# NIH grant: IND-enabling studies of a USP30 inhibitor for acute kidney injury (1R44DK143820-01A1) — retained record

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source: [us-gov-api](https://highsignal.app/data/us-gov-api) (us-gov-api:nih-reporter)  published 2026-08-28 00:00 ingested 2026-08-31 02:41

[original source ↗](https://reporter.nih.gov/project-details/1R44DK143820-01A1)

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NIH grant 1R44DK143820-01A1: IND-enabling studies of a USP30 inhibitor for acute kidney injury
Institute: {'code': 'DK', 'abbreviation': 'NIDDK', 'name': 'National Institute of Diabetes and Digestive and Kidney Diseases', 'admin_org_id': '12500020', 'admin_funding_url': ''}. PI: Bahareh  Behrouz. Award: $1297479.
Start: 2026-08-28T00:00:00.
ABSTRACT
Existing treatments for acute kidney injury (AKI) are limited to supportive care, and there are no current
therapies that can modify the disease course or prevent progression to chronic kidney disease (CKD) and
ultimately end-stage renal disease (ESRD). While AKI has multiple causes, cardiac surgery-associated AKI
(CSA-AKI) is a major etiology. Evidence indicates that damaged mitochondria accumulate in AKI, contributing
significantly to the pathogenesis of the condition. and that impaired mitophagy – the cellular process for
clearance of damaged mitochondria – drives the accumulation. Mitophagy is enhanced by the PINK1/Parkin
pathway and decreased by the deubiquitinase (DUB) USP30. Inhibition or knockdown of USP30 can enhance
mitophagy in various cell types and confers protection against kidney injury in multiple AKI models, including
ischemia-reperfusion injury (IRI), cisplatin-induced nephrotoxicity, and rhabdomyolysis. We have synthesized
900+ small molecule USP30 inhibitors (USP30i) and characterized a subset for potency, pharmacokinetics,
ADME, and efficacy. This work has led to selection of multiple viable molecules with optimal properties for
progression through IND-enabling studies and toward clinical development. Our preliminary data demonstrate
Vincere’s molecules are able to improve renal function in vivo in 3 models of AKI (Rhabdomyolysis, Ischemic
Reperfusion Injury, and Cisplatin-induced Injury). These molecules have high potency against USP30 in vitro
and the ability to enhance mitophagy in renal cells without cytotoxicity. The data also demonstrate high
selectivity over other DUBs and a panel of unrelated targets, overcoming challenges of prior programs.
Vincere’s USP30i molecules exhibit excellent in vitro ADME properties and favorable pharmacokinetic profiles
in rodents. In this Direct Phase II application, we will conduct studies necessary to advance a selected
development candidate (DC) USP30i toward submission of an Investigational New Drug (IND) application. This
project has 3 Aims: Aim 1 involves genotoxicity assessment for the selected DC and acute/short-term
toxicology in two species. Next, Aim 2 involves 28-day GLP toxicology in two species. In Aim 3 cardiovascular,
respiratory, and central nervous system safety will be assessed. Assuming favorable results from this work, we
will submit an IND application and thereafter initiate a first-in-human study. In parallel with the project, we will
continue to nurture relationships with larger pharmaceutical companies and financing partners to facilitate
clinical development and commercialization.
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