TMP195

Catalog No.S8502 Synonyms: TFMO 2

TMP195 Chemical Structure

Molecular Weight(MW): 456.42

TMP195 is a selective, first-in-class, class IIa HDAC inhibitor with IC50 of 300 nM in cell-based class IIa HDAC assays.

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Biological Activity

Description TMP195 is a selective, first-in-class, class IIa HDAC inhibitor with IC50 of 300 nM in cell-based class IIa HDAC assays.
Targets
HDAC9 [1]
(Cell-free assay)
HDAC7 [1]
(Cell-free assay)
HDAC4 [1]
(Cell-free assay)
HDAC5 [1]
(Cell-free assay)
15 nM(Ki) 26 nM(Ki) 59 nM(Ki) 60 nM(Ki)
In vitro

TMP195 has low potency in recombinant class I and IIb HDAC assays, enabling full inhibition of class IIa HDAC activity without inhibition of other HDACs. TMP195 blocks the accumulation of CCL2 protein in the supernatants of monocyte-derived macrophage differentiation cultures and significantly increases the amount of CCL1 protein secreted by the monocytes compared to vehicle (DMSO)-treated M-CSF plus GM-CSF cultures[1]. TMP195 influences human monocyte responses to the colony-stimulating factors CSF-1 and CSF-2 in vitro[2].

In vivo In vivo 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 tumours. TMP195 treatment significantly decreases proliferating tumour cells, most notably at the leading edge of the tumour. The anti-tumour macrophage phenotype induced by TMP195 treatment thus enhances the efficacy and durability of both standard chemotherapeutic regimens and checkpoint blockade immunotherapy in this mouse model of breast cancer[2].

Protocol

Cell Research:

[2]

+ Expand
  • Cell lines: Human monocytes
  • Concentrations: 300 nM
  • Incubation Time: 5 days
  • Method:

    Monocytes were differentiated into antigen presenting cells in RPMI Medium 1640 supplemented with GlutaMAX fetal bovine serum (10% v/v), IL-4 (10 ng/ml), GM-CSF (50 ng/ml), penicillin (100 U/ml), and streptomycin (100 μg/ml) for 5 days in the presence of either 0.1% (v/v) DMSO or 300 nM TMP195. Cells were collected by washing and incubation with a solution of 5 mM EDTA in PBS (Ca2+/Mg2+-free), before flow cytometric analysis.


    (Only for Reference)
Animal Research:

[2]

+ Expand
  • Animal Models: MMTV-PyMT transgenic mice
  • Formulation: DMSO
  • Dosages: 50 mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 91 mg/mL (199.37 mM)
Ethanol 91 mg/mL (199.37 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 456.42
Formula

C23H19F3N4O3

CAS No. 1314891-22-9
Storage powder
Synonyms TFMO 2

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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HDAC Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID