2-amino-3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid

• ChemBase ID: 914
• Molecular Formular: C13H18Cl2N2O2
• Molecular Mass: 305.20022
• Monoisotopic Mass: 304.07453319
• SMILES: ClCCN(c1ccc(CC(N)C(=O)O)cc1)CCCl
• Canonical SMILES: ClCCN(c1ccc(cc1)CC(C(=O)O)N)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)
• InChIKey: SGDBTWWWUNNDEQ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-amino-3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid
• IUPAC Traditional name: sarcolysin
• Brand Name: Alkeran; L-PAM; L-Phenylalanine mustard; L-Sarcolysin; L-Sarcolysine; L-Sarkolysin; Levofalan; Melfalan; Mephalan; Phenylalanine mustard; Phenylalanine nitrogen mustard; Sarcolysine; Sarkolysin
• Synonyms: 4-[bis)2-Chloroethyl)amino-L-phenylalanine; Melphalan

Database IDs

• CAS Number: 148-82-3
• EC Number: 205-726-3
• PubChem SID: 160964377
• PubChem CID: 4053

CALCULATED PROPERTIES

JChem

• Acid pKa: 1.2884431
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 0.25192413
• LogD (pH = 7.4): 0.2493237
• Log P: 0.25219622
• Molar Refractivity: 78.2315 cm^3
• Polarizability: 30.09238 Å^3
• Polar Surface Area: 66.56 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -0.22
• LOG S: -2.93
• Solubility (Water): 3.58e-01 g/l

PROPERTIES

Physical Property

• Solubility: < 0.1 g/100 mL at 22°C
• Melting Point: 175-185°C
• Hydrophobicity(logP): 0.4

Safety Information

• Storage Condition: Room Temperature (15-30°C), Protect from light
• RTECS: AY3675000
• European Hazard Symbols: Highly toxic (T+)
• UN Number: 2811
• Hazard Class: 6.1
• Packing Group: II
• Australian Hazchem: 2XE
• Risk Statements: R:28-45
• Safety Statements: S:28-36/37/39-45-53
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154

Product Information

• Purity: 95%

DETAILS

MP Biomedicals - 02155345

(4-[bis)2-Chloroethyl)amino-L-phenylalanine) Purity: 95% Light yellow powder.

DrugBank - DB01042

• Drug Groups: approved
• Description: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer - medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [PubChem]
• Indication: For the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Has also been used alone or as part of various chemotherapeutic regimens as an adjunct to surgery in the treatment of breast cancer, alone or in combination regimens for palliative treatment of locally recurrent or unresectable in-transit metastatic melanoma of the extremities, as well as for the treatment of amyloidosis with prednisone.
• Pharmacology: Melphalan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
• Toxicity: Vomiting, ulceration of the mouth, diarrhea, and hemorrhage of the gastrointestinal tract; The principal toxic effect is bone marrow suppression. LD₅₀=11.2 mg/kg (orally in rat)
• Affected Organisms: Humans and other mammals
• Biotransformation: Melphalan is not actively metabolised, it spontaneously degrades to mono and dihydroxy products.
• Absorption: Incomplete, variable, 25-89% post oral dose
• Half Life: 1.5 (±0.83) hours
• Protein Binding: Moderate to high (60 to 90%), primarily to albumin and, to a lesser extent, alpha 1-acid glycoprotein. 30% is irreversibly bound.
• Elimination: The 24-hour urinary excretion of parent drug in these patients was 10% ± 4.5%, suggesting that renal clearance is not a major route of elimination of parent drug.
• Distribution: * 0.5 L/kg
• References: Loeber R, Michaelson E, Fang Q, Campbell C, Pegg AE, Tretyakova N: Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem Res Toxicol. 2008 Apr;21(4):787-95. Epub 2008 Feb 14. [Pubmed] ; Souliotis VL, Dimopoulos MA, Episkopou HG, Kyrtopoulos SA, Sfikakis PP: Preferential in vivo DNA repair of melphalan-induced damage in human genes is greatly affected by the local chromatin structure. DNA Repair (Amst). 2006 Aug 13;5(8):972-85. Epub 2006 Jun 15. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Souliotis VL, Dimopoulos MA, Episkopou HG, Kyrtopoulos SA, Sfikakis PP: Preferential in vivo DNA repair of melphalan-induced damage in human genes is greatly affected by the local chromatin structure. DNA Repair (Amst). 2006 Aug 13;5(8):972-85. Epub 2006 Jun 15. Pubmed
• Loeber R, Michaelson E, Fang Q, Campbell C, Pegg AE, Tretyakova N: Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem Res Toxicol. 2008 Apr;21(4):787-95. Epub 2008 Feb 14. Pubmed