Evidence map›Paper›PMID 39747090›Full record

ArticleNature communications2025

Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Brandon Zimmerman, Leslie A Dakin, Anne Fortier, Evanthia Nanou, Angelo Blasio, James Mann, Howard Miller, Marissa Fletcher, Tiansheng Wang, Suganthini Nanthakumar and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Review
  2. Article
  3. Kidney international reports · 2026
    Article
  4. Germline-targeted baboon apolipoprotein L-1 protects mice against African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors.

Brandon Zimmerman *Vertex Pharmaceuticals Incorporated, Boston, MA, USA. brandon_zimmerman@vrtx.com.ORCID 0009-0005-3163-8685
Leslie A Dakin *Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
Anne FortierVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Evanthia NanouVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Angelo BlasioVertex Pharmaceuticals Incorporated, Boston, MA, USA.
James MannVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Howard MillerVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Marissa FletcherVertex Pharmaceuticals Incorporated, Boston, MA, USA.ORCID 0000-0003-1777-8751
Tiansheng WangVertex Pharmaceuticals Incorporated, Boston, MA, USA.ORCID 0000-0001-5073-2670
Suganthini NanthakumarVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Gizelle McCarthyVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Caline MatarVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Prachi MatsyeVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Guanyu WangVertex Pharmaceuticals Incorporated, Boston, MA, USA.ORCID 0009-0000-7698-8201
Phillip SnyderVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Kevin DanielVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Harsha SwamyVertex Pharmaceuticals Incorporated, Boston, MA, USA.ORCID 0000-0002-3840-0195
Kelly SullivanVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Franklin BrightVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Audrey PowersVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Kevin J GagnonVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Fan LuVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Steven PaulaVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Suvarna Khare-PanditVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Larry HenryVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Martine HamelVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Francois DenisVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Olivier NicolasVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Niresh HariparsadVertex Pharmaceuticals Incorporated, Boston, MA, USA.ORCID 0000-0002-6290-5329
Shyamesh KumarVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Jennifer ProctorVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Timothy SenterVertex Pharmaceuticals Incorporated, Boston, MA, USA.ORCID 0000-0003-2766-8353
Brinley FureyVertex Pharmaceuticals Incorporated, Boston, MA, USA.
Mark E BunnageVertex Pharmaceuticals Incorporated, Boston, MA, USA. mark_bunnage@vrtx.com.ORCID 0009-0002-6063-8041

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease. Here we describe the development of preclinical assays and the discovery of potent and specific APOL1 inhibitors with drug-like properties. We provide evidence that APOL1 channel activity drives podocyte injury and that inhibition of this activity stops APOL1-mediated cell death and kidney damage in a transgenic mouse model. These preclinical data, combined with clinical data from our previously published phase 2 proof-of-concept study, support the potential of APOL1 channel inhibition for the treatment of AMKD.

Indexed as

Apolipoprotein L1Mice, TransgenicPodocytesPrecision MedicineAnimalsDisease Models, AnimalFemaleHumansMaleMiceRenal Insufficiency, ChronicAPOL1 protein, humanApolipoprotein L1

Identifiers

PMID39747090
PMCPMC11696124

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.