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Details

Stereochemistry EPIMERIC
Molecular Formula C21H23FN2O4
Molecular Weight 386.4167
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MDL-201053, (DL-ALANINE)-

SMILES

CC(NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)OCC2=CC=CC=C2)C(=O)CF

InChI

InChIKey=ASXVEBPEZMSPHB-PKHIMPSTSA-N
InChI=1S/C21H23FN2O4/c1-15(19(25)13-22)23-20(26)18(12-16-8-4-2-5-9-16)24-21(27)28-14-17-10-6-3-7-11-17/h2-11,15,18H,12-14H2,1H3,(H,23,26)(H,24,27)/t15?,18-/m0/s1

HIDE SMILES / InChI

Description

MDL-201053, (DL-ALANINE)- (Z-FA-FMK) is an irreversible inhibitor of cysteine proteases, such as cathepsin B, L, and S. The compound has also inhibitited papain and cruzain. Z-FA-FMK has been shown to selectively inhibit effector caspase-2, caspase-3, caspase-6, and caspase-7 without affecting initiator caspase-8 and caspase-10 while showing minimal toxicity to normal mammalian cells in vitro. Due to Z-FA-FMK's effector caspase specificity, the compound has been recorded to inhibit some forms of caspase mediated apoptosis. The compound has been observed to be an effective in time dependent inactivation of cathepsin B isozymes from a number of tissues. Studies show Cathepsin B-like activity plays a role in the cascade of proteolytic cartilage destruction. Z-FA-FMK is an inhibitor of cathepsin H. This compound has been shown to block the production of IL1-α, IL1-β, and TNF-α induced by LPS in macrophages by inhibiting NF-κB pathways. Z-FA-FMK blocks not only NF-kappaB activation but inhibits, also, T cell blast formation, and prevents cells from entering and leaving the cell cycle revealing demonstrating immunosuppressive abilities. Z-FA-FMK is a very effective viral inhibitor that can prevent reovirus replication in vitro and reovirus-mediated myocarditis, as well as reovirus-mediated oncolysis, in vivo.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
6.15 µM [IC50]
15.41 µM [IC50]
32.45 µM [IC50]
9.08 µM [IC50]
110.7 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
8 mg/kg in 10% dimethyl sulphoxide
Route of Administration: Intravenous
In Vitro Use Guide
T cell proliferation induced by anti-CD3 was inhibited in a concentration-dependent manner by z-FA-FMK (IC50 ~50 μM).