ß-Secretase Inhibitor 1

Product Name: ß-Secretase Inhibitor 1

Sequence One Letter Code: KTEEISEVN-Sta-VAEF (Sta = statine)

Sequence Three Letter Code: H-Lys-Thr-Glu-Glu-Ile-Ser-Glu-Val-Asn-Sta-Val-Ala-Glu-Phe-OH

Cas No: 350228-37-4

Chemical Formula:C73H118N16O27

Molecular Weight: 1652

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Alzheimer's Disease

SMILES: CCC(C)C(C(=O)NC(CO)C(=O)NC(CCC(=O)O)C(=O)NC(C(C)C)C(=O)NC(CC(=O)N)C(=O)NC(CC(C)C)C(CC(=O)NC(C(C)C)C(=O)NC(C)C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CC=CC=C1)C(=O)O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)O)NC(=O)C(CCCCN)N

IUPAC: 4-[2-[[2-[[4-[[4-amino-2-[[2-[[4-carboxy-2-[[2-[[2-[[4-carboxy-2-[[4-carboxy-2-[[2-(2,6-diaminohexanoylamino)-3-hydroxybutanoyl]amino]butanoyl]amino]butanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]butanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylbutanoyl]amino]propanoylamino]-5-[(1-carboxy-2-phenylethyl)amino]-5-oxopentanoic acid

INCHIKEY: CQTBDEGWLSDJEP-UHFFFAOYSA-N

INCHI:

InChI=1S/C73H118N16O27/c1-11-37(8)59(88-66(108)45(23-27-56(101)102)79-63(105)43(21-25-54(97)98)81-72(114)60(39(10)91)89-62(104)41(75)19-15-16-28-74)71(113)85-49(33-90)68(110)80-44(22-26-55(99)100)65(107)87-58(36(6)7)70(112)83-47(31-51(76)93)67(109)82-46(29-34(2)3)50(92)32-52(94)86-57(35(4)5)69(111)77-38(9)61(103)78-42(20-24-53(95)96)64(106)84-48(73(115)116)30-40-17-13-12-14-18-40/h12-14,17-18,34-39,41-50,57-60,90-92H,11,15-16,19-33,74-75H2,1-10H3,(H2,76,93)(H,77,111)(H,78,103)(H,79,105)(H,80,110)(H,81,114)(H,82,109)(H,83,112)(H,84,106)(H,85,113)(H,86,94)(H,87,107)(H,88,108)(H,89,104)(H,95,96)(H,97,98)(H,99,100)(H,101,102)(H,115,116)

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: β-Secretase Inhibitor 1 is a statine-based substrate analog designed to inhibit β-secretase (BACE1), the aspartyl protease responsible for initiating amyloid precursor protein cleavage and amyloid-β generation in Alzheimer’s disease pathology. Corresponding to the P10–P4′ statV region, this inhibitor is widely applied in biochemical assays using brain homogenates or purified BACE1 to evaluate enzyme activity and inhibition. It serves as a research tool for investigating amyloidogenic processing mechanisms and assessing therapeutic strategies targeting BACE1.

Current Research: β-Secretase Inhibitor 1 is a statine-based peptidomimetic inhibitor designed to target β-secretase (BACE1), the aspartyl protease responsible for the initial cleavage of amyloid precursor protein (APP) in the amyloidogenic pathway. This proteolytic step generates the N-terminus of amyloid-β (Aβ) peptides, which subsequently aggregate and form extracellular plaques characteristic of Alzheimer’s disease (AD) pathology. The inhibitor corresponds to the P10–P4′ statine-containing region (statV core) of the APP substrate sequence, incorporating a hydroxyethylene isostere (statine analog) that mimics the tetrahedral transition state of aspartyl protease–mediated peptide bond hydrolysis. By occupying the active site of BACE1, it competitively blocks substrate access and suppresses Aβ generation in biochemical systems. Mechanistic Rationale BACE1 is an aspartyl protease that cleaves APP at the β-site, a rate-limiting step in Aβ production. The statine residue within β-Secretase Inhibitor 1: Mimics the transition-state geometry of peptide bond cleavage Engages catalytic aspartate residues within the BACE1 active site Confers high-affinity competitive inhibition This mechanism allows the inhibitor to function as a structurally informed substrate analog rather than a nonspecific protease blocker. Research Applications 1. Enzymatic Activity Assays β-Secretase Inhibitor 1 is widely used in assays involving: Purified recombinant BACE1 Brain homogenates containing endogenous BACE1 Fluorogenic or chromogenic APP-derived substrates Inhibition curves generated in these systems support determination of IC₅₀ values and kinetic parameters. 2. Mechanistic Studies of Amyloidogenic Processing By selectively blocking BACE1 activity, the inhibitor enables investigation of: APP cleavage hierarchy Relative contributions of β- and γ-secretase pathways Effects of altered BACE1 expression or mutation It is particularly useful for validating assay specificity in studies evaluating amyloidogenic versus non-amyloidogenic processing. 3. Drug Discovery and Screening Validation Although not itself a therapeutic candidate, β-Secretase Inhibitor 1 serves as a reference compound for benchmarking new BACE1 inhibitors. It helps confirm assay performance and provides a standard for comparative potency assessment. 4. Neurodegeneration Research In cellular and ex vivo systems, BACE1 inhibition models the mechanistic basis of Aβ reduction strategies, supporting translational investigations into AD pathophysiology. Advantages Transition-state–mimicking design Selective inhibition of aspartyl protease BACE1 Suitable for purified enzyme and tissue-based assays Established reference inhibitor in amyloid research Experimental Considerations Assay buffers should maintain optimal pH conditions for BACE1 activity (typically acidic). Enzyme concentration and substrate type may influence apparent inhibitory potency. Controls without inhibitor are essential for baseline activity determination.