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ONCO-SPLICE

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Translating Tudor domain splicing inhibitors for oncological applications

In our effort to characterize metabolic activities in the cell’s nucleus, we discovered that the understudied Tudor domain protein SMNDC1 controls the repression of insulin in pancreatic alpha cells through its role as a splicing... ver más

28/02/2026

CEMM FORSCHUNGSZE...

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CEMM FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZ... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-09-01

ERC-2024-POC: ERC PROOF OF CONCEPT GRANTS Objective:ObjectivesThe ERC Proof of Concept Grants aim at facilitating exploration of the commercia...

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Duración del proyecto: 17 meses Fecha Inicio: 2024-09-01
Fecha Fin: 2026-02-28

Líder del proyecto

CEMM FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZ... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto In our effort to characterize metabolic activities in the cell’s nucleus, we discovered that the understudied Tudor domain protein SMNDC1 controls the repression of insulin in pancreatic alpha cells through its role as a splicing modulator. Based on this finding, we developed the first selective SMNDC1 Tudor domain inhibitors, for which we observe interesting preliminary data on insulin induction in primary human pancreatic islets. However, as a pan-essential gene expressed in most tissues, SMNDC1 is not an ideal therapeutic target in diabetes, where exceptionally high safety margins are required.Interestingly, independent findings published in a preprint established a role for SMNDC1 in cancer. These data show that SMNDC1 controls splicing of the ERK1 exon that bears the phosphorylation signal mediating RAS/RAF/MEK/ERK signaling. A significant fraction of ovarian and pancreatic carcinomas harbor SMNDC1 amplifications, and cells derived from these tumors depend on SMNDC1 both in vitro and in xenograft models. We here propose to evaluate the potential of our SMNDC1 inhibitors for cancer therapy. Experimentally, we will test these compounds in the ERK1 splicing dependent models in collaboration with the groups that described these findings, and we will profile their antiproliferative effects against a panel of >900 cancer cell lines. In parallel, we will conduct detailed analysis on the chemical scaffolds we discovered and develop a medicinal chemistry proposal to expand the scope of the filed patent application. Additionally, we will commission analyses for an optimal translation pathway of these compounds to the clinic, aiming an ideal positioning for certain cancer subtypes based on market size, competitive situation, clinical needs and trial design opportunities.Finally, we will develop a plan for the further translation of our discoveries, ideally by foundation of a new spin-off company following successful completion of the ONCO-SPLICE project.

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