Kinase Chemistry – Just a year and a half behind the times.


Posted by kinasepro on April 19, 2007

My guess is XL-518 is in WO/2007/044515.


362 examples, 15 inventors.

IND beating first app is unusual. kudos.

Wild speculation mode on: The Azetidine 3-hydroxyl residue directly coordinates the Mg atom.

This class of molecules is the closest thing that can be considered allosteric inhibitors of kinases. (No, I don’t care about your 18 uM compounds) They have been called ATP non-competitive, but perhaps more accurately I consider them ATP-collaborative inhibitors, given that they appear to hydrogen bond to ATP within the active site. As such I have a hard time considering them truly allosteric. 1S9I, and 1S9J give an idea how they work.


al·lo·ster·ism (l-strzm) or al·los·ter·y (-lst-r)

n. A change in the activity and conformation of an enzyme resulting from the binding of a compound at a site on the enzyme other than the active binding site.

4 Responses to “XL-518”

  1. Jose said

    A chiral azetidine amide *and* an iodide? That is one strange little beast…

  2. KinasePro said

    The way its drawn is a little misleading.. the azetidine isn’t actually chiral 😛

  3. Kinaser said

    May be trivial, but the PDB ID is 1S9J and not 2S9J!

  4. kinasepro said

    ty. Looks like I had the links right, I’ll fix the img.

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