# SHIPi improves hematologic recovery after chemotherapy

## TL;DR

This study shows that SHIP1 inhibitors can boost recovery of blood cell counts after chemotherapy by increasing natural growth factors.

## Contribution

The discovery of a SHIP1-selective inhibitor, A32, that enhances endogenous G-CSF and TPO production.

## Key findings

- Pan-SHIPi compounds induce G-CSF and TPO production and improve survival after fungal infection.
- SHIP1 inhibitors accelerate neutrophil recovery in mice after chemotherapy.
- A32 is a novel SHIP1-selective inhibitor that boosts steady-state G-CSF and TPO levels.

## Abstract

The use of recombinant growth factors has led to improved hematopoietic function after chemotherapy, but hematologic and immune complications still occur after chemotherapy which can be life-threatening. Here we show that pan-SHIPi compounds can induce endogenous G-CSF and TPO production in vivo and can also increase host survival after a lethal fungal challenge. In addition, we show that consistent with their ability to induce G-CSF, pan-SHIPi compounds can promote increased granulopoiesis in normal mice and speed recovery of neutrophil counts after chemotherapy. We also report the identification of a novel SHIP1-selective inhibitor, A32, that also increases steady state production of both G-CSF and TPO. These findings indicate small molecule inhibitors of SHIP1 can promote hematologic recovery after myeloablative chemotherapy and are a unique means to induce endogenous production of multiple growth factors that promote hematologic recovery.

The online version contains supplementary material available at 10.1186/s10020-025-01383-3.