 pg/mL. Serum intact parathyroid hormone (PTH) levels decreased to approximately 400 pg/mL. Serum fibroblast growth factor 23 (FGF-23) levels decreased to approximately 150 pg/mL. Serum intact parathyroid hormone (PTH) levels decreased to approximately 100 pg/mL. Serum phosphate levels decreased to approximately 6.5 mg/dl. Fecal phosphorus excretion increased from approximately 78 mg/4d to approximately 120 mg/4d. Urinary phosphorus excretion decreased from approximately 3.5 mg/d to near 0 mg/d.

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Animal/Disease Models:F344/DuCrlCrlj (Fisher) (male, anti-Thy1.1 induced chronic kidney disease-mineral bone metabolism disorder) [1]
Doses: 0.1%, 0.3%
Route of Administration: Oral; free access; Day 21 to Day 116
Experimental Results: At the end of the study, serum phosphate levels decreased from approximately 12 mg/dl to approximately 10 mg/dl. Serum FGF-23 or intact PTH levels were not significantly reduced. Aortic calcium content was not significantly reduced. Serum phosphate levels decreased to approximately 8 mg/dl. Serum FGF-23 levels decreased from approximately 240,000 pg/mL to approximately 5,000 pg/mL. Serum intact parathyroid hormone (PTH) levels decreased from approximately 8,000 pg/mL to approximately 4,000 pg/mL. Serum creatinine levels decreased from approximately 3.2 mg/dL to approximately 2.4 mg/dL. Aortic calcium content was suppressed to near-normal levels, and no histopathological calcification was observed in any of the treatment groups. Glomerular sclerosis scores decreased from 2.60 to 2.32, tubular degeneration scores decreased from 2.54 to 2.23, and tubulointerstitial fibrosis scores decreased from 2.39 to 2.01. Compared with the disease control group (0.3% dose), the mRNA expression of transforming growth factor-β1 (TGF-β1), type I collagen α1 chain, type III collagen α1 chain, and α-smooth muscle actin in the kidneys was significantly reduced.

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Animal/Disease Models:Wistar (male, 7 weeks old, glomerulonephritis induced by anti-rat glomerular basement membrane antibody) [2]
Doses: ~100 mg/kg/day; ~200 mg/kg/day
Route of Administration: Mixed with feed; ad libitum; 5 weeks
Experimental Results: Dose-dependent inhibition of disease-induced serum phosphate elevation. Significantly increased fecal phosphate excretion to 89.1 mg/day. Significantly reduced urinary phosphate excretion fraction to 18.5%. Significantly inhibited serum FGF23 elevation. Significantly improved severely reduced serum calcitriol levels. Significantly reduced serum creatinine to 1.31 mg/dL. Significantly reduced urinary albumin excretion fraction to 0.04%. Significantly reduced serum sodium to 140.5 mEq/L. Significantly reduced urinary sodium excretion fraction to 1.15%. Glomerular crescent formation was significantly reduced to 66.1% of the total number of glomeruli. Compared with the disease control group, body weight was significantly increased.

[1]. EOS789, a novel pan-phosphate transporter inhibitor, is effective for the treatment of chronic kidney disease-mineral bone disorder. Kidney Int. 2020;98(2):343-354.

[2]. EOS789, pan-phosphate transporter inhibitor, ameliorates the progression of kidney injury in anti-GBM-induced glomerulonephritis rats. Pharmacol Res Perspect. 2022;10(3):e00973.

C35H36F8N6O5

772.70

1628848-73-6

Light yellow to yellow solid

O=C(NC=1C=CC(=CC1C2=NC=NC(=C2)C(F)(F)F)C(F)(F)F)C=3C(=O)N(N(C)C4(C3O)CCCC4)CC5=CC=C(OCCN(C)CCOC)C(F)=C5F

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~129.42 mM; with sonication)

Solubility in Formulation 1: 2.5 mg/mL (3.24 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Suspended solution; Need ultrasonic.
For example, if 1 mL of working solution is to be prepared, you canAdd 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD saline (4°C, store for one week): Dissolve 2 g of SBE-β-CD powder in 10 mL of saline until completely dissolved and clear.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)