Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C27H24N4O6 |
Molecular Weight | 500.5027 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=NC2=C(C(=O)N1)C3=CC(CNC4=CC=C5C(=O)N(CC5=C4)[C@@H](CCC(O)=O)C(O)=O)=CC=C3C=C2
InChI
InChIKey=BRVFNEZMTRVUGW-QFIPXVFZSA-N
InChI=1S/C27H24N4O6/c1-14-29-21-7-4-16-3-2-15(10-20(16)24(21)25(34)30-14)12-28-18-5-6-19-17(11-18)13-31(26(19)35)22(27(36)37)8-9-23(32)33/h2-7,10-11,22,28H,8-9,12-13H2,1H3,(H,32,33)(H,36,37)(H,29,30,34)/t22-/m0/s1
OSI-7904L is a liposomal formulation of the highly specific, noncompetitive thymidylate synthase inhibitor OSI-7904 (also known as GW1843, BW1843U89, and GS7904). The liposome formulation was developed to enhance the therapeutic index and dose schedule convenience of this potent antifolate compound. This drug was studied in phase II clinical trial in patients to treat head and neck cancer, gastroesophageal adenocarcinoma and advanced biliary cancer, but these studies were discontinued. As an example in case of OSI-7904L, was revealed that its activity was below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilization.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: P04818 Gene ID: 7298.0 Gene Symbol: TYMS Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14982966 |
0.5 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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797 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14982966 |
50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
OSI-7904 plasma | Mus musculus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
16900 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14982966 |
50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
OSI-7904 plasma | Mus musculus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
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Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells. | 1994 |
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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. | 2004 Jun |
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A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer. | 2008 Apr |
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Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors. | 2008 Dec 1 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17364234
Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI-7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5-FU/LV every 14 days.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7987985
The thymidylate synthase-inhibitory effects induced by a 24-h exposure to the folate-based TS inhibitors CB3717, C2-desamino analogs of CB3717 including D1694, and BW1843U89 (OSI-7904L) were quantitated using the MGH-U1 human bladder carcinoma. D1694 and BW1843U89 were the most active TS inhibitors with IC50 values of 2.4 and 0.5 nM, respectively.
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NCI_THESAURUS |
C2021
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NCI_THESAURUS |
C511
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139987-54-5
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DTXSID70930683
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DB05457
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ON177ZCE7M
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OSI-7904
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C079601
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C38694
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ACTIVE MOIETY