OSI-7904L

• CAT Number: I008508
• CAS Number: 139987-54-5
• Molecular Formula: C27H24N4O6
• Molecular Weight: 500.511
• Purity: ≥95%
• Target: thymidylate synthase inhibitor
• Solubility: Soluble in DMSO, not soluble in water.
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: (2S)-2-[6-[(3-methyl-1-oxo-4H-benzo[f]quinazolin-9-yl)methylamino]-3-oxo-1H-isoindol-2-yl]pentanedioic acid
• InChI: 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
• InChIKey: BRVFNEZMTRVUGW-QFIPXVFZSA-N
• SMILES: CC1=NC(=O)C2=C(N1)C=CC3=C2C=C(C=C3)CNC4=CC5=C(C=C4)C(=O)N(C5)C(CCC(=O)O)C(=O)O

OSI-7904L is a novel noncompetitive liposomal thymidylate synthase inhibitor. OSI-7904 is a benzoquinazoline folate analog with antineoplastic activity. As a thymidylate synthase inhibitor, OSI-7904 noncompetitively binds to thymidylate synthase, resulting in inhibition of thymine nucleotide synthesis and DNA replication. OSI-7904L is a liposome-encapsulated formulation of OSI-7904. Liposome encapsulation improves the efficacy and increases the half-life of OSI-7904. Its effect on solid tumours is currently under evaluation.

Reference

1:Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors. Ricart AD, Berlin JD, Papadopoulos KP, Syed S, Drolet DW, Quaratino-Baker C, Horan J, Chick J, Vermeulen W, Tolcher AW, Rowinsky EK, Rothenberg ML.Clin Cancer Res. 2008 Dec 1;14(23):7947-55. doi: 10.1158/1078-0432.CCR-08-0864. PMID: 19047127 Free Article2:A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer. Clamp AR, Schöffski P, Valle JW, Wilson RH, Marreaud S, Govaerts AS, Debois M, Lacombe D, Twelves C, Chick J, Jayson GC; EORTC New Drug Development Group..Cancer Chemother Pharmacol. 2008 Apr;61(4):579-85. Epub 2007 May 23. PMID: 17520255 3:A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers. Ciuleanu T, Diculescu M, Hoepffner NM, Trojan J, Sailer V, Zalupski M, Herrmann T, Roth A, Chick J, Brock K, Albert D, Philip PA.Invest New Drugs. 2007 Aug;25(4):385-90. Epub 2007 Mar 16. PMID: 17364234 4:Multicentre phase II pharmacokinetic and pharmacodynamic study of OSI-7904L in previously untreated patients with advanced gastric or gastroesophageal junction adenocarcinoma. Falk S, Anthoney A, Eatock M, Van Cutsem E, Chick J, Glen H, Valle JW, Drolet DW, Albert D, Ferry D, Ajani J.Br J Cancer. 2006 Aug 21;95(4):450-6. Epub 2006 Aug 1. PMID: 16880795 Free PMC Article5:Phase I study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor in patients with refractory solid tumors. Beutel G, Glen H, Schöffski P, Chick J, Gill S, Cassidy J, Twelves C.Clin Cancer Res. 2005 Aug 1;11(15):5487-95. PMID: 16061865 Free Article6: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. Desjardins J, Emerson DL, Colagiovanni DB, Abbott E, Brown EN, Drolet DW.J Pharmacol Exp Ther. 2004 Jun;309(3):894-902. Epub 2004 Feb 24. PMID: 14982966 Free Article