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HC-5404
- Development stage
- Phase 1
- Lead developer
- AVEO Oncology
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
HC-5404 (also known as HC-5404-FU) is an orally bioavailable, first-in-class small molecule inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK, also known as EIF2AK3). Developed by HiberCell, HC-5404 targets the unfolded protein response (UPR) pathway, which cancer cells utilize to adapt and survive under harsh microenvironmental conditions such as hypoxia, nutrient deprivation, and oxidative stress. By inhibiting PERK, HC-5404 disrupts this adaptive stress response, leading to tumor cell apoptosis, immunomodulatory effects, and inhibition of tumor angiogenesis. In November 2025, HiberCell entered into an exclusive development and option agreement with AVEO Oncology (an LG Chem company) to develop HC-5404 as a monotherapy and in combination with AVEO's VEGFR tyrosine kinase inhibitor FOTIVDA (tivozanib) for the treatment of renal cell carcinoma (RCC) and other solid tumors.
- Other names
- HC 5404HC5404HC-5404HC 5404-FUHC5404-FUHC-5404-FUPERK inhibitor HC-5404PERK inhibitor HC-5404-FU
02
Targets
EIF2AK4 (Eukaryotic translation initiation factor 2-alpha kinase 4)EIF2AK2 (Interferon-induced protein kinase R)EIF2AK3 (Pkr-like endoplasmic reticulum kinase)EIF2AK1 (Eukaryotic translation initiation factor 2-alpha kinase 1)
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