Details of the Drug

General Information of Drug (ID: DMWF5R4)

Drug Name
Melphalan flufenamide
Synonyms J-1; Dipeptide-conjugated melphalan prodrug (iv formulation, ovary tumor), Oncopeptides
Indication
Disease Entry ICD 11 Status REF
Multiple myeloma 2A83 Approved [1]
Ovarian cancer 2C73 Phase 1/2 [2]
Plasma cell myeloma 2A83.1 Phase 1/2 [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 498.4
Topological Polar Surface Area (xlogp) 3.2
Rotatable Bond Count (rotbonds) 14
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 3143 mgh/L [4]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 432 mcg/L [4]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 4-15 min [4]
Clearance
The clearance of drug is 692 L/h [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 2.1 minutes (melphalan flufenamide), and 70 minutes (melphalan) [5]
Metabolism
The drug is metabolized to desethyl-melphalan and melphalan [5]
Vd
The volume of distribution (Vd) of drug is 76 L [5]
Chemical Identifiers
Formula
C24H30Cl2FN3O3
IUPAC Name
ethyl (2S)-2-[[(2S)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate
Canonical SMILES
CCOC(=O)[C@H](CC1=CC=C(C=C1)F)NC(=O)[C@H](CC2=CC=C(C=C2)N(CCCl)CCCl)N
InChI
InChI=1S/C24H30Cl2FN3O3/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)/t21-,22-/m0/s1
InChIKey
YQZNKYXGZSVEHI-VXKWHMMOSA-N
Cross-matching ID
PubChem CID
9935639
CAS Number
380449-51-4
DrugBank ID
DB16627
TTD ID
D01HPY

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Binder [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
2 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033866)
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Wickstrom M, Nygren P, Larsson R, Harmenberg J, Lindberg J, Sjoberg P, Jerling M, Lehmann F, Richardson P, Anderson K, Chauhan D, Gullbo J: Melflufen - a peptidase-potentiated alkylating agent in clinical trials. Oncotarget. 2017 Jun 8;8(39):66641-66655. doi: 10.18632/oncotarget.18420. eCollection 2017 Sep 12.
5 FDA Approved Drug Products: Pepaxto (Melphalan Flufenamide) Intravenous Injection
6 Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
7 Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
8 31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA. Biochemistry. 1989 Apr 4;28(7):2804-12.
9 Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35.
10 O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 1998 Sep 11;77(6):919-22.
11 Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
12 DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect. Cancer Sci. 2004 May;95(5):454-8.
13 Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations... DNA Repair (Amst). 2009 Jan 1;8(1):72-86.
14 Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
15 Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.