Malotilate

Malotilate is a liver protein metabolism improved compound, which selectively inhibit the 5-lipoxygenase. IC50 Value:Target: 5-lipoxygenasein vitro: In an in vitro invasion assay using rat lung endothelial (RLE) cells, invasion of tumor cells which had been treated with MT (10 ng/ml, 24 h) was not affected; however, when RLE cells had been treated with MT, invasion was significantly inhibited in three cell lines (SAS, Ca9-22 and HSC-4) and a tendency to inhibition was also observed in other cell lines [1].in vivo: The improvement rates for choline esterase activity were significantly greater in the malotilate group than in the control group. Serum albumin levels significantly increased in the malotilate group but not in the control group [2]. In the rats treated with MT for 19 days after i.v. inoculation of c-SST-2 cells, lung metastasis was also significantly suppressed [3]. Malotilate prevented increases in serum markers of type III and IV collagen synthesis as well as accumulation of the collagens, laminin and fibronectin in the liver [4].Toxicity: Malotilate cytotoxicity to PBMCs, assessed by trypan blue dye exclusion and lactate dehydrogenase (LDH) release into the culture media, was found to be markedly increased by the addition of the NADPH generating system, indicating that metabolites play a significant role in toxicity [5].

Signaling Pathways >> Metabolic Enzyme/Protease >> 5-Lipoxygenase

Research Areas >> Cancer

Natural Products >> Others

[1]. Shibata T, et al. Inhibitory effects of malotilate on in vitro invasion of lung endothelial cell monolayer by human oral squamous cell carcinoma cells. Tumour Biol. 2000 Sep-Oct;21(5):299-308.

[2]. Takase S, et al. Effects of malotilate treatment on alcoholic liver disease. Alcohol. 1989 May-Jun;6(3):219-22.

[3]. Nagayasu H, et al. Inhibitory effects of malotilate on invasion and metastasis of rat mammary carcinoma cells by modifying the functions of vascular endothelial cells. Br J Cancer. 1998 May;77(9):1371-7.

[4]. Ryhanen L, et al. The effect of malotilate on type III and type IV collagen, laminin and fibronectin metabolism in dimethylnitrosamine-induced liver fibrosis in the rat. J Hepatol. 1996 Feb;24(2):238-45.

[5]. Nomura F, et al. Detection of malotilate toxicity in vitro with peripheral blood mononuclear cells as targets. A preliminary report. J Hepatol. 1990 Jul;11(1):65-9.

U73122 | Zileuton | ML355 | Nordihydroguaiaretic acid | Indirubin-3'-monoxime | Caffeic acid | marmesin | 4',5-Dihydroxyflavone | Enazadrem | LY 178002 | RWJ 63556 | S-2474 | 5-Lipoxygenase-In-1 | A-69412 | AZD 4407

MOLECULAR FORMULA :

C12-H16-O4-S2

MOLECULAR WEIGHT :

288.40

WISWESSER LINE NOTATION :

T45 ESYSTJ FUYVOY1&1&VOY1&1

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 :

2065 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

750 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3120 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1220 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1732 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

SYXUE3 Shenyang Yaoxueyuan Xuebao. Journal of Shenyang College of Pharmacy. (Shenyang Yaoxueyuan, 7, 2-duan, Wenhualu, Shenhequ, Shenyang, Peop. Rep. China) V.1- 1984- Volume(issue)/page/year: 2,269,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

729 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

SYXUE3 Shenyang Yaoxueyuan Xuebao. Journal of Shenyang College of Pharmacy. (Shenyang Yaoxueyuan, 7, 2-duan, Wenhualu, Shenhequ, Shenyang, Peop. Rep. China) V.1- 1984- Volume(issue)/page/year: 2,269,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

706 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - antipsychotic Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

656 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - antipsychotic Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

2101 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

1011 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

2707 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

1533 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 25,387,1978 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

10500 mg/kg/5W-I

TOXIC EFFECTS :

Liver - changes in liver weight Endocrine - changes in spleen weight Blood - normocytic anemia

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 8,131,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

28 gm/kg/4W-I

TOXIC EFFECTS :

Behavioral - food intake (animal) Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 8,155,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

182 gm/kg/52W-I

TOXIC EFFECTS :

Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 8,155,1982 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3200 mg/kg

SEX/DURATION :

female 8-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 28,859,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1920 mg/kg

SEX/DURATION :

female 7-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 28,880,1981