Phototrexate

Phototrexate is a photochromic antifolate drug developed at the Institute for Bioengineering of Catalonia (IBEC, The Barcelona Institute of Science and Technology). In particular, it is a photopharmacological agent[1][2] that behaves as light-regulated inhibitor of the dihydrofolate reductase (DHFR) enzyme.[3][4] Phototrexate is a photoisomerizable structural analogue of the chemotherapy agent methotrexate. It is also an example of "azologization".[5] Pharmacological effects of phototrexate can be switched on and off by UVA and visible light, respectively. Phototrexate is almost inactive in its trans configuration while it behaves as a potent antifolate in its cis configuration. It can also spontaneously self-deactivate in the dark.

cis-Phototrexate
trans-Phototrexate
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • (2S)-2-[(4-[(2,4-Diaminoquinazolin-6-yl)diazenyl]benzoyl)amino]pentanedioic acid
CAS Number
PubChem CID
Chemical and physical data
FormulaC20H19N7O5
Molar mass437.416 g·mol−1
3D model (JSmol)
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
InChI
  • InChI=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
  • Key:IODLJULYGHWOLC-HNNXBMFYSA-N

See also

References
  1. Velema WA, Szymanski W, Feringa BL (February 2014). "Photopharmacology: beyond proof of principle". Journal of the American Chemical Society. 136 (6): 2178–91. doi:10.1021/ja413063e. hdl:11370/d6714f52-c2c8-4e48-b345-238e98bcc776. PMID 24456115.
  2. Broichhagen J, Frank JA, Trauner D (July 2015). "A roadmap to success in photopharmacology". Accounts of Chemical Research. 48 (7): 1947–60. doi:10.1021/acs.accounts.5b00129. PMID 26103428.
  3. Matera C, Gomila AM, Camarero N, Libergoli M, Soler C, Gorostiza P (November 2018). "Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy". Journal of the American Chemical Society. 140 (46): 15764–15773. doi:10.1021/jacs.8b08249. hdl:2445/126377. PMID 30346152.
  4. Mashita T, Kowada T, Takahashi H, Matsui T, Mizukami S (June 2019). "Light-Wavelength-Based Quantitative Control of Dihydrofolate Reductase Activity by Using a Photochromic Isostere of an Inhibitor". ChemBioChem. 20 (11): 1382–1386. doi:10.1002/cbic.201800816. PMID 30656808. S2CID 58567138.
  5. Schoenberger M, Damijonaitis A, Zhang Z, Nagel D, Trauner D (July 2014). "Development of a new photochromic ion channel blocker via azologization of fomocaine". ACS Chemical Neuroscience. 5 (7): 514–8. doi:10.1021/cn500070w. PMC 4102962. PMID 24856540.
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