TMP195 is a selective class IIa histone deacetylase (HDAC) inhibitor with an IC50 of 300 nM.
CAS：1314891-22-9
分子式：C23H19F3N4O3
分子量：456.42
纯度：98%
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Background:

TMP195 is a selective class IIa histone deacetylase (HDAC) inhibitor with an IC50 of 300 nM.

TMP195 blocks the accumulation of CCL2 protein in the supernatants of monocyte-derived macrophage differentiation cultures. TMP195 significantly increases the amount of CCL1 protein secreted by the monocytes compared to vehicle group. In the transcriptional profiling data from the PHA-stimulated PBMC experiments, CCL2 and CCL1 are respectively down- or upregulated by TMP195[1]. TMP195 occupies the acetyllysine-binding site of class IIa HDACs. TMP195 competes against binding of HDAC7 to a variety of side-chain modifications on the same peptide backbone, despite no interference with the activity of other acetyllysine reader proteins BRD4 (IC50>50 uM)[2].

TMP195 treatment alters the tumour microenvironment and reduces tumour burden and pulmonary metastases by modulating macrophage phenotypes. TMP195 induces the recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumors. Combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumour reduction[2].

参考文献:
[1]. Lobera M, et al. Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol. 2013 May;9(5):319-25.
[2]. Guerriero JL, et al. Class IIa HDAC inhibition reduces breast tumors and metastases through anti-tumor macrophages. Nature. 2017 Mar 16;543(7645):428-432.