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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H18Cl2N2O2.ClH
Molecular Weight 341.661
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MELPHALAN HYDROCHLORIDE

SMILES

Cl.N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O

InChI

InChIKey=OUUYBRCCFUEMLH-YDALLXLXSA-N
InChI=1S/C13H18Cl2N2O2.ClH/c14-5-7-17(8-6-15)11-3-1-10(2-4-11)9-12(16)13(18)19;/h1-4,12H,5-9,16H2,(H,18,19);1H/t12-;/m0./s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C13H18Cl2N2O2
Molecular Weight 305.2
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including,http://www.nhs.uk/ipgmedia/National/Macmillan%20Cancer%20Support/assets/MelphalanMCS5pages.pdf http://www.bloodjournal.org/content/bloodjournal/100/1/224.full.pdf

Melphalan, also known as L-phenylalanine mustard, phenylalanine mustard, L-PAM, or L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a bifunctional alkylating agent which produces a number of DNA adducts with the DNA interstrand crosslink (ICL) considered to be the critical cytotoxic lesion. Melphalan is used to treat different cancers including myeloma, melanoma and ovarian cancer.

CNS Activity

Curator's Comment: Melphalan poorly penetrates the central nervous system.

Originator

Curator's Comment: This substance was synthesized simultaneously both at the Chester Beatty Research Institute and in the Soviet Union.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
ALKERAN

Approved Use

ALKERAN Tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.

Launch Date

1964
Palliative
ALKERAN

Approved Use

ALKERAN Tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.

