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MedKoo Cat#: 584309 | Name: OSI-7904L free acid

Description:

WARNING: This product is for research use only, not for human or veterinary use.

OSI-7904L, also known as 1843U89, is a folate-based thymidylate synthase inhibitor with antimalarial and antitumor properties.

Chemical Structure

OSI-7904L free acid
OSI-7904L free acid
CAS#139987-54-5 (free acid)

Theoretical Analysis

MedKoo Cat#: 584309

Name: OSI-7904L free acid

CAS#: 139987-54-5 (free acid)

Chemical Formula: C27H24N4O6

Exact Mass: 500.1696

Molecular Weight: 500.51

Elemental Analysis: C, 64.79; H, 4.83; N, 11.19; O, 19.18

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.
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Related CAS #
2197232-28-1 (racemic) 139987-54-5 (free acid)
Synonym
OSI-7904L; OSI7904L; OSI 7904L; OSI 7904; OSI7904; OSI-7904; 1843U89; BW 1843U89; BW-1843U89; BW1843U89; GW 1843; GW1843; GW-1843; GW 1843U89; OSI 7904L;
IUPAC/Chemical Name
Pentanedioic acid, 2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-, (S)-
InChi Key
BRVFNEZMTRVUGW-QFIPXVFZSA-N
InChi Code
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
SMILES Code
O=C(O)[C@@H](N(CC1=C2C=CC(NCC3=CC=C4C(C5=C(N=C(C)NC5=O)C=C4)=C3)=C1)C2=O)CCC(O)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info

Preparing Stock Solutions

The following data is based on the product molecular weight 500.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
1: Smith GK, Amyx H, Boytos CM, Duch DS, Ferone R, Wilson HR. Enhanced antitumor activity for the thymidylate synthase inhibitor 1843U89 through decreased host toxicity with oral folic acid. Cancer Res. 1995 Dec 15;55(24):6117-25. PubMed PMID: 8521402. 2: Hanlon MH, Ferone R. In vitro uptake, anabolism, and cellular retention of 1843U89 and other benzoquinazoline inhibitors of thymidylate synthase. Cancer Res. 1996 Jul 15;56(14):3301-6. PubMed PMID: 8764125. 3: Wilson RH. Novel therapeutic developments other than EGFR and VEGF inhibition in colorectal cancer. Oncologist. 2006 Oct;11(9):1018-24. Review. PubMed PMID: 17030644. 4: Li WW, Tong WP, Bertino JR. Antitumor activity of antifolate inhibitors of thymidylate and purine synthesis in human soft tissue sarcoma cell lines with intrinsic resistance to methotrexate. Clin Cancer Res. 1995 Jun;1(6):631-6. PubMed PMID: 9816025. 5: Schwartz G, Johnson TR, Goetz A, Burris H, Smetzer L, Lampkin T, Sailstad J, Hohneker JA, Von Hoff DD, Rowinsky EK. A phase I and pharmacokinetic study of 1843U89, a noncompetitive inhibitor of thymidylate synthase, in patients with advanced solid malignancies. Clin Cancer Res. 2001 Jul;7(7):1901-11. PubMed PMID: 11448903. 6: 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. A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer. Cancer Chemother Pharmacol. 2008 Apr;61(4):579-85. Epub 2007 May 23. PubMed PMID: 17520255. 7: Desjardins J, Emerson DL, Colagiovanni DB, Abbott E, Brown EN, Drolet DW. 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. Epub 2004 Feb 24. PubMed PMID: 14982966. 8: Wong SC, Proefke SA, Bhushan A, Matherly LH. Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells. J Biol Chem. 1995 Jul 21;270(29):17468-75. PubMed PMID: 7615551. 9: Jiang L, Lee PC, White J, Rathod PK. Potent and selective activity of a combination of thymidine and 1843U89, a folate-based thymidylate synthase inhibitor, against Plasmodium falciparum. Antimicrob Agents Chemother. 2000 Apr;44(4):1047-50. PubMed PMID: 10722510; PubMed Central PMCID: PMC89811. 10: Pang CK, Hunter JH, Gujjar R, Podutoori R, Bowman J, Mudeppa DG, Rathod PK. Catalytic and ligand-binding characteristics of Plasmodium falciparum serine hydroxymethyltransferase. Mol Biochem Parasitol. 2009 Nov;168(1):74-83. doi: 10.1016/j.molbiopara.2009.06.011. Epub 2009 Jul 8. PubMed PMID: 19591883; PubMed Central PMCID: PMC2741015. 11: Weichsel A, Montfort WR. Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89. Nat Struct Biol. 1995 Dec;2(12):1095-101. PubMed PMID: 8846221. 12: Takimoto CH. Antifolates in clinical development. Semin Oncol. 1997 Oct;24(5 Suppl 18):S18-40-S18-51. Review. PubMed PMID: 9420020. 13: Duch DS, Banks S, Dev IK, Dickerson SH, Ferone R, Heath LS, Humphreys J, Knick V, Pendergast W, Singer S, et al. Biochemical and cellular pharmacology of 1843U89, a novel benzoquinazoline inhibitor of thymidylate synthase. Cancer Res. 1993 Feb 15;53(4):810-8. PubMed PMID: 8428362. 14: 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. Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors. Clin Cancer Res. 2008 Dec 1;14(23):7947-55. doi: 10.1158/1078-0432.CCR-08-0864. PubMed PMID: 19047127. 15: Beutel G, Glen H, Schöffski P, Chick J, Gill S, Cassidy J, Twelves C. Phase I study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor in patients with refractory solid tumors. Clin Cancer Res. 2005 Aug 1;11(15):5487-95. PubMed PMID: 16061865. 16: Laethem RM, Hannun YA, Jayadev S, Sexton CJ, Strum JC, Sundseth R, Smith GK. Increases in neutral, Mg2+-dependent and acidic, Mg2+-independent sphingomyelinase activities precede commitment to apoptosis and are not a consequence of caspase 3-like activity in Molt-4 cells in response to thymidylate synthase inhibition by GW1843. Blood. 1998 Jun 1;91(11):4350-60. PubMed PMID: 9596684. 17: Hunter JH, Gujjar R, Pang CK, Rathod PK. Kinetics and ligand-binding preferences of Mycobacterium tuberculosis thymidylate synthases, ThyA and ThyX. PLoS One. 2008 May 21;3(5):e2237. doi: 10.1371/journal.pone.0002237. PubMed PMID: 18493582; PubMed Central PMCID: PMC2386288. 18: Weichsel A, Montfort WR, Cieśla J, Maley F. Promotion of purine nucleotide binding to thymidylate synthase by a potent folate analogue inhibitor, 1843U89. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3493-7. PubMed PMID: 7724588; PubMed Central PMCID: PMC42193. 19: Schmitz JC, Chen TM, Chu E. Small interfering double-stranded RNAs as therapeutic molecules to restore chemosensitivity to thymidylate synthase inhibitor compounds. Cancer Res. 2004 Feb 15;64(4):1431-5. PubMed PMID: 14973067. 20: Banks SD, Waters KA, Barrett LL, Dickerson S, Pendergast W, Smith GK. Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations. Cancer Chemother Pharmacol. 1994;33(6):455-9. PubMed PMID: 8137455.