Improved synthesis of ADAM10 inhibitor GI254023X.
BACKGROUND
The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation.


OBJECTIVE
The inhibition of these proteases is a promising target in the treatment of inflammation and cancer.


RESULTS
In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling.


CONCLUSIONS
This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations.
Hoettecke
Nicole
N
Clemens Schöpf Institute of Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.
Ludwig
Andreas
A
Foro
Sabine
S
Schmidt
Boris
B
D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072197:ADAM10 Protein; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D018836:Inflammation Mediators / Q000138:chemical synthesis* / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015203:Reproducibility of Results
C555398:3-(formylhydroxyamino)-2-(3-phenyl-1-propyl)butanoic acid (2,2-dimethyl-1-methylcarbamoyl-1-propyl)amide; D000577:Amides; D000970:Antineoplastic Agents; D004151:Dipeptides; D006877:Hydroxamic Acids; D018836:Inflammation Mediators; D008565:Membrane Proteins; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human