In vitro and in vivo activities of MD302 as a novel HPK1 lead compound with good pK property
Hematopoietic Progenitor Kinase 1 (HPK1) regulates various signaling pathways in immune cells. Interestingly, HPK1 attenuates T cell activation by inducing ubiquitination and proteasomal degradation of SLP-76 through its phosphorylation at Ser-376, leading to reduced immune response. Importantly, the genetic ablation or the pharmacological inhibition of HPK1 kinase activity has been shown to improve immune response to cancers by enhancing T cell activation and cytokine production, indicating that HPK1 could be a possible druggable target for T cell-based cancer immunotherapy. Here, we presented the in vitro and in vivo activities of MD302 as a novel HPK1 lead compound with good pK property to enhance T cell activation and anti-tumor efficacy. Furthermore, the combination of MD302 with nivolumab (PD-L1 inhibitor) more potently inhibited the tumor growth with the statistical significance. The safety of the orally bioavailable MD302 in the ongoing toxicological studies would make it as drug candidate in the near future.
2024 Spring Convention