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
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
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 |
DescriptionSources: 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.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.
CNS Activity
Sources: http://pmj.bmj.com/content/64/749/232.full.pdf
Curator's Comment: Melphalan poorly penetrates the central nervous system.
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 |
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 |
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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 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 |
|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
70% |
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: 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%) Sources: Page: p.60Neutropenia (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: 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%) Sources: Page: p.60Neutropenia (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: 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%) Sources: Page: p.248, 250Bacterial 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: 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) Sources: Page: p.1Hypersensitivity reaction (2%) Anaphylaxis Gastrointestinal toxicity Nausea Vomiting Diarrhea Mucositis oral Fetal damage Infertility |
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: 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
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 |
|
[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
Sources: https://clinicaltrials.gov/ct2/show/NCT03151811
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
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 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
Edited
Fri Dec 15 15:15:16 GMT 2023
by
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on
Fri Dec 15 15:15:16 GMT 2023
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Record UNII |
1VXP4V453T
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
281809
Created by
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FDA ORPHAN DRUG |
405413
Created by
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FDA ORPHAN DRUG |
271708
Created by
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NCI_THESAURUS |
C697
Created by
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FDA ORPHAN DRUG |
270508
Created by
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DBSALT001019
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1VXP4V453T
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9927978
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1379300
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3223-07-2
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CHEMBL852
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235857
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C48002
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DTXSID60872785
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1VXP4V453T
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Melphalan hydrochloride
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SUB126965
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100000153126
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