112522-64-2 Usage
Description
4-Acetylamino-N-(2'-aminophenyl)benzamide, also known as CI-994, is an orally active histone deacetylase (HDAC) inhibitor with a unique structure obtained by formal condensation of the carboxy group of 4-acetamidobenzoic acid with one of the amino groups of 1,2-phenylenediamine. It exhibits impressive differential activity against leukemic cells and normal stem cells, making it a promising compound for various pharmaceutical applications.
Uses
Used in Anticancer Applications:
4-Acetylamino-N-(2'-aminophenyl)benzamide is used as an anti-cancer agent for its ability to block angiogenesis, arrest cell growth, and induce differentiation and apoptosis in tumor cells. It has shown effectiveness against acute myeloid leukemia in vitro and in vivo when used in combination with conventional anti-cancer agents.
Used in Combination Therapy:
In the pharmaceutical industry, 4-Acetylamino-N-(2'-aminophenyl)benzamide is used as a component in combination therapy for selected tumors, including non-small cell lung, pancreatic, breast, and colorectal cancers. Its unique properties allow it to enhance the efficacy of other treatments and provide better outcomes for patients.
Used in Neuroplasticity Enhancement:
4-Acetylamino-N-(2'-aminophenyl)benzamide is also used to increase neuroplasticity during memory extinction, which can have potential applications in the treatment of neurological disorders and cognitive enhancement.
Used in Beta Cell Protection:
In the field of diabetes research and treatment, 4-Acetylamino-N-(2'-aminophenyl)benzamide is used to protect beta cells from cytokine-induced apoptosis, which can contribute to the development of novel therapies for diabetes management.
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
Check Digit Verification of cas no
The CAS Registry Mumber 112522-64-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,2,5,2 and 2 respectively; the second part has 2 digits, 6 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 112522-64:
(8*1)+(7*1)+(6*2)+(5*5)+(4*2)+(3*2)+(2*6)+(1*4)=82
82 % 10 = 2
So 112522-64-2 is a valid CAS Registry Number.
112522-64-2Relevant 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
Gediya, Lalji K.,Belosay, Aashvini,Khandelwal, Aakanksha,Purushottamachar, Puranik,Njar, Vincent C.O.
, p. 3352 - 3360 (2008)
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
Adams, Grace E.,Cowley, Shaun Michael,Hodgkinson, James T.,Millard, Christopher J.,Norris, James K. S.,Schwabe, John W. R.,Smalley, Joshua P.,Song, Yun
, p. 4476 - 4479 (2020/05/13)
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
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Page/Page column 52-53, (2012/01/15)
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.
