# A new kinase inhibitor for glioblastoma

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $184,875

## Abstract

Abstract:
The tumor suppressor PTEN counteracts Class 1 PI3-kinase functions in membranes, leading to
the massive kinase inhibitor development efforts currently attempting to counteract loss of PTEN in
human tumors. However, we discovered a new PTEN signaling pathway in the nucleus that is
completely decoupled from Class 1 PI3-kinases. The “decoupling” is important for anti-cancer drug
design because if a tumor is growing due to loss of nuclear PTEN, Class 1 PI3-kinase inhibitors
would be ineffective against those tumors. Indeed, PI3-kinase inhibitors often fail to rescue loss of
PTEN function in clinical trials, for incompletely understood reasons. Further, this new PTEN
pathway has never been studied in any model of cancer, as we discovered it fortuitously while
examining endocrine disorders. The kinase opposing PTEN in the nuclear pathway is a poorly
characterized member of the inositol kinase superfamily called “Inositol Polyphosphate Multikinase”
(IPMK). IPMK is a nuclear PIP2-kinase with ubiquitous expression in all human tissues, structurally
unrelated to Class 1 PI3-kinases. Alfred Yung showed certain glioblastoma cell lines halted growth
when complemented with nuclear, not cytoplasmic PTEN2. Based on the nuclear pathway, we
hypothesized IPMK knockout might mimic nuclear PTEN complementation in these cells. Indeed,
preliminary data show CRSIPR knockout of IPMK phenocopies nuclear PTEN complementation in
these cells. Wild type but not kinase-dead IPMK rescues the phenotype, suggesting an IPMK
inhibitor could be an effective therapy. This grant develops a chemical genetic mutant of IPMK to
determine if IPMK inhibitors would be effective in glioblastoma. Future projects will use
physiologically relevant mouse models to establish IPMK as a validated target for full scale
industrial kinase inhibitor efforts.

## Key facts

- **NIH application ID:** 10019480
- **Project number:** 5R21CA243036-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Raymond Daniel Blind
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,875
- **Award type:** 5
- **Project period:** 2019-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019480

## Citation

> US National Institutes of Health, RePORTER application 10019480, A new kinase inhibitor for glioblastoma (5R21CA243036-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019480. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*