Tacedinaline Chemical Properties

Melting point:

216.1 °C

Boiling point:

450.6±30.0 °C(Predicted)

Density 

1.322±0.06 g/cm3(Predicted)

RTECS 

CU8702023

storage temp. 

Keep in dark place,Inert atmosphere,2-8°C

solubility 

Soluble in DMSO

pka

13.15±0.70(Predicted)

form 

powder

color 

off-white

Sensitive 

Air Sensitive

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.

InChIKey

VAZAPHZUAVEOMC-UHFFFAOYSA-N

Safety Information

Hazard Codes 

Xi

Risk Statements 

36

Safety Statements 

26

WGK Germany 

3

HS Code 

2924.29.7790

Tacedinaline Usage And Synthesis

Description

CI-994 (112522-64-2) is an orally active histone deacetylase (HDAC) inhibitor, IC50 = 0.9, 0.9, 1.2 and >20 μM for HDAC1, HDAC2, HDAC3 and HDAC8 respectively.1 Mediates G1 cell cycle arrest, inhibits proliferation and induces apoptosis in vitro and in vivo.2,3 Increases neuroplasticity during memory extinction.4 Protects beta cells from cytokine-induced apoptosis.4

Uses

Tacedinaline is a histone deacetylase (HDAC) inhibitor. Tacedinaline is an anti-cancer agent as HDAC inhibitors block angiogenesis, arrest cell growth, and lead to differentiation and apoptosis in tumor cells. Studies show Tacedinaline to be effective against acute myeloid leukemia in vitro and in vivo when used in combination with conventional anti-cancer agents.

Definition

ChEBI: A benzamide obtained by formal condensation of the carboxy group of 4-acetamidobenzoic acid with one of the amino groups of 1,2-phenylenediamine. An oral cytostatic drug with impressive differential activity against leukemic cells and normal stem-cells. Al o used in combination therapy for selected tumors including non-smoll cell lung, pancreatic, breast, and colorectal cancers.

Biological Activity

Orally active histone deacetylase (HDAC) inhibitor (K i values are 0.41, 0.75, >100 and >100 μ M for HDAC1, HDAC3, HDAC6 and HDAC8 respectively). Mediates G 1 cell cycle arrest, inhibits proliferation and induces apoptosis in vitro and in vivo .

Synthesis

GENERAL STEPS: Trifluoroacetic acid (22 mL) was added slowly and dropwise to a solution of tert-butyl (2-(4-acetylaminobenzoyl)phenyl)carbamate 1.5 (3.5 g, 9.5 mmol) in anhydrous dichloromethane (55 mL) at 0 °C. The reaction mixture was slowly warmed to 23 °C and stirred at this temperature for 2 h until the reaction was complete. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was diluted with water and the pH was adjusted with saturated aqueous sodium bicarbonate to about 8. The precipitate precipitated was filtered, washed sequentially with water and ether, and finally dried under vacuum to afford 4-acetamido-N-(2-aminophenyl)benzamide 1.6 as an off-white solid in a yield of 2.4 g (96% yield).1H NMR (500 MHz, d6-DMSO) δ 10.18 (s, 1H), 9.54 (s, 1H), 7.93 (d, J = 8.5Hz, 2H), 7.69 (d, J = 8.5Hz, 2H), 7.15 (d, J = 7.5Hz, 1H), 6.96 (t, J = 7.5Hz, 1H), 6.78 (d, J = 7.5Hz, 1H), 6.59 (t, J = 7.5Hz, 1H ), 4.88 (s, 2H), 2.08 (s, 3H).MS (ESI+): m/z 269.9 [M + H]+.

target

HDAC1

storage

+4°C

References

[1] OSCAR M. MORADEI. Novel Aminophenyl Benzamide-Type Histone Deacetylase Inhibitors with Enhanced Potency and Selectivity[J]. Journal of Medicinal Chemistry, 2007, 50 23: 5543-5546. DOI:10.1021/jm701079h
[2] THOMAS BECKERS. Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group[J]. International Journal of Cancer, 2007, 121 5: 1138-1148. DOI:10.1002/ijc.22751
[3] MAURA LOPREVITE. In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines.[J]. Oncology Research, 2005, 15 1: 39-48. DOI:10.3727/096504005775082066
[4] DANNY HUNG-CHIEH CHOU. Inhibition of histone deacetylase 3 protects beta cells from cytokine-induced apoptosis.[J]. Chemistry & biology, 2012: 669-673. DOI:10.1016/j.chembiol.2012.05.010

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