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
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
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 |
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214383s000lbl.pdf | https://pubmed.ncbi.nlm.nih.gov/35196605 | https://www.ncbi.nlm.nih.gov/pubmed/23584492 | https://www.ncbi.nlm.nih.gov/pubmed/29029544 | https://www.oncopeptides.se/en/about-ygalo/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdfCurator'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
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214383s000lbl.pdf | https://pubmed.ncbi.nlm.nih.gov/35196605 | https://www.ncbi.nlm.nih.gov/pubmed/23584492 | https://www.ncbi.nlm.nih.gov/pubmed/29029544 | https://www.oncopeptides.se/en/about-ygalo/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdf
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.
Originator
Sources: https://adisinsight.springer.com/drugs/800033866http://pmj.bmj.com/content/34/398/622.full.pdf
Curator's Comment: This substance was synthesized simultaneously both at the Chester Beatty Research Institute and in the Soviet Union.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2311221 |
0.078 µM [IC50] | ||
Target ID: CHEMBL2311221 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | ALKERAN Approved UseALKERAN Tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Launch Date1964 |
|||
Palliative | ALKERAN Approved UseALKERAN Tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Launch Date1964 |
|||
Primary |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26879446 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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 |
DLT: Thrombocytopenia, Neutropenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 57%) Sources: Neutropenia (grade 4, 57%) |
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 |
DLT: Thrombocytopenia, Neutropenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 44%) Sources: Neutropenia (grade 4, 44%) |
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 |
Disc. AE: Toxic reaction (NOS), Bacterial infection... AEs leading to discontinuation/dose reduction: Toxic reaction (NOS) (grade 4, 1.8%) Sources: Bacterial infection (grade 5, 3.6%) Systemic herpes zoster infection (grade 5, 1.8%) |
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 Health Status: unhealthy Sources: |
Disc. AE: Bone marrow depression, Hypersensitivity reaction... AEs leading to discontinuation/dose reduction: Bone marrow depression (severe) Sources: Hypersensitivity reaction (2%) Anaphylaxis Gastrointestinal toxicity Nausea Vomiting Diarrhea Mucositis oral Fetal damage Infertility |
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%) Other AEs: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%) Death (grade 5, 3.2%) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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 victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes [IC50 41.8 uM] | ||||
Sources: https://www.mdpi.com/1424-8247/15/2/222 |
yes | |||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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A novel alkylating agent Melflufen induces irreversible DNA damage and cytotoxicity in multiple myeloma cells. | 2016 Aug |
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In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia. | 2017 Jan 24 |
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Melflufen - a peptidase-potentiated alkylating agent in clinical trials. | 2017 Sep 12 |
Patents
Sample Use Guides
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27044263
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
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FDA ORPHAN DRUG |
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METABOLITE ACTIVE -> PRODRUG |
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ACTIVE MOIETY |
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