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

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	MOL RATIO 1 MOL RATIO (average)

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	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 282	Crosslinking Agent 83		0.078 µM [IC50]
DNA 282	Crosslinking Agent 83

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159	Palliative	Approved 8,583	ALKERAN
Epithelial carcinoma of the ovary 4	Palliative	Approved 8,583	ALKERAN
Relapsed or refractory multiple myeloma 5	Primary	Withdrawn

C_max

Value	Dose	Analyte	Population
432 ng/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
419 ng/mL	40 mg 1 times / 4 weeks steady-state, intravenous	MELPHALAN plasma	Homo sapiens
580 ng/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
580 ng/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
516 ng/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
503 ng/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
161 ng/mL	40 mg single, intravenous	MELPHALAN FLUFENAMIDE plasma	Homo sapiens
87 ng/mL	40 mg single, intravenous	MELPHALAN FLUFENAMIDE plasma	Homo sapiens
433 ng/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
429 ng/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
212 ng/mL	14 mg single, oral	MELPHALAN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
3143 ng × h/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
2933 ng × h/mL	40 mg 1 times / 4 weeks steady-state, intravenous	MELPHALAN plasma	Homo sapiens
8233 ng × h/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
8233 ng × h/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
62222 ng × h/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
72466 ng × h/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
3839 ng × h/mL	40 mg single, intravenous	MELPHALAN FLUFENAMIDE plasma	Homo sapiens
1872 ng × h/mL	40 mg single, intravenous	MELPHALAN FLUFENAMIDE plasma	Homo sapiens
52192 ng × h/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
53938 ng × h/mL	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
498 ng × h/mL	14 mg single, oral	MELPHALAN plasma	Homo sapiens
12.84 mg × h/L	200 mg/m² single, intravenous	MELPHALAN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
2.1 min	single, intravenous	MELPHALAN FLUFENAMIDE plasma	Homo sapiens
70 min	single, intravenous	MELPHALAN plasma	Homo sapiens
80 min	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
80 min	40 mg single, intravenous	MELPHALAN plasma	Homo sapiens
1 h	14 mg single, oral	MELPHALAN plasma	Homo sapiens
75 min	100 mg/m² 1 times / day multiple, intravenous	MELPHALAN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
70%	100 mg/m² 1 times / day multiple, intravenous		MELPHALAN plasma	Homo sapiens

Doses

Show entries

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

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

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1,087 activator 150 inhibitor 2,252	inhibitor 2,438	inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP4 290 MRP2 499 BSEP 550 CYP2A6 879 CYP1A2 2,153 CYP2E1 1,060 CYP19A1 429 MRP3 246 P-gp 1,741 CYP2C19 2,057	MRP1 113 BCRP 697 P-gp 2,052 Aminopepetidase N (CD13) 4

Drug as perpetrator

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Target	Modality	Activity	Metabolite
CYP3A4 2,633	inducer 1,966	inconclusive [Activation 17.7828 uM]	Melphalan 4
CYP19A1 430	inhibitor 4,027	inconclusive [IC50 32.954 uM]	Melphalan 4
CYP3A4 2,633	activator 342	no [Activation 3.1623 uM]	Melphalan 4
BSEP 554	inhibitor 4,027	no [IC50 >133 uM]	Melphalan 4
MRP2 625	inhibitor 4,027	no [IC50 >133 uM]	Melphalan 4

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Drug as victim

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Target	Modality	Activity	Metabolite
BCRP 697	substrate 4,014	no
MRP1 113	substrate 4,014	no
P-gp 2,052	substrate 4,014	yes [IC50 41.8 uM]	Melphalan 4
Aminopepetidase N (CD13) 4	substrate 4,014	yes
P-gp 2,052	substrate 4,014	yes

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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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
eMolecules	525665	https://www.emolecules.com/cgi-bin/more?vid=525665
MolPort	MolPort-003-665-535	https://www.molport.com/shop/molecule-link/MolPort-003-665-535
ZINC	ZINC000000001673	http://zinc15.docking.org/substances/ZINC000000001673

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PubMed

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Title	Date	PubMed
[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
Lymphocyte transformation studies in drug hypersensitivity.	1979 May 5	445303
Interaction of melphalan and dexamethasone in a human myeloma cell line.	1991 Dec	1806033
Acute left ventricular failure following melphalan and fludarabine conditioning.	2001 Jul	11498753

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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

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
Record UNII	1VXP4V453T
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

ALKERAN HYDROCHLORIDE

Preferred Name

English

Melphalan hydrochloride

Common Name

English

CB-3025 HYDROCHLORIDE

Code

English

SARCOLYSIN HYDROCHLORIDE, L-

Common Name

English

MELPHALAN HYDROCHLORIDE [USP-RS]

Common Name

English

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Classification Tree

Code System

Code

Designated

FDA ORPHAN DRUG

281809

Designated

FDA ORPHAN DRUG

405413

Designated

FDA ORPHAN DRUG

271708

Mustard Agent

NCI_THESAURUS

C697

Designated

FDA ORPHAN DRUG

270508

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Code System

Code

Type

Description

DRUG BANK

DBSALT001019

PRIMARY

FDA UNII

1VXP4V453T

PRIMARY

PUBCHEM

9927978

PRIMARY

RS_ITEM_NUM

1379300

PRIMARY

CAS

3223-07-2

PRIMARY

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator