TP-064 is a potent and specific protein arginine methyltransferase 4 (PRMT4; CARM1) inhibitor (IC50 <10 nM). TP-064 inhibits the dimethylation of BAF155 (IC50 of 340 nM) and MED12 (IC50 of 43 nM). TP-064 is inactive against other family members except PRMT6 (IC50 of 1.3 μM). TP-064 has anti-cancer effect.

Physicochemical Properties

Molecular Formula	C28H34N4O2
Molecular Weight	458.606
Exact Mass	458.268
CAS #	2080306-20-1
PubChem CID	122707126
Appearance	White to light yellow solid powder
Density	1.1±0.1 g/cm3
Boiling Point	642.8±55.0 °C at 760 mmHg
Flash Point	342.5±31.5 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.588
LogP	2.56
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	9
Heavy Atom Count	34
Complexity	603
Defined Atom Stereocenter Count	0
InChi Key	VUIITYLFSAXKIQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C28H34N4O2/c1-29-15-18-32-16-12-23(13-17-32)27-19-22(11-14-30-27)21-31(2)28(33)24-7-6-10-26(20-24)34-25-8-4-3-5-9-25/h3-11,14,19-20,23,29H,12-13,15-18,21H2,1-2H3
Chemical Name	N-methyl-N-[[2-[1-[2-(methylamino)ethyl]piperidin-4-yl]pyridin-4-yl]methyl]-3-phenoxybenzamide
Synonyms	TP064 TP 064 TP-064
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	NCI-H929 cells treated with TP-064 (1 μM) for 72 hours show an increase in the G1 phase and a decrease in the S and G2/M phase proportions [1]. In both TP-064-sensitive and -insensitive cells, treatment with TP-064 (0.03-3 μM; 72 hours) lowers dimethyl-BAF155 levels in a dose-dependent manner [1]. A dose-dependent manner was observed in the inhibition of NCI-H929, RPMI8226, and MM.1R cell growth by TP-064 (10 nM-10 μM; 6 days) treatment, but no effect was observed on acute myeloid leukemia, colon, or lung cancer cell lines [1].
ln Vivo	In C57BL/6 mice, TP-064 (10 mg/kg; intraperitoneal injection; three times within five days) causes neutrophilia associated to peritonitis [2].
Cell Assay	Cell cycle analysis[1] Cell Types: NCI-H929 cells Tested Concentrations: 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induced G1 cell cycle arrest in NCI-H929 cells. Western Blot Analysis[1] Cell Types: NCI-H929, KMS-27 and U266B1 Cell Tested Concentrations: 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Duration: 72 hrs (hours) Experimental Results: Dimethyl-BAF155 levels diminished.
References	[1]. TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma. Oncotarget. 2018 Apr 6;9(26):18480-18493. [2]. PRMT4 inhibitor TP-064 inhibits the pro-inflammatory macrophage lipopolysaccharide response in vitro and ex vivo and induces peritonitis-associated neutrophilia in vivo. Biochim Biophys Acta Mol Basis Dis. 2021 Jul 24;1867(11):166212.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~272.57 mM) H2O : ≥ 50 mg/mL (~109.03 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1805 mL	10.9025 mL	21.8050 mL
	5 mM	0.4361 mL	2.1805 mL	4.3610 mL
	10 mM	0.2181 mL	1.0903 mL	2.1805 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.