Talotrexin ammonium

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

MedKoo CAT#: 202770

CAS#: 648420-92-2

Description: Talotrexin ammonium, also known as PT-523, is t he ammonium salt of an antimetabolite analogue of aminopterin with potential antineoplastic activity. As a folate antagonist, talotrexin binds to and inhibits the function of dihydrofolate reductase, resulting in the inhibition of folate metabolism, DNA synthesis, and cell division. Hydrosoluble, talotrexin is actively transported into cells by the reduced folate carrier (RFC) and, therefore, is unlikely to be associated with P-glycoprotein-mediated multidrug resistance.


Chemical Structure

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Talotrexin ammonium
CAS# 648420-92-2

Theoretical Analysis

MedKoo Cat#: 202770
Name: Talotrexin ammonium
CAS#: 648420-92-2
Chemical Formula: C28H34N10O6
Exact Mass:
Molecular Weight: 606.644
Elemental Analysis: C, 55.44; H, 5.65; N, 23.09; O, 15.82

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Pricing updated 2021-02-26. Prices are subject to change without notice.

Talotrexin ammonium is not in stock, but 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.

Related CAS #: 648420-92-2 (ammonium)   113857-87-7 (free)  

Synonym: PT523, PT-523, PT-523, NSC 712783, Talotrexin ammonium, Talvesta

IUPAC/Chemical Name: .2-((4-carboxy-4-(4-(((5,7-diaminopyrido[3,4-b]pyrazin-3-yl)methyl)amino)benzamido)butyl)carbamoyl)benzoic acid, ammonia salt

InChi Key: DFLPSPFJDJNVAM-UHFFFAOYSA-N

InChi Code: InChI=1S/C28H28N8O6.2H3N/c29-22-12-21-23(24(30)36-22)34-17(14-33-21)13-32-16-9-7-15(8-10-16)25(37)35-20(28(41)42)6-3-11-31-26(38)18-4-1-2-5-19(18)27(39)40;;/h1-2,4-5,7-10,12,14,20,32H,3,6,11,13H2,(H,31,38)(H,35,37)(H,39,40)(H,41,42)(H4,29,30,36);2*1H3

SMILES Code: O=C([O-])C1=CC=CC=C1C(NCCCC(C([O-])=O)NC(C2=CC=C(NCC3=NC4=C(N)N=C(N)C=C4N=C3)C=C2)=O)=O.[NH4+].[NH4+]

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).

HS Tariff Code:
2934.99.9001

Handling Instructions:

Preparing Stock Solutions

The following data is based on the product molecular weight 606.644 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Norris RE, Adamson PC. Clinical potency of methotrexate, aminopterin, talotrexin and pemetrexed in childhood leukemias. Cancer Chemother Pharmacol. 2010 May;65(6):1125-30. doi: 10.1007/s00280-009-1120-8. Epub 2009 Sep 27. PubMed PMID: 19784838.

2: Kumar M, Vijayakrishnan R, Subba Rao G. In silico structure-based design of a novel class of potent and selective small peptide inhibitor of Mycobacterium tuberculosis Dihydrofolate reductase, a potential target for anti-TB drug discovery. Mol Divers. 2010 Aug;14(3):595-604. doi: 10.1007/s11030-009-9172-6. Epub 2009 Aug 21. PubMed PMID: 19697148.

3: Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, Goldman ID. The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol Pharmacol. 2008 Sep;74(3):854-62. doi: 10.1124/mol.108.045443. Epub 2008 Jun 4. PubMed PMID: 18524888; PubMed Central PMCID: PMC2716086.

4: Veryard C. AACR-NCI-EORTC--17th symposium: Molecular targets and cancer therapeutics. 14-18th November 2005, Philadelphia, PA, USA. IDrugs. 2006 Jan;9(1):1-3. PubMed PMID: 16374720.

5: Kaufman Y, Ifergan I, Rothem L, Jansen G, Assaraf YG. Coexistence of multiple mechanisms of PT523 resistance in human leukemia cells harboring 3 reduced folate carrier alleles: transcriptional silencing, inactivating mutations, and allele loss. Blood. 2006 Apr 15;107(8):3288-94. Epub 2005 Dec 20. PubMed PMID: 16368880.

6: Zhao R, Hanscom M, Chattopadhyay S, Goldman ID. Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway. Cancer Res. 2004 May 1;64(9):3313-9. PubMed PMID: 15126375.

