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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Serum amyloid P component (SAP). GSK3039294 is a prodrug that is converted to the active metabolite miridesap (CPHPC), which inhibits the binding of SAP to amyloid fibrils. SAP is a protein that binds to amyloid fibrils and contributes to the pathogenesis of amyloidosis and other amyloid-related diseases. By depleting SAP from the circulation, the compound facilitates the clearance of amyloid deposits.
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| ln Vitro |
GSK3039294 is a prodrug that is converted to miridesap (CPHPC), the active SAP depleter. The active metabolite inhibits the binding of SAP to amyloid fibrils, leading to the depletion of circulating SAP. In rats, GSK3039294 provides 56-80% oral bioavailability of miridesap and achieves 85% SAP depletion within 2 hours. The compound is rapidly converted in liver microsomes with stability in intestinal microsomes.
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| ln Vivo |
GSK3039294 has been designed to overcome the limitation of miridesap, which has negligible oral absorption and requires repeated parenteral injections. The prodrug supports once-daily oral gavage and eliminates injection-related stress and variability in preclinical models. It has potential applications in research models of systemic amyloidosis, Alzheimer's disease, type 2 diabetes, and osteoarthritis.
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| Enzyme Assay |
In vitro assays for GSK3039294 typically involve measuring its conversion to the active metabolite miridesap in liver microsomes. The compound is incubated with rat, canine, or human liver microsomes, and the formation of the monoester intermediate and miridesap is monitored. The rate of conversion and the stability of the prodrug in intestinal microsomes can also be assessed.
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| Cell Assay |
In vitro cell-based assays for GSK3039294 are not typically performed, as the compound is a prodrug that requires metabolic conversion to its active form. However, the activity of the active metabolite miridesap can be assessed in cell-based systems by measuring its effects on SAP binding or amyloid fibril formation. The compound is soluble in DMSO at ≥34 mg/mL.
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| Animal Protocol |
In vivo studies of GSK3039294 have been conducted in preclinical models of amyloidosis. The compound is administered orally, typically by once-daily gavage. Endpoints include measurement of circulating SAP levels, which are depleted by approximately 85% within 2 hours. The compound's effects on amyloid deposition and disease progression can also be assessed in appropriate animal models.
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| ADME/Pharmacokinetics |
GSK3039294 is orally bioavailable, providing 56-80% oral bioavailability of the active metabolite miridesap in rats. The compound is a double-ester prodrug that is rapidly converted in liver microsomes. It is designed to support once-daily oral dosing in preclinical studies. Detailed pharmacokinetic parameters such as half-life and Cmax are available from primary literature.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GSK3039294 are not detailed in the available literature. As a prodrug of miridesap, its safety profile would be expected to be similar to that of miridesap. Comprehensive toxicology studies would be required for clinical development. The compound is for research use only.
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| References | |
| Additional Infomation |
GSK3039294 is a research tool for studying SAP depletion and amyloidosis. It is an orally bioavailable alternative to the parenterally administered SAP depleter miridesap (CPHPC). The compound is used in research models of systemic amyloidosis, Alzheimer's disease, type 2 diabetes, and osteoarthritis. It is not an approved therapeutic agent.
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| Molecular Formula |
C30H44N2O14
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|---|---|
| Molecular Weight |
656.67537021637
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| Exact Mass |
656.279
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| Elemental Analysis |
C, 54.87; H, 6.75; N, 4.27; O, 34.11
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| CAS # |
1819986-22-5
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| PubChem CID |
92136018
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
46
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| Complexity |
976
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1C[C@@H](N(C1)C(=O)CCCCC(=O)N2CCC[C@@H]2C(=O)OCOC(=O)OC3CCOCC3)C(=O)OCOC(=O)OC4CCOCC4
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| InChi Key |
KSKLDMGKWDUQCT-DNQXCXABSA-N
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| InChi Code |
InChI=1S/C30H44N2O14/c33-25(31-13-3-5-23(31)27(35)41-19-43-29(37)45-21-9-15-39-16-10-21)7-1-2-8-26(34)32-14-4-6-24(32)28(36)42-20-44-30(38)46-22-11-17-40-18-12-22/h21-24H,1-20H2/t23-,24-/m1/s1
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| Chemical Name |
oxan-4-yloxycarbonyloxymethyl (2R)-1-[6-[(2R)-2-(oxan-4-yloxycarbonyloxymethoxycarbonyl)pyrrolidin-1-yl]-6-oxohexanoyl]pyrrolidine-2-carboxylate
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| Synonyms |
GSK 3039294; GSK-3039294; GSK3039294
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| HS Tariff Code |
2934.99.03.00
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| 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)
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| Solubility (In Vitro) |
DMSO : ≥ 34 mg/mL (~51.78 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5228 mL | 7.6141 mL | 15.2281 mL | |
| 5 mM | 0.3046 mL | 1.5228 mL | 3.0456 mL | |
| 10 mM | 0.1523 mL | 0.7614 mL | 1.5228 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.
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