MELPHALAN HYDROCHLORIDE

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 Search

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
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdf	Crosslinking Agent 81

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdf	Palliative		Approved 8429	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
Epithelial carcinoma of the ovary 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdf	Palliative		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
212 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s030lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s030lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s030lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207155s000lbl.pdf			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: https://pubmed.ncbi.nlm.nih.gov/10656432 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: https://pubmed.ncbi.nlm.nih.gov/10656432 Page: p.60	DLT: Thrombocytopenia, Neutropenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 57%) Neutropenia (grade 4, 57%) Sources: https://pubmed.ncbi.nlm.nih.gov/10656432 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: https://pubmed.ncbi.nlm.nih.gov/10656432 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: https://pubmed.ncbi.nlm.nih.gov/10656432 Page: p.60	DLT: Thrombocytopenia, Neutropenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 44%) Neutropenia (grade 4, 44%) Sources: https://pubmed.ncbi.nlm.nih.gov/10656432 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: https://pubmed.ncbi.nlm.nih.gov/9720737 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: https://pubmed.ncbi.nlm.nih.gov/9720737 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: https://pubmed.ncbi.nlm.nih.gov/9720737 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207155s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Multiple myeloma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207155s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207155s000lbl.pdf Page: p.1

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28876	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28876
ChemicalBook	CB2492687	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2492687
MolPort	MolPort-003-665-535	https://www.molport.com/shop/molecule-link/MolPort-003-665-535
ZINC	ZINC000000001673	http://zinc15.docking.org/substances/ZINC000000001673
eMolecules	525665	https://www.emolecules.com/cgi-bin/more?vid=525665

PubMed

Title	Date	PubMed
Prolonged apnea after succinylcholine in a case treated with cytostatics for cancer.	1972 Sep-Oct	4672170
[Diagnosis and treatment of plasma cell leukemia].	1973 Apr 27	4571885
Carcinoma of the breast. Occurence after treatment with melphalan for multiple myeloma.	1976 Oct 4	183029
[Refractory anemia with partial myeloblastosis in multiple myeloma treated with melphalan].	1977 Apr 9-16	194338
Cytomegalovirus pneumonia after treatment with melphalan and prednisone. Report of a case.	1978	206105
Lymphocyte transformation studies in drug hypersensitivity.	1979 May 5	445303
Drug testing using a soft agar stem cell assay on patient and xenograft tumor material.	1984 Sep	6207157
Syndrome of inappropriate antidiuretic hormone secretion. A complication of high-dose intravenous melphalan.	1985 Jan 1	3965085
Successful treatment of peripheral neuropathy with chemotherapy in osteosclerotic myeloma.	1987 May	3039073
Interaction of melphalan and dexamethasone in a human myeloma cell line.	1991 Dec	1806033
Absence of severe systemic toxicity after leakage-controlled isolated limb perfusion with tumor necrosis factor-alpha and melphalan.	1999 Jun	10379864
Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.	2000 Aug	10955873
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	10830723
Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.	2002 Oct	12368962
Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.	2004 Aug	15325671
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	15591903
Deletion of 5q31 and 7q31 in patients with stable melphalan treated multiple myeloma.	2004 Jul 1	15193449
Overexpression of glutathione-S-transferase, MGSTII, confers resistance to busulfan and melphalan.	2005	15779864
New treatments for multiple myeloma.	2005 Dec	16506632
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
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	17915620
Hypercalcemia induced by 13 cis-retinoic acid in patients with neuroblastoma.	2008 Apr	18353067
Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards.	2008 Apr	18324787
Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma.	2008 May	18388930
Cutaneous involvement in multiple myeloma and bortezomib.	2009 Nov	19259673
In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells.	2013 Jun 1	23584492
Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms.	2015 Sep 22	26208482
Melflufen - a peptidase-potentiated alkylating agent in clinical trials.	2017 Sep 12	29029544

Patents

Sample Use Guides

In Vivo Use Guide

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

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

Download

Name

Type

Language

MELPHALAN HYDROCHLORIDE

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