OTERACIL POTASSIUM

Possibly Marketed Outside US

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 8504
uridine monophosphate synthetase 2 Target ID: 288051.0 Gene Symbol: Umps Sources: https://www.ncbi.nlm.nih.gov/pubmed/7689420	Inhibitor 8504		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 8583	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.

C_max

Value	Dose	Co-administered	Analyte	Population
1.21 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21143703/	11.8 mg/m² 2 times / day multiple, oral dose: 11.8 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.93 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21143703/	11.8 mg/m² 2 times / day multiple, oral dose: 11.8 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
55 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17683513/	15.7 mg/m² single, oral dose: 15.7 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
210 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17683513/	15.7 mg/m² single, oral dose: 15.7 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
7.81 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21143703/	11.8 mg/m² 2 times / day multiple, oral dose: 11.8 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21143703/	11.8 mg/m² 2 times / day multiple, oral dose: 11.8 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
276 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17683513/	15.7 mg/m² single, oral dose: 15.7 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1004 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17683513/	15.7 mg/m² single, oral dose: 15.7 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17683513/	15.7 mg/m² single, oral dose: 15.7 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17683513/	15.7 mg/m² single, oral dose: 15.7 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	OTERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inducer 24

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP1A1 132 CYP2A6 879 CYP2C8 1057 CYP2E1 1060 MATE1 415 CYP2C19 2057		CYP2C8 198 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity
CYP2B6 1160	inducer 1966 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	likely
CYP2C8 1117	inducer 1966 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	likely
CYP3A4 2633	inducer 1966 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	likely
CYP1A1 272	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 18.0	no
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/30951542/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inducer 28 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: 15.0

PubMed

Title	Date	PubMed
Phase I study with pharmacokinetics of S-1 on an oral daily schedule for 28 days in patients with solid tumors.	2003-01	12538461
[Effectiveness of chemotherapy for outpatients with gastric or colorectal cancer].	2002-12	12536832
[Three cases of advanced and recurrent gastric cancer treated with paclitaxel after TS-1 administration].	2002-12	12506482
[A case of stage IV gastric carcinoma with lymph nodes metastases of the paraaorta responding markedly to TS-1].	2002-12	12506481
[A case of stomach cancer in which TS-1 neoadjuvant therapy was effective against multiple hepatic metastasis, allowing a radical cure A surgery].	2002-12	12506480
A role for uric acid in the progression of renal disease.	2002-12	12444207
[Adverse reactions to TS-1 for outpatients with recurrent head and neck cancer].	2002-11	12465408
[A case of recurrent advanced gastric cancer suggesting the efficacy of TS-1 and CDDP combination chemotherapy].	2002-11	12465403
Mild hyperuricemia induces glomerular hypertension in normal rats.	2002-11	12372787
High response rates in patients with pancreatic cancer using the novel oral fluoropyrimidine S-1.	2002-10-11	12375048
Hyperuricemia causes glomerular hypertrophy in the rat.	2002-10-10	12373074
Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue tegafur in rats.	2002-10-05	12364819
[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].	2002-10	12402438
[TS-1/CDDP therapy for advanced gastric cancer as neoadjuvant chemotherapy].	2002-10	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].	2002-10	12402436
Advanced gastric cancer with liver metastases successfully treated with S-1.	2002-10	12402069
Potassium oxonate modulation of 5-fluorouracil-induced myelotoxicity in murine and human colony forming assays of hematopoietic precursor cells.	2002-09-05	12243859
Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity.	2002-09-01	12231557
[Every-other-day TS-1 administration for recurrent or non-curative advanced gastric carcinoma].	2002-09	12355955
[A case of advanced gastric cancer with invasion of pancreas effectively treated by combined chemotherapy of TS-1 and paclitaxel (TXL)].	2002-09	12355952
[Gastric cancer with multiple liver metastases, which responded significantly to oral administration of TS-1 following intravenous FMP therapy under hospitalization].	2002-09	12355951
[A pilot study of TS-1 combined with cisplatin in patients with advanced gastric cancer].	2002-09	12355943
[Long-term complete response to treatment with TS-1 in a patient with oropharyngeal squamous cell carcinoma].	2002-08	12214481
[Complete response in a case of recurrent gastric cancer treated with TS-1].	2002-08	12214478
[Two cases of stage IV type 4 gastric cancer with good response to TS-1].	2002-08	12214477
[A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP as neoadjuvant chemotherapy].	2002-08	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].	2002-08	12214472
[A case of residual gastric cancer accompanied by esophageal invasion in which residual lesions were eradicated by half-dose administration of TS-1].	2002-08	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].	2002-08	12214468
[The principles of cancer treatment--changes in chemotherapy].	2002-07	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].	2002-07	12146009
[A novel combined chemotherapy using TS-1 and low-dose cisplatin against liver metastasis of gastric cancer].	2002-07	12146007
[Complete response in an elderly patient with advanced gastric scirrhous cancer treated with combined chemotherapy of TS-1 and CDDP].	2002-07	12146006
[Clinical study of individual TS-1 therapy for inoperable gastric cancer].	2002-07	12145996
Phase I and pharmacokinetic study of once daily oral administration of S-1 in patients with advanced cancer.	2002-07	12114411
Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function.	2002-07	12111108
Functional analysis and molecular model of the human urate transporter/channel, hUAT.	2002-07	12060597
Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with peritoneal dissemination.	2002-06-18	12066214
[Successful treatment of gastric cancer accompanied by multiple liver metastases with TS-1 followed by curative gastrectomy affiliation].	2002-06	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].	2002-06	12090047
[A case report of advanced gastric cancer responding to TS-1, a novel oral fluorouracil derivative].	2002-06	12090046
A novel mutant allele of the CYP2A6 gene (CYP2A6*11 ) found in a cancer patient who showed poor metabolic phenotype towards tegafur.	2002-06	12042667
[Evaluation of the efficacy of TS-1 for peritoneal dissemination of gastric cancer using a newly-developed animal model].	2002-05	12048883
[A case of gastric cancer with multiple liver metastases responding to TS-1].	2002-05	12040683
[Three cases of recurrent gastric cancer responding to TS-1 therapy following combination therapy with 5-fluorouracil, mitomycin C and cisplatin].	2002-05	12040682
[A case in which TS-1, an orally-administered 5-FU chemotherapeutic agent, showed marked effectiveness against scirrhous type gastric cancer with multiple organ metastases].	2002-05	12040681
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
Oral fluoropyrimidine treatment of colorectal cancer.	2001-08	12445367

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

TEYSUNO COMPONENT OTERACIL POTASSIUM

Preferred Name

English

OTERACIL POTASSIUM

Common 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

OXONIC ACID, POTASSIUM SALT

Common Name

English

POTASSIUM OXONATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471