NP-ALT

NP-ALT (also known as IpY) is a first-in-class, preclinical-stage liposomal peptide therapeutic being developed by Concarlo Therapeutics (licensed from SUNY Downstate Medical Center) for the treatment of drug-resistant cancers, primarily metastatic breast cancer. It consists of the peptide ALT (a naturally occurring, alternatively spliced variant of breast tumor kinase [BRK] that lacks the kinase domain) encapsulated in a liposomal delivery vehicle. NP-ALT acts by binding to the intrinsically disordered tumor suppressor protein p27Kip1 (CDKN1B), preventing its tyrosine phosphorylation by BRK. This blocks the activation of cyclin-dependent kinases CDK4, CDK6, and CDK2, locking them in an inactive state. Unlike conventional ATP-competitive CDK inhibitors that cause cytostasis, NP-ALT induces reactive oxygen species (ROS) and RIPK1/RIPK3-dependent necroptosis specifically in hormone receptor-positive (HR+) breast cancer cells, including those resistant to CDK4/6 inhibitors (such as palbociclib) and endocrine therapies.

Other names

ALTCCL-19CCL19CCL 19CCL-2CCL2CCL 2IpY.19