Details of the Drug

General Information of Drug (ID: DMOLNHF)

Drug Name
Melphalan
Synonyms
Alkeran; Levofalan; Levofolan; Levopholan; Melfalan; Melfalano; Melphalanum; Alanine Nitrogen Mustard; Phenylalanine mustard; Phenylalanine nitrogen mu stard; Phenylalanine nitrogen mustard; AY3360000; CB 3025; ALKERAN (TN); Alkeran (TN); At-290; CB-3025; L-PAM; L-Phenylalanine mustard; L-Sarcolysin; L-Sarcolysine; L-Sarkolysin; Melfalano [INN-Spanish]; Melphalanum [INN-Latin]; SK-15673; TRANSGENIC MODEL EVALUATION (MELPHALAN); MELPHALAN (SEE ALSO TRANSGENIC MODEL EVALUATION (MELPHALAN)); P-L-Sarcolysin; P-L-sarcolysine; TRANSGENIC LEP (MELPHALAN) (SEE ALSO MELPHALAN); Melphalan (JP15/USP/INN); Melphalan [USAN:INN:BAN:JAN]; P-Bis(beta-chloroethyl)aminophenylalanine; P-N-Di(chloroethyl)aminophenylalanine; P-N-di(chloroethyl)aminophenylala nine; P-Di-(2-chloroethyl)amino-L-phenylalanine; P-N-Bis(2-chloroethyl)amino-L-phenylalanine; L-3-(p-(Bis(2-chloroethyl)amino)phenyl)alanine; L-3-(para-(Bis(2-chloroethyl)amino)phenyl)alanine; P-N,N-bis(2-chloroethyl)amino-L-phenylalanine; (2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoic acid; (2s)-2-amino-3-(4-[bis(2-chloroethyl)amino]phenyl)propanoic acid; 3-(p-(Bis(2-chloroethyl)amino)phenyl)-L-alanine; 3-(p-(Bis(2-chloroethyl)amino)phenyl)alanine; 3-p-(Di(2-chloroethyl)amino)-phenyl-L-alanine; 4-(Bis(2-chloroethyl)amino)-L-phenylalanine; 4-[Bis(2-chloroethyl)amino]-L-phenylalanine; 4-[Bis-(2-chloroethyl)amino]-L-phenylalanine
Indication
Disease Entry ICD 11 Status REF
Hematologic disease 3C0Z Approved [1]
Leukemia N.A. Approved [1]
Multiple myeloma 2A83 Approved [2]
Myeloproliferative neoplasm 2A20 Approved [1]
Ovarian cancer 2C73 Approved [3]
Plasma cell myeloma 2A83.1 Approved [1]
Refractory plasma cell neoplasm N.A. Approved [1]
Intrahepatic cholangiocarcinoma 2C12.10 Phase 3 [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Classic Hodgkin lymphoma N.A. Investigative [1]
Neuroblastoma 2D11.2 Investigative [1]
Retinoblastoma 2D02.2 Investigative [1]
⏷ Show the Full List of Indication(s)
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 305.2
Logarithm of the Partition Coefficient (xlogp) -0.5
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [6]
Bioavailability
71% of drug becomes completely available to its intended biological destination(s) [7]
Clearance
The drug present in the plasma can be removed from the body at the rate of 7 mL/min/kg [8]
Elimination
12% of drug is excreted from urine in the unchanged form [6]
Half-life
The concentration or amount of drug in body reduced by one-half in 1 hour [8]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.32765 micromolar/kg/day [9]
Unbound Fraction
The unbound fraction of drug in plasma is 0.14% [8]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.48 L/kg [8]
Water Solubility
The ability of drug to dissolve in water is measured as 0.1 mg/mL [6]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Chromosomal abnormalities and abnormal gene carriers Not Available TRIB3 OTG5OS7X [10]
Injury Not Available CD80 OTJBLUQE [10]
Injury Not Available IKBKAP OTYEWBF7 [10]
Chemical Identifiers
Formula
C13H18Cl2N2O2
IUPAC Name
(2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoic acid
Canonical SMILES
C1=CC(=CC=C1C[C@@H](C(=O)O)N)N(CCCl)CCCl
InChI
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
InChIKey
SGDBTWWWUNNDEQ-LBPRGKRZSA-N
Cross-matching ID
PubChem CID
460612
ChEBI ID
CHEBI:28876
CAS Number
148-82-3
DrugBank ID
DB01042
TTD ID
D00FGO
VARIDT ID
DR00379
INTEDE ID
DR1021
ACDINA ID
D00394
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [11]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Glutathione S-transferase alpha-1 (GSTA1)
Main DME 		DE4ZHS1 GSTA1_HUMAN Substrate [13]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial (CYP27B1) OTTK98BH CP27B_HUMAN Gene/Protein Processing [14]
Actin remodeling regulator NHS (NHS) OTKE8QAT NHS_HUMAN Gene/Protein Processing [14]
Activator of basal transcription 1 (ABT1) OT9YGIDB ABT1_HUMAN Gene/Protein Processing [14]
Activin receptor type-1C (ACVR1C) OTOTYERF ACV1C_HUMAN Gene/Protein Processing [14]
Alpha-(1,3)-fucosyltransferase 10 (FUT10) OT8TI57X FUT10_HUMAN Gene/Protein Processing [14]
Alpha/beta hydrolase domain-containing protein 17C (ABHD17C) OTB1MTOI AB17C_HUMAN Gene/Protein Processing [14]
AMMECR1-like protein (AMMECR1L) OTFPJEC1 AMERL_HUMAN Gene/Protein Processing [14]
AMSH-like protease (STAMBPL1) OTI4CYTF STALP_HUMAN Gene/Protein Processing [14]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Gene/Protein Processing [14]
Ankyrin and armadillo repeat-containing protein (ANKAR) OTR49F4J ANKAR_HUMAN Gene/Protein Processing [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Melphalan (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Roflumilast DMPGHY8 Moderate Additive immunosuppressive effects by the combination of Melphalan and Roflumilast. Asthma [CA23] [15]
Ofloxacin DM0VQN3 Minor Decreased absorption of Melphalan due to intestinal mucosa variation caused by Ofloxacin. Bacterial infection [1A00-1C4Z] [16]
Sparfloxacin DMB4HCT Minor Decreased absorption of Melphalan due to intestinal mucosa variation caused by Sparfloxacin. Bacterial infection [1A00-1C4Z] [16]
Gemifloxacin DMHT34O Minor Decreased absorption of Melphalan due to intestinal mucosa variation caused by Gemifloxacin. Bacterial infection [1A00-1C4Z] [16]
Norfloxacin DMIZ6W2 Minor Decreased absorption of Melphalan due to intestinal mucosa variation caused by Norfloxacin. Bacterial infection [1A00-1C4Z] [16]
ABT-492 DMJFD2I Minor Decreased absorption of Melphalan due to intestinal mucosa variation caused by ABT-492. Bacterial infection [1A00-1C4Z] [16]
Levofloxacin DMS60RB Minor Decreased absorption of Melphalan due to intestinal mucosa variation caused by Levofloxacin. Bacterial infection [1A00-1C4Z] [16]
Teriflunomide DMQ2FKJ Major Additive myelosuppressive effects by the combination of Melphalan and Teriflunomide. Hyper-lipoproteinaemia [5C80] [17]
Givosiran DM5PFIJ Moderate Increased risk of nephrotoxicity by the combination of Melphalan and Givosiran. Inborn porphyrin/heme metabolism error [5C58] [18]
Denosumab DMNI0KO Moderate Additive immunosuppressive effects by the combination of Melphalan and Denosumab. Low bone mass disorder [FB83] [19]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Melphalan and Tecfidera. Multiple sclerosis [8A40] [20]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Melphalan and Siponimod. Multiple sclerosis [8A40] [18]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Melphalan and Fingolimod. Multiple sclerosis [8A40] [21]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Melphalan and Ocrelizumab. Multiple sclerosis [8A40] [22]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Melphalan and Ozanimod. Multiple sclerosis [8A40] [15]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive immunosuppressive effects by the combination of Melphalan and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [23]
Gatifloxacin DMSL679 Minor Decreased absorption of Melphalan due to intestinal mucosa variation caused by Gatifloxacin. Respiratory infection [CA07-CA4Z] [16]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Melphalan and Canakinumab. Rheumatoid arthritis [FA20] [24]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Melphalan and Golimumab. Rheumatoid arthritis [FA20] [25]
Leflunomide DMR8ONJ Major Additive immunosuppressive effects by the combination of Melphalan and Leflunomide. Rheumatoid arthritis [FA20] [17]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Melphalan when combined with Anthrax vaccine. Sepsis [1G40-1G41] [26]
Plazomicin DMKMBES Moderate Increased risk of nephrotoxicity by the combination of Melphalan and Plazomicin. Urinary tract infection [GC08] [18]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Melphalan and Valganciclovir. Virus infection [1A24-1D9Z] [18]
⏷ Show the Full List of 23 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Crospovidone E00626 Not Available Disintegrant
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 400 E00653 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Melphalan 2 mg tablet 2 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Melphalan FDA Label
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7620).
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 201379.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 ClinicalTrials.gov (NCT04380376) Low-doses Melphalan Inhalation in Patients With COVID-19 (CoronavIrus Disease 2019) Pneumonia. U.S. National Institutes of Health.
6 BDDCS applied to over 900 drugs
7 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
8 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
10 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
11 Alkylation of DNA by melphalan in relation to immunoassay of melphalan-DNA adducts: characterization of mono-alkylated and cross-linked products fr... Chem Biol Interact. 1990;73(2-3):183-94.
12 Multidrug resistance protein-mediated transport of chlorambucil and melphalan conjugated to glutathione. Br J Cancer. 1998;77(2):201-9.
13 Metabolism of melphalan by rat liver microsomal glutathione S-transferase. Chem Biol Interact. 2005 Apr 15;152(2-3):101-6.
14 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
15 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
16 Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
17 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
18 Cerner Multum, Inc. "Australian Product Information.".
19 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
20 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
21 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
22 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
23 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
24 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
25 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
26 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]