WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200776
CAS#: 200484-11-3 (free)
Description: CHS-828, also known as GMX-1778, is a potent and selective NAMPT inhibitor. CHS-828 inhibits cellular synthesis of NAD. CHS 828 kill tumour cells by inhibiting the nuclear factor-kappaB translocation but unlikely through down-regulation of proteasome. CHS 828 has shown promising anticancer activity in experimental tumor models and primary cultures of cancer cells from patients. CHS 828 showed a synergistic effect with melphalan in 67%, doxorubicin in 47%, etoposide in 38% and Ara-C in 14% of AML samples.
MedKoo Cat#: 200776
CAS#: 200484-11-3 (free)
Chemical Formula: C19H22ClN5O
Exact Mass: 371.15129
Molecular Weight: 371.86
Elemental Analysis: C, 61.37; H, 5.96; Cl, 9.53; N, 18.83; O, 4.30
CHS-828, purity > 98%, is in stock. The same day shipping out after order is received.
Synonym: CHS 828; CHS828; CHS-828; GMX-1778; GMX1778; GMX 1778.
IUPAC/Chemical Name: (E)-1-(6-(4-chlorophenoxy)hexyl)-2-cyano-3-(pyridin-4-yl)guanidine
InChi Key: BOIPLTNGIAPDBY-UHFFFAOYSA-N
InChi Code: InChI=1S/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)
SMILES Code: N#C/N=C(NC1=CC=NC=C1)\NCCCCCCOC2=CC=C(Cl)C=C2
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|Soluble in DMSO, not in water||100.0|
The following data is based on the product molecular weight 371.86 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: von Heideman A, Berglund A, Larsson R, Nygren P. Safety and efficacy of NAD depleting cancer drugs: results of a phase I clinical trial of CHS 828 and overview of published data. Cancer Chemother Pharmacol. 2010 May;65(6):1165-72. doi: 10.1007/s00280-009-1125-3. Epub 2009 Sep 30. PubMed PMID: 19789873.
2: LÃ¶vborg H, Burman R, Gullbo J. Structure-activity relationship analysis of cytotoxic cyanoguanidines: selection of CHS 828 as candidate drug. BMC Res Notes. 2009 Jun 29;2:114. doi: 10.1186/1756-0500-2-114. PubMed PMID: 19563661; PubMed Central PMCID: PMC2709656.
3: Olesen UH, Christensen MK, BjÃ¶rkling F, JÃ¤Ã¤ttelÃ¤ M, Jensen PB, Sehested M, Nielsen SJ. Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804. doi: 10.1016/j.bbrc.2008.01.019. Epub 2008 Jan 15. PubMed PMID: 18201551.
4: Hassan SB, LÃ¶vborg H, Lindhagen E, Karlsson MO, Larsson R. CHS 828 kill tumour cells by inhibiting the nuclear factor-kappaB translocation but unlikely through down-regulation of proteasome. Anticancer Res. 2006 Nov-Dec;26(6B):4431-6. PubMed PMID: 17201165.
5: Johanson V, Arvidsson Y, KÃ¶lby L, Bernhardt P, SwÃ¤rd C, Nilsson O, Ahlman H. Antitumoural effects of the pyridyl cyanoguanidine CHS 828 on three different types of neuroendocrine tumours xenografted to nude mice. Neuroendocrinology. 2005;82(3-4):171-6. Epub 2006 Feb 24. PubMed PMID: 16508338.
6: Friberg LE, Hassan SB, Lindhagen E, Larsson R, Karlsson MO. Pharmacokinetic-pharmacodynamic modelling of the schedule-dependent effect of the anti-cancer agent CHS 828 in a rat hollow fibre model. Eur J Pharm Sci. 2005 May;25(1):163-73. PubMed PMID: 15854812.
7: Ravaud A, Cerny T, Terret C, Wanders J, Bui BN, Hess D, Droz JP, Fumoleau P, Twelves C. Phase I study and pharmacokinetic of CHS-828, a guanidino-containing compound, administered orally as a single dose every 3 weeks in solid tumours: an ECSG/EORTC study. Eur J Cancer. 2005 Mar;41(5):702-7. PubMed PMID: 15763645.
8: Olsen LS, Hjarnaa PJ, Latini S, Holm PK, Larsson R, Bramm E, Binderup L, Madsen MW. Anticancer agent CHS 828 suppresses nuclear factor-kappa B activity in cancer cells through downregulation of IKK activity. Int J Cancer. 2004 Aug 20;111(2):198-205. PubMed PMID: 15197771.
9: LÃ¶vborg H, Nygren P, Larsson R. Multiparametric evaluation of apoptosis: effects of standard cytotoxic agents and the cyanoguanidine CHS 828. Mol Cancer Ther. 2004 May;3(5):521-6. PubMed PMID: 15141009.
Review of Phase I trials of CHS-828. Seven patients with previously treated solid tumours received oral administration of CHS 828 in the dose range 20-80 mg once weekly for 3 weeks in 4 weeks cycles. Toxicity was dominated by gastrointestinal symptoms including nausea, vomiting, diarrhoea, constipation, subileus and gastric ulcer. One patient had thrombocytopenia grade 2. There were two cases each of grade 3-4 hyperuricemia and hypokalemia. Safety and efficacy of the NAD depleting drugs CHS 828 and FK866 have been reported from four phase I clinical trials, including a total of 97 patients with previously treated solid tumours. Outstanding toxicity reported was thrombocytopenia and various gastrointestinal symptoms. No objective tumour remission has been observed in the total of 104 patients treated in the above early trials. Critical toxicity from NAD depleting cancer drugs to consider in future trials seems to be thrombocytopenia and various gastrointestinal symptoms. Efficacy of NAD depleting drugs when used alone is expected to be low. (source: Cancer Chemother Pharmacol. 2010 May;65(6):1165-72 ).
Phase I study of CHS-828. CHS 828 was given orally once every 3 weeks. The starting dose was 50 mg, which was escalated to 500 mg. A total of 107 courses was administered to 37 patients. At the 500-mg dose level, two of three patients experienced dose-limiting toxicities (DLT) (grade 3 mucositis and grade 4 thrombocytopenia), establishing this as the MTD. One of seven patients treated at 420 mg dose experienced DLT (grade 4 leucopenia, grade 4 mucositis and grade 4 diarrhoea), and this was considered the recommended dose for phase II studies. Vomiting, haematuria, leucopenia and thrombocytopenia were other significant toxicities. The pharmacokinetics of CHS 828 showed large variations both between and within patients. No objective responses were seen. A dose of 420 mg of CHS 828 administered every 3 weeks is the recommended dose, while 500 mg is the MTD. (source: Eur J Cancer. 2005 Mar;41(5):702-7.).
Phase I study of CHS-828.
(source: Eur J Cancer. 2005 Mar;41(5):702-7.).