Ac-FLTD-CMK

Ac-FLTD-CMK, a gasdermin D (GSDMD)-derived inhibitor, is a specific inflammatory caspases inhibitor. Ac-FLTD-CMK is effective against caspases-1 (IC50 of 46.7 nM), caspases-4 (IC50 of 1.49 μM), caspases-5 (IC50 of 329 nM), and caspases-11 , but not the apoptotic caspases such as caspase-3.

Product information

CAS Number: 2376255-48-8

Molecular Weight: 569.05

Formula: C26H37ClN4O8

Chemical Name: (3S)-5-chloro-3-[(2S, 3R)-2-[(2S)-2-[(2S)-2-acetamido-3-phenylpropanamido]-4-methylpentanamido]-3-hydroxybutanamido]-4-oxopentanoic acid

Smiles: CC(=O)N[C@@H](CC1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)CCl

InChiKey: UCWNTWGHVCSMJP-WPUDHWPRSA-N

InChi: InChI=1S/C26H37ClN4O8/c1-14(2)10-19(30-24(37)20(28-16(4)33)11-17-8-6-5-7-9-17)25(38)31-23(15(3)32)26(39)29-18(12-22(35)36)21(34)13-27/h5-9,14-15,18-20,23,32H,10-13H2,1-4H3,(H,28,33)(H,29,39)(H,30,37)(H,31,38)(H,35,36)/t15-,18+,19+,20+,23+/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 100 mg/mL (175.73 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Ac-FLTD-CMK, inhibits GSDMD cleavage by caspases-1, -4, -5, and -11 in vitro, suppresses pyroptosis downstream of both canonical and noncanonical inflammasomes, as well as reduces IL-1β release following activation of the NLRP3 inflammasome in macrophages. By contrast, Ac-FLTD-CMK does not target caspase-3 or apoptotic cell death. Crystal structure of caspase-1 in complex with Ac-FLTD-CMK reveals extensive enzyme-inhibitor interactions involving both hydrogen bonds and hydrophobic contacts.

References:

1. Jie Yang, et al. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6792-6797.

Products are for research use only. Not for human use.