Orotic acid

Names

[ CAS No. ]:
65-86-1

[ Name ]:
Orotic acid

[Synonym ]:
Orotonsan
orotic
Oropur
2,6-dihydroxypyrimidine-4-carboxylic acid
Uracil-6-carboxylic acid
Orotic acid
[3H]-Orotic acid
vitamin B13
Oroturic
4-Pyrimidinecarboxylic acid, 1,2,3,6-tetrahydro-2,6-dioxo-
H-ORO-OH
Orotsaure
MFCD00006027
1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidine carboxylic acid
EINECS 200-619-8
2,6-Dioxo-1,2,3,6-tetrahydro-4-pyrimidinecarboxylic acid
1,2,3,6-TETRAHYDRO-2,6-DIOXO-4-PYRIMIDINECARBOXYLIC ACID
2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid
Orotonin
Whey factor
Orotyl
Orodin
6-Carboxyuracil
orodin[qr]
6-uracilic acid
1,2,3,6-Tetrahydro-2,6-dioxopyrimidine-4-carboxylic acid
Animal galactose factor

Biological Activity

[Description]:

Orotic acid (OA) is an intermediate in pyrimidine metabolism.IC50 Value: Target: Nucleoside antimetabolite/analogin vitro: OA increases cell proliferation and decreases apoptosis in serum-starved SK-Hep1 hepatocellular carcinoma cells, which may ascribe to the inhibition of AMP-activated protein kinase (AMPK) phosphorylation and thus activation of mammalian target of rapamycin complex 1 (mTORC1) [1].in vivo: male Fischer 344 rats (130-150 g) to two-thirds PH in the absence or in the presence of OA (a 300-mg tablet of OA methyl ester implanted intraperitoneally at the time of two-thirds PH). treatment with OA resulted in a near-100% inhibition of RNR induced by two-thirds PH in rat liver, as monitored by enzyme activity and protein level [2]. The increases of hepatic OA and betaine levels in OA feeding rats was also found when compared to the normal rats [3]. Feeding 1% OA with diet decreased the phosphorylation of AMPK and increased the maturation of SREBP-1 and the expression of SREBP-responsive genes in the rat liver. OA-induced lipid accumulation was also completely inhibited by rapamycin. Mouse hepatocytes and mice were resistant to OA-induced lipogenesis because of little if any response in AMPK and downstream effectors [4].

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog

Natural Products >> Alkaloid

Research Areas >> Cancer

[Target]

Human Endogenous Metabolite

[References]

[1]. Jung, E.J., K.Y. Lee, and B.H. Lee, Proliferating effect of orotic acid through mTORC1 activation mediated by negative regulation of AMPK in SK-Hep1 hepatocellular carcinoma cells. J Toxicol Sci, 2012. 37(4): p. 813-21.

[2]. Manjeshwar, S., et al., The regulation of ribonucleoside diphosphate reductase by the tumor promoter orotic acid in normal rat liver in vivo. Mol Carcinog, 1999. 24(3): p. 188-96.

[3]. Cha, J.Y., et al., Effect of betaine on the hepatic damage from orotic acid-induced fatty liver development in rats. J Enzyme Inhib Med Chem, 2011.

[4]. Jung, E.J., et al., Role of the AMPK/SREBP-1 pathway in the development of orotic acid-induced fatty liver. J Lipid Res, 2011. 52(9): p. 1617-25.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.8±0.1 g/cm3

[ Boiling Point ]:
656.9±65.0 °C at 760 mmHg

[ Melting Point ]:
>300°C

[ Molecular Formula ]:
C₅H₄N₂O₄

[ Molecular Weight ]:
156.096

[ Flash Point ]:
351.1±34.3 °C

[ Exact Mass ]:
156.017105

[ PSA ]:
103.02000

[ LogP ]:
-1.40

[ Vapour Pressure ]:
0.0±2.1 mmHg at 25°C

[ Index of Refraction ]:
1.705

[ Stability ]:
Stable. Incompatible with strong oxidizing agents.

[ Water Solubility ]:
Slightly soluble

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RM3180000

CHEMICAL NAME :: Orotic acid

CAS REGISTRY NUMBER :: 65-86-1

LAST UPDATED :: 199701

DATA ITEMS CITED :: 8

MOLECULAR FORMULA :: C5-H4-N2-O4

MOLECULAR WEIGHT :: 156.11

WISWESSER LINE NOTATION :: T6MVMVJ FVQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2 gm/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 :: 841 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 :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 770 mg/kg

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

TYPE OF TEST :: Morphological transformation

TYPE OF TEST :: DNA inhibition

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Rodent - rat Liver

DOSE/DURATION :: 120 umol/L

REFERENCE :: CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 9,675,1988

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn:Harmful

[ Risk Phrases ]:
R22;R36/37/38

[ Safety Phrases ]:
S26-S36/37/39-S22

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
RM3180000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

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