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TOFA

Names

[ CAS No. ]:
54857-86-2

[ Name ]:
TOFA

[Synonym ]:
5-Tetradecyloxy-2-furonic acid
TOFA
2-Furancarboxylic acid, 5-(tetradecyloxy)-
5-tetradecoxyfuran-2-carboxylic acid
5-(Tetradecyloxy)-2-furoic acid
MFCD01726059

Biological Activity

[Description]:

TOFA (RMI14514;MDL14514) is an allosteric inhibitor of acetyl-CoA carboxylase-α (ACCA ).

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Acetyl-CoA Carboxylase
Research Areas >> Cancer

[In Vitro]

TOFA (5-tetradecyloxy-2-furoic acid) is cytotoxic to lung cancer cells NCI-H460 and colon carcinoma cells HCT-8 and HCT-15, with an IC50 at approximately 5.0, 5.0, and 4.5 μg/mL, respectively. TOFA at 1.0–20.0 μg/mL effectively blocks fatty acid synthesis and induces cell death in a dose-dependent manner[1]. TOFA is found to be cytotoxic to COC1 and COC1/DDP cells with IC50 values of ~26.1 and 11.6 µg/mL, respectively. TOFA inhibits the proliferation of the cancer cells examined in a time and dose dependent manner, arrests the cells in the G0/G1 cell cycle phase and induces apoptosis[2]. Acetyl-CoA-carboxylase-α (ACCA) is a key enzyme in the regulation of fatty acids synthesis. Inhibition of ACCA by TOFA decreases fatty acid synthesis and induces caspase activation and cell death in most PCa cell lines[3].

[In Vivo]

TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. The tumor growth rate is signifi¬cantly inhibited by TOFA compared with the DMSO treated control mice (1649±356.3 vs. 5128±390.4 mm3. No toxicity is observed in the heart, liver, spleen, lung, kidney and intestinal tissues. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy[2].

[Cell Assay]

NCI-H460, human lung cancer cells, and HCT-8 and HCT-15 cells (5,000/well) are seeded in 96-well plates overnight and then exposed to TOFA at indicated concentrations (0, 1, 5, 10, 20, 50 µg/mL) for 72 hours. Viable cells are detected using MTT assay[1].

[Animal admin]

Mice: Mice are treated with 50 μL DMSO (control group) or treated with TOFA (50 mg/kg). The drugs are injected intraperitoneally daily for two weeks. Tumor volumes are recorded every two days by measuring dimensions (length and width) with Vernier calipers. The mice are sacrificed four weeks after the final treatment. Tumor weights are measured by a scale[2].

[References]

[1]. Wang C, et al. Acetyl-CoA carboxylase-alpha inhibitor TOFA induces human cancer cell apoptosis. Biochem Biophys Res Commun. 2009 Jul 31;385(3):302-6.

[2]. Li S, et al. TOFA suppresses ovarian cancer cell growth in vitro and in vivo. Mol Med Rep. 2013 Aug;8(2):373-8.

[3]. Guseva NV, et al. TOFA (5-tetradecyl-oxy-2-furoic acid) reduces fatty acid synthesis, inhibits expression of AR, neuropilin-1 and Mcl-1 and kills prostate cancer cells independent of p53 status. Cancer Biol Ther. 2011 Jul 1;12(1):80-5.


[Related Small Molecules]

ND-630 | ND-646 | CP-640186 hydrochloride | PF 05175157 | Olumacostat glasaretil | MK-4074

Chemical & Physical Properties

[ Density]:
1.0±0.1 g/cm3

[ Boiling Point ]:
441.7±25.0 °C at 760 mmHg

[ Melting Point ]:
112-115ºC

[ Molecular Formula ]:
C19H32O4

[ Molecular Weight ]:
324.455

[ Flash Point ]:
220.9±23.2 °C

[ Exact Mass ]:
324.230072

[ PSA ]:
59.67000

[ LogP ]:
7.82

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.483

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
LU0288000
CHEMICAL NAME :
2-Furancarboxylic acid, 5-(tetradecyloxy)-
CAS REGISTRY NUMBER :
54857-86-2
LAST UPDATED :
199612
DATA ITEMS CITED :
4
MOLECULAR FORMULA :
C19-H32-O4
MOLECULAR WEIGHT :
324.51

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
>5 gm/kg
TOXIC EFFECTS :
Gastrointestinal - hypermotility, diarrhea
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 1,19,1981
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
>1 gm/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified Behavioral - somnolence (general depressed activity)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 1,19,1981 ** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
18200 mg/kg/26W-C
TOXIC EFFECTS :
Liver - changes in liver weight
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 1,19,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
9100 mg/kg/13W-C
TOXIC EFFECTS :
Liver - changes in liver weight
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 1,19,1981

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2932190090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2932190090

[ Summary ]:
2932190090 other compounds containing an unfused furan ring (whether or not hydrogenated) in the structure VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:20.0%

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