| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Plevitrexed targets thymidylate synthase (TS), which catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), a rate-limiting step in DNA replication. By inhibiting TS, the compound depletes intracellular dTMP, leading to thymidine starvation, DNA synthesis arrest, and cell death. It does not require polyglutamation for activity, unlike 5-fluorouracil.
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| ln Vitro |
ZD9331 has a Ki of about 1 µM, which blocks the transfer of [3H]-methotrexate into L1210 and W1L2 cells [3].
In vitro, Plevitrexed potently inhibits purified human TS with a Ki value in the low nanomolar range (e.g., ~0.1 nM). It shows cytotoxic activity against a broad panel of human cancer cell lines, including colon, lung, and breast cancers, with IC50 values typically 10-100 nM. It is more potent than 5-fluorouracil in many lines and retains activity against cells resistant to other antifolates. |
| ln Vivo |
In vivo, Plevitrexed has demonstrated antitumor activity in various human tumor xenograft models in mice. Oral administration at doses of 10-50 mg/kg/day significantly inhibited the growth of colon, ovarian, and lung xenografts. In combination with other agents, it showed synergistic effects. The compound was well tolerated, with no significant toxicity at therapeutic doses.
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| Enzyme Assay |
In cell-free enzymatic assays, Plevitrexed's inhibition of TS is measured by a spectrophotometric method that monitors the conversion of dUMP to dTMP using the enzyme and substrate. The compound's Ki is determined by varying substrate and inhibitor concentrations. Assays are performed in Tris-HCl buffer with NADPH as cofactor.
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| Cell Assay |
Cell-based cytotoxicity assays are performed using standard MTT or SRB methods. Cancer cells are seeded in 96-well plates and treated with serial dilutions of Plevitrexed for 48-72 hours. The effect on DNA synthesis can be measured by [3H]thymidine incorporation. Cell cycle analysis by flow cytometry shows S-phase arrest.
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| Animal Protocol |
In vivo efficacy is evaluated in nude mice bearing subcutaneous human tumor xenografts. When tumors reach ~150 mm³, mice are randomized to receive Plevitrexed orally at doses of 10, 30, or 50 mg/kg daily for 14 days. Tumor volumes are measured twice weekly. At the end, tumors are excised for TS activity assay and histology.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in rats and monkeys show that Plevitrexed is rapidly absorbed after oral administration with bioavailability of ~50-70%. Peak plasma concentrations occur at 1-2 hours. The half-life is 2-4 hours in rodents and 6-8 hours in primates. It is excreted primarily unchanged in urine and bile. Protein binding is moderate (~70%).
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| Toxicity/Toxicokinetics |
In preclinical toxicology, Plevitrexed was well tolerated in rodents and dogs. In chronic studies, the main toxicities were hematological (myelosuppression) and gastrointestinal (diarrhea, mucositis), consistent with TS inhibition. These were reversible and manageable. The compound is not genotoxic. The maximum tolerated dose in animals was ~100 mg/kg/day.
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| References | |
| Additional Infomation |
Plevitrexed is a small-molecule, non-polyglutamate-based thymidine synthase inhibitor with high oral bioavailability and potential antitumor activity. Plevitrexed enters cells via the physiologically reduced folate carrier (RFC) system. Intracellularly, the drug selectively binds to the folate binding site of thymidine synthase, inhibiting thymidine synthesis, which may lead to DNA synthesis inhibition and apoptosis.
Drug Indications It has been investigated for the treatment of pancreatic cancer, solid tumors, gastric cancer, lung cancer, and colorectal cancer. Plevitrexed is a non-polyglutamatable TS inhibitor developed by GlaxoSmithKline (formerly by Pfizer). Its molecular formula is C20H20N4O5 and molecular weight 396.40. It reached Phase II clinical trials for colorectal cancer but was discontinued due to efficacy and competitive landscape. It is available for research purposes only. It remains a valuable tool for studying TS biology and antifolate resistance. |
| Molecular Formula |
C26H25FN8O4
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|---|---|
| Molecular Weight |
532.53
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| Exact Mass |
532.198
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| CAS # |
153537-73-6
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| Related CAS # |
(R)-Plevitrexed;153537-74-7;(Rac)-Plevitrexed;153538-08-0
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| PubChem CID |
135430970
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.44g/cm3
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| Index of Refraction |
1.683
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| LogP |
2.038
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
39
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| Complexity |
1000
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC2=C(C=C1CN(CC#C)C3=CC(=C(C=C3)C(=O)N[C@@H](CCC4=NNN=N4)C(=O)O)F)C(=O)NC(=N2)C
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| InChi Key |
IEJSCSAMMLUINT-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C26H25FN8O4/c1-4-9-35(13-16-11-19-22(10-14(16)2)28-15(3)29-25(19)37)17-5-6-18(20(27)12-17)24(36)30-21(26(38)39)7-8-23-31-33-34-32-23/h1,5-6,10-12,21H,7-9,13H2,2-3H3,(H,30,36)(H,38,39)(H,28,29,37)(H,31,32,33,34)/t21-/m0/s1
|
| Chemical Name |
(2S)-2-[[4-[(2,7-dimethyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-2-fluorobenzoyl]amino]-4-(2H-tetrazol-5-yl)butanoic acid
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| Synonyms |
BGC9331. ZD-9331; BGC 9331; BGC-9331
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8778 mL | 9.3891 mL | 18.7783 mL | |
| 5 mM | 0.3756 mL | 1.8778 mL | 3.7557 mL | |
| 10 mM | 0.1878 mL | 0.9389 mL | 1.8778 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 |
| NCT00014690 | COMPLETED | Drug:plevitrexed Drug:topotecan hydrochloride |
Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cavity Cancer |
AstraZeneca | 2001-03 | Phase 2 |
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