A small molecule HIF-1α stabilizer that accelerates diabetic wound healing #smallmolecule @naturecomms

There are precious few small molecule (aka drug) solutions for wound healing. Perhaps this is one of an emerging trend.

Impaired wound healing and ulcer complications are a leading cause of death in diabetic
patients. In this study, we report the design and synthesis of a cyclometalated iridium(III)
metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical
and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and
inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in
cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In
in vivo mouse models, the compound significantly accelerates wound closure in both normal
and diabetic mice, with a greater effect being observed in the diabetic group. We also
demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1,
SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including,
db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of
HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates
the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction

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