Oncology
DA-4511
Unmet needs
SHP1, a member of the src homology 2 (SH2) domain-containing protein phosphatases,
has been implicated as an attractive immuno-oncology therapeutic target by its negative regulation of immune cell activation.
It has been known that SHP1 interacts with proteins of the inhibitory-receptor superfamily containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within cytoplasmic tails.
Its inhibition might be able to address additional therapeutic options with immune checkpoint inhibitors for cancer patients.
Although a few agents targeting its catalytic site have been reported, they have low cell permeability, bioavailability, and selectivity among other PTPs.
Despite these unique drug discovery challenges, we identified a series of potent, selective, and orally efficacious SHP1 allosteric inhibitors.
MoA
(Mechanism of Action)
Shp1 is an Exciting IO Target with Pleiotropic Effects in Innate and Adaptive Immune Cells. Unlike SHP2, which is ubiquitously expressed in mammalian cells and mainly serves as a positive regulator, SHP1 is primarily expressed in hematopoietic cells and is generally considered a negative regulator of innate and adaptive immunity. Our SHP1 allosteric inhibitors enhanced innate and tumor-associated adaptive immune responses, facilitating its robust anti-tumor responses through interrupting ITIM signaling pathway.
