112522-64-2

Basic information

• Product Name: 4-Acetylamino-N-(2'-aminophenyl)benzamide
• Synonyms: Benzamide, 4-(acetylamino)-N-(2-aminophenyl)-;acetyldinaline;Tacedinaline;CI 994;N-Acetyldinaline;4-AcetaMido-N-(2-aMinophenyl)benzaMide;Cl-994(Tacedinalin,N-Acetyldinalin);CI994 (Tacedinaline)
• CAS NO: 112522-64-2
• Molecular Formula: C₁₅H₁₅N₃O₂
• Molecular Weight: 269.3
• EINECS: 200-256-5
• Product Categories: Apoptosis Inducers;Inhibitor;Inhibitors
• Mol File: 112522-64-2.mol
• Article Data: 8

Chemical Properties

• Melting Point: 216.1 °C
• Boiling Point: 450.6 °C at 760 mmHg
• Flash Point: 226.3 °C
• Appearance: off-white/
• Density: 1.322 g/cm³
• Storage Temp.: Store at +4°C
• Solubility: Soluble in DMSO
• PKA: 13.15±0.70(Predicted)
• 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.
• CAS DataBase Reference: 4-Acetylamino-N-(2'-aminophenyl)benzamide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Acetylamino-N-(2'-aminophenyl)benzamide(112522-64-2)
• EPA Substance Registry System: 4-Acetylamino-N-(2'-aminophenyl)benzamide(112522-64-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• WGK Germany: 3
• RTECS: CU8702023
• Hazardous Substances Data: 112522-64-2(Hazardous Substances Data)

Usage

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

Different sources of media describe the Uses of 112522-64-2 differently. You can refer to the following data:
1. 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 tum or 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.
2. 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 .

References

1) Moradei et al. (2007), Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity; J. Med. Chem., 50 5543 2) Beckers et al. (2007), Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group; Int. J. Cancer, 121 1138 3) Loprevite et al. (2005), In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines; Oncol. Res., 15 39 4) Chou et al. (2012), Inhibition of histone deacetylase 3 protects beta cells from cytokine-induced apoptosis; Chem. Biol., 19 669

Upstream product

• 1075719-57-1 6-{4-[(2-(4-acetylamino-benzoylamino)-phenylcarbamoyl)oxymethyl]-2-nitro-phenoxy}-tetrahydro-2H-pyran-2-carboxylic acid 
• 1075719-58-2 6-[2-(4-acetylamino-benzoylamino)-phenylcarbamoyloxy]-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid 
• 95-54-5 1,2-diamino-benzene 
• 1353653-79-8 4-acetamido-N-(2-aminophenyl)benzamide trifluoroacetate salt 
• 1299346-13-6 tert-butyl (2-(4-acetamidobenzamido)phenyl)carbamate 
• 54614-93-6 (2-nitro-phenyl)-carbamic acid tert-butyl ester 
• 88-74-4 2-nitro-aniline 
• 146651-75-4 tert–butyl (2–aminophenyl)carbamate 
• 556-08-1 p-(acetylamino)benzoic acid 

Downstream Products

• 1075719-60-6 3,4,5-triacetoxy-6-{4-[(2-(4-acetylamino-benzoylamino)-phenylcarbamoyl)oxymethyl]-2-nitro-phenoxy}-tetrahydro-2H-pyran-2-carboxylic acid methyl ester 
• 1037543-20-6 (N-{[N-(2-{[4-(acetylamino)phenyl]carbonylamino}phenyl)-carbamoyl]methyl}carbamoyloxy)methyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoate 
• 1037543-19-3 N-(2-{[4-(acetylamino)phenyl]carbonylamino}phenyl)-2-aminoacetamide 
• 1299346-14-7 4-(acetylamino)-N-(2aminophenyl)benzamide hydrochloride 
• 1037543-25-1 4-{[N-(2-{[4-{acetylamino}phenyl]carbonylamino}phenyl)carbamoyloxy]methyl}phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoate 
• 1037543-18-2 N-(2-{[4-(acetylamino)phenyl]carbonylamino}phenyl)-2-[(tert-butoxy)carbonylamino]acetamide 

Relevant articles and documents

Improved synthesis of histone deacetylase inhibitors (HDIs) (MS-275 and CI-994) and inhibitory effects of HDIs alone or in combination with RAMBAs or retinoids on growth of human LNCaP prostate cancer cells and tumor xenografts

We have developed new, simple, and efficient procedures for the synthesis of two promising histone deacetylase inhibitors (HDIs), CI-994, (N-(2-aminophenyl)-4-acetylaminobenzamide), and MS-275 (N-(2-aminophenyl)4-[N-(pyridine-3-yl-methoxycarbonyl)aminomethyl]benzamide) from commercially available acetamidobenzoic acid and 3-(hydroxymethyl)pyridine, respectively. The procedures provide CI-994 and MS-275 in 80% and 72% overall yields, respectively. We found that the combination of four HDIs (CI-994, MS-275, SAHA, and TSA) with retinoids all-trans-retinoic acid (ATRA) or 13-cis-retinoic acid (13-CRA) or our atypical retinoic acid metabolism blocking agents (RAMBAs) 1 (VN/14-1) or 2 (VN/66-1) produced synergistic anti-neoplastic activity on human LNCaP prostate cancer cells. The combination of 2 and SAHA induced G1 and G2/M cell cycle arrest and a decrease in the S phase in LNCaP cells. 2 + SAHA treatment effectively down-regulated cyclin D1 and cdk4, and up-regulated pro-differentiation markers cytokeratins 8/18 and pro-apoptotic Bad and Bax. Following subcutaneous administration, 2, SAHA or 2 + SAHA were well tolerated and caused significant suppression/regression of tumor growth compared with control. These results demonstrate that compound 2 and its combination with SAHA are potentially useful agents that warrant further preclinical development for treatment of prostate cancer.

PROTAC-mediated degradation of class i histone deacetylase enzymes in corepressor complexes

We have identified a proteolysis targeting chimera (PROTAC) of class I HDACs 1, 2 and 3. The most active degrader consists of a benzamide HDAC inhibitor, an alkyl linker, and the von Hippel-Lindau E3 ligand. Our PROTAC increased histone acetylation levels and compromised colon cancer HCT116 cell viability, establishing a degradation strategy as an alternative to class I HDAC inhibition.

NOVEL SOLID FORMS OF TACEDINALINE

Novel solid forms of tacedinaline (4-(acetylamino)-N-(2-aminophenyl)benzamide), including crystalline tacedinaline Forms A, B, and D, a novel crystalline tacedinaline TFA salt, and amorphous tacedinaline, are disclosed. Pharmaceutical compositions comprising crystalline tacedinaline Forms A, B, and D, the novel crystalline tacedinaline TFA salt, and/or amorphous tacedinaline, and methods of treating various conditions by administering those novel solid forms, are also disclosed.