MELPHALAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H18Cl2N2O2
Molecular Weight	305.2
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

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

InChI

InChIKey=SGDBTWWWUNNDEQ-LBPRGKRZSA-N

InChI=1S/C13H18Cl2N2O2/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)/t12-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C13H18Cl2N2O2
Molecular Weight	305.2
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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	Crosslinking Agent 81

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple myeloma 159	Palliative		Approved 8,429	ALKERAN
Epithelial carcinoma of the ovary 4	Palliative		Approved 8,429	ALKERAN

C_max

Value	Dose	Co-administered	Analyte	Population
212 ng/mL	0.25 mg/kg single, oral		MELPHALAN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
12.84 mg × h/L	200 mg/m² single, intravenous		MELPHALAN plasma	Homo sapiens
498 ng × h/mL	0.25 mg/kg single, oral		MELPHALAN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
1 h	0.25 mg/kg single, oral		MELPHALAN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
70%			MELPHALAN plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
40 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose	unhealthy, 18–74 n = 7	DLT: Thrombocytopenia, Neutropenia...
30 mg/m2 1 times / 3 weeks multiple, intravenous MTD	unhealthy, 18–74 n = 9	DLT: Thrombocytopenia, Neutropenia...
200 mg/m2 1 times / 70 days multiple, intravenous MTD	unhealthy, 33–65 n = 55	Disc. AE: Toxic reaction (NOS), Bacterial infection...
100 mg/m2 1 times / day multiple, intravenous Recommended	unhealthy	Disc. AE: Bone marrow depression, Hypersensitivity reaction...

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AEs

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AE	Significance	Dose	Population
Neutropenia	grade 4, 57% DLT	40 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose	unhealthy, 18–74 n = 7
Thrombocytopenia	grade 4, 57% DLT	40 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose	unhealthy, 18–74 n = 7
Neutropenia	grade 4, 44% DLT	30 mg/m2 1 times / 3 weeks multiple, intravenous MTD	unhealthy, 18–74 n = 9
Thrombocytopenia	grade 4, 44% DLT	30 mg/m2 1 times / 3 weeks multiple, intravenous MTD	unhealthy, 18–74 n = 9
Toxic reaction (NOS)	grade 4, 1.8% Disc. AE	200 mg/m2 1 times / 70 days multiple, intravenous MTD	unhealthy, 33–65 n = 55

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Sourcing

Sourcing

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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

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PubMed

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Title	Date	PubMed
Encephalopathy complicating high-dose melphalan.	1999 Nov	10578165
The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange.	2001 Dec	11751423
Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.	2001 May	11846301
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	12189532
Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.	2002 Oct	12368962

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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
Record UNII	Q41OR9510P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MELPHALAN

Official Name

English

melphalan [INN]

Common Name

English

L-SARCOLYSIN

Common Name

English

Melphalan [WHO-DD]

Common Name

English

NSC-241286

Code

English

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Classification Tree

Code System

Code

Designated

FDA ORPHAN DRUG

485515

Physiochemical Activity

NDF-RT

N0000000236

Mustard Agent

NCI_THESAURUS

C697

Designated/Withdrawn

FDA ORPHAN DRUG

64291

Nitrogen mustard analogues

WHO-ATC

L01AA03

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Code System

Code

Type

Description

PUBCHEM

460612

PRIMARY

MESH

D008558

PRIMARY

EVMPD

SUB08728MIG

PRIMARY

RXCUI

6718

PRIMARY

RxNorm

WIKIPEDIA

MELPHALAN

PRIMARY

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Related Record

Type

Details


					1VXP4V453T

MELPHALAN HYDROCHLORIDE

SALT/SOLVATE -> PARENT

Amount:

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Type

Details


					ESL4D945VL

MONOHYDROXYMELPHALAN

METABOLITE -> PARENT

Amount:


					F70C5K4786

MELPHALAN FLUFENAMIDE

PRODRUG -> METABOLITE ACTIVE

Amount:


					3412470A0V

MELPHALAN FLUFENAMIDE HYDROCHLORIDE

PRODRUG -> METABOLITE ACTIVE

FB8B918966

DIHYDROXYMELPHALAN

METABOLITE -> PARENT

Amount:

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Type

Details


					B035PIS86W

DIETHYLAMINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (GC)

Qualification:

EP

Amount:

[<0.5] PERCENT PEAK AREA (limits)


					W83QP8L98W

4-BIS(2-CHLOROETHYL)AMINO-L-PHENYLALANINE METHYL ESTER

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.5] PERCENT PEAK AREA (limits)

FB8B918966

DIHYDROXYMELPHALAN

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.1] PERCENT PEAK AREA (limits)


					PWL89DKF98

4-((2-((4-(BIS(2-CHLOROETHYL)AMINO)-L-PHENYLALANYL)OXY)ETHYL)(2-CHLOROETHYL)AMINO)-L-PHENYLALANINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<1] PERCENT PEAK AREA (limits)


					5Q37AUV88K

3-CHLOROMELPHALAN

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.1] PERCENT PEAK AREA (limits)

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Related Record

Type

Details


					Q41OR9510P

MELPHALAN

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Referenced Substance	Parameters
Biological Half-life	PHARMACOKINETIC			Elimination PHARMACOKINETIC 1.5 hours [1 to 2] (average) Oral Elimination PHARMACOKINETIC 75 minutes (average) Terminal

Tmax	PHARMACOKINETIC	[4 to 15] minutes (average)	`Q41OR9510P` MELPHALAN

Volume of Distribution	PHARMACOKINETIC	0.5 Liters/Kilogram (average) Low penetration into CSF.

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound