| 产品介绍 |
Tasquinimod (ABR-215050) is a potent and selective allosteric HDAC4 inhibitor. It allosterically binds (Kd 10-30 nmol/L) to the regulatory Zn(2+) binding domain of HDAC4 that locks the protein in a conformation preventing HDAC4/N-CoR/HDAC3 complex formation. This binding inhibited colocalization of N-CoR/HDAC3, thereby inhibiting deacetylation of histones and HDAC4 client transcription factors, such as HIF-1α, which are bound at promoter/enhancers where epigenetic reprogramming is required for cancer cell survival and angiogenic response. In vivo Tasquinimod was effective as a monotherapeutic agent against human prostate, breast, bladder, and colon tumor xenografts by oral dosing. Tasquinimod also targets infiltrating myeloid cells, and modulates local tumour immunity by blocking the interaction between S100A9 and its ligands receptor of advanced glycation end products and Toll-like receptor 4. Currently it is in phase III clinical trials to treat advanced tumors.
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