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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H30Cl2FN3O3.ClH
Molecular Weight 534.879
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MELPHALAN FLUFENAMIDE HYDROCHLORIDE

SMILES

Cl.CCOC(=O)[C@H](CC1=CC=C(F)C=C1)NC(=O)[C@@H](N)CC2=CC=C(C=C2)N(CCCl)CCCl

InChI

InChIKey=ZCMWSKHHXLCVHI-VROPFNGYSA-N
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

HIDE SMILES / InChI

Molecular Formula C24H30Cl2FN3O3
Molecular Weight 498.418
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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

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
0.078 µM [IC50]
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
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
432 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
419 ng/mL
40 mg 1 times / 4 weeks steady-state, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
580 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
580 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
516 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
503 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
161 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN FLUFENAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
87 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN FLUFENAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
433 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
429 ng/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
212 ng/mL
14 mg single, oral
dose: 14 mg
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
3143 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
2933 ng × h/mL
40 mg 1 times / 4 weeks steady-state, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
8233 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
8233 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
62222 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
72466 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
3839 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN FLUFENAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
1872 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN FLUFENAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
52192 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
53938 ng × h/mL
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
498 ng × h/mL
14 mg single, oral
dose: 14 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.1 min
single, intravenous
MELPHALAN FLUFENAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
70 min
single, intravenous
MELPHALAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
80 min
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
80 min
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
1 h
14 mg single, oral
dose: 14 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
75 min
100 mg/m² 1 times / day multiple, intravenous
dose: 100 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
MELPHALAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
70%
100 mg/m² 1 times / day multiple, intravenous
dose: 100 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
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:
unhealthy, 18–74
Health Status: unhealthy
Age Group: 18–74
Sex: M+F
Sources:
DLT: Thrombocytopenia, Neutropenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 57%)
Neutropenia (grade 4, 57%)
Sources:
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:
unhealthy, 18–74
Health Status: unhealthy
Age Group: 18–74
Sex: M+F
Sources:
DLT: Thrombocytopenia, Neutropenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 44%)
Neutropenia (grade 4, 44%)
Sources:
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:
unhealthy, 33–65
Health Status: unhealthy
Age Group: 33–65
Sex: M+F
Sources:
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:
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:
unhealthy
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:
55 mg 1 times / week multiple, intravenous
MTD|Highest studied dose
Dose: 55 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 55 mg, 1 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Disc. AE: Thrombocytopenia, Anemia...
Other AEs: Death...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (10.8%)
Anemia (9.6%)
Leukopenia (5.7%)
Neutropenia (28.7%)
Pyrexia (4.5%)
Respiratory tract infection (7%)
Thrombocytopenia (42.7%)
Neutropenia (5.7%)
Thrombocytopenia (22.3%)
Other AEs:
Death (grade 5, 3.2%)
Sources:
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:
unhealthy, 18–74
Health Status: unhealthy
Age Group: 18–74
Sex: M+F
Sources:
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:
unhealthy, 18–74
Health Status: unhealthy
Age Group: 18–74
Sex: M+F
Sources:
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:
unhealthy, 18–74
Health Status: unhealthy
Age Group: 18–74
Sex: M+F
Sources:
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:
unhealthy, 18–74
Health Status: unhealthy
Age Group: 18–74
Sex: M+F
Sources:
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:
unhealthy, 33–65
Health Status: unhealthy
Age Group: 33–65
Sex: M+F
Sources:
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:
unhealthy, 33–65
Health Status: unhealthy
Age Group: 33–65
Sex: M+F
Sources:
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:
unhealthy, 33–65
Health Status: unhealthy
Age Group: 33–65
Sex: M+F
Sources:
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
Thrombocytopenia 10.8%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Thrombocytopenia 22.3%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Neutropenia 28.7%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Pyrexia 4.5%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Thrombocytopenia 42.7%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Leukopenia 5.7%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Neutropenia 5.7%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Respiratory tract infection 7%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Anemia 9.6%
Disc. AE
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Death grade 5, 3.2%
40 mg 1 times / 4 weeks multiple, intravenous
Studied dose
Dose: 40 mg, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / 4 weeks
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [Activation 17.7828 uM]
inconclusive [IC50 32.954 uM]
no [Activation 3.1623 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
unspecified [IC50 93.75 uM]
unspecified [IC50 >10 uM]
unspecified [IC50 >10 uM]
yes [IC50 17.0994 uM]
yes [IC50 19.4971 uM]
yes [IC50 24.5454 uM]
yes [IC50 3.1623 uM]
yes [IC50 8.57 uM]
yes
Drug as victimTox targets

