22978-25-2

Basic information

• Product Name: GW9662
• Synonyms: 2-CHLORO-5-NITRO-N-PHENYLBENZAMIDE;2-CHLORO-5-NITROBENZANILIDE;GW9662;TIMTEC-BB SBB006523;2-Chloro-5-nitro-N-4-phenylbenzamide;BenzaMide,2-chloro-5-nitro-N-phenyl-;N-[(2-chloro-5-nitrophenyl)-phenylmethylidene]hydroxylamine;2-Chloro-5-nitrobenzanilide 97%
• CAS NO: 22978-25-2
• Molecular Formula: C₁₃H₉ClN₂O₃
• Molecular Weight: 276.68
• EINECS: 1592732-453-0
• Product Categories: Inhibitors;Amides;Carbonyl Compounds;Organic Building Blocks;Intracellular receptor;Inhibitor
• Mol File: 22978-25-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 171-175 °C(lit.)
• Boiling Point: 360.9°Cat760mmHg
• Flash Point: 172°C
• Appearance: white/solid
• Density: 1.44g/cm³
• Vapor Pressure: 2.15E-05mmHg at 25°C
• Refractive Index: 1.676
• Storage Temp.: 2-8°C
• Solubility: DMSO: 26 mg/mL, soluble
• PKA: 11.77±0.70(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
• CAS DataBase Reference: GW9662(CAS DataBase Reference)
• NIST Chemistry Reference: GW9662(22978-25-2)
• EPA Substance Registry System: GW9662(22978-25-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36-43
• Safety Statements: 26-36/37-24/25-22
• WGK Germany: 3
• Hazardous Substances Data: 22978-25-2(Hazardous Substances Data)

Usage

Description

GW9662, also known as GW-9662, is a selective peroxisome proliferator-activated receptor gamma (PPARγ) antagonist. It is an off-white solid that has been used in various applications due to its ability to irreversibly bind to PPARγ, a nuclear receptor involved in several cellular processes. GW9662 has demonstrated potential in the field of cancer research and has been utilized as a tool to study the role of PPARγ in cellular physiology.

Uses

Used in Pharmaceutical Research:
GW9662 is used as an irreversible PPARγ antagonist for studying the role of PPARγ in cellular processes and its potential involvement in various diseases. It has been particularly useful in dissecting the involvement of PPARγ in cellular physiology.
Used in Cancer Research:
GW9662 is used as an anticancer agent, displaying activity against the growth of human mammary tumor cell lines. It has shown potential in inhibiting the growth of cancer cells and has been used to study the role of PPARγ in cancer development and progression.
Used in Cell Biology:
GW9662 has been used in human pluripotent stem cells and phenylephrine-stimulated cardiomyocytes to study the effects of PPARγ inhibition on cellular processes. It has also been used to inhibit the protective effect of telmisartan in pheochromocytoma PC12 cells, providing insights into the role of PPARγ in cell signaling and function.
Used in Drug Development:
GW9662 is used as a selective and cell-permeable PPAR antagonist in the development of new drugs targeting PPARγ. Its ability to covalently modify a cysteine residue in the binding site of PPARγ makes it a valuable tool for drug discovery and development.

Biological Activity

Selective PPAR γ antagonist (IC 50 values are 3.3, 32 and 2000 nM for PPAR γ , PPAR α and PPAR δ respectively). Blocks the inhibition of osteoclast formation induced by IL-4 in the low micromolar range (1-2 μ M), therefore is more potent than BADGE (2,2-Bis[4-(2,3-epoxypropoxy)phenyl]propane ). Anticancer, inhibits growth of human mammary tumor cell lines.

Biochem/physiol Actions

GW9662 (2-chloro-5-nitrobenzanilide) binds to the ligand binding site of the peroxisome proliferator activated receptor γ (PPARγ) and results in the inhibition of adipocyte differentiation. It favors cell growth suppression in breast cancer cell lines even in the presence of PPARγ agonist rosiglitazone. It stimulates M2c macrophages differentiation and triggers growth arrest-specific 6 (Gas6) expression. GW9662 co treatment with other PPARγ ligands elicits antiproliferative effects on the glioblastoma stem cells and could be a potent therapeutic agent.

