200484-11-3

Basic information

• Product Name: CHS-828
• Synonyms: GMX 1778;N-[6-(4-Chlorophenoxy)hexyl]-N'-cyano-N''-4-pyridinylguanidine;1-(6-(4-chlorophenoxy)hexyl)-2-cyano-3-(pyridin-4-yl)guanidine;GMX1778(CHS-828);2-[6-(4-chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine
• CAS NO: 200484-11-3
• Molecular Formula: C₁₉H₂₂ClN₅O
• Molecular Weight: 371.87
• Product Categories: Inhibitors
• Mol File: 200484-11-3.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 526.9 °C at 760 mmHg
• Flash Point: 272.4 °C
• Appearance: white to beige/
• Density: 1.18 g/cm³
• Vapor Pressure: 3.44E-11mmHg at 25°C
• Refractive Index: 1.587
• Storage Temp.: ?20°C
• Solubility: DMSO: soluble20mg/mL, clear
• PKA: 7.36±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: CHS-828(CAS DataBase Reference)
• NIST Chemistry Reference: CHS-828(200484-11-3)
• EPA Substance Registry System: CHS-828(200484-11-3)

Safety Data

• Hazard Codes: T
• Statements: 25-36/37/38
• Safety Statements: 26-45
• WGK Germany: 3
• Hazardous Substances Data: 200484-11-3(Hazardous Substances Data)

Usage

Description

CHS-828 is a pyridyl cyanoguanidine anti-tumor agent that has been identified as a competitive inhibitor of Nampt (Nicotinamide phosphoribosyltransferase) as well as an inhibitor of the NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) pathway activity. It is known for its potent cytotoxic effects in human breast and lung cancer cells, both in vitro and in vivo.

Uses

Used in Pharmaceutical Industry:
CHS-828 is used as an anticancer agent for its potent cytotoxic effects on human breast (IC50 = 7.3 nM) and lung cancer (IC50 = 0.5 nM) cells. It has demonstrated the ability to inhibit the growth of MCF-7 breast cancer tumors and induce regression of NYH small cell lung cancer tumors in nude mice bearing human tumor xenografts when administered at doses of 20-50 mg/kg/day.
Additionally, CHS-828 is used as an inhibitor of the NF-κB pathway, which plays a crucial role in regulating cellular responses to various stimuli, including stress, cytokines, and bacterial or viral antigens. By inhibiting this pathway, CHS-828 may help in controlling the uncontrolled cell growth and inflammation associated with cancer.

References

1) Olesen?et al.?(2008),?Anticancer agent CHS-828 inhibits cellular synthesis of NAD; Biochem. Biophys. Res. Commun.?376?799 2) Hassan?et al. (2006),?CHS 828 kill tumor cells by inhibiting the nuclear factor-kappaB translocation but unlikely through down-regulation of proteasome; Anticancer Res.?26?4431 3) Hjarnaa?et al.?(1999),?CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo; Cancer Res.?59?5751 4) Cerna?et al.?(2012)?Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) activity by small molecule GMX1778 regulates reactive oxygen species (ROS)-mediated cytotoxicity in a p53- and nicotinic acid phosphoribosyltransferase1 (NAPRT1)-dependent manner; J. Biol. Chem.?287?22408

InChI:InChI=1/C19H22ClN5O/c20-16-5-7-18(8-6-16)26-14-4-2-1-3-11-23-19(24-15-21)25-17-9-12-22-13-10-17/h5-10,12-13H,1-4,11,14H2,(H2,22,23,24,25)

Upstream product

• 420-04-2 CYANAMID 
• 200484-41-9 6-(4-chlorophenoxy)hexyl-1-amine 
• 200483-99-4 (Z)-N'-cyano-N-(pyridin-4-yl) methylsulfanylmethanimidamide 
• 504-24-5 4-aminopyridine 

Downstream Products

• 432037-78-0 1-[N-(tert-butoxycarbonylmethyl)-carbamoyloxymethyl]-4-[N'-cyano-N-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide 
• 432037-74-6 1-[5-(N-tert-butoxycarbonylamino)-pentanoyloxymethyl]-4-[N'-cyano-N-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide 
• 432037-58-6 1-Pivaloyloxymethyl-4-[N'-cyano-N-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium chloride 
• 432037-76-8 1-[3-(tert-butoxycarbonyl)-propionyloxymethyl]-4-[N'-cyano-N-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium chloride 
• 432037-72-4 1-[3-(N-tert-butoxycarbonylamino)-propyl-carbamoyloxymethyl]-4-[N'-cyano-N-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide 
• 431894-79-0 1-[2-(2-(2-Methoxyethoxy)-ethoxy)-ethoxy-carbonyloxymethyl]-4-[N'-cyano-N-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium chloride 

Relevant articles and documents

PHARMACEUTICAL COMPOSITIONS COMPRISING PYRIDYL CYANOGUANIDINE, PROCESS FOR PREPARING THE SAME AND USE THEREOF

Disclosed are a composition comprising a pyridyl cyanoguanidine and a cyclodextrin, a cyclodextrin derivative and/or a surfactant with solubilization, process for preparing the same and use thereof.

Method of modulating NF-kB activity

A method of modulating the level of activated, NF-κB in cells by contacting cells with a cyanoguanidine compound of general formula I wherein n is 0, 1 or 2; each R independently represents halogen, trifluoromethyl, hydroxy, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, nitro, cyano, amino, sulfo or carboxy groups; Q is a straight or branched, saturated or unsaturated C4-20 divalent hydrocarbon radical; X Is a bond, O, S, amino, carbonyl, carbonylamino, aminocarbonyl, oxycarbonyloxy, oxycarbonyl, carbonyloxy, aminocarbonyloxy, aminothlocarbonyloxy, oxycarbonylamino or oxythiocarbonylamino; A is di-(C1-4 alkoxy)phosphinoyloxy, C1-4 alkoxycarbonyl, C1-4 alkoxycarbonylamino, saturated or unsaturated C3-12 carbocyclic ring or C3-12 heterocarbocyclic ring optionally substituted with one or more R1; R1 being independently selected from the group consisting of halogen, trifluoromethyl, hydroxy, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, nitro, cyano, amino, carboxy, sulfo, carboxamido, sulfamoyl or C1-4 hydroxyalkyl; or a pharmaceutically acceptable salt, N-oxide or N-substituted prodrug thereof, in an amount effective to modulate the activity of IKK.