SB6299

SB6299 (also known as DA-4511) is a first-in-class, orally bioavailable, potent, and highly selective allosteric inhibitor of Src homology region 2 domain-containing phosphatase 1 (SHP1), developed by Dong-A ST. SHP1 is a protein tyrosine phosphatase primarily expressed in hematopoietic cells that acts as a negative regulator of immune cell activation. By binding to non-catalytic sites of the inactive conformation of SHP1, SB6299 stabilizes its autoinhibited state, preventing its phosphatase activity. This selective inhibition enhances innate and adaptive immune responses, promoting cytokine secretion (such as IL-2, IFN-γ, and TNF-α) and cytotoxic effects in primary immune cells. In preclinical studies, SB6299 has demonstrated robust anti-tumor efficacy as a monotherapy and synergistic tumor growth inhibition when combined with anti-PD-1 immune checkpoint blockade.