Canfosfamide HCl

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

MedKoo CAT#: 200610

CAS#: 439943-59-6 (HCl)

Description: Canfosfamide, also known as TLK286, is a modified glutathione analogue with potential antineoplastic activity. Canfosfamide is selectively activated by glutathione S-transferase P1-1 into an alkylating metabolite that forms covalent linkages with nucleophilic centers in tumor cell DNA, which may induce a cellular stress response and cytotoxicity, and decrease tumor proliferation. S-transferase P1-1 is an enzyme that is overexpressed in many human malignancies.


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Canfosfamide HCl is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 200610
Name: Canfosfamide HCl
CAS#: 439943-59-6 (HCl)
Chemical Formula: C26H41Cl5N5O10PS
Exact Mass:
Molecular Weight: 823.93
Elemental Analysis: C, 37.90; H, 5.02; Cl, 21.51; N, 8.50; O, 19.42; P, 3.76; S, 3.89


Synonym: TLK286; TLK-286; TLK 286; TER286; TER-286; TER286; Canfosfamide HCl; US brand name: TELCYTA.

IUPAC/Chemical Name: N5-(((2-((bis(bis(2-chloroethyl)amino)phosphoryl)oxy)ethyl)sulfonyl)-D-alanyl)-N5-((R)-carboxy(phenyl)methyl)-L-glutamine hydrochloride

InChi Key: SIDNMYODVYPVSQ-XVGZVFJZSA-N

InChi Code: InChI=1S/C26H40Cl4N5O10PS.ClH/c27-8-12-33(13-9-28)46(42,34(14-10-29)15-11-30)45-16-17-47(43,44)18-21(32)24(37)35(22(36)7-6-20(31)25(38)39)23(26(40)41)19-4-2-1-3-5-19;/h1-5,20-21,23H,6-18,31-32H2,(H,38,39)(H,40,41);1H/t20-,21-,23+;/m0./s1

SMILES Code: O=C(O)[C@@H](N)CCC(N([C@@H](C(O)=O)C1=CC=CC=C1)C([C@@H](N)CS(=O)(CCOP(N(CCCl)CCCl)(N(CCCl)CCCl)=O)=O)=O)=O.[H]Cl


Technical Data

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, not in water

Shelf Life:
>5 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).

Harmonized System Code:
293490


Additional Information

Related:
439943-59-6 (Canfosfamide HCl)
158382-37-7 (Canfosfamide free base).
The activation of canfosfamide occurs when GST P1-1 splits canfosfamide into two active fragments: a glutathione analog fragment and an active cytotoxic fragment. The cytotoxic fragment reacts with important cell components, including RNA, DNA and proteins, leading to cell death. The glutathione analog fragment of canfosfamide may remain bound to GST P1-1, which may limit the ability of GST P1-1 to inactivate other cancer drugs.
 
 


References

 1: Kavanagh JJ, Levenback CF, Ramirez PT, Wolf JL, Moore CL, Jones MR, Meng L, Brown GL, Bast RC Jr. Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer. J Hematol Oncol. 2010 Mar 11;3:9. PubMed PMID: 20222977; PubMed Central PMCID: PMC2851575.

2: Sequist LV, Fidias PM, Temel JS, Kolevska T, Rabin MS, Boccia RV, Burris HA, Belt RJ, Huberman MS, Melnyk O, Mills GM, Englund CW, Caldwell DC, Keck JG, Meng L, Jones M, Brown GL, Edelman MJ, Lynch TJ. Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer. J Thorac Oncol. 2009 Nov;4(11):1389-96. PubMed PMID: 19701107.

3: Vergote I, Finkler N, del Campo J, Lohr A, Hunter J, Matei D, Kavanagh J, Vermorken JB, Meng L, Jones M, Brown G, Kaye S; ASSIST-1 Study Group. Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer. Eur J Cancer. 2009 Sep;45(13):2324-32. Epub 2009 Jun 8. PubMed PMID: 19515553.

4: Edelman MJ. Novel cytotoxic agents for non-small cell lung cancer. J Thorac Oncol. 2006 Sep;1(7):752-5. Review. PubMed PMID: 17409954.

5: Raez LE, Lilenbaum R. New developments in chemotherapy for advanced non-small cell lung cancer. Curr Opin Oncol. 2006 Mar;18(2):156-61. Review. PubMed PMID: 16462185.

