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Pralatrexate

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Pralatrexate
Clinical data
Trade namesFolotyn
AHFS/Drugs.comMonograph
License data
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Identifiers
  • N-(4-{1-[(2,4-diaminopteridin-6-yl)methyl]but-3-yn-1-yl}benzoyl)-L-glutamic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.205.791 Edit this at Wikidata
Chemical and physical data
FormulaC23H23N7O5
Molar mass477.481 g·mol−1
3D model (JSmol)
  • O=C(O)[C@@H](NC(=O)c1ccc(cc1)C(CC#C)Cc2nc3c(nc2)nc(nc3N)N)CCC(=O)O
  • InChI=1S/C23H23N7O5/c1-2-3-14(10-15-11-26-20-18(27-15)19(24)29-23(25)30-20)12-4-6-13(7-5-12)21(33)28-16(22(34)35)8-9-17(31)32/h1,4-7,11,14,16H,3,8-10H2,(H,28,33)(H,31,32)(H,34,35)(H4,24,25,26,29,30)/t14?,16-/m0/s1 checkY
  • Key:OGSBUKJUDHAQEA-WMCAAGNKSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Pralatrexate, sold under the brand name Folotyn, is a medication used for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL).[3][4]

Pralatrexate was approved for medical use in the United States in September 2009, as the first treatment for Peripheral T-cell Lymphoma (PTCL), an often aggressive type of non-Hodgkins lymphoma.[4][5]

Medical uses

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Pralatrexate is indicated for the treatment of people with relapsed or refractory peripheral T-cell lymphoma (PTCL).[3]

Mechanism

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Pralatrexate is a dihydrofolate reductase inhibitor.[3]

Discovery

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Research on this class of drugs began in the 1950s at SRI International, where scientists were focused on developing new chemotherapies and antifolates that would be effective against tumor cells.[6]

In the late 1970s, researchers at Memorial Sloan Kettering Cancer Center discovered that cancerous cells take in natural folate through a protein identified as plasma membrane transporter (now referred to as "reduced folate carrier type 1" or "RFC-1"). Further research showed that when normal cells evolve into cancerous cells they often overproduce RFC-1 to ensure they get enough folate.[7]

A subsequent scientific collaboration was ultimately formed among SRI International, Memorial Sloan Kettering Cancer Center, and the Southern Research Institute with the intention of developing an antifolate with greater therapeutic selectivity – an agent that could be more effectively internalized into tumors (transported into the cells through RFC-1) and would be more toxic to cancer cells than normal cells.[7]

This collaboration, supported by the National Cancer Institute,[8] led to the identification of pralatrexate in the mid-1990s. Pralatrexate was later licensed to Allos Therapeutics in 2002 for further development.[9] Allos Therapeutics, Inc. was acquired by Spectrum Pharmaceuticals, Inc. on September 5, 2012. Allos is a wholly owned subsidiary of Spectrum.[10]

Society and culture

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Pralatrexate was approved for medical use in the United States in September 2009.[5][4]

Economics

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Some oncologists, patient groups, and insurance companies criticized the cost of $30,000 a month or more, which could reach a total of $126,000 during a course of treatment.[11]

References

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  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. ^ "Summary Basis of Decision (SBD) for Folotyn". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  3. ^ a b c "Folotyn- pralatrexate injection". DailyMed. 28 May 2020. Retrieved 21 October 2020.
  4. ^ a b c "FDA Approves First Drug for Treatment of Peripheral T-cell Lymphoma". U.S. Food and Drug Administration (FDA) (Press release). 25 September 2009. Archived from the original on 1 October 2009. Retrieved 21 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  5. ^ a b "Drug Approval Package: Folotyn (Pralatrexate) Injection NDA #022468". U.S. Food and Drug Administration (FDA). 23 November 2009. Retrieved 21 October 2020.
  6. ^ "Allos Therapeutics: News". Archived from the original on 2013-01-17. Retrieved 2010-09-20., Allos Therapeutics Press Release, "Allos Therapeutics' Pralatrexate Demonstrates Anticancer Activity in Multiple Cancer Cell Lines".
  7. ^ a b [1], Memorial Sloan Kettering Cancer Center Press Release, "FDA Approves Lymphoma Drug Developed at Memorial Sloan Kettering".
  8. ^ "The NExT Steps in Drug Development at NCI". NCI Cancer Bulletin. 20 October 2009. Archived from the original on 5 October 2014. Retrieved 21 October 2020.
  9. ^ "FDA Approves Pralatrexate for Treatment of Peripheral T-Cell Lymphoma" (Press release). SRI International. 2009-09-25. Archived from the original on 2013-07-03. Retrieved 2013-07-10.
  10. ^ Avery G (2012-09-07). "Purchase of Allos Therapeutics is completed". Denver Business Journal. Retrieved 2013-07-10.
  11. ^ Pollack A (December 4, 2009). "Questioning a Cancer Drug That Costs $30,000 a Month". New York Times. Retrieved 2009-12-05. The price of the new drug, called Folotyn, is at least triple that of other drugs that critics have said are too expensive for the benefits they offer to patients.
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