BridgeBio has committed USD30 m and a team of senior business managers to the company, while MD Anderson, through its Institute for Applied Cancer Sciences (IACS), provides intellectual property and an oncology drug development team to advance SHP2 inhibitors toward clinical studies.
SHP2 inhibition therefore offers a new approach to treat tumors relying on this pathway.
SHP2 also suppresses T-cell activity against growing tumors through regulation of the adaptive immune response by binding to PD-1 and dephosphorylating CD28 and the protein LCK.
In a physiological setting, SHP2 is required for full activation of the Ras-ERK mitogen-activated protein kinase (MAPK) pathway and is also involved in cell morphogenesis as well as cell motility.
Investigation of a new SHP2 substrate(s) potentially involved in CagA-mediated oncogenesis revealed parafibromin/Cdc73, a core component of the RNA polymerase II-associated factor (PAF) complex.
75) SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture)-based phosphoproteomics study showed that, in addition to the above-described SH2-containing proteins, the EPIYA-A peptide can bind to SHP1, the EPIYA-B peptide can bind to SHP1, Grb2, and SHP2, and the EPIYA-C peptide can bind to Grb2, Grb7, SHP1, and Ras-GTPase activating protein (GAP) in a manner that is dependent on EPIYA tyrosine phosphorylation, indicating the potential of tyrosine-phosphorylated EPIYA segments in promiscuously binding with numerous SH2 domains.
SHP1, the one and the only SHP2 homologue in mammals, is primarily expressed in hematopoietic cells, where it negatively regulates immune cell activation.
This simulation-measurement similarity is also observable for CTP2 and SHP2
in free space.
The finding is also encouraging because SHP2 is a member of a large family of enzymes called protein tyrosine phosphotases (PTPs), which are important in the signaling processes that control all essential cellular functions.
Until now these targets, including SHP2 for leukemia and other cancers, have been deemed undruggable," he said.
One of the key steps in lymphomagenesis appears to be the interaction of the SHP2
(PTPN11)/GRB2 complex with ALK through SHC to enhance phosphorylation of ERK1/2 via SRC and son of sevenless.
This proposal focuses on the role of SHP2
and other protein tyrosine phosphatase (PTP) in BC metastasis and comprises three parallel approaches.