GIMERACIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C5H4ClNO2
Molecular Weight	145.544
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC(=O)NC=C1Cl

InChI

InChIKey=ZPLQIPFOCGIIHV-UHFFFAOYSA-N

InChI=1S/C5H4ClNO2/c6-3-2-7-5(9)1-4(3)8/h1-2H,(H2,7,8,9)

HIDE SMILES / InChI

Molecular Formula	C5H4ClNO2
Molecular Weight	145.544
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001242/WC500104417.pdf
Curator's Comment: description was created based on several sources, including, www.ncbi.nlm.nih.gov/pubmed/24014883

Gimeracil is a component of an oral fixed combination known under the name Teysuno or S-1 (tegafur, gimeracil and oteracil potassium at a molar ratio of 1:0.4:1). The formulation was approved in Asia and Europe for the treatment of a rare condition of gastric cancer. Given in combination, gimeracil enhances the efficacy of tegafur by inhibiting dihydropyrimidine dehydrogenase, an enzyme involved in metabolism of tegafur and its active metabolite 5-fluorouracil.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydropyrimidine dehydrogenase [NADP(+)] 4 Target ID: Q12882\|\|\|Q16761 Gene ID: 1806.0 Gene Symbol: DPYD Target Organism: Homo sapiens (Human) Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001242/WC500104417.pdf	Inhibitor 8297		95.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastric cancer 53 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001242/WC500104417.pdf	Primary		Approved 8429	TEYSUNO Approved Use Treatment of gastric cancer.

C_max

Value	Dose	Co-administered	Analyte	Population
374.9 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23289150	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	GIMERACIL unknown	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/14650374	25 mg/m² single, oral dose: 25 mg/m² route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	GIMERACIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23289150	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: TEGAFUR	TEGAFUR	GIMERACIL unknown	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
67.8% OTHER GOV https://www.ema.europa.eu/en/documents/product-information/teysuno-epar-product-information_en.pdf			GIMERACIL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
80 mg 1 times / day steady, oral (typical) Studied dose Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Co-administed with:: tegafur oteracil Sources: https://pubmed.ncbi.nlm.nih.gov/30830659	unhealthy, 65 years (range: 23–85 years) n = 358 Health Status: unhealthy Condition: cell lung cancer Age Group: 65 years (range: 23–85 years) Population Size: 358 Sources: https://pubmed.ncbi.nlm.nih.gov/30830659	Other AEs: Leucopenia, Neutropenia... Other AEs: Leucopenia (grade 3-5, 1.7%) Neutropenia (grade 3-5, 6.7%) Febrile neutropenia (grade 3-5, 1.1%) Anaemia (grade 3-5, 2.8%) Thrombocytopenia (grade 3-5, 1.7%) Stomatitis (grade 3-5, 3.4%) Nausea (grade 3-5, 1.4%) Vomiting (grade 3-5, 2%) Decreased appetite (grade 3-5, 9.8%) Diarrhoea (grade 3-5, 8.4%) Constipation (grade 3-5, 0.8%) Maculopapular rash (grade 3-5, 1.4%) Weight loss (grade 3-5, 0.6%) Dyspnea (grade 3-5, 0.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/30830659
25 mg/m2 2 times / day multiple, oral Recommended Dose: 25 mg/m2, 2 times / day Route: oral Route: multiple Dose: 25 mg/m2, 2 times / day Co-administed with:: tegafur oteracil Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: p.53	unhealthy, adult n = 11 Health Status: unhealthy Condition: advanced gastric cancer Age Group: adult Population Size: 11 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: p.53	Other AEs: Nausea, Fatigue... Other AEs: Nausea (all grades, 35%) Fatigue (all grades, 32%) Diarrhoea (all grades, 30%) Vomiting (all grades, 17%) Anorexia (all grades, 18%) Rash (all grades, 17%) Diarrhoea (grade 3-5, 9.6%) Nausea (grade 3-5, 2.5%) Vomiting (grade 3-5, 2.5%) Abdominal pain (grade 3-5, 2.5%) Stomatitis (grade 3-5, 1.9%) Dehydration (grade 3-5, 5.1%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: p.53
25 mg/m2 2 times / day multiple, oral Recommended Dose: 25 mg/m2, 2 times / day Route: oral Route: multiple Dose: 25 mg/m2, 2 times / day Co-administed with:: tegafur oteracil Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: p.53	unhealthy, adult n = 700 Health Status: unhealthy Condition: advanced gastric cancer Age Group: adult Population Size: 700 Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: p.53	Other AEs: Anorexia, Hyponatraemia... Other AEs: Anorexia (grade 3-4, 12.4%) Hyponatraemia (grade 3-4, 5.2%) Nausea (grade 3-4, 5.6%) Neutrophil count decreased (grade 3-4, 5.6%) Anaemia (grade 3-4, 12.8%) Leucopenia (grade 3-4, 0.9%) Neutropenic infection (grade 3-4, 0.4%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf Page: p.53
40 mg/m2 2 times / day steady, oral Dose: 40 mg/m2, 2 times / day Route: oral Route: steady Dose: 40 mg/m2, 2 times / day Co-administed with:: tegafur oteracil Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22162925	unhealthy, adult Health Status: unhealthy Condition: advanced gastric cancer Age Group: adult Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22162925	Sources: https://www.ema.europa.eu/en/documents/assessment-report/teysuno-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22162925

