MedKoo Biosciences/TAS-103 HCl salt (BMS-247615)/202834/50mg
TAS-103, also known as BMS-247615, is a quinoline derivative that displays antitumor activity in murine and human tumor models. TAS-103 has been reported to be a potent topoisomerase II poison. TAS-103 showed the strongest antitumor activity among the conventional anticancer agents for colorectal cancer (p<0.05). The combination with CDDP augmented the antitumor activity of TAS-103 (p<0.05), indicating that CDDP is one of the most potent candidates to be used in combination with TAS-103 . TAS-103 may be useful in the chemotherapy of colorectal cancer.

MedKoo Cat#: 202834
Name: TAS-103 HCl salt (BMS-247615)
CAS#: 174634-09-4
Chemical Formula: C20H21Cl2N3O2
Exact Mass:
Molecular Weight: 406.31
Elemental Analysis: C, 59.12; H, 5.21; Cl, 17.45; N, 10.34; O, 7.88


Related CAS #: 174634-09-4 (HCl salt)   174634-08-3 (free base)  

Synonym: TAS103; TAS-103; TAS 103; BMS247615; BMS 247615; BMS-247615.

IUPAC/Chemical Name: .6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride

InChi Key: HAYAYGFVSIWSGQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H19N3O2.2ClH/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;;/h4-8,11,24H,9-10H2,1-2H3,(H,21,22);2*1H

SMILES Code: O=C(C1=C2C3=CC=C(O)C=C3N=C1NCCN(C)C)C4=C2C=CC=C4.[H]Cl.[H]Cl


Technical Data

Appearance:
Red solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Certificate of Analysis:
View CoA: current batch, Lot#BBC40717

QC Data:
View QC data: current batch, Lot#BBC40717

Safety Data Sheet (MSDS):
View Material Safety Data Sheet (MSDS)

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 water, not soluble in DMSO, not soluble in chloroform.

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in water.

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Yoshida M, Kabe Y, Wada T, Asai A, Handa H. 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. Epub 2007 Dec 18. PubMed PMID: 18089836.

2: Fujimoto S. Promising antitumor activity of a novel quinoline derivative, TAS-103, against fresh clinical specimens of eight types of tumors measured by flow cytometric DNA analysis. Biol Pharm Bull. 2007 Oct;30(10):1923-9. PubMed PMID: 17917263.

3: Torigoe T, Izumi H, Wakasugi T, Niina I, Igarashi T, Yoshida T, Shibuya I, Chijiiwa K, Matsuo K, Itoh H, Kohno K. DNA topoisomerase II poison TAS-103 transactivates GC-box-dependent transcription via acetylation of Sp1. J Biol Chem. 2005 Jan 14;280(2):1179-85. Epub 2004 Nov 8. PubMed PMID: 15533934.

4: Shimizu K, Takada M, Asai T, Kuromi K, Baba K, Oku N. Cancer chemotherapy by Liposomal 6-[12-(dimethylamino)ethyl]aminol-3-hydroxy-7H-indeno[2,1-clquinolin-7-one dihydrochloride (TAS-103), a novel anti-cancer agent. Biol Pharm Bull. 2002 Oct;25(10):1385-7. PubMed PMID: 12392102.

5: Ishida K, Asao T. Self-association and unique DNA binding properties of the anti-cancer agent TAS-103, a dual inhibitor of topoisomerases I and II. Biochim Biophys Acta. 2002 Jul 18;1587(2-3):155-63. Review. PubMed PMID: 12084457.

6: Tsunoda T, Tanimura H, Yamaue H, Ishimoto K, Kobunai T, Yamada Y. In vitro antitumor activity of TAS-103 against freshly-isolated human colorectal cancer. Anticancer Res. 2001 Nov-Dec;21(6A):3897-902. PubMed PMID: 11911266.

7: Azuma R, Saeki M, Yamamoto Y, Hagiwara Y, Grochow LB, Donehower RC. Metabolism and urinary excretion of a new quinoline anticancer drug, TAS-103, in humans. Xenobiotica. 2002 Jan;32(1):63-72. PubMed PMID: 11820510.

