ONX 0801 (BGC 945) trisodium is a thymidylate synthase (TS) inhibitor, targeted to α-folate receptor–overexpressing tumors[1][2].
体外研究 (In Vitro)
ONX 0801 (BGC 945) is designed to further reduce toxicity by more effectively targeting cancer cells that overexpress the α-FR[1]. ONX 0801 (BGC 945) exhibits IC50 values of of 6.6 μM, 1.1 nM, 3.3 nM, 90 nM and 0.32 μM in A431, A431-FBP, KB, IGROV-1 and JEG-3 cells[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
BGC 945 (100 mg/kg, ip/iv injection) in the tumor had a longer half-life (28 hours) compared with other tissues[2]. BGC 945 (100 mg/kg daily for 16 days) does not lead to body weight loss, macroscopic signs of toxicity to the major organs, or a change in renal function[2]. BGC 945 at 100mg/kg induces a 5-20-fold increase in tumor dUrd at 4-72h without increases in the plasma, consistent with tumor targeting[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Mice (on the folate-free diet for 5 days were transplanted with tumor and the implants)[2].
Dosage:
100 mg/kg (Pharmacokinetic Analysis).
Administration:
Single i.p. or iv injection.
Result:
After i.p. injection, the compound was well absorbed from the peritoneal cavity. The plasma AUC was 50% higher for i.p. compared with i.v. administration and was also higher in spleen, kidney, and liver by this route. Tumor AUC was similar via either route.
分子量
713.58
Formula
C32H30N5Na3O10
CAS 号
1097638-00-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anna Tochowicz, et al. Development and binding mode assessment of N-[4-[2-propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-D-glutamic acid (BGC 945), a novel thymidylate synthase inhibitor that targets tumor cells. J Med Chem. 2013 Jul 11;56(13):5446-55.
[2]. David D Gibbs, et al. BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. Cancer Res. 2005 Dec 15;65(24):11721-8.
[3]. Chau Ng, et al. Efficacy and tolerability of the thymidylate synthase (TS) inhibitor, BGC 945 is mediated through its selective uptake via the α-folate receptor (α-FR) in IGROV-1 human tumor xenografts. AACR Annual Meeting– Apr 12-16, 2008; San Diego, CA.
