Beta-Sheet Breaker Peptide iAβ5 is a potent brain amyloid-beta (Abeta) degrader. Abeta deposition is associated with AD/Alzheimer's disease, and the associated toxicity results from its β-sheet conformation and aggregation. β-Sheet Breaker Peptide iAβ5 reproducibly induces the breakdown of fibrillar amyloid deposits in vivo. Thus, β-Sheet Breaker Peptide iAβ5 prevents and/or reverses Abeta-induced neuronal shrinkage and reduces the extent of interleukin IL-1beta-positive microglia-like cells surrounding Abeta deposits. β-Sheet Breaker Peptide iAβ5 reduces the size and/or number of brain amyloid plaques in AD. β-Sheet Breaker Peptide iAβ5 is labeled with a hydrophobic benzyl alcohol (HBA) tag and displays a bright blue color under acidic conditions, allowing for quantitative determination.

Physicochemical Properties

Molecular Formula	C33H43N5O8
Molecular Weight	637.72
Exact Mass	637.311
CAS #	182912-74-9
PubChem CID	10146049
Appearance	White to off-white solid powder
LogP	2.66
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	16
Heavy Atom Count	46
Complexity	1070
Defined Atom Stereocenter Count	5
SMILES	CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CC(=O)O)C(=O)O)N
InChi Key	RALAXQOLLAQGTI-IRGGMKSGSA-N
InChi Code	InChI=1S/C33H43N5O8/c1-20(2)16-23(34)32(44)38-15-9-14-27(38)31(43)36-25(18-22-12-7-4-8-13-22)29(41)35-24(17-21-10-5-3-6-11-21)30(42)37-26(33(45)46)19-28(39)40/h3-8,10-13,20,23-27H,9,14-19,34H2,1-2H3,(H,35,41)(H,36,43)(H,37,42)(H,39,40)(H,45,46)/t23-,24-,25-,26-,27-/m0/s1
Chemical Name	(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]butanedioic 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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	β-Sheet Breaker Peptide iAβ5 (1.5 μg/μL; 7 days) suppresses the development of amyloid beta fibrils, degrades preexisting fibrils in vitro, and shields cell culture neurons from fibril-induced mortality [1]. Following a two-day treatment with 50 μM aggregated Aβ1-42 in human neuroblastoma (IMR-32) cells, β-Sheet Breaker Peptide iAβ5 (60 μM; 48 hours) demonstrated no cytotoxicity [1].
ln Vivo	Aβ1-42 (5 nmol) was co-injected into the rat amygdala along with β-Sheet Breaker Peptide iAβ5 (100 nmol/rat; intra-amygdala injection; 7 days) to prevent Aβ1-42 neurotoxicity in tissue culture. as well as the rat models' development of amyloid fibrils [1]. When administered intraamygdally seven days after treatment with Aβ1-42 (5 nmol), β-Sheet Breaker Peptide iAβ5 (100 nmol/rat, 200 nmol/rat; intra-amygdala injection) causes the body's pre-existing Aβ fibrils to break down, which in turn reverses or prevents Aβ-induced histopathological alterations in rat models [2].
References	[1]. Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy. Nat Med. 1998 Jul;4(7):822-6. [2]. In vivo reversal of amyloid-beta lesions in rat brain. J Neuropathol Exp Neurol. 2000 Jan;59(1):11-7. [3]. Acid-Triggered Colorimetric Hydrophobic Benzyl Alcohols for Soluble Tag-Assisted Liquid-Phase Synthesis. Org Lett. 2015 Sep 4;17(17):4264-7.

Solubility Data

Solubility (In Vitro)

H2O: 50 mg/mL (78.40 mM)

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	1.5681 mL	7.8404 mL	15.6809 mL
	5 mM	0.3136 mL	1.5681 mL	3.1362 mL
	10 mM	0.1568 mL	0.7840 mL	1.5681 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.