AEs

PubMed

Title	Date	PubMed
Involvement of microsomal cytochrome P450 and cytosolic thymidine phosphorylase in 5-fluorouracil formation from tegafur in human liver.	2001 Mar	11297264
The significance of dihydropyrimidine dehydrogenase (DPD) activity in bladder cancer.	2001 Mar	11290431
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
S-1 in gastric cancer: a comprehensive review.	2003	12775012
Thymidylate synthase predictive power is overcome by irinotecan combination therapy with S-1 for gastric cancer.	2004 Oct 4	15354215
Enhancement of the anti-tumor activity of S-1 by low-dose cisplatin in mice bearing the sarcoma-180 model.	2005 Nov	16222153
The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.	2007 Mar	17092280
Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene.	2008 Dec	19093184
Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer.	2008 Mar 25	18319719
[Case report of gastric cancer patient who suffered life-threatening adverse events including severe myelosuppression during neoadjuvant chemotherapy with S-1 and CDDP combination].	2008 Sep	18799915
Development history and concept of an oral anticancer agent S-1 (TS-1): its clinical usefulness and future vistas.	2009 Jan	19052037
Fixed dosing and pharmacokinetics of S-1 in Japanese cancer patients with large body surface areas.	2009 May	19150953
A Phase II Study of S-1 Monotherapy as a First-line Combination Therapy of S-1 Plus Cisplatin as a Second-line Therapy, and Weekly Paclitaxel Monotherapy as a Third-line Therapy in Patients with Advanced Gastric Carcinoma: A Second Report.	2010 Mar 24	20567630
An early phase II trial of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma.	2010 Nov	20157711
Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry.	2011 Jun	21737628

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of gimeracil is 10 mg/m2 (as a part of oral combination consisting of tegafur, gimeracil and oteracil potassium at a molar ratio of 1:0.4:1) twice a day, for 21 consecutive days followed by 7 days rest.

Route of Administration: Oral

In Vitro Use Guide

TE-5 and TE-5R cells were plated in a 96-well plate and cultured for 24 h, and then they were treated with the indicated concentrations of 5-FU in the presence of gimeracil for 72 h at a molar ratio of 1:0.2 (5-FU:gimeracil). IC50 values with and without gimeracil in TE-5 cells were 4.9 and 4.8 uM, respectively, and those in TE-5R cells were 20.8 and 59.0 uM, respectively.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:06:05 UTC 2023` Edited by `admin` on `Fri Dec 15 16:06:05 UTC 2023`
Record UNII	UA8SE1325T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GIMERACIL

Official Name

English

5-CHLORO-2,4-DIHYDROXYPYRIDINE

Systematic Name

English

GIMERACIL [JAN]

Common Name

English

Gimeracil [WHO-DD]

Common Name

English

TEYSUNO COMPONENT GIMERACIL

Brand Name

English

GIMESTAT

Common Name

English

GIMERACIL [MI]

Common Name

English

GIMERACIL [EMA EPAR]

Common Name

English

GIMERACIL COMPONENT OF TEYSUNO

Brand Name

English

gimeracil [INN]

Common Name

English

5-CHLORO-2,4-PYRIDINEDIOL

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

225006