OTERACIL POTASSIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H2N3O4.K
Molecular Weight	195.1747
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[K+].[O-]C(=O)C1=NC(=O)NC(=O)N1

InChI

InChIKey=IAPCTXZQXAVYNG-UHFFFAOYSA-M

InChI=1S/C4H3N3O4.K/c8-2(9)1-5-3(10)7-4(11)6-1;/h(H,8,9)(H2,5,6,7,10,11);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001242/WC500104415.pdf
Curator's Comment: description was created based on several sources, including: http://ec.europa.eu/health/documents/community-register/2011/2011031497328/anx_97328_en.pdf | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001242/WC500104417.pdf | https://www.ncbi.nlm.nih.gov/pubmed/22162925

Oteracil is an adjunct to antineoplastic therapy, used in combination with Gimeracil and Tegafur. Gimeracil/oteracil/tegafur combination is approved for the gastric cancer treatment. Oteracil is an orotate phosphoribosyltransferase (OPRT) inhibitor that decreases the activity of 5-fluorocil (tegafur is a prodrug of 5-fluorocil) in normal gastrointestinal mucosa.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
urate oxidase 2 Target ID: 114768.0 Gene Symbol: Uox Sources: https://www.ncbi.nlm.nih.gov/pubmed/367691	Inhibitor 8297
uridine monophosphate synthetase 2 Target ID: 288051.0 Gene Symbol: Umps Sources: https://www.ncbi.nlm.nih.gov/pubmed/7689420	Inhibitor 8297		3.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastric cancer 53 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22162925	Secondary		Approved 8429	S-1 Approved Use Gimeracil/oteracil/tegafur combination is indicated in adults for the treatment of advanced gastric cancer when given in combination with cisplatin.

PubMed

Title	Date	PubMed
[A case of recurrent gastric cancer successfully treated with TS-1].	2001 Apr	11329792
[5-fluorouracil and dihydropyrimidine dehydrogenase].	2001 Apr	11329775
Other fluorinated pyrimidines in the treatment of solid tumors.	2001 Jan	11219980
[A case of stage IV gastric cancer with multiple liver metastases and carcinomatous ascites responding to TS-1 for six months before progression].	2001 Jan	11201387
Potassium citrate administration ameliorates tubulointerstitial lesions in rats with uric acid nephropathy.	2001 Jan	11200869
Purine nucleotide catabolism in rat liver: labelling of uric acid and allantoin after treatment with oxonic acid and allopurinol.	2001 Jan 26	11228097
[A case of advanced gastric cancer that was resectable after asctic fluid had disappeared following administration of TS-1].	2001 Jul	11478151
[Two elderly patients with advanced gastric cancer responding to chronomodulation chemotherapy with tegafur + cisplatin + isovorin followed by oral administration of S-1].	2001 Jul	11478129
Dihydrooxonate is a substrate of dihydroorotate dehydrogenase (DHOD) providing evidence for involvement of cysteine and serine residues in base catalysis.	2001 Jul 15	11437361
Interstitial pneumonia possibly due to a novel anticancer drug, TS-1: first case report.	2001 Jun	11463808
Effects of 5-fluorouracil on the drug-metabolizing enzymes of the small intestine and the consequent drug interaction with nifedipine in rats.	2001 Jun	11356943
Correct fluorouracil (5-FU) half-life comparator for a 5-FU prodrug plus a dihydropyrimidine dehydrogenase inhibitor.	2001 Jun 1	11387375
[A complete response persisting for twelve months with the use of TS-1 in a patient with paraaortic lymph node metastasis of gastric cancer].	2001 Nov	11729487
Fluorouracil (5FU) pharmacokinetics in 5FU prodrug formulations with a dihydropyrimidine dehydrogenase inhibitor.	2001 Nov 15	11709571
[A pilot study of low-dose TS-1 and cisplatin combination chemotherapy for advanced gastric cancer].	2001 Oct	11681250
[A new therapeutic approach to advanced and recurrent gastric cancer by TS-1].	2001 Oct	11681248
[Long-term complete response to treatment with TS-1 in a patient with oropharyngeal squamous cell carcinoma].	2002 Aug	12214481
[Complete response in a case of recurrent gastric cancer treated with TS-1].	2002 Aug	12214478
[A case of gastric carcinoma with metastasis in a paraaortic lymph node that responded to TS-1/CDDP combination therapy, in which the patient was able to undergo extirpation with grade B curability].	2002 Aug	12214472
[A case of residual gastric cancer accompanied by esophageal invasion in which residual lesions were eradicated by half-dose administration of TS-1].	2002 Aug	12214471
[Three cases of advanced and recurrent gastric cancer treated with paclitaxel after TS-1 administration].	2002 Dec	12506482
[A case of stomach cancer in which TS-1 neoadjuvant therapy was effective against multiple hepatic metastasis, allowing a radical cure A surgery].	2002 Dec	12506480
Recent development of anti-cancer drugs for treatment of GI malignancies in Japan.	2002 Feb	11890118
Aesculin possesses potent hypouricemic action in rodents but is devoid of xanthine oxidase/dehydrogenase inhibitory activity.	2002 Feb	11859475
[The principles of cancer treatment--changes in chemotherapy].	2002 Jul	12146011
Phase I and pharmacokinetic study of once daily oral administration of S-1 in patients with advanced cancer.	2002 Jul	12114411
Functional analysis and molecular model of the human urate transporter/channel, hUAT.	2002 Jul	12060597
[Successful treatment of gastric cancer accompanied by multiple liver metastases with TS-1 followed by curative gastrectomy affiliation].	2002 Jun	12090048
A novel mutant allele of the CYP2A6 gene (CYP2A6*11 ) found in a cancer patient who showed poor metabolic phenotype towards tegafur.	2002 Jun	12042667
Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism.	2002 Jun	11997315
[Complete response in a case of simultaneous esophageal and gastric cancer treated by combined radiotherapy and chemotherapy of TS-1 and CDDP].	2002 Mar	11915739
Hyperuricemia causes glomerular hypertrophy in the rat.	2003 Jan-Feb	12373074

Patents

Sample Use Guides

In Vivo Use Guide

25 mg/m2 (expressed as tegafur content) twice daily, morning and evening, for 21 consecutive days followed by 7 days rest (1 treatment cycle). This treatment cycle is repeated every 4 weeks.

Route of Administration: Oral

In Vitro Use Guide

In vitro evaluation using primary cultures of human hepatocytes indicated that tegafur (0.7-70 uM), gimeracil (0.2-25 uM) and oteracil (0.04-4 uM) had little or no inductive effect on CYP1A2, CYP2B6 or CYP3A4/5 metabolic activities.

Name

Type

Language

OTERACIL POTASSIUM

Common Name

English

TEYSUNO COMPONENT OTERACIL POTASSIUM

Brand Name

English

Oteracil potassium [WHO-DD]

Common Name

English

S-1 COMPONENT OTERACIL POTASSIUM

Common Name

English

NSC-28841

Code

English

OTERACIL POTASSIUM [JAN]

Common Name

English

OTERACIL POTASSIUM COMPONENT OF TEYSUNO

Brand Name

English

OXONIC ACID, POTASSIUM SALT

Common Name

English

POTASSIUM OXONATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471