Launch Date

1964
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
212 ng/mL
0.25 mg/kg single, oral
dose: 0.25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
12.84 mg × h/L
200 mg/m² single, intravenous
dose: 200 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
498 ng × h/mL
0.25 mg/kg single, oral
dose: 0.25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1 h
0.25 mg/kg single, oral
dose: 0.25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
70%
MELPHALAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
40 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 40 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 40 mg/m2, 1 times / 3 weeks
Sources: Page: p.60
unhealthy, 18–74
n = 7
Health Status: unhealthy
Condition: Advanced cancer
Age Group: 18–74
Sex: M+F
Population Size: 7
Sources: Page: p.60
DLT: Thrombocytopenia, Neutropenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 57%)
Neutropenia (grade 4, 57%)
Sources: Page: p.60
30 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 30 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 30 mg/m2, 1 times / 3 weeks
Sources: Page: p.60
unhealthy, 18–74
n = 9
Health Status: unhealthy
Condition: Advanced cancer
Age Group: 18–74
Sex: M+F
Population Size: 9
Sources: Page: p.60
DLT: Thrombocytopenia, Neutropenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 44%)
Neutropenia (grade 4, 44%)
Sources: Page: p.60
200 mg/m2 1 times / 70 days multiple, intravenous
MTD
Dose: 200 mg/m2, 1 times / 70 days
Route: intravenous
Route: multiple
Dose: 200 mg/m2, 1 times / 70 days
Sources: Page: p.248, 250
unhealthy, 33–65
n = 55
Health Status: unhealthy
Condition: Multiple myeloma
Age Group: 33–65
Sex: M+F
Population Size: 55
Sources: Page: p.248, 250
Disc. AE: Toxic reaction (NOS), Bacterial infection...
AEs leading to
discontinuation/dose reduction:
Toxic reaction (NOS) (grade 4, 1.8%)
Bacterial infection (grade 5, 3.6%)
Systemic herpes zoster infection (grade 5, 1.8%)
Sources: Page: p.248, 250
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Disc. AE: Bone marrow depression, Hypersensitivity reaction...
AEs leading to
discontinuation/dose reduction:
Bone marrow depression (severe)
Hypersensitivity reaction (2%)
Anaphylaxis
Gastrointestinal toxicity
Nausea
Vomiting
Diarrhea
Mucositis oral
Fetal damage
Infertility
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Neutropenia grade 4, 57%
DLT
40 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 40 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 40 mg/m2, 1 times / 3 weeks
Sources: Page: p.60
unhealthy, 18–74
n = 7
Health Status: unhealthy
Condition: Advanced cancer
Age Group: 18–74
Sex: M+F
Population Size: 7
Sources: Page: p.60
Thrombocytopenia grade 4, 57%
DLT
40 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 40 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 40 mg/m2, 1 times / 3 weeks
Sources: Page: p.60
unhealthy, 18–74
n = 7
Health Status: unhealthy
Condition: Advanced cancer
Age Group: 18–74
Sex: M+F
Population Size: 7
Sources: Page: p.60
Neutropenia grade 4, 44%
DLT
30 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 30 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 30 mg/m2, 1 times / 3 weeks
Sources: Page: p.60
unhealthy, 18–74
n = 9
Health Status: unhealthy
Condition: Advanced cancer
Age Group: 18–74
Sex: M+F
Population Size: 9
Sources: Page: p.60
Thrombocytopenia grade 4, 44%
DLT
30 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 30 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 30 mg/m2, 1 times / 3 weeks
Sources: Page: p.60
unhealthy, 18–74
n = 9
Health Status: unhealthy
Condition: Advanced cancer
Age Group: 18–74
Sex: M+F
Population Size: 9
Sources: Page: p.60
Toxic reaction (NOS) grade 4, 1.8%
Disc. AE
200 mg/m2 1 times / 70 days multiple, intravenous
MTD
Dose: 200 mg/m2, 1 times / 70 days
Route: intravenous
Route: multiple
Dose: 200 mg/m2, 1 times / 70 days
Sources: Page: p.248, 250
unhealthy, 33–65
n = 55
Health Status: unhealthy
Condition: Multiple myeloma
Age Group: 33–65
Sex: M+F
Population Size: 55
Sources: Page: p.248, 250
Systemic herpes zoster infection grade 5, 1.8%
Disc. AE
200 mg/m2 1 times / 70 days multiple, intravenous
MTD
Dose: 200 mg/m2, 1 times / 70 days
Route: intravenous
Route: multiple
Dose: 200 mg/m2, 1 times / 70 days
Sources: Page: p.248, 250
unhealthy, 33–65
n = 55
Health Status: unhealthy
Condition: Multiple myeloma
Age Group: 33–65
Sex: M+F
Population Size: 55
Sources: Page: p.248, 250
Bacterial infection grade 5, 3.6%
Disc. AE
200 mg/m2 1 times / 70 days multiple, intravenous
MTD
Dose: 200 mg/m2, 1 times / 70 days
Route: intravenous
Route: multiple
Dose: 200 mg/m2, 1 times / 70 days
Sources: Page: p.248, 250
unhealthy, 33–65
n = 55
Health Status: unhealthy
Condition: Multiple myeloma
Age Group: 33–65
Sex: M+F
Population Size: 55
Sources: Page: p.248, 250
Hypersensitivity reaction 2%
Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Anaphylaxis Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Diarrhea Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Fetal damage Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Gastrointestinal toxicity Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Infertility Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Mucositis oral Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Nausea Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Vomiting Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
Bone marrow depression severe
Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple myeloma
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
Prolonged apnea after succinylcholine in a case treated with cytostatics for cancer.
1972 Sep-Oct
[Diagnosis and treatment of plasma cell leukemia].
1973 Apr 27
Carcinoma of the breast. Occurence after treatment with melphalan for multiple myeloma.
1976 Oct 4
[Refractory anemia with partial myeloblastosis in multiple myeloma treated with melphalan].
1977 Apr 9-16
Cytomegalovirus pneumonia after treatment with melphalan and prednisone. Report of a case.
1978
Lymphocyte transformation studies in drug hypersensitivity.
1979 May 5
Drug testing using a soft agar stem cell assay on patient and xenograft tumor material.
1984 Sep
Syndrome of inappropriate antidiuretic hormone secretion. A complication of high-dose intravenous melphalan.
1985 Jan 1
Successful treatment of peripheral neuropathy with chemotherapy in osteosclerotic myeloma.
1987 May
Interaction of melphalan and dexamethasone in a human myeloma cell line.
1991 Dec
Absence of severe systemic toxicity after leakage-controlled isolated limb perfusion with tumor necrosis factor-alpha and melphalan.
1999 Jun
Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.
2000 Aug
Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicistronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts.
2000 May
Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.
2002 Oct
Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.
2004 Aug
Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.
2004 Dec
Deletion of 5q31 and 7q31 in patients with stable melphalan treated multiple myeloma.
2004 Jul 1
Overexpression of glutathione-S-transferase, MGSTII, confers resistance to busulfan and melphalan.
2005
New treatments for multiple myeloma.
2005 Dec
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Multicentric Castleman disease with secondary AA renal amyloidosis, nephrotic syndrome and chronic renal failure, remission after high-dose melphalan and autologous stem cell transplantation.
2007 Sep
Hypercalcemia induced by 13 cis-retinoic acid in patients with neuroblastoma.
2008 Apr
Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards.
2008 Apr
Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma.
2008 May
Cutaneous involvement in multiple myeloma and bortezomib.
2009 Nov
In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells.
2013 Jun 1
Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms.
2015 Sep 22
Melflufen - a peptidase-potentiated alkylating agent in clinical trials.
2017 Sep 12
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: IV dose is 16 mg/m2
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
Curator's Comment: RPMI-8226 (multiple myeloma) cells were treated with 10 uM or 100 uM of melphalan.
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 Fri Dec 15 15:15:16 GMT 2023
Edited
by admin
on Fri Dec 15 15:15:16 GMT 2023
Record UNII
1VXP4V453T
Record Status Validated (UNII)
Record Version
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Name Type Language
MELPHALAN HYDROCHLORIDE
ORANGE BOOK   USP-RS   VANDF   WHO-DD  
Common Name English
CB-3025 HYDROCHLORIDE
Code English
SARCOLYSIN HYDROCHLORIDE, L-
Common Name English
MELPHALAN HYDROCHLORIDE [USP-RS]
Common Name English
MELPHALAN HYDROCHLORIDE [VANDF]
Common Name English
L-PHENYLALANINE, 4-(BIS(2-CHLOROETHYL)AMINO)-, HYDROCHLORIDE (1:1)
Systematic Name English
EVOMELA
Brand Name English
CB 3025 HYDROCHLORIDE
Code English
MELPHALAN HYDROCHLORIDE [ORANGE BOOK]
Common Name English
ALKERAN HYDROCHLORIDE
Brand Name English
L-PHENYLALANINE, 4-(BIS(2-CHLOROETHYL)AMINO)-, MONOHYDROCHLORIDE
Common Name English
MELPHALAN HCL
Common Name English
ALANINE, 3-(P-(BIS(2-CHLOROETHYL)AMINO)PHENYL)-, MONOHYDROCHLORIDE, L-
Common Name English
Melphalan hydrochloride [WHO-DD]
Common Name English
HEPZATO
Brand Name English
PHENYLALANINE MUSTARD HYDROCHLORIDE
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 281809
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
FDA ORPHAN DRUG 405413
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
FDA ORPHAN DRUG 271708
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
NCI_THESAURUS C697
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
FDA ORPHAN DRUG 270508
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
Code System Code Type Description
DRUG BANK
DBSALT001019
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
FDA UNII
1VXP4V453T
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
PUBCHEM
9927978
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
RS_ITEM_NUM
1379300
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
CAS
3223-07-2
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
ChEMBL
CHEMBL852
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
RXCUI
235857
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY RxNorm
NCI_THESAURUS
C48002
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
EPA CompTox
DTXSID60872785
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
DAILYMED
1VXP4V453T
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
WIKIPEDIA
Melphalan hydrochloride
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
EVMPD
SUB126965
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
SMS_ID
100000153126
Created by admin on Fri Dec 15 15:15:16 GMT 2023 , Edited by admin on Fri Dec 15 15:15:16 GMT 2023
PRIMARY
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