MELPHALAN FLUFENAMIDE HYDROCHLORIDE

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

Structure of MELPHALAN FLUFENAMIDE HYDROCHLORIDE

Structure Search

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

HIDE SMILES / InChI

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

Description
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2311221 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214383s000lbl.pdf	Crosslinking Agent 83		0.078 µM [IC50]
DNA 282 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdf	Crosslinking Agent 83

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s029lbl.pdf	Palliative	Approved 8583	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 8583	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
Relapsed or refractory multiple myeloma 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214383s000lbl.pdf	Primary	Withdrawn

C_max

Value	Dose	Analyte	Population
432 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=48	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=48	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=53	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=53	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s030lbl.pdf	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	Analyte	Population
3143 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=48	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=48	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=53	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=53	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=56	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s030lbl.pdf	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

T_1/2

Value	Dose	Analyte	Population
2.1 min OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=47	single, intravenous	MELPHALAN FLUFENAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
70 min OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=47	single, intravenous	MELPHALAN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
80 min OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=53	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 OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf3page=53	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/014691s030lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207155s000lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207155s000lbl.pdf	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: https://pubmed.ncbi.nlm.nih.gov/10656432	unhealthy, 18–74 Health Status: unhealthy Age Group: 18–74 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10656432	DLT: Thrombocytopenia, Neutropenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 57%) Neutropenia (grade 4, 57%) Sources: https://pubmed.ncbi.nlm.nih.gov/10656432
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	unhealthy, 18–74 Health Status: unhealthy Age Group: 18–74 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10656432	DLT: Thrombocytopenia, Neutropenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 44%) Neutropenia (grade 4, 44%) Sources: https://pubmed.ncbi.nlm.nih.gov/10656432
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	unhealthy, 33–65 Health Status: unhealthy Age Group: 33–65 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/9720737	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
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207155s000lbl.pdf	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
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf#page=87	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf#page=87	Disc. AE: Thrombocytopenia, Anemia... Other AEs: Death... AEs leading to discontinuation/dose reduction: Thrombocytopenia (10.8%) 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%) Other AEs: Death (grade 5, 3.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf#page=87

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 activator 150 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP4 290 MRP2 499 BSEP 550 CYP2A6 879 CYP1A2 2153 CYP2E1 1060 CYP19A1 429 MRP3 246 P-gp 1741 CYP2C19 2057	MRP1 113 BCRP 697 P-gp 2052 Aminopepetidase N (CD13) 4

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144204561	inconclusive [Activation 17.7828 uM]	Melphalan 4
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144209720	inconclusive [IC50 32.954 uM]	Melphalan 4
CYP3A4 2633	activator 342 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/885#sid=17389837	no [Activation 3.1623 uM]	Melphalan 4
BSEP 554	inhibitor 4027 Sources: https://transportal.compbio.ucsf.edu/compounds/melphalan/ \| https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]	Melphalan 4
MRP2 625	inhibitor 4027 Sources: https://transportal.compbio.ucsf.edu/compounds/melphalan/ \| https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]	Melphalan 4
MRP3 326	inhibitor 4027 Sources: https://transportal.compbio.ucsf.edu/compounds/melphalan/ \| https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]	Melphalan 4
MRP4 345	inhibitor 4027 Sources: https://transportal.compbio.ucsf.edu/compounds/melphalan/ \| https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]	Melphalan 4
BSEP 554	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1449628#sid=103223867	unspecified [IC50 93.75 uM]	Melphalan 4
CYP2A6 911	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625246#sid=103223867	unspecified [IC50 >10 uM]	Melphalan 4
CYP2E1 1146	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625250#sid=103223867	unspecified [IC50 >10 uM]	Melphalan 4
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671198#sid=144209720	yes [IC50 17.0994 uM]	Melphalan 4
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170464727	yes [IC50 19.4971 uM]	Melphalan 4
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671199#sid=170464727	yes [IC50 24.5454 uM]	Melphalan 4
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/884#sid=17389837	yes [IC50 3.1623 uM]	Melphalan 4
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671197#sid=144209720	yes [IC50 8.57 uM]	Melphalan 4
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/377#sid=10321915	yes	Melphalan 4

