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« Folic Acid (Not just for pregnant women) | Main | POPOP (Gets a treat?) »

Methotrexate (Fakin' folate)

Category: Drugs
Posted on: March 7, 2007 9:00 AM, by Molecule of the Day

See also: yesterday's entry on folate.

Methotrexate is a mimic of folic acid. Shortly after we discovered what folate was, we started looking into what else we could do with it.

# InChI=1/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1

During the 1940's, George Hitchings and Gertrude Elion started work on a number of nucleic acid-related compounds that would prove astonishingly successful and later garner them a piece of a Nobel prize. One of these was methotrexate - the structure of folic acid is below for comparison.

# InChI=1/C19H19N7O6/c1-26(12-8-21-15-14(23-12)17(30)25-19(20)24-15)10-4-2-9(3-5-10)16(29)22-11(18(31)32)6-7-13(27)28/h2-5,8,11H,6-7H2,1H3,(H,22,29)(H,27,28)(H,31,32)(H3,20,21,24,25,30)/t11-/m0/s1

As mentioned yesterday, folate plays a key role in nucleic acid synthesis - something rapidly-dividing cells need by the boatload. Attacking this pathway throws a wrench in cell division (hopefully, most of this will be cancer cells).

Among their many other drug hits was acyclovir, which is still used today as an antiviral. Check here for more information on their Nobel.

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