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MedKoo product information:
TAS-102
Description of TAS-102:
TAS-102 is an orally bioavailable combination agent composed of the
cytotoxic pyrimidine analog
Trifluridine
(5-trifluoro-2’-deoxythymidine or TFT) and a thymidine phosphorylase
inhibitor (TPI) tipiracil hydrochloride, in
a molar ratio of 1.0:0.5 (TFT:TPI), with potential antineoplastic
activity. After oral administration of TAS-102,
TFT is phosphorylated to
the active monophosphate form TF-TMP, which binds covalently to the
active site of thymidylate synthase, thereby reducing the nucleotide
pool levels required for DNA replication. Furthermore, the triphosphate
form TF-TTP can be incorporated into DNA, which induces DNA
fragmentation and leads to the inhibition of tumor growth. TPI exhibits
a dual effect: 1) an anti-angiogenic effect mediated through the
inhibition of thymidine phosphorylase, which plays an important role in
nucleotide metabolism and a variety of development processes, including
angiogenesis, 2) increased bioavailability of the normally short-lived
antimetabolite TFT by preventing its degradation into the inactive form
trifluorothymine (TF-Thy). The synergistic effect of the components in
TAS-102 may demonstrate antitumor activity in 5-FU-resistant cancer
cells. Check for
active clinical trials or
closed clinical trials using this agent. (NCI
Thesaurus)
Current developer:
Taiho Pharma.
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MedKoo Code#:
205641
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Name:
TAS-102
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CAS#:
733030-01-8 (TAS-102); 183204-74-2(Tipiracil); (183204-72-0
(Tipiracil -HCl );
Trifluridine
(70-00-8)
Synonym of
TAS-102:
TAS-102; TAS102; TAS 102.
IUPAC/Chemical name:
Trifluridine: 1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione.
Tipiracil (TPI):
5-chloro-6-((2-iminopyrrolidin-1-yl)methyl)pyrimidine-2,4(1H,3H)-dione
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Chemical structure
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Theoretical analysis
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Trifluridine
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MedKoo#206038
Name: Trifluridine
CAS#70-00-8
Chemical Formula: C10H11F3N2O5
Exact Mass: 296.06201
Molecular Weight: 296.19995
Elemental Analysis: C, 40.55; H, 3.74; F,
19.24; N, 9.46; O, 27.01
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Tipiracil
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MedKoo#206037
Name: Tipiracil-HCl
salt
CAS#183204-72-0
Chemical Formula: C9H12Cl2N4O2
Molecular Weight: 279.12
Tipiracil (free
base)
Chemical Formula: C9H11ClN4O2
Exact Mass: 242.05705
Molecular Weight: 242.66224
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Availability and price:
This agent is
not in stock, which may be available through custom synthesis.
To inquire quotation and lead time or to ask questions, please send email to
sales@medkoo.com to describe your needs. A representative
will respond your email shortly. We offer big discount for orders of bulk quantities.
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References
1: Peters GJ, Bijnsdorp IV. TAS-102: more than an
antimetabolite. Lancet Oncol. 2012 Dec;13(12):e518-9. doi:
10.1016/S1470-2045(12)70426-6. PubMed PMID: 23182191.
2: Yoshino T, Mizunuma N, Yamazaki K, Nishina T, Komatsu Y, Baba H,
Tsuji A, Yamaguchi K, Muro K, Sugimoto N, Tsuji Y, Moriwaki T, Esaki T,
Hamada C, Tanase T, Ohtsu A. TAS-102 monotherapy for pretreated
metastatic colorectal cancer: a double-blind, randomised,
placebo-controlled phase 2 trial. Lancet Oncol. 2012
Oct;13(10):993-1001. doi: 10.1016/S1470-2045(12)70345-5. Epub 2012 Aug
28. PubMed PMID: 22951287.
3: Sobrero A. TAS-102 in refractory colorectal cancer: caution is
needed. Lancet Oncol. 2012 Oct;13(10):959-61. doi:
10.1016/S1470-2045(12)70376-5. Epub 2012 Aug 28. PubMed PMID: 22951286.
4: Doi T, Ohtsu A, Yoshino T, Boku N, Onozawa Y, Fukutomi A, Hironaka S,
Koizumi W, Sasaki T. Phase I study of TAS-102 treatment in Japanese
patients with advanced solid tumours. Br J Cancer. 2012 Jul
24;107(3):429-34. doi: 10.1038/bjc.2012.274. Epub 2012 Jun 26. PubMed
PMID: 22735906; PubMed Central PMCID: PMC3405214.
5: Suzuki N, Nakagawa F, Nukatsuka M, Fukushima M. Trifluorothymidine
exhibits potent antitumor activity via the induction of DNA
double-strand breaks. Exp Ther Med. 2011 May;2(3):393-397. Epub 2011 Mar
21. PubMed PMID: 22977515; PubMed Central PMCID: PMC3440718.
6: Shintani M, Urano M, Takakuwa Y, Kuroda M, Kamoshida S.
Immunohistochemical characterization of pyrimidine synthetic enzymes,
thymidine kinase-1 and thymidylate synthase, in various types of cancer.
Oncol Rep. 2010 May;23(5):1345-50. PubMed PMID: 20372850.