Drug as victim

Target	Modality	Activity	Metabolite
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23637844/	no
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23637844/	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19447222/	yes [IC50 41.8 uM]	Melphalan 4
Aminopepetidase N (CD13) 4	substrate 4014 Sources: https://www.mdpi.com/1424-8247/15/2/222	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23637844/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214383Orig1s000MultidisciplineR.pdf#page=36 Page: 36.0

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
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

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
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
Cyclophosphamide-associated carcinoma of urothelium: modalities for prevention.	1991 Nov	1949449
Deletion 5q31 in patients with stable, melphalan-treated multiple myeloma.	1999 Aug	10459345
Myeloblastoma (chloroma) in leukemia: case 2. Meningeal granulocytic sarcoma (chloroma) in essential thrombocythemia.	2000 Dec 1	11099330
The role of autologous transplantation in patients with multiple myeloma aged 65 years and over.	2000 Mar	10713631
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
Cytotoxic N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidones and related compounds.	2002 Dec	12660021
A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients.	2002 Oct	12481892
Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma.	2003 Oct 1	12791655
Overexpression of glutathione-S-transferase, MGSTII, confers resistance to busulfan and melphalan.	2005	15779864
Cross-talk between DNA damage and cell survival checkpoints during G2 and mitosis: pharmacologic implications.	2005 Dec	16373717
The nitrogen mustard melphalan activates mitogen-activated phosphorylated kinases (MAPK), nuclear factor-kappaB and inflammatory response in lung epithelial cells.	2005 Jul-Aug	16025434
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Inhibition of thioredoxin reductase but not of glutathione reductase by the major classes of alkylating and platinum-containing anticancer compounds.	2005 Sep 1	16085187
The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat cells to chemotherapy agents.	2006 Oct	16951922
Fatal leukoencephalopathy after reduced-intensity allogeneic stem cell transplantation.	2007 Feb	17264526
delta-Aminolevulinate dehydratase activity and oxidative stress during melphalan and cyclophosphamide-BCNU-etoposide (CBV) conditioning regimens in autologous bone marrow transplantation patients.	2009 Apr	19162187
Common peroneal nerve palsy following TNF-based isolated limb perfusion for irresectable extremity desmoid tumor.	2009 Dec	19944662
Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto SCT on patients with non-Hodgkin's lymphoma.	2010 Apr	19767780
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	20067466
Inhalation of alkylating mustard causes long-term T cell-dependent inflammation in airways and growth of connective tissue.	2011 Feb 27	21129433
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	20874823
In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells.	2013 Jun 1	23584492
The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo.	2013 Oct 1	23933387
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013 Sep 5	23769903
Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms.	2015 Sep 22	26208482
In vitro and in vivo activity of melflufen (J1)in lymphoma.	2016 Apr 4	27044263
A novel alkylating agent Melflufen induces irreversible DNA damage and cytotoxicity in multiple myeloma cells.	2016 Aug	27098276
In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia.	2017 Jan 24	27974676
Melflufen - a peptidase-potentiated alkylating agent in clinical trials.	2017 Sep 12	29029544

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 Created by `admin` on `Tue Apr 01 18:32:27 GMT 2025` Edited by `admin` on `Tue Apr 01 18:32:27 GMT 2025`
Record UNII	3412470A0V
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

J-1 HYDROCHLORIDE

Preferred Name

English

MELPHALAN FLUFENAMIDE HYDROCHLORIDE

Official Name

English

L-PHENYLALANINE, 4-(BIS(2-CHLOROETHYL)AMINO)-L-PHENYLALANYL-4-FLUORO-, ETHYL ESTER, MONOHYDROCHLORIDE

Systematic Name

English

MELFLUFEN

Common Name

English

MELPHALAN FLUFENAMIDE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

ETHYL (2S)-2-((2S)-2-AMINO-3-(4-(BIS(2-CHLOROETHYL)AMINO)PHENYL)PROPANAMIDO)-3-(4-FLUOROPHENYL)PROPANOATE, HYDROCHLORIDE (1:1)

Common Name

English

MELPHALAN FLUFENAMIDE HYDROCHLORIDE [USAN]

Common Name

English

PEPAXTO

Brand Name

English

CK-1535

Code

English

J1 HYDROCHLORIDE

Code

English

MELPHALANYL-P-L-FLUOROPHENYLALANINE ETHYL ESTER HYDROCHLORIDE

Common Name

English

MELFLUFEN HYDROCHLORIDE

Common Name

English

Melphalan flufenamide hydrochloride [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

465314