8: Okamoto R, Takano H, Sekikawa T, Tanaka T, Toyada M, Ukon K, Tanimoto K, Kumazaki T, Nishiyama M. Unique action determinants of double acting topoisomerase inhibitor, TAS-103. Int J Oncol. 2001 Nov;19(5):921-7. PubMed PMID: 11604989.

9: Ewesuedo RB, Iyer L, Das S, Koenig A, Mani S, Vogelzang NJ, Schilsky RL, Brenckman W, Ratain MJ. 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. PubMed PMID: 11283142.

10: Etiévant C, Kruczynski A, Barret JM, Perrin D, van Hille B, Guminski Y, Hill BT. F 11782, a dual inhibitor of topoisomerases I and II with an original mechanism of action in vitro, and markedly superior in vivo antitumour activity, relative to three other dual topoisomerase inhibitors, intoplicin, aclarubicin and TAS-103. Cancer Chemother Pharmacol. 2000;46(2):101-13. PubMed PMID: 10972479.

11: Kluza J, Lansiaux A, Wattez N, Mahieu C, Osheroff N, Bailly C. Apoptotic response of HL-60 human leukemia cells to the antitumor drug TAS-103. Cancer Res. 2000 Aug 1;60(15):4077-84. PubMed PMID: 10945613.

12: Padget K, Stewart A, Charlton P, Tilby MJ, Austin CA. An investigation into the formation of N- [2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) and 6-[2-(dimethylamino)ethylamino]- 3-hydroxy-7H-indeno[2, 1-C]quinolin-7-one dihydrochloride (TAS-103) stabilised DNA topoisomerase I and II cleavable complexes in human leukaemia cells. Biochem Pharmacol. 2000 Sep 15;60(6):817-21. PubMed PMID: 10930536.

13: Aoyagi Y, Kobunai T, Utsugi T, Wierzba K, Yamada Y. Establishment and characterization of 6-[[2-(Dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103)-resistant cell lines. Jpn J Cancer Res. 2000 May;91(5):543-50. PubMed PMID: 10835500.

14: Ishida K, Asao T. Interaction of a novel antitumor agent TAS-103 with DNA. Nucleic Acids Symp Ser. 1999;(42):129-30. PubMed PMID: 10780413.

15: Minderman H, Wrzosek C, Cao S, Utsugi T, Kobunai T, Yamada Y, Rustum YM. Mechanism of action of the dual topoisomerase-I and -II inhibitor TAS-103 and activity against (multi)drug resistant cells. Cancer Chemother Pharmacol. 2000;45(1):78-84. PubMed PMID: 10647506.

16: Parajuli P, Yano S, Nishioka Y, Nokihara H, Hanibuchi M, Nishimura N, Utsugi T, Sone S. 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. PubMed PMID: 10608616.

17: Fortune JM, Velea L, Graves DE, Utsugi T, Yamada Y, Osheroff N. DNA topoisomerases as targets for the anticancer drug TAS-103: DNA interactions and topoisomerase catalytic inhibition. Biochemistry. 1999 Nov 23;38(47):15580-6. PubMed PMID: 10569942.

18: Byl JA, Fortune JM, Burden DA, Nitiss JL, Utsugi T, Yamada Y, Osheroff N. DNA topoisomerases as targets for the anticancer drug TAS-103: primary cellular target and DNA cleavage enhancement. Biochemistry. 1999 Nov 23;38(47):15573-9. PubMed PMID: 10569941.

19: Ohyama T, Li Y, Utsugi T, Irie S, Yamada Y, Sato T. A dual topoisomerase inhibitor, TAS-103, induces apoptosis in human cancer cells. Jpn J Cancer Res. 1999 Jun;90(6):691-8. PubMed PMID: 10429663.

20: Aoyagi Y, Kobunai T, Utsugi T, Oh-hara T, Yamada Y. In vitro antitumor activity of TAS-103, a novel quinoline derivative that targets topoisomerases I and II. Jpn J Cancer Res. 1999 May;90(5):578-87. PubMed PMID: 10391099.