melphalan flufenamide   Click here for help

GtoPdb Ligand ID: 11605

Synonyms: Melflufen | Pepaxti® | Pepaxto® | Prodrug J 1 | Prodrug J-1
Approved drug
melphalan flufenamide is an approved drug (FDA (2021), EMA (2022))
Compound class: Synthetic organic
Comment: Melphalan flufenamide is a peptide-conjugated prodrug of the cytotoxic DNA alkylating drug melphalan [3]. It is highly lipophilic and is rapidly transported into cells where it is quickly hydrolysed by aminopeptidases that are overexpressed by some cancer cells. Melphalan flufenamide is being evaluated as a treatment for multiple myeloma [2,5-6].
The IUPAC Condensed peptide sequence for melphalan flufenamide is H-Phe(Unk)-Phe(4-F)-OEt.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 15
Topological polar surface area 84.66
Molecular weight 497.16
XLogP 4.57
No. Lipinski's rules broken 1
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Canonical SMILES ClCCN(c1ccc(cc1)C[C@@H](C(=O)N[C@H](C(=O)OCC)Cc1ccc(cc1)F)N)CCCl
Isomeric SMILES ClCCN(c1ccc(cc1)C[C@@H](C(=O)N[C@H](C(=O)OCC)Cc1ccc(cc1)F)N)CCCl
InChI 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
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Summary of Clinical Use Click here for help
In February 2021, melphalan flufenamide (in combination with dexamethasone) was granted its first approval by the FDA. It was indicated for the treatment of extensively previously treated relapsed or refractory multiple myeloma [4]. As of July 2021, there were nine melflufen/J-1 clinical studies registered on
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Once inside aminopeptidase-positive tumour cells, melphalan flufenamide is hydrolysed to release the active alkylating agent melphalan.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03151811 A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide Phase 3 Interventional Oncopeptides AB
NCT01897714 Safety and Efficacy of Melflufen and Dexamethasone in Relapsed and/or Relapsed-Refractory Multiple Myeloma Patients Phase 1/Phase 2 Interventional Oncopeptides AB 1