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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H30Cl2FN3O3
Molecular Weight 498.418
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MELPHALAN FLUFENAMIDE

SMILES

CCOC(=O)[C@H](CC1=CC=C(F)C=C1)NC(=O)[C@@H](N)CC2=CC=C(C=C2)N(CCCl)CCCl

InChI

InChIKey=YQZNKYXGZSVEHI-VXKWHMMOSA-N
InChI=1S/C24H30Cl2FN3O3/c1-2-33-24(32)22(16-18-3-7-19(27)8-4-18)29-23(31)21(28)15-17-5-9-20(10-6-17)30(13-11-25)14-12-26/h3-10,21-22H,2,11-16,28H2,1H3,(H,29,31)/t21-,22-/m0/s1

HIDE SMILES / InChI

Description

Melphalan flufenamide ethyl ester (melflufen, previously denoted J1) is a peptidase-potentiated dipeptide prodrug of alkylating agent melphalan. Melflufen readily penetrates membranes and an equilibrium is rapidly achieved, followed by enzymatic cleavage in aminopeptidase positive cells, which results in trapping of less lipophilic metabolites. This targeting effect results in very high intracellular concentrations of its metabolite melphalan and subsequent apoptotic cell death. This results in a potency increase (melflufen vs melphalan) ranging from 10- to several 100-fold in different in vitro models. Melflufen triggers a rapid, robust, and an irreversible DNA damage which may account for its ability to overcome melphalan-resistance in multiple myeloma cells. Melflufen has been granted orphan drug designation for the treatment of multiple myeloma.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells.
2013 Jun 1
The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo.
2013 Oct 1
In vitro and in vivo activity of melflufen (J1)in lymphoma.
2016 Apr 4
A novel alkylating agent Melflufen induces irreversible DNA damage and cytotoxicity in multiple myeloma cells.
2016 Aug
In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia.
2017 Jan 24
Melflufen - a peptidase-potentiated alkylating agent in clinical trials.
2017 Sep 12
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Phase 3 clinical study (OCEAN, OP-103). Melflufen 40 mg i.v. on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.
Route of Administration: Intravenous
In Vitro Use Guide
Melflufen showed activity with cytotoxic IC50-values in the submicromolar range (0.011-0.92 μM) in the cell lines. In the primary cultures melflufen yielded slightly lower IC50-values (2.7 nM to 0.55 μM). Treated cell lines exhibited a clear accumulation in the G2/M-phase of the cell cycle.
Name Type Language
MELPHALAN FLUFENAMIDE
INN   WHO-DD  
INN  
Official Name English
L-PHENYLALANINE, 4-(BIS(2-CHLOROETHYL)AMINO)-L-PHENYLALANYL-4-FLUORO-, ETHYL ESTER
Common Name English
PRODRUG J 1
Code English
J-1
Code English
MFF
Common Name English
J 1
Code English
MELPHALAN FLUFENAMIDE [INN]
Common Name English
J 1 (PRODRUG)
Code English
J-1 (PRODRUG)
Code English
MELPHALAN FLUFENAMIDE [WHO-DD]
Common Name English
ETHYL (2S)-2-((2S)-2-AMINO-3-(4-(BIS(2-CHLOROETHYL)AMINO)PHENYL)PROPANAMIDO)-3-(4-FLUOROPHENYL)PROPANOATE
Systematic Name English
PRODRUG J-1
Code English
Classification Tree Code System Code
NCI_THESAURUS C697
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
NCI_THESAURUS C1742
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
EU-Orphan Drug EU/3/15/1463
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
Code System Code Type Description
EPA CompTox
380449-51-4
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
PRIMARY
PUBCHEM
9935639
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
PRIMARY
NCI_THESAURUS
C107680
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
PRIMARY
CAS
380449-51-4
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
PRIMARY
INN
9493
Created by admin on Mon Oct 21 20:56:47 UTC 2019 , Edited by admin on Mon Oct 21 20:56:47 UTC 2019
PRIMARY