GEO series
Heterobifunctional proteomimetic polymers for targeted degradation of MYC and KRAS
GSE269664
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
33 samples
Submitted 2025/12/01
Platform GPL21103Platform GPL20301
Summary
Targeted protein degradation has unlocked new strategies for modulating previously undruggable proteins; however, existing small molecule approaches are challenging to optimize and largely limited to targets with ligandable pockets. To overcome these challenges, we introduce the HYbrid DegRAding Copolymer (HYDRAC), a polymer-based platform that integrates target-binding peptides with peptide or small-molecule degrons for the selective degradation of disease-relevant proteins. HYDRACs are synthesized easily, exhibit structural tunability, and facilitate the attachment of multivalent payloads. The modular payload capability accommodates diverse target-binding motifs and E3 ligase recruiters—such as VHL, KEAP1, and CRBN—broadening the design space. We apply HYDRACs against two historically intractable targets, MYC and KRAS, achieving robust degradation in vitro and sustained tumor inhibition in murine models. Notably, HYDRACs containing consensus RAS-binding motifs effectively degrade KRAS in cells harboring different alleles, suggesting pan-KRAS potential. We envision the HYDRAC platform as a generalizable approach, greatly expanding the armamentarium for TPD.
Published in
Wang MM, Truica MI, Gattis BS et al.
· Nature communications 2026
· PMID 41735327
· doi:10.1038/s41467-026-68913-3
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE269664_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 33 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1123183 and SRA study SRP513585. Searching any of these in the dataset finder brings you back here.
Study design
11 conditions, mostly in triplicate
P-shR, 24hours, ×3
HYDRAC, 24hours, ×3
Vehicle, 24hours, ×3
A549 HYDRAC 24hr ×3
A549 sHR 24hr ×3
MycCaP HYDRAC 24hr ×3
MycCaP sHR 24hr ×3
PC3 HYDRAC 24hr ×3
+3 more
Supports a between-group comparison across 33 samples.
11 replicated groups read from 33 sample titles; they account for 33 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8324339 P-shR, 24hours, rep1
- GSM8324340 P-shR, 24hours, rep2
- GSM8324341 P-shR, 24hours, rep3
- GSM8324342 HYDRAC, 24hours, rep1
- GSM8324343 HYDRAC, 24hours, rep2
- GSM8324344 HYDRAC, 24hours, rep3
- GSM8324345 Vehicle, 24hours, rep1
- GSM8324346 Vehicle, 24hours, rep2
- GSM8324347 Vehicle, 24hours, rep3
- GSM9337567 A549 HYDRAC 24hr rep1
- GSM9337568 A549 HYDRAC 24hr rep2
- GSM9337569 A549 HYDRAC 24hr rep3
- GSM9337570 A549 sHR 24hr rep1
- GSM9337571 A549 sHR 24hr rep2
- GSM9337572 A549 sHR 24hr rep3
- GSM9337573 MycCaP HYDRAC 24hr rep1
- GSM9337574 MycCaP HYDRAC 24hr rep2
- GSM9337575 MycCaP HYDRAC 24hr rep3
- GSM9337576 MycCaP sHR 24hr rep1
- GSM9337577 MycCaP sHR 24hr rep2
- GSM9337578 MycCaP sHR 24hr rep3
- GSM9337579 PC3 HYDRAC 24hr rep1
- GSM9337580 PC3 HYDRAC 24hr rep2
- GSM9337581 PC3 HYDRAC 24hr rep3
- GSM9337582 PC3 sHR 24hr rep1
- GSM9337583 PC3 sHR 24hr rep2
- GSM9337584 PC3 sHR 24hr rep3
- GSM9337585 PC3 siCNT rep1
- GSM9337586 PC3 siCNT rep2
- GSM9337587 PC3 siCNT rep3
- GSM9337588 PC3 siMYC rep1
- GSM9337589 PC3 siMYC rep2
- GSM9337590 PC3 siMYC rep3
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