CI-994

Names

[ Name ]:
CI-994

[Synonym ]:
Tacedinaline
4-Acetamido-N-(2-aminophenyl)benzamide
4-(Acetylamino)-N-(2-aminophenyl)benzamide
Goe 5549
N-acetyldinaline
Acetyldinaline
Tacedinalina
Benzamide, 4-(acetylamino)-N-(2-aminophenyl)-
CI994
CI-994

Biological Activity

[Description]:

CI-994 (Tacedinaline) is an inhibitor of the histone deacetylase (HDAC) with IC50s of 0.9, 0.9, 1.2 μM for recombinant HDAC 1, 2 and 3 respectively.

[Related Catalog]:

Research Areas >> Cancer

[Target]

HD1:0.9 μM (IC50)

HD2:0.9 μM (IC50)

HD3:1.2 μM (IC50)

[In Vitro]

CI-994 (N-acetyldinaline) is a novel oral compound with a wide spectrum of antitumor activity in preclinical models. The mechanism of action may involve inhibition of histone deacetylation and cell cycle arrest. CI-994 is combined with antineoplastic agents commonly used in non-small cell lung cancer cell line management, a marked synergism of action (R=1.8, R=1.5) is observed between CI-994 (40 μM) and gemcitabine (0.01 μM) at 48 and 72 h of treatment[2].CI-994 inhibits mitogen-stimulated blood lymphocyte proliferation with an IC50 value of 3 μM[4].

[In Vivo]

CI-994 has activity against 8/8 solid tumors tested: pancreatic ductal adenocarcinoma #02 (4.7); pancreatic adenocarcinoma #03 (3.0; 1/6 cures); colon adenocarcinoma #38 (1.6); colon adenocarcinoma #51/A (1.1); mammary adenocarcinoma #25 (1.7); mammary adenocarcinoma #17/ADR (0.5); Dunning osteogenic sarcoma (4.0); and the human prostate carcinoma LNCaP (1.2). CI-994 is the acetylated metabolite of dinaline and has the same spectrum of activity in vivo as dinaline. It also behaves similarly in schedule comparison/toxicity trials[3]. CI-994 can effect lymphoid tissue in rats within 1 day of a single oral dose, that effects are generally reversible within 7 days[4].

[Animal admin]

Rats: To characterize the effects of CI-994 on lymphoid tissue, male rats are administered single oral doses at 0 (vehicle control), 10, 23, and 45 mg/kg and killed up to 7 days after dosing for evaluation of white blood cell differentials, bone marrow differentials, lymphoid tissue weights, and selected histopathology of lymphoid tissue[4].

[References]

[1]. Moradei OM, et al. Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. J Med Chem. 2007 Nov 15;50(23):5543-6.

[2]. Loprevite M, etal. In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines. Oncol Res. 2005;15(1):39-48.

[3]. LoRusso PM, et al. Preclinical antitumor activity of CI-994. Invest New Drugs. 1996;14(4):349-56.

[4]. Graziano MJ, et al. Immunotoxicity of the anticancer drug CI-994 in rats: effects on lymphoid tissue. Arch Toxicol. 1999 Apr-May;73(3):168-74.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
450.6±30.0 °C at 760 mmHg

[ Melting Point ]:
242 °C(dec.)

[ Molecular Formula ]:
C₁₅H₁₅N₃O₂

[ Molecular Weight ]:
269.298

[ Flash Point ]:
226.3±24.6 °C

[ Exact Mass ]:
269.116425

[ PSA ]:
84.22000

[ LogP ]:
0.96

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.707

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H319

[ Precautionary Statements ]:
P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36

[ Safety Phrases ]:
26

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
CU8702023

[ HS Code ]:
2924299090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2924299090

[ Summary ]:
2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles

Role of a small molecular weight phosphoprotein in the mechanism of action of CI-994 (N-acetyldinaline).

Int. J. Cancer 62(5) , 636-42, (1995)

The mechanism of action of the novel anti-cancer compound CI-994 was studied in C26 murine colon tumor and HCT-8 human colon adenocarcinoma cells. Treatment of either cell line resulted in the specifi...

Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors.

Cancer Invest. 22(6) , 886-96, (2004)

To determine maximum tolerated dose of CI-994, a novel oral histone deacetylase inhibitor, in combination with carboplatin and paclitaxel in patients with advanced solid tumors.Patients with advanced ...

Cytotoxic chemotherapy regimens that increase dose per cycle (dose intensity) by extending daily dosing from 5 consecutive days to 28 consecutive days and beyond.

Clin. Cancer Res. 6(6) , 2474-81, (2000)

Dose intensity, defined as dose administered per unit time, has emerged as a potentially important measurement of anticancer drug exposure and determinant of efficacy. There are several strategies for...