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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H30Cl2FN3O3.ClH
Molecular Weight 534.879
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MELPHALAN FLUFENAMIDE HYDROCHLORIDE

SMILES

Cl.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=ZCMWSKHHXLCVHI-VROPFNGYSA-N
InChI=1S/C24H30Cl2FN3O3.ClH/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);1H/t21-,22-;/m0./s1

HIDE SMILES / InChI

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

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.
Substance Class Chemical
Created
by admin
on Mon Oct 21 21:38:05 UTC 2019
Edited
by admin
on Mon Oct 21 21:38:05 UTC 2019
Record UNII
3412470A0V
Record Status Validated (UNII)
Record Version
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Name Type Language
MELPHALAN FLUFENAMIDE HYDROCHLORIDE
Common Name English
L-PHENYLALANINE, 4-(BIS(2-CHLOROETHYL)AMINO)-L-PHENYLALANYL-4-FLUORO-, ETHYL ESTER, MONOHYDROCHLORIDE
Systematic Name English
J-1 HYDROCHLORIDE
Code English
MELFLUFEN
Common Name English
MELPHALANYL-P-L-FLUOROPHENYLALANINE ETHYL ESTER HYDROCHLORIDE
Common Name English
MELFLUFEN HYDROCHLORIDE
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 465314
Created by admin on Mon Oct 21 21:38:05 UTC 2019 , Edited by admin on Mon Oct 21 21:38:05 UTC 2019
Code System Code Type Description
CAS
380449-54-7
Created by admin on Mon Oct 21 21:38:05 UTC 2019 , Edited by admin on Mon Oct 21 21:38:05 UTC 2019
PRIMARY
EVMPD
SUB193789
Created by admin on Mon Oct 21 21:38:05 UTC 2019 , Edited by admin on Mon Oct 21 21:38:05 UTC 2019
PRIMARY
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