7: Kamal MA, Christopherson RI. Accumulation of 5-phosphoribosyl-1-pyrophosphate in human CCRF-CEM leukaemia cells treated with antifolates. Int J Biochem Cell Biol. 2004 Mar;36(3):545-51. Erratum in: Int J Biochem Cell Biol. 2004 May;36(5):957. PubMed PMID: 14687931.

8: Pineda P, Kanter A, McIvor RS, Benkovic SJ, Rosowsky A, Wagner CR. Dihydrofolate reductase mutant with exceptional resistance to methotrexate but not to trimetrexate. J Med Chem. 2003 Jul 3;46(14):2816-8. PubMed PMID: 12825924.

9: Wright JE, Yurasek GK, Chen YN, Rosowsky A. Further studies on the interaction of nonpolyglutamatable aminopterin analogs with dihydrofolate reductase and the reduced folate carrier as determinants of in vitro antitumor activity. Biochem Pharmacol. 2003 May 1;65(9):1427-33. PubMed PMID: 12732354.

10: Gáspár G, De Clercq E, Neyts J. Gammaherpesviruses encode functional dihydrofolate reductase activity. Biochem Biophys Res Commun. 2002 Oct 4;297(4):756-9. PubMed PMID: 12359216.

11: Vaidya CM, Wright JE, Rosowsky A. Synthesis and in vitro antitumor activity of new deaza analogues of the nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523). J Med Chem. 2002 Apr 11;45(8):1690-6. PubMed PMID: 11931624.

12: Mauritz R, Peters GJ, Priest DG, Assaraf YG, Drori S, Kathmann I, Noordhuis P, Bunni MA, Rosowsky A, Schornagel JH, Pinedo HM, Jansen G. Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis. Biochem Pharmacol. 2002 Jan 15;63(2):105-15. PubMed PMID: 11841783.

13: Wright JE, Rosowsky A. Synthesis and enzymatic activation of N-[N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithiny]-L-phenyl alanine, a candidate for antibody-directed enzyme prodrug therapy (ADEPT). Bioorg Med Chem. 2002 Mar;10(3):493-500. PubMed PMID: 11814834.

14: Zhao R, Gao F, Goldman ID. Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells. Biochem Pharmacol. 2001 Apr 1;61(7):857-65. PubMed PMID: 11274972.

15: Wright JE, Vaidya CM, Chen Y, Rosowsky A. Efficient utilization of the reduced folate carrier in CCRF-CEM human leukemic lymphoblasts by the potent antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L- ornithine (PT523) and its B-ring analogues. Biochem Pharmacol. 2000 Jul 1;60(1):41-6. PubMed PMID: 10807943.

16: Rosowsky A, Wright JE, Vaidya CM, Forsch RA, Bader H. Analogues of the potent nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, p-aminobenzoyl moiety, or 9,10-bridge: synthesis and in vitro antitumor activity. J Med Chem. 2000 Apr 20;43(8):1620-34. PubMed PMID: 10780919.

17: Rosowsky A, Wright JE, Vaidya CM, Forsch RA. The effect of side-chain, para-aminobenzoyl region, and B-ring modifications on dihydrofolate reductase binding, influx via the reduced folate carrier, and cytotoxicity of the potent nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L- ornithine. Pharmacol Ther. 2000 Mar;85(3):191-205. PubMed PMID: 10739874.

18: Rosowsky A. PT523 and other aminopterin analogs with a hemiphthaloyl-L-ornithine side chain: exceptionally tight-binding inhibitors of dihydrofolate reductase which are transported by the reduced folate carrier but cannot form polyglutamates. Curr Med Chem. 1999 Apr;6(4):329-52. Review. PubMed PMID: 10101216.

19: Rosowsky A, Wright JE, Vaidya CM, Bader H, Forsch RA, Mota CE, Pardo J, Chen CS, Chen YN. Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl- L-ornithine (PT523). J Med Chem. 1998 Dec 17;41(26):5310-9. PubMed PMID: 9857098.

20: Wright JE, Pardo M, Tretyakov A, Alperin WL, Trites D, Rosowsky A. Pharmacokinetics, antifolate activity and tissue distribution of PT523 in SCC VII tumor-bearing mice. Cancer Chemother Pharmacol. 1998;42(4):300-6. Erratum in: Cancer Chemother Pharmacol 1999;43(6):522. PubMed PMID: 9744775.