Gimestat,chlorodihydroxypyridine; CDHP;Gimeracil
| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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| 2g |
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Gimeracil (chlorodihydroxypyridine; CDHP; Gimestat), a pyridine/pyridone analog and an approved anticancer drug, is a potent inhibitor of the dihydropyrimidine dehydrogenase (DPYD) enzyme with potential anti-neoplastic activity. It is used as an adjunct to or in combination with other anticancer therapeutics to increase the systemic concentrations and therapeutic effectiveness of other antineoplastic drugs. Gimeracil inhibits the early steps in homologous recombination for double strand breaks repair of DNA.
| ln Vitro |
The frequency of new positive clones is decreased by gemeracil. Moreover, it increases the sensitivity of S phase cells compared to G0/G1 phase cells [1]. Gimeracil inhibits HR-mediated DNA repair pathways, which may increase the effectiveness of radiation therapy [1]. While pretreatment with gigeracil increased the number of foci of Nbs1, Mre11, Rad50, and FancD2, it dramatically reduced the development of radiation-induced Rad51 and RPA foci [2].
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| ln Vivo |
Gimeracil (oral, 2.5–25 mg/kg) may prevent tumor DNA damage from X-rays from healing quickly [3].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: DLD-1, HeLa, and LC-11 cell lines. Tested Concentrations: 1 mM. Incubation Duration: 48 h. Experimental Results: Inhibits the repair of irradiation-induced DNA double strand breaks. Did not increase the c-H2AX foci residual at 24 h in unirradiated cells. |
| Animal Protocol |
Animal/Disease Models: Nude mice (Lu-99, LC-11, KB/C3 and PAN-4 tumors were xenografted)[3].
Doses: 2.5-25 mg/kg. Route of Administration: Orally. Experimental Results: demonstrated anti-tumor activity. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Mean 5-FU maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) values were approximately 3-fold higher after Teysuno administration than after administration of tegafur alone, despite a 16-fold lower Teysuno dose (50 mg of tegafur) compared to tegafur alone (800 mg), and are attributed to inhibition of DPD by gimeracil. Maximum plasma uracil concentration was observed at 4 hours, with a return to baseline levels within approximately 48 hours after dosing, indicating the reversibility of the DPD inhibition by gimeracil. After administration of a single dose of 50 mg Teysuno (expressed as tegafur content), median Tmax for Teysuno components tegafur, gimeracil, and oteracil was 0.5, 1.0, and 2.0 hours, respectively. Following a single dose of Teysuno, approximately 3.8% to 4.2% of administered tegafur, 65% to 72% of administered gimeracil, and 3.5% to 3.9% of administered oteracil were excreted unchanged in the urine. Although no intravenous data are available for Teysuno in humans, the volume of distribution could be roughly estimated from the apparent volume of distribution and urinary excretion data as 16 l/m2, 17 l/m2, and 23 l/m2 for tegafur, gimeracil and oteracil, respectively. Biological Half-Life Following a single dose of Teysuno, T1/2 values ranged from 6.7 to 11.3 hours for tegafur, from 3.1 to 4.1 hours for gimeracil, and from 1.8 to 9.5 hours for oteracil. |
| Toxicity/Toxicokinetics |
Protein Binding
Oteracil, gimeracil, 5-FU, and tegafur are 8.4%, 32.2%, 18.4%, and 52.3% protein bound, respectively. |
| References |
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| Additional Infomation |
Gimeracil is an organic molecular entity.
Gimeracil is an adjunct to antineoplastic therapy, used to increase the concentration and effect of the main active componets within chemotherapy regimens. Approved by the European Medicines Agency (EMA) in March 2011, Gimeracil is available in combination with [DB03209] and [DB09256] within the commercially available product "Teysuno". The main active ingredient in Teysuno is [DB09256], a pro-drug of [DB00544] (5-FU), which is a cytotoxic anti-metabolite drug that acts on rapidly dividing cancer cells. By mimicking a class of compounds called "pyrimidines" that are essential components of RNA and DNA, 5-FU is able to insert itself into strands of DNA and RNA, thereby halting the replication process necessary for continued cancer growth. Gimeracil's main role within Teysuno is to prevent the breakdown of [DB00544] (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells. It functions by reversibly and selectively blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU. This allows higher concentrations of 5-FU to be achieved with a lower dose of tegafur, thereby also reducing toxic side effects. Gimeracil is a pyridine derivative with antitumor activity. Gimeracil enhances the antitumor activity of fluoropyrimidines by competitively and reversibly inhibiting the enzyme dihydropyrimidine dehydrogenase causing decreased degradation of the fluoropyrimidines. Drug Indication Gimeracil is used as an adjunct to antineoplastic therapy. When used within the product Teysuno, gimeracil is indicated for the treatment of adults with advanced gastric (stomach) cancer when given in combination with cisplatin. Mechanism of Action Gimeracil's main role within Teysuno is to prevent the breakdown of [DB00544] (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells. It functions by reversibly blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU. |
| Molecular Formula |
C5H4CLNO2
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| Molecular Weight |
145.54
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| Exact Mass |
144.993
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| CAS # |
103766-25-2
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| Related CAS # |
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| PubChem CID |
54679224
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| Appearance |
White to light brown solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
524.2±45.0 °C at 760 mmHg
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| Melting Point |
274 °C
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| Flash Point |
270.8±28.7 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.641
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| LogP |
-1.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
9
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| Complexity |
207
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZPLQIPFOCGIIHV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H4ClNO2/c6-3-2-7-5(9)1-4(3)8/h1-2H,(H2,7,8,9)
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| Chemical Name |
5-chloro-2-hydroxypyridin-4(1H)-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (17.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (17.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (17.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.8710 mL | 34.3548 mL | 68.7096 mL | |
| 5 mM | 1.3742 mL | 6.8710 mL | 13.7419 mL | |
| 10 mM | 0.6871 mL | 3.4355 mL | 6.8710 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06255379 | Not yet recruiting | Drug: Fuquinitinib+Tegafur Gimeracil Oteracil |
Metastasis Colorectal Cancer Colon Cancer |
Guangzhou University of Traditional Chinese Medicine |
March 22, 2024 | Phase 2 |
| NCT04310774 | Not yet recruiting | Drug: Tegafur, Gimeracil and Oteracil Potassium Capsules (one drug) |
Cervical Cancer Chemotherapy |
Peking Union Medical College Hospital | April 15, 2020 | Phase 1 Phase 2 |
| NCT03267121 | Completed | Drug: Tegafur Gimeracil Oteracil Potassium Capsules |
Head and Neck Squamous Cell Carcinoma |
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University |
October 1, 2017 | Phase 2 |
| NCT03192735 | Active, not recruiting | Drug: ApatinibMesylateTablets | Apatinib Combined SOX |
Chang-Ming Huang, Prof. | September 1, 2017 | Phase 2 |
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