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Melphalan Flufenamide Hydrochloride

PubChem CID
70675838
Structure
Melphalan Flufenamide Hydrochloride_small.png
Melphalan Flufenamide Hydrochloride_3D_Structure.png
Molecular Formula
Synonyms
  • Melflufen hydrochloride
  • 380449-54-7
  • J-1 hydrochloride
  • Pepaxto
  • Melphalan flufenamide hydrochloride
Molecular Weight
534.9 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2012-12-03
  • Modify:
    2025-01-18
Description
Melphalan Flufenamide Hydrochloride is the hydrochloride salt form of melphalan flufenamide, a peptide-drug conjugate composed of a peptide conjugated, via an aminopeptidase-targeting linkage, to the alkylating agent melphalan, with potential antineoplastic and anti-angiogenic activities. Upon administration, the highly lipophilic melphalan flufenamide penetrates cell membranes and enters cells. In aminopeptidase-positive tumor cells, melphalan flufenamide is hydrolyzed by peptidases to release the hydrophilic alkylating agent melphalan. This results in the specific release and accumulation of melphalan in aminopeptidase-positive tumor cells. Melphalan alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages. This results in the inhibition of DNA and RNA synthesis and the induction of apoptosis, thereby inhibiting tumor cell proliferation. Peptidases are overexpressed by certain cancer cells. The administration of melphalan flufenamide allows for enhanced efficacy and reduced toxicity compared to melphalan.
MELPHALAN FLUFENAMIDE HYDROCHLORIDE is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 2021 and is indicated for multiple myeloma and has 1 investigational indication.
See also: Melphalan flufenamide (has active moiety).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Melphalan Flufenamide Hydrochloride.png

1.2 3D Conformer

3D Conformer of Parent

2 Biologic Description

SVG Image
SVG Image
Sequence
XX

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

ethyl (2S)-2-[[(2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate;hydrochloride
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

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
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

ZCMWSKHHXLCVHI-VROPFNGYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

CCOC(=O)[C@H](CC1=CC=C(C=C1)F)NC(=O)[C@H](CC2=CC=C(C=C2)N(CCCl)CCCl)N.Cl
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

3.2 Molecular Formula

C24H31Cl3FN3O3
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

380449-54-7

3.3.2 European Community (EC) Number

3.3.3 UNII

3.3.4 ChEMBL ID

3.3.5 KEGG ID

3.3.6 NCI Thesaurus Code

3.3.7 Wikidata

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • melflufen
  • melphalan-flufenamide
  • pepaxto

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
534.9 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
14
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
533.141503 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
533.141503 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
84.7 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
34
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
579
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
2
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
2
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

4.2 Chemical Classes

4.2.1 Drugs

4.2.1.1 Human Drugs
Human drugs -> Antineoplastic agents -> Human pharmacotherapeutic group -> EMA Drug Category

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation (see section 4. 4).

7.2 Clinical Trials

7.2.1 ClinicalTrials.gov

7.2.2 EU Clinical Trials Register

7.3 EMA Drug Information

Medicine
Category
Human drugs
Therapeutic area
Multiple Myeloma
Active Substance
Melphalan flufenamide hydrochloride
INN/Common name
melphalan flufenamide
Pharmacotherapeutic Classes
Antineoplastic agents
Status
This medicine is authorized for use in the European Union
Company
Oncopeptides AB
Market Date
2022-08-17

8 Pharmacology and Biochemistry

8.1 ATC Code

L01AA10

9 Use and Manufacturing

9.1 Uses

9.1.1 Use Classification

Human drugs -> Antineoplastic agents -> Human pharmacotherapeutic group -> EMA Drug Category

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

Pictogram(s)
Acute Toxic
Irritant
Health Hazard
Signal
Danger
GHS Hazard Statements

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

H340 (100%): May cause genetic defects [Danger Germ cell mutagenicity]

H350 (100%): May cause cancer [Danger Carcinogenicity]

H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

Precautionary Statement Codes

P203, P264, P270, P280, P301+P316, P302+P352, P318, P321, P330, P332+P317, P362+P364, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

10.1.2 Hazard Classes and Categories

Acute Tox. 2 (100%)

Skin Irrit. 2 (100%)

Muta. 1B (100%)

Carc. 1B (100%)

Repr. 2 (100%)

11 Associated Disorders and Diseases

12 Literature

12.1 NLM Curated PubMed Citations

12.2 Chemical Co-Occurrences in Literature

12.3 Chemical-Gene Co-Occurrences in Literature

12.4 Chemical-Disease Co-Occurrences in Literature

13 Patents

13.1 WIPO PATENTSCOPE

14 Classification

14.1 MeSH Tree

14.2 NCI Thesaurus Tree

14.3 KEGG: ATC

14.4 ChemIDplus

14.5 UN GHS Classification

14.6 MolGenie Organic Chemistry Ontology

15 Information Sources

  1. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    Ethyl (2S)-2-[[(2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate hydrochloride
    https://echa.europa.eu/substance-information/-/substanceinfo/100.252.189
    Ethyl (2S)-2-[[(2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate hydrochloride (EC: 817-853-7)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/259949
  4. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  5. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  6. EU Clinical Trials Register
  7. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  8. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
    MELPHALAN FLUFENAMIDE HYDROCHLORIDE
    https://platform.opentargets.org/drug/CHEMBL4297403
  9. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
  10. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  11. Wikidata
    melphalan flufenamide hydrochloride
    https://www.wikidata.org/wiki/Q120177846
  12. PubChem
  13. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  14. GHS Classification (UNECE)
  15. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  16. PATENTSCOPE (WIPO)
CONTENTS