MDL-28170

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H26N2O4
Molecular Weight	382.4528
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)[C@H](NC(=O)OCC1=CC=CC=C1)C(=O)N[C@@H](CC2=CC=CC=C2)C=O

InChI

InChIKey=NGBKFLTYGSREKK-PMACEKPBSA-N

InChI=1S/C22H26N2O4/c1-16(2)20(24-22(27)28-15-18-11-7-4-8-12-18)21(26)23-19(14-25)13-17-9-5-3-6-10-17/h3-12,14,16,19-20H,13,15H2,1-2H3,(H,23,26)(H,24,27)/t19-,20-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12820680
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20874056 | https://www.ncbi.nlm.nih.gov/pubmed/15013018 | https://www.ncbi.nlm.nih.gov/pubmed/11012026 | https://www.ncbi.nlm.nih.gov/pubmed/28663009

MDL-28170 is a potent, selective inhibitor of calpain and cathepsin B that does not inhibit trypsin-like serine proteases. In vitro MDL-28170 reduces capsaicin-mediated cell death in cultured dorsal root ganglion, block Ca2+-induced suppression of neurite outgrowth in isolated hippocampal pyramidal neurons. MDL28170 was able to significantly reduce the viability of bloodstream trypomastigotes in mouse macrophages pre-infected with trypomastigotes. In vivo MDL-28170 rapidly penetrates the blood-brain barrier following systemic administration and displays neuroprotective effects in vivo.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Calpain 1 3 Target ID: CHEMBL3891 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15013018	Inhibitor 8504		11.0 nM [IC50]
Cathepsin B 9 Target ID: CHEMBL4072 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11012026	Inhibitor 8504		25.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Axonal injury 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12820680	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Redox-control of the alarmin, Interleukin-1α.	2013	24024155
A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells.	2012-01-15	22155090
Calpain activation is involved in acute manganese neurotoxicity in the rat striatum in vivo.	2012-01	21985864
Neuroprotective effects of MAPK/ERK1/2 and calpain inhibitors on lactacystin-induced cell damage in primary cortical neurons.	2011-12	21683092
Calpain is involved in cisplatin-induced endothelial injury in an in vitro three-dimensional blood vessel model.	2010-11	20878076
Role of GRP78/BiP degradation and ER stress in deoxynivalenol-induced interleukin-6 upregulation in the macrophage.	2009-06	19336499
Calpain mediates the dioxin-induced activation and down-regulation of the aryl hydrocarbon receptor.	2006-11	16891617
The calpain inhibitor MDL 28170 prevents inflammation-induced neurofilament light chain breakdown in the spinal cord and reduces thermal hyperalgesia.	2004-07	15275793
Protective effect of MDL28170 against thioacetamide-induced acute liver failure in mice.	2004-01-20	15316131
Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and beta-D-N4-hydroxycytidine.	2004-01	15074711
Calpain released from dying hepatocytes mediates progression of acute liver injury induced by model hepatotoxicants.	2003-09-15	13678654
In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease.	1993-08-15	8356053
Peptide aldehydes as inhibitors of HIV protease.	1993-03-22	8458418

Patents

Sample Use Guides

In Vivo Use Guide

A single tail vein bolus injection of 30 mg/kg MDL-28170 (courtesy of Aventis Pharmaceuticals) dissolved in 1 mL of the vehicle (PEG300/EtOH, 9:1) was administered to Wistar rats.

Route of Administration: Intravenous

In Vitro Use Guide

Peritoneal macrophages from female BALB/c mice were incubated in the absence or presence of MDL28170 at 30 μM (from a stock solut ion at 5 mM) and dimethylsulfoxide (DMSO, inhibitor diluent ) in triplicate for 72 h. The effect of MDL28170 on the viability of murine peritoneal macrophages was assessed by lack of Trypan blue vital dye staining.

Name

Type

Language

MDL-28170

Common Name

English

CALPAIN INHIBITOR III

Preferred Name

English

CARBAMIC ACID, N-((1S)-1-(((1-FORMYL-2-PHENYLETHYL)AMINO)CARBONYL)-2-METHYLPROPYL)-, PHENYLMETHYL ESTER

Systematic Name

English

N-CBZ-VAL-PHE-AL

Common Name

English

Code System Code Type Description

FDA UNII

WCJ9LQ197S