CAS 157-03-9|L-DON

Ki: 6 μM (glutaminases)[4]

[1]. Kulkarni RM, et al. Evaluation of genetic toxicity of 6-diazo-5-oxo-l-norleucine (DON). Toxicol Mech Methods. 2017 Sep;27(7):518-527.

[2]. Thangavelu K, et al. Structural basis for the active site inhibition mechanism of human kidney-type glutaminase (KGA). Sci Rep. 2014 Jan 23;4:3827.

[3]. Willis RC, et al. The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast. J Cell Physiol. 1977 Dec;93(3):375-82.

[4]. Sharma NS, et al. Targeting tumor-intrinsic hexosamine biosynthesis sensitizes pancreatic cancer to anti-PD1 therapy. J Clin Invest. 2019 Oct 15.

CHEMICAL IDENTIFICATION

RTECS NUMBER :

RC6340000

CHEMICAL NAME :

Norleucine, 6-diazo-5-oxo, L-

CAS REGISTRY NUMBER :

157-03-9

BEILSTEIN REFERENCE NO. :

1725815

LAST UPDATED :

199706

DATA ITEMS CITED :

18

MOLECULAR FORMULA :

C6-H9-N3-O3

MOLECULAR WEIGHT :

171.18

WISWESSER LINE NOTATION :

QVYZ2V1UNN

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

80 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intracerebral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>200 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

76 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

197 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

220 mg/kg

TOXIC EFFECTS :

Gastrointestinal - peritonitis Gastrointestinal - other changes Liver - fatty liver degeneration

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

76 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

5 mg/kg

SEX/DURATION :

female 15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

100 ug/kg

SEX/DURATION :

female 7-8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

300 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

400 ug/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

500 ug/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

400 ug/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

MUTATION DATA

TYPE OF TEST :

DNA damage

TEST SYSTEM :

Microorganism - not otherwise specified

DOSE/DURATION :

30 mmol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 360,95,1996 *** REVIEWS *** TOXICOLOGY REVIEW JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 172,1765,1960 TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 TOXICOLOGY REVIEW ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI. Volume(issue)/page/year: 5,447,1965

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