TAS-103

• CAT Number: I002277
• CAS Number: 174634-08-3
• Molecular Formula: C₂₀H₁₉N₃O₂
• Molecular Weight: 333.38
• Purity: ≥95%
• Target: Topoisomerase
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• InChI: InChI=1S/C20H19N3O2/c1-23(2)10-9-21-20-18-17(13-5-3-4-6-14(13)19(18)25)15-8-7-12(24)11-16(15)22-20/h3-8,11,21-22H,9-10H2,1-2H3
• InChIKey: YXKRRCXCDMNRAU-UHFFFAOYSA-N
• SMILES: CN(C)CCNC1=C2C(=C3C=CC(=O)C=C3N1)C4=CC=CC=C4C2=O

TAS-103(BMS-247615) is a dual inhibitor of topoisomerase-I (topo-I) and topoisomerase-II (topoII).IC50 value:Target: Topoisomerasein vitro: TAS-103 was effective in inhibiting in vitro proliferation of human SCLC (SBC-3 and H69) cells and their drug-resistant variants SBC-3/ADM or SBC-3/CDDP and H-69/VP, respectively. SBC-3/ADM and H-69/VP expressed high P-gp, whereas SBC-3/CDDP did not [1]. TAS-103 disrupts SRP complex formation and reduces the amount of SRP14 and SRP19. TAS-103 treatment and RNAi-mediated knockdown of SRP54 or SRP14 promoted accumulation of the exogenously expressed chimeric protein interleukin-6-FLAG inside cells [2]. In 13 human cancer cell lines, MGMT expression correlated with IC50 for TAS-103, whereas gamma-GCS expression inversely correlated with the IC50 value, suggesting MGMT may work to decrease TAS-103 activity but gamma-GCS may increase it [3].in vivo: TAS-103 also effectively reduced the tumor growth (more than 50% inhibition) of the parental as well as MDR SCLC cells grown SC in nude mice [1]. Thirty-two patients were treated with escalating doses (50 to 200 mg/m(2)) of TAS-103, administered intravenously over 1 hour each week for 3 weeks. Pharmacokinetic analysis was performed at the 130-, 160-, and 200-mg/m(2) dose levels [4].

Reference

[1]. Parajuli P, et al. Therapeutic efficacy of a new topoisomerase I and II inhibitor TAS-103, against both P-glycoprotein-expressing and -nonexpressing drug-resistant human small-cell lung cancer. Oncol Res. 1999;11(5):219-24.

[2]. Yoshida M, et al. A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads. Mol Pharmacol. 2008 Mar;73(3):987-94.

[3]. Okamoto R, et al. Unique action determinants of double acting topoisomerase inhibitor, TAS-103. Int J Oncol. 2001 Nov;19(5):921-7.

[4]. Ewesuedo RB, et al. Phase I clinical and pharmacogenetic study of weekly TAS-103 in patients with advanced cancer. J Clin Oncol. 2001 Apr 1;19(7):2084-90.