References

1) Leesnitzer et al. (2002), Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662; Biochemistry, 41 6640 2) Bendixen et al. (2001), IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor gamma 1; Proc. Natl. Acad. Sci. USA, 98 2443 3) Seargent et al. (2004), GW9662, a potent antagonist of PPARgamma inhibits growth of breast cancer tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation; Br. J. Pharmacol., 143 933 4) Cheng et al. (2014), β-Caryophyllene Ameliorates the Alzheimer-Like Phenotype in APP/PS1 Mice through CB2 Receptor Activation and the PPARγ Pathway; Pharmacology, 94 1 5) Liu et al. (2014), Curcumin protects neurons against oxygen-glucose deprivation/reoxygenation-induced injury through activation of peroxisome proliferator-activated-γ function; J. Neuro. Sci. Res., 92 1549

InChI:InChI=1/C13H9ClN2O3/c14-12-7-6-10(16(18)19)8-11(12)13(17)15-9-4-2-1-3-5-9/h1-8H,(H,15,17)

Upstream product

• 25784-91-2 2-chloro-5-nitrobenzoylchloride 
• 62-53-3 aniline 
• 60-29-7 diethyl ether 
• 10026-13-8 phosphorus pentachloride 
• 141883-38-7 2-chloro-5-nitro-benzophenone oxime 
• 2516-96-3 2-chloro-5-nitrobenzoic acid 

Downstream Products

• 861294-05-5 2-methoxy-5-nitro-benzoic acid anilide 
• 136146-76-4 3-Amino-7-nitro-2,4-diphenyl-2H-isoquinolin-1-one 
• 1060674-96-5 2-(tert-butylthio)-5-nitro-N-phenylbenzamide 
• 111362-57-3 5-amino-2-chloro-N-phenylbenzamide 
• 1192927-99-3 N-(4-chloro-3-(phenylcarbamoyl)phenylcarbamothioyl)-3,4,5-trimethoxybenzamide 
• 1263131-89-0 N-(N-(4-chloro-3-(phenylcarbamoyl)phenyl)carbamimidoyl)-3,4,5-trimethoxybenzamide 
• 1421846-60-7 6-chloro-2-nitro-10-phenyldibenzo[b,f][1,4]thiazepin-11(10H)-one 
• 1421846-71-0 8-nitro-11-phenyl-3-(trifluoromethyl)benzo[f]pyrido[3,2-b][1,4]thiazepin-10(11H)one 

Relevant articles and documents

Covalent Occlusion of the RORγt Ligand Binding Pocket Allows Unambiguous Targeting of an Allosteric Site

The nuclear receptor RORγt is a key positive regulator in the differentiation and proliferation of T helper 17 (Th17) cells and the production of proinflammatory cytokines like IL-17a. Dysregulation of this pathway can result in the development of various

Thioimides: New reagents for effective synthesis of thiolesters from carboxylic acids

(Chemical Equation Presented) Thioimides and carboxylic acids are used as the precursors for the convenient synthesis of thiolesters in the phosphine mediated process. Cyclic and acyclic thioimides show equal efficiency, furnishing the desired thiolesters in good to excellent yields. The general, highly efficient transformation tolerates various functional groups and the resulting thiolesters are obtained in high purity after a simple separation. The reaction scope has been demonstrated on the preparation of several highly functionalized target molecules.

Synthesis, antimicrobial, and QSAR studies of substituted benzamides

A series of new substituted benzamides were synthesized and tested in vitro for their antibacterial activity against Gram-positive and Gram-negative bacteria and as well for antifungal activity. The compounds 8i and 9 showed better activity among the different benzamides synthesized. The structural characteristics governing antibacterial activities of substituted benzamides were studied using QSAR methodology. The results showed that the antimicrobial activity could be modeled using the topological descriptors, molecular connectivity indices (2χv and 2χ) and Kiers shape index (κα1). The low residual activity and high cross-validated r2 values (rcv2) observed indicated the predictive ability of the developed QSAR models.