Ronacaleret (SB 751689) is an orally active, highly potent, and selective calcium sensing receptor (CaSR) antagonist that stimulates the release of endogenous parathyroid hormone from the parathyroid glands. Ronacaleret (SB 751689) is used to study postmenopausal osteoporosis.

Physicochemical Properties

Molecular Formula	C25H31F2NO4
Molecular Weight	447.51
Exact Mass	449.238
CAS #	753449-67-1
PubChem CID	10345214
Appearance	Typically exists as solid at room temperature
LogP	4.749
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	11
Heavy Atom Count	32
Complexity	591
Defined Atom Stereocenter Count	1
SMILES	CC(C)(CC1CC2=CC=CC=C2C1)NC[C@H](COC3=C(C(=CC(=C3)CCC(=O)O)F)F)O
InChi Key	FQJISUPNMFRIFZ-HXUWFJFHSA-N
InChi Code	InChI=1S/C25H31F2NO4/c1-25(2,13-17-9-18-5-3-4-6-19(18)10-17)28-14-20(29)15-32-22-12-16(7-8-23(30)31)11-21(26)24(22)27/h3-6,11-12,17,20,28-29H,7-10,13-15H2,1-2H3,(H,30,31)/t20-/m1/s1
Chemical Name	3-[3-[(2R)-3-[[1-(2,3-dihydro-1H-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4,5-difluorophenyl]propanoic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Ronacaleret inhibits the in vitro activities of OATP1B1 (IC50 = 11 μM) and OATP2B1 (IC50 = 12 μM) without inhibiting BCRP[3]. Ronacaleret was shown to inhibit the uptake of the probe substrate estradiol-glucuronide mediated by OATP1B1 and OATP1B3 with relatively low potency (IC50 values of 11 and 60 μM, respectively)[3]. Ronacaleret inhibits OATP2B1-mediated transport of rosuvastatin at pH 7.4 and pH 6.0 with IC50 values of 16 and 12 μM, respectively[3].
ln Vivo	Ronacaleret (SB 751689, 3 mg/kg/day) preserved klotho expression and renal function while reducing serum phosphorus and albuminuria in 5/6 nephrectomized rats[3].
Animal Protocol	Animal/Disease Models: 7-week-old Wistar rats[2]. Doses: 3 mg/kg/day (dissolved in 10% β-cyclodextrin solution). Route of Administration: Administered by an osmotic pump that was implanted subcutaneously. Experimental Results: Increased renal expression of klotho in a dose-dependent manner. Decreased serum phosphate and FGF23 with the increased fractional excretion of phosphate without changes in serum calcium. Appeared to similarly protect podocytes. Reduced FGF23 and because FGF23 enhanced klotho expression.
References	[1].Discovery of dihydropyrazino-benzimidazole derivatives as metabotropic glutamate receptor-2 (mGluR2) positive allosteric modulators (PAMs). Eur J Med Chem. 2020 Jan 15:186:111881. [2].Antialbuminuric actions of calcilytics in the remnant kidney. Am J Physiol Renal Physiol. 2015 Aug 1;309(3):F216-26. [3].Inhibition of Intestinal OATP2B1 by the Calcium Receptor Antagonist Ronacaleret Results in a Significant Drug-Drug Interaction by Causing a 2-Fold Decrease in Exposure of Rosuvastatin. Drug Metab Dispos. 2017 Jan;45(1):27-34.
Additional Infomation	Ronacaleret is a calcium-sensing receptor antagonist. Drug Indication Post-menopausal women with osteoporosis Mechanism of Action 751689 is novel small molecules that work by antagonizing calcium-sensing receptors on the surface of the parathyroid gland, thereby triggering a transient release of the body's own stores of parathyroid hormone (PTH). This release of PTH may have the potential to rebuild the bone mass lost as a result of osteoporosis and improve overall bone microarchitecture in these patients.

Solubility Data

Solubility (In Vitro)

Typically soluble in DMSO (e.g. 10 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2346 mL	11.1729 mL	22.3459 mL
	5 mM	0.4469 mL	2.2346 mL	4.4692 mL
	10 mM	0.2235 mL	1.1173 mL	2.2346 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.