RAGE antagonist peptide is an advanced glycation end product (RAGE) antagonist. RAGE antagonist peptide (RAP) blocks the binding of RAGE to several important ligands HMGB-1, S100P, and S100A4. RAGE antagonist peptide (RAP) has antitumor and anti-inflammatory activities.

Physicochemical Properties

Molecular Formula	C57H101N13O17S
Molecular Weight	1272.56
Exact Mass	1271.715
CAS #	1092460-91-7
Related CAS #	RAGE antagonist peptide TFA
PubChem CID	127021052
Appearance	White to off-white solid powder
LogP	-4.4
Hydrogen Bond Donor Count	16
Hydrogen Bond Acceptor Count	20
Rotatable Bond Count	47
Heavy Atom Count	88
Complexity	2330
Defined Atom Stereocenter Count	10
SMILES	S(C)CC[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N)=O)CC(C)C)=O)CCC(=O)O)=O)CCCCN)=O)CCC(=O)O)=O)NC([C@H](CC(C)C)NC([C@H](C(C)C)NC([C@H](CCCCN)NC([C@H](CC(C)C)NC([C@H](CCC(=O)O)NC(C)=O)=O)=O)=O)=O)=O
InChi Key	UPCWJIBXKJZZLN-RBQIHDOFSA-N
InChi Code	InChI=1S/C57H101N13O17S/c1-30(2)27-41(48(60)78)67-52(82)39(19-22-46(76)77)64-49(79)35(15-11-13-24-58)62-51(81)38(18-21-45(74)75)65-53(83)40(23-26-88-10)66-56(86)43(29-32(5)6)69-57(87)47(33(7)8)70-54(84)36(16-12-14-25-59)63-55(85)42(28-31(3)4)68-50(80)37(61-34(9)71)17-20-44(72)73/h30-33,35-43,47H,11-29,58-59H2,1-10H3,(H2,60,78)(H,61,71)(H,62,81)(H,63,85)(H,64,79)(H,65,83)(H,66,86)(H,67,82)(H,68,80)(H,69,87)(H,70,84)(H,72,73)(H,74,75)(H,76,77)/t35-,36-,37-,38-,39-,40-,41-,42-,43-,47-/m0/s1
Chemical Name	(4S)-4-acetamido-5-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic 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

ln Vitro	The ability of ligands to promote RAGE activation of NFκB in cancer cells in vitro is reduced by RAGE antagonist peptide (RAP)[1].
ln Vivo	In vivo, PDAC cells' RAGE-mediated Basal NFκB Activity is inhibited by RAGE antagonist peptide (RAP, 100 µg)[1]. RAGE antagonist peptide (RAP) inhibits the growth of glioma tumors and decreases the growth and spread of pancreatic cancers[1]. RAGE antagonist peptide (RAP; 4 mg/kg; ip) blunts goblet cell metaplasia, airway inflammation, and airway responsiveness in asthmatic mice while also reducing Th2 cytokine secretion. In addition, RAGE antagonist peptide decreases β-catenin levels in the cytoplasm, nucleus, and total body. It also increases β-catenin phosphorylation at Ser33/37/Thr41, which results in ubiquitination, downregulates the expression of genes targeted by β-catenin, and keeps β-catenin at the cytomembrane, converting it from an active signaling pattern to an adhesive function[2].
Animal Protocol	Animal/Disease Models: Cancer cells expressing the NFκB-luc reporter implanted into immune-deficient mice[1]. Doses: 100 µg. Route of Administration: Intratumoral delivery (or intraperitoneally). Experimental Results: Systemic administration caused a substantial reduction ( p<0.05) in the NFκB signal 5 h after injection.
References	[1]. S100P-derived RAGE antagonistic peptide reduces tumor growth and metastasis. Clin Cancer Res. 2012 Aug 15;18(16):4356-64. [2]. The receptor for advanced glycation end products is required for β-catenin stabilization in a chemical-induced asthma model. Br J Pharmacol. 2016 Sep;173(17):2600-13.

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	0.7858 mL	3.9291 mL	7.8582 mL
	5 mM	0.1572 mL	0.7858 mL	1.5716 mL
	10 mM	0.0786 mL	0.3929 mL	0.7858 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.