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Purity: ≥98%
WAY 316606 is a novel and potent small molecule inhibitor of the secreted protein sFRP-1 (secreted frizzled-related protein) which is an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related disorders. WAY-316606 bound to sFRP-1 with a K(D) of 0.08 microM and inhibited it with an EC(50) of 0.65 microM. Moreover, this compound increased total bone area in a murine calvarial organ culture assay at concentrations as low as 0.0001 microM. This work demonstrates the feasibility of developing small molecules that inhibit sFRP-1 and stimulate canonical Wnt signaling to increase bone formation. Canonical Wnt signaling has been demonstrated to increase bone formation, and Wnt pathway components are being pursued as potential drug targets for osteoporosis and other metabolic bone diseases. Deletion of the Wnt antagonist sFRP-1 in mice activates canonical signaling in bone and increases trabecular bone formation in aged animals.
| ln Vitro |
WAY-316606's EC50 on U2-OS cells' Wnt-luciferase activity is 0.65 μM[1]. Frizzled-related protein (sFRP)-1 dye is bound by WAY-316606, which has a KD of 0.08 μM and an EC50 of 0.65 μM for sFRP-1 inhibition. Similar to KD of 1 μM, WAY-316606 binds to sFRP-2, but with a strength that is almost ten times weaker. WAY-316606 has an IC50 of 0.5 μM when it comes to a collagen binding assay that uses a fluorescent material and a sealed human sFRP-1 fingerprint in a competitive binding format [2].
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| ln Vivo |
In neonatal calvarial osteometry, WAY-316606 resulted in an increase. With an EC50 of about 1 nM, WAY-316606 exhibits a dose-dependent increase in total bone area of up to 60%. Good solubility, moderate or low inhibition of cytochrome p450 isoenzymes (3A4, 2D6, 2C9), and good stability in locus and human liver microsomes (per species t1/2>60 minutes) are the characteristics of WAY-316606. After a single intravenous bolus dosage (2 mg/kg), female Sprague-Dawley WAY-316606 shows strong network clearance (77 mL/min/kg, higher hepatic blood flow), which led to a quick drug decrease in the central area despite drug routes [2].
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| References |
[1]. Moore, WJ, et al. Modulation of Wnt Signaling Through Inhibition of Secreted Frizzled-Related Protein I (sFRP-1) with N-Substituted Piperidinyl Diphenylsulfonyl Sulfonamides. Journal of Medicinal Chemistry (2009), 52(1), 105-116.
[2]. Bodine PV, et al. A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation. Bone. 2009 Jun;44(6):1063-8 |
| Molecular Formula |
C18H19F3N2O4S2
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| Molecular Weight |
448.48
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| CAS # |
915759-45-4
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| Related CAS # |
915759-45-4;1781835-02-6 (HCl);
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| SMILES |
O=S(C1=CC(S(=O)(C2=CC=CC=C2)=O)=CC=C1C(F)(F)F)(NC3CCNCC3)=O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2298 mL | 11.1488 mL | 22.2975 mL | |
| 5 mM | 0.4460 mL | 2.2298 mL | 4.4595 mL | |
| 10 mM | 0.2230 mL | 1.1149 mL | 2.2298 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
J Med Chem.2009 Jan 8;52(1):105-16.
Bone.2009 Jun;44(6):1063-8 |
Bone.2009 Jun;44(6):1063-8 |
Bone.2009 Jun;44(6):1063-8 |
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