Phototrexate: Difference between revisions

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{{short description|Photopharmacological agent}}
{{Short description|A light-activated prodrug of methotrexate}}
{{Infobox drug
| drug_name        = ''trans''-Phototrexate
| IUPAC_name        = (2''S'')-2-[(4-[(2,4-Diaminoquinazolin-6-yl)diazenyl]benzoyl)amino]pentanedioic acid
| image            = Phototrexate skeletal.svg
| alt              =
| caption          =
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<!-- Identifiers -->
| CAS_number        =
| class            =
| ATCvet            =
| ATC_prefix        = None
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<!-- Chemical and physical data -->
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| C=20 | H=19 | N=7 | O=5
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| smiles = C1(=NC(=NC2=C1C=C(C=C2)N=NC3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N)N
| StdInChI=1S/C20H19N7O5/c21-17-13-9-12(5-6-14(13)24-20(22)25-17)27-26-11-3-1-10(2-4-11)18(30)23-15(19(31)32)7-8-16(28)29/h1-6,9,15H,7-8H2,(H,23,30)(H,28,29)(H,31,32)(H4,21,22,24,25)/t15-/m0/s1
| StdInChIKey = IODLJULYGHWOLC-HNNXBMFYSA-N
}}


'''Phototrexate''' is a [[Photopharmacology|photopharmacological agent]]<ref name="VelemaSzymanski2014">{{cite journal|last1=Velema|first1=Willem A.|last2=Szymanski|first2=Wiktor|last3=Feringa|first3=Ben L.|title=Photopharmacology: Beyond Proof of Principle|journal=Journal of the American Chemical Society|volume=136|issue=6|year=2014|pages=2178–2191|issn=0002-7863|doi=10.1021/ja413063e}}</ref><ref name="BroichhagenFrank2015">{{cite journal|last1=Broichhagen|first1=Johannes|last2=Frank|first2=James Allen|last3=Trauner|first3=Dirk|title=A Roadmap to Success in Photopharmacology|journal=Accounts of Chemical Research|volume=48|issue=7|year=2015|pages=1947–1960|issn=0001-4842|doi=10.1021/acs.accounts.5b00129}}</ref> that behaves as light-regulated inhibitor of the [[dihydrofolate reductase]] (DHFR).<ref name="MateraGomila2018">{{cite journal|last1=Matera|first1=Carlo|last2=Gomila|first2=Alexandre M. J.|last3=Camarero|first3=Núria|last4=Libergoli|first4=Michela|last5=Soler|first5=Concepció|last6=Gorostiza|first6=Pau|title=Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy|journal=Journal of the American Chemical Society|volume=140|issue=46|year=2018|pages=15764–15773|issn=0002-7863|doi=10.1021/jacs.8b08249}}</ref><ref name="MashitaKowada2019">{{cite journal|last1=Mashita|first1=Takato|last2=Kowada|first2=Toshiyuki|last3=Takahashi|first3=Hiroto|last4=Matsui|first4=Toshitaka|last5=Mizukami|first5=Shin|title=Light‐Wavelength‐Based Quantitative Control of Dihydrofolate Reductase Activity by Using a Photochromic Isostere of an Inhibitor|journal=ChemBioChem|year=2019|issn=1439-4227|doi=10.1002/cbic.201800816}}</ref> It is a [[Photoisomerization|photoisomerizable]] structural analogue of the [[chemotherapy]] agent [[methotrexate]]. Pharmacological effects of phototrexate can be switched on and off by [[Ultraviolet|UVA]] and visible [[light]], respectively. Phototrexate is almost inactive in its [[Cis–trans isomerism|''trans'']] configuration while it behaves as a potent [[antifolate]] in its ''cis'' configuration. It can also spontaneously self-deactivate in the dark.
'''Phototrexate''' is a [[prodrug]] of [[methotrexate]], designed to be activated by light. It is part of a class of drugs known as [[photopharmacology]], which involves the use of light to control the activity of pharmaceutical agents. This approach allows for spatial and temporal control of drug activation, potentially reducing side effects and increasing therapeutic efficacy.


[[File:Cis-Phototrexate skeletal.svg|thumb|left|''cis''-Phototrexate]]
==Mechanism of Action==
{{clear left}}
Phototrexate is an inactive form of methotrexate that becomes active upon exposure to specific wavelengths of light. Methotrexate itself is a well-known [[antimetabolite]] and [[antifolate]] drug that inhibits the enzyme [[dihydrofolate reductase]] (DHFR), leading to a decrease in [[tetrahydrofolate]] and subsequent inhibition of [[DNA synthesis]], [[RNA synthesis]], and [[protein synthesis]]. By using light to activate phototrexate, it is possible to target the drug's effects to specific tissues or cells, minimizing systemic exposure and reducing potential side effects.


