15 July 2024
The enzyme GTP cyclohydrolase I (GCH1) catalyzes the first and rate limiting step in the biosynthesis of tetrahydrobiopterin (BH4) from GTP. BH4 is a critical cofactor in the degradation of the amino acid phenylalanine, the production of the signaling molecule nitric oxide (NO), as well as the synthesis of the neurotransmitters serotonine, dopamine, and norepinephrine, among others. GCH1’s activity is regulated by intracellular levels of both phenylalanine and BH4, via distinct feedback loop mechanisms. Increased phenylalanine levels stimulate GCH1 activity whereas BH4 has an opposing effect.
AXPSP0056 is a selective allosteric GCH1 inhibitor that acts as a mimic of tetrahydrobiopterin (BH4) by occupying the latter’s binding site on GCH1. To facilitate further research into the biological role GCH1, AXSP0056 as well as its negative control
D X 373 are now available from opnMe.com. You can order both molecules free of charge and by doing so, you retain full ownership and control of your results, which we encourage you to publish.
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About AXSP0056:
AXSP0056 utilizes its aminopyrimidinone moiety to bind to key residues in the BH4 allosteric pocket at the interface of two GCH1 subunits. This inhibits GCH1 activity by triggering the BH4-mediated feedback inhibition mechanism. The negative control D X 373 is structurally similar to AXSP0056 but features a di-methylation on the exocyclic nitrogen atom which prohibits binding to the GCH1 allosteric site.
About opnMe:
opnMe.com, the open innovation portal of Boehringer Ingelheim, fosters science and collaboration initiatives in areas of high unmet medical need. With “Molecules to Order”, we share well-characterized tool compounds free of charge with no IP strings attached. These are complemented by “Molecules for Collaboration” where we offer access to unprecedented molecules, with the chance to get your research proposal funded. With our “opn2EXPERTS” and “techMATCH” programs, we enlist scientific advice on key scientific issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs. Our newly launched “opn2TALENTS” postdoc grants awards opportunities for high-level talents to pitch their scientific ideas and approaches for a well-defined research question, to conduct their research at one of our discovery research sites in Germany, Austria, or the US.