Tox targets

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
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
Cyclophosphamide-associated carcinoma of urothelium: modalities for prevention.
1991 Nov
Deletion 5q31 in patients with stable, melphalan-treated multiple myeloma.
1999 Aug
Myeloblastoma (chloroma) in leukemia: case 2. Meningeal granulocytic sarcoma (chloroma) in essential thrombocythemia.
2000 Dec 1
The role of autologous transplantation in patients with multiple myeloma aged 65 years and over.
2000 Mar
Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.
2002 Aug
Cytotoxic N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidones and related compounds.
2002 Dec
A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients.
2002 Oct
Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma.
2003 Oct 1
Overexpression of glutathione-S-transferase, MGSTII, confers resistance to busulfan and melphalan.
2005
Cross-talk between DNA damage and cell survival checkpoints during G2 and mitosis: pharmacologic implications.
2005 Dec
The nitrogen mustard melphalan activates mitogen-activated phosphorylated kinases (MAPK), nuclear factor-kappaB and inflammatory response in lung epithelial cells.
2005 Jul-Aug
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Inhibition of thioredoxin reductase but not of glutathione reductase by the major classes of alkylating and platinum-containing anticancer compounds.
2005 Sep 1
The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat cells to chemotherapy agents.
2006 Oct
Fatal leukoencephalopathy after reduced-intensity allogeneic stem cell transplantation.
2007 Feb
delta-Aminolevulinate dehydratase activity and oxidative stress during melphalan and cyclophosphamide-BCNU-etoposide (CBV) conditioning regimens in autologous bone marrow transplantation patients.
2009 Apr
Common peroneal nerve palsy following TNF-based isolated limb perfusion for irresectable extremity desmoid tumor.
2009 Dec
Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto SCT on patients with non-Hodgkin's lymphoma.
2010 Apr
Glutathione S-transferase M1 inhibits dexamethasone-induced apoptosis in association with the suppression of Bim through dual mechanisms in a lymphoblastic leukemia cell line.
2010 Mar
Inhalation of alkylating mustard causes long-term T cell-dependent inflammation in airways and growth of connective tissue.
2011 Feb 27
Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study.
2011 Jan
In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells.
2013 Jun 1
The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo.
2013 Oct 1
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.
2013 Sep 5
Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms.
2015 Sep 22
In vitro and in vivo activity of melflufen (J1)in lymphoma.
2016 Apr 4
A novel alkylating agent Melflufen induces irreversible DNA damage and cytotoxicity in multiple myeloma cells.
2016 Aug
In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia.
2017 Jan 24
Melflufen - a peptidase-potentiated alkylating agent in clinical trials.
2017 Sep 12
Patents

Sample Use Guides

In Vivo Use Guide
Relapsed or refractory multiple myeloma: recommended dosage of PEPAXTO is 40 mg intravenously over 30 minutes on Day 1 of each 28-day treatment cycle, in combination with dexamethasone.
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 uM) in the cell lines. In the primary cultures melflufen yielded slightly lower IC50-values (2.7 nM to 0.55 uM). Treated cell lines exhibited a clear accumulation in the G2/M-phase of the cell cycle.
Substance Class Chemical
Created
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on Tue Apr 01 18:32:27 GMT 2025
Edited
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on Tue Apr 01 18:32:27 GMT 2025
Record UNII
3412470A0V
Record Status Validated (UNII)
Record Version
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Name Type Language
J-1 HYDROCHLORIDE
Preferred Name English
MELPHALAN FLUFENAMIDE HYDROCHLORIDE
USAN  
Official Name English
L-PHENYLALANINE, 4-(BIS(2-CHLOROETHYL)AMINO)-L-PHENYLALANYL-4-FLUORO-, ETHYL ESTER, MONOHYDROCHLORIDE
Systematic Name English
MELFLUFEN
Common Name English
MELPHALAN FLUFENAMIDE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
ETHYL (2S)-2-((2S)-2-AMINO-3-(4-(BIS(2-CHLOROETHYL)AMINO)PHENYL)PROPANAMIDO)-3-(4-FLUOROPHENYL)PROPANOATE, HYDROCHLORIDE (1:1)
Common Name English
MELPHALAN FLUFENAMIDE HYDROCHLORIDE [USAN]
Common Name English
PEPAXTO
Brand Name English
CK-1535
Code English
J1 HYDROCHLORIDE
Code English
MELPHALANYL-P-L-FLUOROPHENYLALANINE ETHYL ESTER HYDROCHLORIDE
Common Name English
MELFLUFEN HYDROCHLORIDE
Common Name English
Melphalan flufenamide hydrochloride [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 465314
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
Code System Code Type Description
NCI_THESAURUS
C175815
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
USAN
GH-115
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
FDA UNII
3412470A0V
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
SMS_ID
100000178184
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
RXCUI
2531370
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
CAS
380449-54-7
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
EVMPD
SUB193789
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
PUBCHEM
70675838
Created by admin on Tue Apr 01 18:32:27 GMT 2025 , Edited by admin on Tue Apr 01 18:32:27 GMT 2025
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
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METABOLITE ACTIVE -> PRODRUG
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ACTIVE MOIETY