Phototrexate Explained

Drug Name:	trans-Phototrexate
Iupac Name:	(2S)-2-[(4-[(2,4-Diaminoquinazolin-6-yl)diazenyl]benzoyl)amino]pentanedioic acid
Cas Number:	2268033-83-4
Atc Prefix:	None
Pubchem:	139030983
C:	20
H:	19
N:	7
O:	5
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 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.

See also

• Cancer
• Psoriasis
• Psoriatic arthritis

External links

• The Barcelona Institute of Science and Technology

Notes and References

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