7: Temmink OH, Bijnsdorp IV, Prins HJ, Losekoot N, Adema AD, Smid K,
Honeywell RJ, Ylstra B, Eijk PP, Fukushima M, Peters GJ.
Trifluorothymidine resistance is associated with decreased thymidine
kinase and equilibrative nucleoside transporter expression or increased
secretory phospholipase A2. Mol Cancer Ther. 2010 Apr;9(4):1047-57. doi:
10.1158/1535-7163.MCT-09-0932. Epub 2010 Apr 6. PubMed PMID: 20371715.
8: Bijnsdorp IV, Kruyt FA, Fukushima M, Smid K, Gokoel S, Peters GJ.
Molecular mechanism underlying the synergistic interaction between
trifluorothymidine and the epidermal growth factor receptor inhibitor
erlotinib in human colorectal cancer cell lines. Cancer Sci. 2010
Feb;101(2):440-7. doi: 10.1111/j.1349-7006.2009.01375.x. Epub 2009 Sep
29. PubMed PMID: 19886911.
9: Bijnsdorp IV, Peters GJ, Temmink OH, Fukushima M, Kruyt FA.
Differential activation of cell death and autophagy results in an
increased cytotoxic potential for trifluorothymidine compared to
5-fluorouracil in colon cancer cells. Int J Cancer. 2010 May
15;126(10):2457-68. doi: 10.1002/ijc.24943. PubMed PMID: 19816940.
10: Bijnsdorp IV, Kruyt FA, Gokoel S, Fukushima M, Peters GJ.
Synergistic interaction between trifluorothymidine and docetaxel is
sequence dependent. Cancer Sci. 2008 Nov;99(11):2302-8. doi:
10.1111/j.1349-7006.2008.00963.x. Epub 2008 Oct 18. PubMed PMID:
18957056.
11: Overman MJ, Kopetz S, Varadhachary G, Fukushima M, Kuwata K, Mita A,
Wolff RA, Hoff P, Xiong H, Abbruzzese JL. Phase I clinical study of
three times a day oral administration of TAS-102 in patients with solid
tumors. Cancer Invest. 2008 Oct;26(8):794-9. doi:
10.1080/07357900802087242. PubMed PMID: 18798063.
12: Overman MJ, Varadhachary G, Kopetz S, Thomas MB, Fukushima M, Kuwata
K, Mita A, Wolff RA, Hoff PM, Xiong H, Abbruzzese JL. Phase 1 study of
TAS-102 administered once daily on a 5-day-per-week schedule in patients
with solid tumors. Invest New Drugs. 2008 Oct;26(5):445-54. doi:
10.1007/s10637-008-9142-3. Epub 2008 Jun 5. PubMed PMID: 18528634.
13: Temmink OH, Emura T, de Bruin M, Fukushima M, Peters GJ. Therapeutic
potential of the dual-targeted TAS-102 formulation in the treatment of
gastrointestinal malignancies. Cancer Sci. 2007 Jun;98(6):779-89. Epub
2007 Apr 18. Review. PubMed PMID: 17441963.
14: Temmink OH, Hoebe EK, van der Born K, Ackland SP, Fukushima M,
Peters GJ. Mechanism of trifluorothymidine potentiation of oxaliplatin-induced
cytotoxicity to colorectal cancer cells. Br J Cancer. 2007 Jan
29;96(2):231-40. PubMed PMID: 17242697; PubMed Central PMCID:
PMC2360012.
15: Temmink OH, Prins HJ, van Gelderop E, Peters GJ. The Hollow Fibre
Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in
colon cancer cells. Br J Cancer. 2007 Jan 15;96(1):61-6. Epub 2006 Dec
19. PubMed PMID: 17179993; PubMed Central PMCID: PMC2360204.
16: Temmink OH, Hoebe EK, Fukushima M, Peters GJ. Irinotecan-induced
cytotoxicity to colon cancer cells in vitro is stimulated by
pre-incubation with trifluorothymidine. Eur J Cancer. 2007
Jan;43(1):175-83. Epub 2006 Oct 16. PubMed PMID: 17049227.
17: Hong DS, Abbruzzese JL, Bogaard K, Lassere Y, Fukushima M, Mita A,
Kuwata K, Hoff PM. Phase I study to determine the safety and
pharmacokinetics of oral administration of TAS-102 in patients with
solid tumors. Cancer. 2006 Sep 15;107(6):1383-90. PubMed PMID: 16902987.
18: Cleverley J. American Society of Clinical Oncology--42nd annual
meeting. Poster presentations on leukemia and cytotoxic chemotherapy.
2-6 June 2006, Atlanta, GA, USA. IDrugs. 2006 Aug;9(8):520-2. PubMed
PMID: 16871453.
19: Temmink OH, Hoogeland MF, Fukushima M, Peters GJ. Low folate
conditions may enhance the interaction of trifluorothymidine with
antifolates in colon cancer cells. Cancer Chemother Pharmacol. 2006
Jan;57(2):171-9. Epub 2005 Jul 12. PubMed PMID: 16010590.
20: Temmink OH, de Bruin M, Comijn EM, Fukushima M, Peters GJ.
Determinants of trifluorothymidine sensitivity and metabolism in colon
and lung cancer cells. Anticancer Drugs. 2005 Mar;16(3):285-92. PubMed
PMID: 15711180.
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