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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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key YQZNKYXGZSVEHI-VXKWHMMOSA-N
References
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]