6: Townsend DM, Findlay VL, Tew KD. Glutathione S-transferases as regulators of kinase pathways and anticancer drug targets. Methods Enzymol. 2005;401:287-307. Review. PubMed PMID: 16399394.

7: Tew KD. TLK-286: a novel glutathione S-transferase-activated prodrug. Expert Opin Investig Drugs. 2005 Aug;14(8):1047-54. Review. PubMed PMID: 16050796.

8: Kavanagh JJ, Gershenson DM, Choi H, Lewis L, Patel K, Brown GL, Garcia A, Spriggs DR. Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer. Int J Gynecol Cancer. 2005 Jul-Aug;15(4):593-600. PubMed PMID: 16014111.

9: Verschraegen CF, Smith HO, Lee FC, Cathcart C, Norenberg JP. TLK-286. IDrugs. 2004 Aug;7(8):771-81. Review. PubMed PMID: 15334311.

10: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jun;26(5):357-91. PubMed PMID: 15319815.

11: TLK 286. Drugs R D. 2004;5(2):116-8. Review. PubMed PMID: 15293875.

12: Current data and ongoing trials in patients with recurrent non-small-cell lung cancer. Clin Lung Cancer. 2004 May;5(6):337-9. Review. PubMed PMID: 15217532.

13: Rosen LS, Laxa B, Boulos L, Wiggins L, Keck JG, Jameson AJ, Parra R, Patel K, Brown GL. Phase 1 study of TLK286 (Telcyta) administered weekly in advanced malignancies. Clin Cancer Res. 2004 Jun 1;10(11):3689-98. PubMed PMID: 15173075.

14: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Nov;25(9):747-71. PubMed PMID: 14685303.

15: Chen ZJ, Gaté L, Davis W, Ile KE, Tew KD. Sensitivity and fidelity of DNA microarray improved with integration of Amplified Differential Gene Expression (ADGE). BMC Genomics. 2003 Jul 14;4(1):28. PubMed PMID: 12859795; PubMed Central PMCID: PMC179896.

16: Rosen LS, Brown J, Laxa B, Boulos L, Reiswig L, Henner WD, Lum RT, Schow SR, Maack CA, Keck JG, Mascavage JC, Dombroski JA, Gomez RF, Brown GL. Phase I study of TLK286 (glutathione S-transferase P1-1 activated glutathione analogue) in advanced refractory solid malignancies. Clin Cancer Res. 2003 May;9(5):1628-38. PubMed PMID: 12738715.

17: Townsend DM, Shen H, Staros AL, Gaté L, Tew KD. Efficacy of a glutathione S-transferase pi-activated prodrug in platinum-resistant ovarian cancer cells. Mol Cancer Ther. 2002 Oct;1(12):1089-95. PubMed PMID: 12481432.

18: Rosario LA, O'Brien ML, Henderson CJ, Wolf CR, Tew KD. Cellular response to a glutathione S-transferase P1-1 activated prodrug. Mol Pharmacol. 2000 Jul;58(1):167-74. PubMed PMID: 10860939.

19: Kauvar LM, Morgan AS, Sanderson PE, Henner WD. Glutathione based approaches to improving cancer treatment. Chem Biol Interact. 1998 Apr 24;111-112:225-38. Review. PubMed PMID: 9679557.

20: Morgan AS, Sanderson PE, Borch RF, Tew KD, Niitsu Y, Takayama T, Von Hoff DD, Izbicka E, Mangold G, Paul C, Broberg U, Mannervik B, Henner WD, Kauvar LM. Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin activated by glutathione S-transferase. Cancer Res. 1998 Jun 15;58(12):2568-75. PubMed PMID: 9635580.

21: Tew KD, Dutta S, Schultz M. Inhibitors of glutathione S-transferases as therapeutic agents. Adv Drug Deliv Rev. 1997 Jul 7;26(2-3):91-104. PubMed PMID: 10837536.

22: Izbicka E, Lawrence R, Cerna C, Von Hoff DD, Sanderson PE. Activity of TER286 against human tumor colony-forming units. Anticancer Drugs. 1997 Apr;8(4):345-8. PubMed PMID: 9180387.