Ompenaclid (RGX-202) is an orally bioactive SLC6A8 transporter inhibitor. Ompenaclid strongly inhibits creatine import in vitro and in vivo, reduces intracellular phosphocreatine and ATP levels, and induces tumor apoptosis (apoptosis). Ompenaclid may be used in cancer and Duchenne muscular dystrophy research.

Physicochemical Properties

Molecular Formula	C4H9N3O2
Molecular Weight	131.14
Exact Mass	131.069
CAS #	353-09-3
PubChem CID	67701
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	299.1±42.0 °C at 760 mmHg
Melting Point	222 °C (dec.)(lit.)
Flash Point	134.7±27.9 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.575
LogP	-1.68
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	9
Complexity	128
Defined Atom Stereocenter Count	0
InChi Key	KMXXSJLYVJEBHI-UHFFFAOYSA-N
InChi Code	InChI=1S/C4H9N3O2/c5-4(6)7-2-1-3(8)9/h1-2H2,(H,8,9)(H4,5,6,7)
Chemical Name	3-(diaminomethylideneamino)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

Targets	Human Endogenous Metabolite
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].
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].
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.
References	[1]. Therapeutic targeting of SLC6A8 creatine transporter suppresses colon cancer progression and modulates human creatine levels. Sci Adv. 2021 Oct 8;7(41):eabi7511. [2]. TRPC1 and TRPC3 involvement in DMD physiopathology and as potential targets for treatment in complement to rAAV-microdystrophin. 2021 Oct 1;13.
Additional Infomation	3-guanidinopropanoic acid is a guanidine compound bearing an N-(2-carboxyethyl) substituent. It is a creatine analogue that has been found to decreases plasma glucose levels It has a role as a hypoglycemic agent. It is functionally related to a propionic acid. It is a tautomer of a 3-guanidinopropanoic acid zwitterion. RGX-202 is a recombinant AAV8 that contains a vector genome encoding a miniaturized dystrophin protein (microdystrophin). Ompenaclid is an orally available, small molecule inhibitor of the creatine transporter, solute carrier family 6, member 8 (SLC6a8), with potential antineoplastic activity. Upon oral administration, ompenaclid inhibits phosphocreatine uptake by SLC6a8, thereby reducing intracellular levels of phosphocreatine available for ATP synthesis in tumor cells. SLC6a8 is overexpressed in some cancer types and inhibition of its activity may potentially limit tumor cell growth and metastasis.

Solubility Data

Solubility (In Vitro)

H2O : ≥ 50 mg/mL (381.27 mM) DMSO : < 1 mg/mL

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	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.