OTERACIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H3N3O4
Molecular Weight	157.0843
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)C1=NC(=O)NC(=O)N1

InChI

InChIKey=RYYCJUAHISIHTL-UHFFFAOYSA-N

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

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
Oral fluoropyrimidine treatment of colorectal cancer.	2001 Aug	12445367
Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review.	2002	12185293
An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection.	2002	12111585
Unusual survival for more than 2 years with peritoneal metastases of gastric cancer.	2002	12021860
[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
[Two cases of stage IV type 4 gastric cancer with good response to TS-1].	2002 Aug	12214477
[A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP as neoadjuvant chemotherapy].	2002 Aug	12214473
[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
[A new regimen for TS-1 therapy designed to minimize adverse reactions by introducing a one-week interval after each two-week dosing session].	2002 Aug	12214468
[Effectiveness of chemotherapy for outpatients with gastric or colorectal cancer].	2002 Dec	12536832
[Three cases of advanced and recurrent gastric cancer treated with paclitaxel after TS-1 administration].	2002 Dec	12506482
[A case of stage IV gastric carcinoma with lymph nodes metastases of the paraaorta responding markedly to TS-1].	2002 Dec	12506481
[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
A role for uric acid in the progression of renal disease.	2002 Dec	12444207
Recent development of anti-cancer drugs for treatment of GI malignancies in Japan.	2002 Feb	11890118
[The principles of cancer treatment--changes in chemotherapy].	2002 Jul	12146011
[Concentration of FT and CDHP and 5-FU in the ascites fluid of patient with peritoneal carcinomatosis after new anti-cancer drug TS-1 oral administration].	2002 Jul	12146009
[A novel combined chemotherapy using TS-1 and low-dose cisplatin against liver metastasis of gastric cancer].	2002 Jul	12146007
[Complete response in an elderly patient with advanced gastric scirrhous cancer treated with combined chemotherapy of TS-1 and CDDP].	2002 Jul	12146006
[Clinical study of individual TS-1 therapy for inoperable gastric cancer].	2002 Jul	12145996
Phase I and pharmacokinetic study of once daily oral administration of S-1 in patients with advanced cancer.	2002 Jul	12114411
Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function.	2002 Jul	12111108
Functional analysis and molecular model of the human urate transporter/channel, hUAT.	2002 Jul	12060597
Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with peritoneal dissemination.	2002 Jul-Aug	12066214
[Successful treatment of gastric cancer accompanied by multiple liver metastases with TS-1 followed by curative gastrectomy affiliation].	2002 Jun	12090048
[A case of unresectable gastric cancer complicated by a serious hepatic disorder and Virchow lymph node metastasis in which FP therapy and TS-1 administration were effective].	2002 Jun	12090047
[A case report of advanced gastric cancer responding to TS-1, a novel oral fluorouracil derivative].	2002 Jun	12090046
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
[Evaluation of the efficacy of TS-1 for peritoneal dissemination of gastric cancer using a newly-developed animal model].	2002 May	12048883
[A case of gastric cancer with multiple liver metastases responding to TS-1].	2002 May	12040683
[Three cases of recurrent gastric cancer responding to TS-1 therapy following combination therapy with 5-fluorouracil, mitomycin C and cisplatin].	2002 May	12040682
[Adverse reactions to TS-1 for outpatients with recurrent head and neck cancer].	2002 Nov	12465408
[A case of recurrent advanced gastric cancer suggesting the efficacy of TS-1 and CDDP combination chemotherapy].	2002 Nov	12465403
Mild hyperuricemia induces glomerular hypertension in normal rats.	2002 Nov	12372787
High response rates in patients with pancreatic cancer using the novel oral fluoropyrimidine S-1.	2002 Nov-Dec	12375048
[Effective use of TS-1 in a case of advanced gastric cancer, both in treating the tumor and in maintaining the patient's quality of life].	2002 Oct	12402438
[TS-1/CDDP therapy for advanced gastric cancer as neoadjuvant chemotherapy].	2002 Oct	12402437
[Complete response in a case of advanced scirrhous type 3 gastric cancer of with bulky N2 para-aorta lymph node metastases treated by combined chemotherapy of TS-1 and CDDP].	2002 Oct	12402436
Advanced gastric cancer with liver metastases successfully treated with S-1.	2002 Oct	12402069
[Every-other-day TS-1 administration for recurrent or non-curative advanced gastric carcinoma].	2002 Sep	12355955
[A case of advanced gastric cancer with invasion of pancreas effectively treated by combined chemotherapy of TS-1 and paclitaxel (TXL)].	2002 Sep	12355952
[Gastric cancer with multiple liver metastases, which responded significantly to oral administration of TS-1 following intravenous FMP therapy under hospitalization].	2002 Sep	12355951
[A pilot study of TS-1 combined with cisplatin in patients with advanced gastric cancer].	2002 Sep	12355943
Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity.	2002 Sep 1	12231557
Potassium oxonate modulation of 5-fluorouracil-induced myelotoxicity in murine and human colony forming assays of hematopoietic precursor cells.	2002 Sep 5	12243859
Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue tegafur in rats.	2002 Sep-Oct	12364819
Phase I study with pharmacokinetics of S-1 on an oral daily schedule for 28 days in patients with solid tumors.	2003 Jan	12538461
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

Official Name

English

OTERACIL [EMA EPAR]

Common Name

English

oteracil [INN]

Common Name

English

Oteracil [WHO-DD]

Common Name

English

S-TRIAZINE-2,4-DIONE-6-CARBOXYLIC ACID

Common Name

English

5-AZAOROTIC ACID

Common Name

English

OXONIC ACID

Common Name

English

ALLANTOXANIC ACID

Common Name

English

OXONIC ACID [MI]

Common Name

English

1,4,5,6-TETRAHYDRO-4,6-DIOXO-S-TRIAZINE-2-CARBOXYLIC ACID

Systematic Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

TEYSUNI (AUTHORIZED: STOMACH NEOPLASMS)