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SML1117

Sigma-Aldrich

ML345

≥98% (HPLC)

Synonym(s):

5-Fluoro-2-[5-(morpholine-4-sulfonyl)-2-morpholin-4-yl-phenyl]-benzo[d]isothiazol-3-one, CID 57390068

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About This Item

Empirical Formula (Hill Notation):
C21H22FN3O5S2
CAS Number:
Molecular Weight:
479.54
UNSPSC Code:
51111800
PubChem Substance ID:
NACRES:
NA.77

Assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 5 mg/mL, clear (warmed)

storage temp.

2-8°C

SMILES string

O=S(C1=CC(N(C2=O)SC3=C2C=C(F)C=C3)=C(N4CCOCC4)C=C1)(N5CCOCC5)=O

InChI

1S/C21H22FN3O5S2/c22-15-1-4-20-17(13-15)21(26)25(31-20)19-14-16(32(27,28)24-7-11-30-12-8-24)2-3-18(19)23-5-9-29-10-6-23/h1-4,13-14H,5-12H2

InChI key

FVKOFZKSMMIUTL-UHFFFAOYSA-N

Biochem/physiol Actions

ML345 has effective concentration (EC50) value of 188 nM.
ML345 is a cell penetrant, potent and moderately selective insulin degrading enzyme (IDE) inhibitor that targets Cys819 in IDE. IDE is involved in β-chain of insulin degradation and linked to β-amyloid degradation. Recent findings indicate that IDE inhibition is a valid strategy for diabetes mellitus type 2 (DMT2) treatment.

Pictograms

Exclamation mark

Signal Word

Warning

Hazard Statements

Precautionary Statements

Hazard Classifications

Acute Tox. 4 Oral

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable


Certificates of Analysis (COA)

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Selective Targeting of Extracellular Insulin-Degrading Enzyme by Quasi-Irreversible Thiol-Modifying Inhibitors
Abdul. A SO, et al.
ACS Chemical Biology null
Selective Targeting of Extracellular Insulin-Degrading Enzyme by Quasi-Irreversible Thiol-Modifying Inhibitors
Abdul. A SO, et al.
ACS chemical biology null
Helen A Rowland et al.
Neuronal signaling, 7(4), NS20230016-NS20230016 (2023-10-09)
Alzheimer's disease (AD) is characterised by the aggregation and deposition of amyloid-β (Aβ) peptides in the human brain. In age-related late-onset AD, deficient degradation and clearance, rather than enhanced production, of Aβ contributes to disease pathology. In the present study

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The aim of the Cravatt research group is to understand the roles that mammalian enzymes play in physiological and pathological processes and to use this knowledge to identify novel therapeutic targets for the treatment of human disease. To achieve these goals, they develop and apply new technologies that bridge the fields of chemistry and biology, ascribing to the philosophy that the most significant biomedical problems require creative multidisciplinary approaches for their solution. The group's technological innovations address fundamental challenges in systems biology that are beyond the scope of contemporary methods. For instance, enzymes are tightly regulated by post-translational events in vivo, meaning that their activity may not correlate with expression as measured by standard genomic and proteomic approaches. Considering that it is an enzyme's activity, rather than abundance that ultimately dictates its role in cell physiology and pathology, the Cravatt group has introduced a set of proteomic technologies that directly measures this parameter. These activity-based protein profiling (ABPP) methods exploit the power of chemistry to engender new tools and assays for the global analysis of enzyme activities. The enzyme activity profiles generated by ABPP constitute unique molecular portraits of cells and tissues that illuminate how metabolic and signaling networks are regulated in vivo. Additionally, by evaluating enzymes based on functional properties rather than mere abundance, ABPP acquires high-content proteomic information that is enriched in novel markers and targets for the diagnosis and treatment of human disease.

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