Fotemustine

Names

[ Name ]:
Fotemustine

[Synonym ]:
Phosphonic acid, P-[1-[[[(2-chloroethyl)nitrosoamino]carbonyl]amino]ethyl]-, diethyl ester
MFCD00866278
Diethyl (1-{[(2-chloroethyl)(nitroso)carbamoyl]amino}ethyl)phosphonate
1-(2-chloroethyl)-3-(1-diethoxyphosphorylethyl)-1-nitrosourea
Fotemustine

Biological Activity

[Description]:

Fotemustine is a DNA-alkylating agent, with antitumor activity.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

Research Areas >> Cancer

[Target]

DNA Alkylator[1]

[In Vitro]

Fotemustine is a DNA-alkylating agent. Fotemustine (800 μM) decreases GSH and intracellular GSSG levels but increases the extracellular GSSG-levels rapidly in isolated rat hepatocytes[1]. Fotemustine shows inhibitory effect on several tumor cell lines, with IC50s ranging form 0.05 to 0.18 mM[2].

[Cell Assay]

Cell proliferation assays are performed using MTT. Briefly, cell suspensions containing 2 × 104 viable cells/mL are plated into 96-well dishes and allowed to attach for 48 h at 371C in a 5% CO2 atmosphere. The culture medium is then removed and the cells are incubated for two doubling times at 37°C in the culture medium containing fotemustine (10-3 to 10 mM). When tested, amifostine or WR-1065 (10-4 to 10 mM) is added before Fotemustine for 15 min. Control cultures are exposed to saline for 15 min and then allowed to grow for the same duration in complete culture medium[2].

[References]

[1]. Brakenhoff JP, et al. Molecular mechanisms of toxic effects of fotemustine in rat hepatocytes and subcellular rat liver fractions. Carcinogenesis. 1996 Apr;17(4):715-24.

[2]. Merlin JL, et al. Enhancement of fotemustine (Muphoran) cytotoxicity by amifostine in malignant melanoma cell lines. Anticancer Drugs. 2002 Feb;13(2):141-7.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
188 °C(lit.)

[ Melting Point ]:
85ºC

[ Molecular Formula ]:
C₉H₁₉ClN₃O₅P

[ Molecular Weight ]:
315.691

[ Flash Point ]:
104 °F

[ Exact Mass ]:
315.075073

[ PSA ]:
107.11000

[ LogP ]:
1.26

[ Index of Refraction ]:
1.524

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: SZ7115500

CHEMICAL NAME :: Phosphonic acid, (1-((((2-chloroethyl)nitrosoamino)carbonyl)amino)ethy l)-, diethyl ester

CAS REGISTRY NUMBER :: 92118-27-9

LAST UPDATED :: 199410

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C9-H19-Cl-N3-O5-P

MOLECULAR WEIGHT :: 315.73

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 60 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Micronucleus test

MUTATION DATA

TEST SYSTEM :: Rodent - mouse

DOSE/DURATION :: 5 mg/kg

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 286,101,1993

Safety Information

[ Symbol ]:

GHS08

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H351

[ Precautionary Statements ]:
P281

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
R10:Flammable. R36/37:Irritating to eyes and respiratory system . R43:May cause sensitization by skin contact.

[ Safety Phrases ]:
S16-S26-S36

[ RIDADR ]:
UN 3336 3/PG 2

[ WGK Germany ]:
3

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

Articles

Multiple bone metastases from glioblastoma multiforme without local brain relapse: a case report and review of the literature.

Tumori 99(5) , e237-40, (2013)

Extracranial metastases from glioblastoma multiforme (GBM) are a very rare event, even if an increasing incidence has been documented. We report the case of a young woman with primary GBM who develope...

Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant melanoma.

J. Transl. Med. 11 , 38, (2013)

The effect of the addition of fotemustine and/or interferon (IFN) to standard therapy with dacarbazine alone in patients with advanced malignant melanoma was investigated in a multicenter, randomized ...

Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma.

Am. J. Hematol. 88(2) , 102-6, (2013)

Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new thre...