TMP195

TMP195 (TFMO 2) is a selective, first-in-class, class IIa HDAC inhibitor with IC50 of 300 nM in cell-based class IIa HDAC assays.

Product information

CAS Number: 1314891-22-9

Molecular Weight: 456.42

Formula: C23H19F3N4O3

Synonym:

TFMO 2

Chemical Name: N-[2-methyl-2-(2-phenyl-1,3-oxazol-4-yl)propyl]-3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide

Smiles: CC(C)(CNC(=O)C1C=C(C=CC=1)C1N=C(ON=1)C(F)(F)F)C1=COC(=N1)C1C=CC=CC=1

InChiKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N

InChi: InChI=1S/C23H19F3N4O3/c1-22(2,17-12-32-20(28-17)14-7-4-3-5-8-14)13-27-19(31)16-10-6-9-15(11-16)18-29-21(33-30-18)23(24,25)26/h3-12H,13H2,1-2H3,(H,27,31)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 82 mg/mL (179.7 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. TMP195 influences human monocyte responses to the colony-stimulating factors CSF-1 and CSF-2 in vitro.

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.

References:

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.

Products are for research use only. Not for human use.