FCN-011 is a highly potent and selective inhibitor of tropomyosin receptor kinases (TRKA, TRKB and TRKC). TRKA, TRKB and TRKC are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Chromosomal rearrangements of these genes fused in-frame with partner genes result in constitutively activated chimeric TRK fusion proteins that act as oncogenic factors to promote cell proliferation and survival in tumor cells.
FCN-098 is a highly potent and selective second-generation small molecule inhibitor of tropomyosin receptor kinases (TRKA, TRKB and TRKC), which inhibits the phosphorylation of TRK fusion protein and its downstream ERK1/2 proteins by competing with ATP to bind to the kinase domain of wild-type or drug-resistant mutant TRK, thereby inhibiting tumor growth.
FCN-289 is a selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. By inhibiting the expression of PI3Kδ and reducing the phosphorylation of AKT protein, it induces the apoptosis of malignant B lymphocytes and inhibits malignant B lymphocyte proliferation.
FCN-589 is a potent and selective inhibitor of Bruton's tyrosine kinase (BTK) and the most common resistant mutation BTK C481S. BTK is a key regulator in the B-cell receptor (BCR) signaling pathway. Dysregulated BCR signaling is associated with the survival of malignant B cells and ultimately leads to the formation of cancer in B cells, namely B-cell malignancies
The inhibitor of anti-apoptotic protein B-cell lymphoma-2 (BCL-2) directly binds to BCL-2 to suppress the interaction of BCL-2 with pro-apoptotic proteins (such as BAK), which in turn triggers the mitochondrial outer membrane permeabilization, leading to the release of cytochrome c from mitochondria to the cytoplasm, and activation of cysteine proteases. BCL-2 inhibitor induces tumor cell apoptosis, and effectively inhibits the growth of BCL-2-dependent tumors, thus exerting anti-tumor activities.
Phosphoinositide 3-kinase (PI3Ks) are intracellular lipid kinases that catalyze the phosphorylation of inositol at position 3 (PIP2→PIP3). Membrane-bound PIP3 provides targeting anchors for PH domain-containing signaling proteins, which in turn mediate various important signaling pathways, such as activation of downstream PI3K/Akt/mTOR signaling pathways. Mutations in PIK3CA, the gene encoding PI3Kα, are the most common mutations in tumorigenesis.
Cyclin-dependent kinase 2 (CDK2) drives cells enter the S and M phases of the cell cycle. In late G1 phase, cyclin E (CCNE) binds to CDK2 to further phosphorylate retinoblastoma protein (Rb), releasing and fully activating E2F, thereby triggering the transcription of S-phase proteins. Abnormal cyclin E (CCNE) overactivates CDK2, leading to cell cycle dysregulation and tumor proliferation.