RAGE 229 is a small molecule ctRAGE-DIAPH1 inhibitor (antagonist) with oral activity. RAGE 229 inhibits intracellular RAGE signaling by inhibiting the interaction of ctRAGE with DIAPH1.

Physicochemical Properties

Molecular Formula	C23H22N4O2
Molecular Weight	386.446384906769
Exact Mass	386.174
CAS #	2143072-85-7
PubChem CID	132020228
Appearance	White to off-white solid powder
LogP	2.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	29
Complexity	603
Defined Atom Stereocenter Count	0
InChi Key	VDYYVNHJRNDKDO-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H22N4O2/c1-16(28)25-20-5-3-18(4-6-20)22-13-19(15-27-8-10-29-11-9-27)21-7-2-17(14-24)12-23(21)26-22/h2-7,12-13H,8-11,15H2,1H3,(H,25,28)
Chemical Name	N-[4-[7-cyano-4-(morpholin-4-ylmethyl)quinolin-2-yl]phenyl]acetamide
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	RAGE229 inhibits SMC migration with an IC50 value of 26 nM and has an affinity for ctRAGE with a KD value of 2 nM[1].
ln Vivo	In mice, RAGE229 (oral gavage, 5 mg/kg twice daily for 4 days) reduces both the immediate and long-term consequences of diabetes [1]. TNF-α, IL-6, and CCL2/JE-MCP1 are reduced in the plasma of diabetic mice by RAGE229 (oral or intravenous; 150, 50, and 15 ppm chow; 30, 10, and 3 mg/kg per mouse per day) (5 mg/kg intraperitoneally every 12 hours for a total of four doses) and these reductions also affect the pathological and functional indices of diabetic nephropathy [1].
Cell Assay	Cell migration assay[1] Cell Types: SMC Tested Concentrations: 0.00006 -10 μM. Incubation Duration: 1.5 hrs (hours) Experimental Results: Inhibits SMC migration with IC50 value of 26 nM.
Animal Protocol	Animal/Disease Models: Female CF-1 mice and male diabetic mice [1] Doses: 5 mg/kg Route of Administration: po (oral gavage), 5 mg/kg, twice a day for 4 days Experimental Results: diminished inflammation scores in mice and infarct size. Animal/Disease Models: C57BL/6J mice and BTBR ob/obmice[1] Doses: 30, 10 and 3 mg/kg; 5 mg/kg Route of Administration: oral or intravenous (iv) (iv)injection; 150, 50 and 15 ppm food; each Mice were given 30, 10 and 3 mg/kg; 5 mg/kg intraperitoneally (ip) (ip) every 12 hrs (hrs (hours)) for a total of four doses per day. Experimental Results: diminished concentrations of CCL2, TNF-α and IL-6.
References	[1]. Michaele B Manigrasso, et al. Small-molecule antagonism of the interaction of the RAGE cytoplasmic domain with DIAPH1 reduces diabetic complications in mice. Sci Transl Med. 2021 Nov 24;13(621):eabf7084.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	2.5877 mL	12.9383 mL	25.8766 mL
	5 mM	0.5175 mL	2.5877 mL	5.1753 mL
	10 mM	0.2588 mL	1.2938 mL	2.5877 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.