| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| Other Sizes |
| Targets |
Human Endogenous Metabolite
SLC6A8 (creatine transporter). Ompenaclid inhibits the SLC6A8 transporter, blocking cellular creatine uptake. This leads to depletion of intracellular phosphocreatine and ATP, activation of AMPK, and induction of apoptosis in cancer cells. The compound also alters skeletal muscle energy expenditure, making it relevant for muscular dystrophy research. |
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| ln Vitro |
Ompenaclid (RGX-202; 10 μM; 96 hours) inhibits cell growth and shows almost total phosphocreatine depletion (>99%), cellular creatine reduction of over 79%, and a significant (46%) reduction in intracellular ATP levels in comparison to control cells under hypoxia[1].
In vitro, Ompenaclid strongly inhibits creatine import in cultured cells. It reduces intracellular phosphocreatine and ATP levels, leading to AMPK activation and induction of apoptosis. The compound shows antiproliferative effects in various cancer cell lines by depleting energy stores and disrupting cellular metabolism. It also alters skeletal muscle energy expenditure in cellular models of muscular dystrophy. |
| ln Vivo |
In B6129SF1/J mice, ommepenaclid (RGX-202; 800 mg/kg; po for 35 days) lowers the levels of UN-KPC-961 pancreatic tumoral creatine[1]. In NOD-SCID mice, omepenaclid (around 650 mg/kg; intraperitoneally every day for 14 days) inhibits treatment-induced liver metastatic colonization of Lvm3b cells by an eight-fold margin[1].
In vivo, Ompenaclid robustly inhibits creatine import and reduces intracellular phosphocreatine and ATP levels. It induces tumor apoptosis in preclinical cancer models. The compound activates AMPK and stimulates PPARγ coactivator 1α (PGC-1α), affecting energy metabolism. In models of Duchenne muscular dystrophy, it alters skeletal muscle energy expenditure and may improve muscle function. Clinical development is ongoing for cancer and DMD indications. |
| Enzyme Assay |
SLC6A8 transporter inhibition is measured using radiolabeled creatine uptake assays in SLC6A8-expressing cells. Cells are treated with Ompenaclid at varying concentrations, and [14C]-creatine uptake is quantified by scintillation counting. Intracellular ATP and phosphocreatine levels are measured using commercial assay kits or HPLC. AMPK activation is assessed by Western blot for phosphorylated AMPK (Thr172).
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| Cell Assay |
Cancer cell lines are cultured and treated with Ompenaclid at varying concentrations. Creatine uptake is measured using radiolabeled creatine. Cell viability and proliferation are assessed by CellTiter-Glo or MTT assays. Apoptosis is detected by Annexin V/PI staining, caspase activity assays, and PARP cleavage by Western blot. Metabolic changes (ATP levels, phosphocreatine) are measured using biochemical assays.
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| Animal Protocol |
Animal/Disease Models: UN-KPC-961 pancreatic tumor-bearing B6129SF1/J mice[1]
Doses: 800 mg/kg Route of Administration: po for 35 days Experimental Results: Suppressed tumoral d3-creatine import by 50% at 800 mg/kg. Animal/Disease Models: 6- to 9weeks old C57BL/6J male wild- type mice[1] Doses: 100, 250, 500 mg/KG in sterile 0.9% NaCl Route of Administration: po for 35 days Experimental Results: Inhibited tissue uptake of d3-creatine in a dose-dependent manner by up to 75% at 500 mg/ kg. Xenograft models are established using human cancer cell lines in immunodeficient mice. Ompenaclid is administered orally at doses determined from pharmacokinetic studies. Tumor volume is measured, and tumors are harvested for ATP/phosphocreatine measurement, apoptosis detection (TUNEL, cleaved caspase-3), and AMPK activation assessment. For Duchenne muscular dystrophy models, muscle function tests (e.g., grip strength, treadmill) are performed, and muscle tissue is analyzed for energy metabolites. |
| ADME/Pharmacokinetics |
Ompenaclid is an orally active compound with molecular formula C4H9N3O2 and molecular weight 131.14. It is a creatine analog (3-guanidinopropionic acid) with CAS number 353-09-3. The compound shows good oral bioavailability and is formulated for oral administration. Pharmacokinetic parameters such as half-life, Cmax, and AUC are available from clinical and preclinical studies (RGX-202 development program).
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| Toxicity/Toxicokinetics |
Toxicity data for Ompenaclid are available from preclinical and clinical studies. The compound is generally well-tolerated at therapeutic doses. As a creatine analog, it has a favorable safety profile. However, comprehensive toxicological data should be reviewed from the manufacturer's documentation or clinical trial reports. Standard safety monitoring (hematology, chemistry, urinalysis) is performed in clinical studies.
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| References |
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| Additional Infomation |
3-Guidinopropionic acid is a guanidine compound with an N-(2-carboxyethyl) substituent. It is a creatine analog and has been found to lower plasma glucose levels, exhibiting hypoglycemic effects. Functionally related to propionic acid, it is a zwitterionic tautomer of 3-guanidinopropionic acid. RGX-202 is a recombinant AAV8 virus whose vector genome encodes a micromyotrophic dystrophin. Omeprazole is an orally administered small-molecule creatine transporter SLC6a8 inhibitor with potential antitumor activity. After oral administration, omeprazole inhibits the uptake of phosphocreatine by SLC6a8, thereby reducing the level of phosphocreatine available for ATP synthesis in tumor cells. SLC6a8 is overexpressed in certain cancer types, and inhibiting its activity may limit tumor cell growth and metastasis.
Ompenaclid (also known as RGX-202, RGX-202-01, 3-guanidinopropionic acid, β-guanidinopropionic acid) is an orally active SLC6A8 transporter inhibitor under investigation for cancer and Duchenne muscular dystrophy. It depletes cellular creatine and ATP, activates AMPK, and induces apoptosis. The compound is in clinical development (RGX-202 program) but has not received FDA approval as of this writing. It is also used as a research tool for studying creatine metabolism and energy homeostasis. |
| Molecular Formula |
C4H9N3O2
|
|---|---|
| Molecular Weight |
131.14
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| Exact Mass |
131.069
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| CAS # |
353-09-3
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| PubChem CID |
67701
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
299.1±42.0 °C at 760 mmHg
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| Melting Point |
222 °C (dec.)(lit.)
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| Flash Point |
134.7±27.9 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
|
| Index of Refraction |
1.575
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| LogP |
-1.68
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
9
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| Complexity |
128
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KMXXSJLYVJEBHI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C4H9N3O2/c5-4(6)7-2-1-3(8)9/h1-2H2,(H,8,9)(H4,5,6,7)
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| Chemical Name |
3-(diaminomethylideneamino)propanoic acid
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| HS Tariff Code |
2934.99.9001
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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) |
H2O : ≥ 50 mg/mL (381.27 mM)
DMSO : < 1 mg/mL |
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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 | 7.6254 mL | 38.1272 mL | 76.2544 mL | |
| 5 mM | 1.5251 mL | 7.6254 mL | 15.2509 mL | |
| 10 mM | 0.7625 mL | 3.8127 mL | 7.6254 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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