392721-37-8

Basic information

• Product Name: N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide
• Synonyms: N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide;Fasentin
• CAS NO: 392721-37-8
• Molecular Formula: C₁₁H₉ClF₃NO₂
• Molecular Weight: 279.64
• Mol File: 392721-37-8.mol
• Article Data: 1

Chemical Properties

• Appearance: white to off-white/
• Storage Temp.: room temp
• Solubility: DMSO: >10mg/mL
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide(392721-37-8)
• EPA Substance Registry System: N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide(392721-37-8)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 392721-37-8(Hazardous Substances Data)

Usage

Description

N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide, also known as Fasentin, is a novel compound that functions as an inhibitor of glucose uptake. It acts by inhibiting the glucose transporters GluT1 and GluT4, with an IC50 value of 68 μM. Fasentin is characterized by its ability to block glucose uptake in a cell type-specific manner, making it a promising candidate for cancer therapeutics. Additionally, it has been shown to rescue cardiac progenitor cell dysfunction and mitochondrial fission induced by high glucose levels and to sensitize cells to FAS-induced cell death.

Uses

Used in Cancer Therapeutics:
Fasentin is used as a glucose transporter (GLUT1) inhibitor for its potential in treating a wide range of triple-negative breast cancer (TNBC) cell lines. By inhibiting glucose uptake, it can assess the vulnerability of these cancer cells and study the effects of cytotoxic drugs induced by hydrocortisone (HC). Fasentin's ability to block glucose uptake can lead to the development of new cancer therapeutics, as it targets the energy supply of cancer cells, which heavily rely on glucose for their rapid growth and proliferation.
Used in Cardiac Research:
Fasentin is also used in the study of cardiac progenitor cell dysfunction and mitochondrial fission induced by high glucose levels. Its role in rescuing these cells from the detrimental effects of high glucose can contribute to a better understanding of the mechanisms underlying cardiac diseases and the development of potential treatments.
Used in Apoptosis Research:
Fasentin is used to sensitize cells to FAS-induced cell death, which is an important aspect of cancer treatment. By enhancing the sensitivity of cancer cells to apoptosis-inducing stimuli, Fasentin can potentially improve the effectiveness of existing cancer therapies and contribute to the development of novel treatment strategies.

Biochem/physiol Actions

Fasentin is a novel inhibitor of glucose uptake, GluT1 inhibitor. Fasentin is a novel inhibitor of glucose uptake that sensitizes cells to FAS-induced cell death. Fasentin selectively sensitized to death ligands, but did not decrease FLIP expression. It alters expression of genes associated with nutrient and glucose deprivation. Fasentin interacted with a unique site in the intracellular channel of the glucose transport protein GLUT1.

References

1) Granchi?et al.?(2016),?Anticancer agents interacting with membrane glucose transporters; Med. Chem. Comm.,?7?1716 2) Kraus?et al. (2018),?Targeting glucose transport and the NAD pathway in tumor cells with STF-31: a re-evaluation; Cell. Oncol. (Dordr),?41?485 3) Adekola?et al. (2012),?Glucose transporters in cancer metabolism; Curr. Opin. Oncol.,?24?650 4) Choi?et al.?(2016),?High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker; Prog. Biomol. Ther. (Seoul),?24?363 5) Schimmer?et al.?(2006),?Identification of small molecules that sensitize resistant tumor cells to tumor necrosis factor-family death receptors; Cancer Res.,?66?2367 6) Wood?et al.?(2008),?A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death; Mol. Cancer Ther.,?7?3546

Upstream product

• 141-97-9 ethyl acetoacetate 
• 320-51-4 4-chloro-3-trifluoromethyl-aniline 

Relevant articles and documents

5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors

Chronic hepatitis B virus (HBV) infection represents a major health threat. Current FDA-approved drugs do not cure HBV. Targeting HBV core protein (Cp) provides an attractive approach toward HBV inhibition and possibly infection cure. We have previously identified and characterized a 5-amino-3-methylthiophene-2,4-dicarboxamide (ATDC) compound as a structurally novel hit for capsid assembly effectors (CAEs). We report herein hit validation through studies on absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK), and hit optimization via analogue synthesis aiming to probe the structure-activity relationship (SAR) and structure-property relationship (SPR). In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC50 = 0.11 μM, CC50 > 100 μM, F = 25%) and 19k (EC50 = 0.31 μM, CC50 > 100 μM, F = 46%), displayed overall lead profiles superior to reported CAEs 7–10 used in our studies.