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
1. Bringhen S, Voorhees PM, Plesner T, Mellqvist UH, Reeves B, Sonneveld P, Byrne C, Nordström E, Harmenberg J, Obermüller J et al.. (2021)
Melflufen plus dexamethasone in relapsed/refractory multiple myeloma: long-term survival follow-up from the Phase II study O-12-M1.
Br J Haematol, 193 (6): 1105-1109. [PMID:33403663]
2. Byrgazov K, Besse A, Kraus M, Slipicevic A, Lehmann F, Driessen C, Besse L. (2021)
Novel Peptide-drug Conjugate Melflufen Efficiently Eradicates Bortezomib-resistant Multiple Myeloma Cells Including Tumor-initiating Myeloma Progenitor Cells.
Hemasphere, 5 (7): e602. [PMID:34136753]
3. Delforoush M, Strese S, Wickström M, Larsson R, Enblad G, Gullbo J. (2016)
In vitro and in vivo activity of melflufen (J1)in lymphoma.
BMC Cancer, 16: 263. [PMID:27044263]
4. Dhillon S. (2021)
Melphalan Flufenamide (Melflufen): First Approval.
Drugs, 81 (8): 963-969. [PMID:33961277]
5. Oriol A, Larocca A, Leleu X, Hajek R, Hassoun H, Rodríguez-Otero P, Paner A, Schjesvold FH, Gullbo J, Richardson PG. (2020)
Melflufen for relapsed and refractory multiple myeloma.
Expert Opin Investig Drugs, 29 (10): 1069-1078. [PMID:32924646]
6. Richardson PG, Oriol A, Larocca A, Bladé J, Cavo M, Rodriguez-Otero P, Leleu X, Nadeem O, Hiemenz JW, Hassoun H et al.. (2021)
Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma.
J Clin Oncol, 39 (7): 757-767. [PMID:33296242]