OSI-7904L
Based on 1 publication(s) in Google Scholar
OSI-7904L (GW1843; 1843U89; OSI-7904) is a thymidylate synthase (TS) inhibitor with a Ki of 90 pM. OSI-7904L blocks de novo synthesis of thymidine nucleotides, DNA synthesis and induces cell death. OSI-7904L inhibits the growth of human cells, induces tumor regression, and achieves durable antitumor effects in mouse xenograft models. OSI-7904L can be used in research related to colon adenocarcinoma.
For research use only. We do not sell to patients.
- CAS No.: 139987-54-5
- Formula: C27H24N4O6
- Molecular Weight:500.50
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) OSI-7904L
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Biological Activity
OSI-7904L potently inhibits the growth of all tested human cell lines with sub-1 nM IC50, with thymidine alone reversing this effect; murine cell lines are 80-1300-fold less sensitive than human cell lines[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | AUC0-∞ | AUC0-last | CL | Cmax | MRT0-∞ | Vss |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1.0 mg/kg | i.v. | 133 μg·h/mL | 118 μg·h/mL | 7.69 mL/h/kg | 13.9 μg/mL | 10.8 h | 81.4 mL/kg |
| Mice[1] | 10.0 mg/kg | i.v. | 2530 μg·h/mL | 2530 μg·h/mL | 3.97 mL/h/kg | 154 μg/mL | 17.0 h | 67.1 mL/kg |
| Mice[1] | 50.0 mg/kg | i.v. | 16900 μg·h/mL | 16800 μg·h/mL | 2.97 mL/h/kg | 797 μg/mL | 25.8 h | 76.4 mL/kg |
OSI-7904L (7.5-25 mg/kg; i.v.; three distinct schedules: daily × 5 for 2 weeks, on days 1,3,5 for 2 weeks, or on days 1 and 8) achieves 95-97% TGI, 86-88% tumor regression, and 1 durable cure per group in HCT-8 TK-/- tumor-bearing Nu/Nu mice[1].
OSI-7904L (5-25 mg/kg; i.v.; on days 1 and 8) produces a dose-dependent response in HCT-8 TK-/- tumor-bearing Nu/Nu mice, with 80-99% TGI, 0-100% tumor regression, and 0-4 durable cures at day 60[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nu/Nu nude (female, 18-25 g)[1]
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Dosage:7.5 mg/kg (total dose 52.5 mg/kg)
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Administration:i.v.; every other day; 14 days
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Result:Achieved 83% tumor regression, a log cell kill (LCK) index of 4.6, and 97.5% tumor growth inhibition (TGI) on day 23.
Produced transient, reversible body weight loss that never exceeded 10%.
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Animal Model:Nu/Nu nude (female, 18-25 g)[1]
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Dosage:7.5 mg/kg (daily on days 1-5 for 2 consecutive weeks); 15 mg/kg (on days 1, 3, 5 for 2 consecutive weeks); 25 mg/kg (on days 1 and 8)
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Administration:i.v.; daily on days 1-5 for 2 consecutive weeks; i.v.; on days 1, 3, 5 for 2 consecutive weeks; i.v.; on days 1 and 8
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Result:Demonstrated 96% TGI, 88% tumor regression on day 22, LCK of 3.9, and 1/8 durable cures with the 7.5 mg/kg schedule.
Demonstrated 95% TGI, 86% tumor regression on day 22, LCK of 3.2, and 1/8 durable cures with the 15 mg/kg schedule.
Demonstrated 97% TGI, 88% tumor regression on day 22, LCK of 4.2, and 1/8 durable cures with the 25 mg/kg schedule.
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Animal Model:Nu/Nu nude (female, 18-25 g)[1]
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Dosage:5 mg/kg; 10 mg/kg; 15 mg/kg; 20 mg/kg; 25 mg/kg
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Administration:i.v.; on days 1 and 8
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Result:Produced 80% TGI on day 26, 0% tumor regression, and 0 cures at 5 mg/kg.
Produced 92% TGI on day 26, 58% tumor regression, and 0 cures at 10 mg/kg.
Produced 95% TGI on day 26, 65% tumor regression, and 1 cure at 15 mg/kg.
Produced 97% TGI on day 26, 100% tumor regression, and 2 cures at 20 mg/kg.
Produced 99% TGI on day 26, 100% tumor regression, and 4 cures at 25 mg/kg.
Caused no appreciable body weight effects in any dose group.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 139987-54-5
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Molecular Weight 500.50
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Formula C27H24N4O6
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SMILES
O=C1C2=C3C(C=CC(CNC4=CC=C(C(N(C5)[C@H](C(O)=O)CCC(O)=O)=O)C5=C4)=C3)=CC=C2NC(C)=N1
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Synonyms
GW1843; 1843U89; OSI-7904
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (1)
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Journal Impact Factor
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Most Recent
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Cell Rep
2026 Jun 18;45(7):117576. PMID: 42313565
Purity & Documentation
References
[1].
Desjardins J, et al. Pharmacokinetics, safety, and efficacy of a liposome encapsulated thymidylate synthase inhibitor, OSI-7904L [(S)-2-[5-[(1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl]amino-1-oxo-2-isoindolynl]-glutaric acid] in mice. J Pharmacol Exp Ther. 2004 Jun;309(3):894-902.
[Content Brief]
[2].
Duch DS, et al. Biochemical and cellular pharmacology of 1843U89, a novel benzoquinazoline inhibitor of thymidylate synthase. Cancer Res. 1993 Feb 15;53(4):810-8.
[Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
OSI-7904L Related Classifications
HY-10823 Related Classifications
Powered by Bioz
- OSI-7904L
- 139987-54-5
- GW1843
- 1843U89
- OSI-7904
- GW 1843
- GW-1843
- OSI7904
- OSI 7904
- OSI-7904
- Thymidylate Synthase
- DNA/RNA Synthesis
- reduced folate carrier
- colon adenocarcinoma
- HCT-8 TK-/-
- murine L1210 cells
- mouse xenograft models
- human cells
- MOLT-4 cells
- thymidylate synthase
- mice
- hog liver folylpolyglutamate synthetase
- Inhibitor
- inhibitor
- inhibit