==See also==
==Applications==
* [[Cancer]]
Phototrexate is primarily being investigated for its potential use in treating [[cancer]] and [[autoimmune diseases]]. In cancer therapy, the ability to activate the drug in a localized area could allow for higher concentrations of the active drug in the tumor while sparing healthy tissues. In autoimmune diseases, such as [[rheumatoid arthritis]], targeted activation could reduce the immunosuppressive effects on the entire body.
* [[Psoriasis]]
* [[Psoriatic arthritis]]


== References ==
==Advantages of Photopharmacology==
{{reflist}}
The use of light to control drug activity offers several advantages:
* '''Spatial Control''': Drugs can be activated in specific locations, reducing off-target effects.
* '''Temporal Control''': Activation can be timed precisely, allowing for synchronization with biological rhythms or other treatments.
* '''Reversibility''': Some photopharmacological agents can be deactivated by light, providing an additional layer of control.


[[Category:Dihydrofolate reductase inhibitors]]
==Challenges and Considerations==
[[Category:Chemotherapy]]
While photopharmacology offers promising advantages, there are challenges to its implementation:
* '''Light Penetration''': The effectiveness of light activation depends on the ability of light to penetrate tissues, which can be limited in deeper tissues.
* '''Safety''': The safety of repeated light exposure and the potential for unintended activation must be considered.
* '''Delivery Systems''': Effective delivery systems are needed to ensure that the prodrug reaches the target tissue before activation.


{{antineoplastic-drug-stub}}
==Future Directions==
{{dictionary-stub1}}
Research is ongoing to improve the efficacy and safety of phototrexate and other photopharmacological agents. Advances in light delivery systems, such as [[optical fibers]] and [[biocompatible]] light sources, are being explored to enhance the clinical applicability of these therapies.
 
==Related Pages==
* [[Methotrexate]]
* [[Photopharmacology]]
* [[Antimetabolite]]
* [[Dihydrofolate reductase]]
* [[Cancer therapy]]
* [[Autoimmune disease]]
 
[[Category:Prodrugs]]
[[Category:Photopharmacology]]
[[Category:Antimetabolites]]

Latest revision as of 19:12, 22 March 2025

A light-activated prodrug of methotrexate


Phototrexate is a prodrug of methotrexate, designed to be activated by light. It is part of a class of drugs known as photopharmacology, which involves the use of light to control the activity of pharmaceutical agents. This approach allows for spatial and temporal control of drug activation, potentially reducing side effects and increasing therapeutic efficacy.

Mechanism of Action[edit]

Phototrexate is an inactive form of methotrexate that becomes active upon exposure to specific wavelengths of light. Methotrexate itself is a well-known antimetabolite and antifolate drug that inhibits the enzyme dihydrofolate reductase (DHFR), leading to a decrease in tetrahydrofolate and subsequent inhibition of DNA synthesis, RNA synthesis, and protein synthesis. By using light to activate phototrexate, it is possible to target the drug's effects to specific tissues or cells, minimizing systemic exposure and reducing potential side effects.

Applications[edit]

Phototrexate is primarily being investigated for its potential use in treating cancer and autoimmune diseases. In cancer therapy, the ability to activate the drug in a localized area could allow for higher concentrations of the active drug in the tumor while sparing healthy tissues. In autoimmune diseases, such as rheumatoid arthritis, targeted activation could reduce the immunosuppressive effects on the entire body.

Advantages of Photopharmacology[edit]

The use of light to control drug activity offers several advantages:

  • Spatial Control: Drugs can be activated in specific locations, reducing off-target effects.
  • Temporal Control: Activation can be timed precisely, allowing for synchronization with biological rhythms or other treatments.
  • Reversibility: Some photopharmacological agents can be deactivated by light, providing an additional layer of control.

Challenges and Considerations[edit]

While photopharmacology offers promising advantages, there are challenges to its implementation:

  • Light Penetration: The effectiveness of light activation depends on the ability of light to penetrate tissues, which can be limited in deeper tissues.
  • Safety: The safety of repeated light exposure and the potential for unintended activation must be considered.
  • Delivery Systems: Effective delivery systems are needed to ensure that the prodrug reaches the target tissue before activation.

Future Directions[edit]

Research is ongoing to improve the efficacy and safety of phototrexate and other photopharmacological agents. Advances in light delivery systems, such as optical fibers and biocompatible light sources, are being explored to enhance the clinical applicability of these therapies.

Related Pages[edit]

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