CAD204520

CAD204520 is a selective **small molecule inhibitor** targeting **SERCA (sarcoplasmic/endoplasmic reticulum calcium ATPase)** with high specificity for cancer cells harboring activating mutations in **NOTCH1**, particularly mutations within the **PEST degradation domain**. Unlike earlier SERCA inhibitors, CAD204520 demonstrates a favorable safety profile, achieving anti-tumor activity in preclinical leukemia and lymphoma models—including T-cell acute lymphoblastic leukemia (T-ALL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL)—by **preferentially inhibiting mutated over wild-type NOTCH1 signaling**. Its preclinical data show marked suppression of NOTCH1-mutated tumor cell proliferation and survival with reduced risk of cardiac toxicity, and CAD204520 has also shown the capacity to enhance the efficacy of combination regimens with agents like venetoclax and ibrutinib in NOTCH1-mutant models.[1][2][3][7] The drug remains under preclinical investigation and has not entered clinical trials.

Other names

CAD204520CAD-204520CAD 204520