Cambinol | CAS#14513-15-6 | SIRT inhibitor

MedKoo Cat#: 540055 | Name: Cambinol

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Cambinol is a SIRT inhibitor. It inhibits expression of pro-inflammatory cytokines, improves survival in models of endotoxic shock and septic shock, and prevents proliferation and increases differentiation and senescence in hepatocellular carcinoma cells.

Chemical Structure

Cambinol

CAS#14513-15-6

Theoretical Analysis

MedKoo Cat#: 540055

Name: Cambinol

CAS#: 14513-15-6

Chemical Formula: C21H16N2O2S

Exact Mass: 360.0932

Molecular Weight: 360.43

Elemental Analysis: C, 69.98; H, 4.47; N, 7.77; O, 8.88; S, 8.89

Price and Availability

Size	Price	Availability
50mg	USD 250.00	2 Weeks
100mg	USD 450.00	2 Weeks
200mg	USD 850.00	2 Weeks
500mg	USD 1,650.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 5,250.00	2 Weeks

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Synonym

SIRT 1/2 inhibitor IV; NSC112546; NSC-112546; NSC 112546; SIRT1 Inhibitor II; SIRT2 Inhibitor VI; Cambinol

IUPAC/Chemical Name

5-((2-hydroxynaphthalen-1-yl)methyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one

InChi Key

RVNSQVIUFZVNAU-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H16N2O2S/c24-18-11-10-13-6-4-5-9-15(13)16(18)12-17-19(14-7-2-1-3-8-14)22-21(26)23-20(17)25/h1-11,24H,12H2,(H2,22,23,25,26)

SMILES Code

O=C(C(CC1=C2C=CC=CC2=CC=C1O)=C(C3=CC=CC=C3)N4)NC4=S

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Cambinol is a SIRT1 and SIRT2 inhibitor with IC50 values of 56 μM and 59 μM, respectively. Cambinol is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor).

In vitro activity:

In the present study we identify cambinol, a sirtuin inhibitor, as a potent regulator of lysosome trafficking and inducer of JLA. Cambinol stimulates JLA independently from Rab7, NHE inhibition or gene expression changes, indicating that cambinol acts to aggregate lysosomes by a mechanism that is highly distinct from that of Tro. Additionally, cambinol does not activate autophagy as a means to drive JLA and sirtuin inhibition alone is not sufficient to drive JLA. It was found that cambinol treatment, similar to Tro, does activate ERK, which is required for JLA. Reference: Biochem Biophys Rep. 2015 Jul 26;3:83-93. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29124170/

In vivo activity:

As Daudi cells are tumorigenic in immunodeficient mice, these cells provided the opportunity to determine if cambinol might be active in xenografts after systemic administration to mice. Initial studies in Balb-c mice suggested that i.v. doses of 100 mg/kg cambinol are well tolerated. For xenograft studies, 20 × 106 Daudi cells were administered s.c. to the flank region of nonobese diabetic/severe combined immunodeficient mice. After palpable tumors were formed, cambinol, at the dose of 100 mg/kg, or vehicle alone, were administered i.v. into the tail vein or i.p. daily for 2 weeks (five injections weekly). No significant weight loss occurred in cambinol-treated animals relative to controls. Animals were euthanized on day 21 because of the large tumor size in the control group. Treatment with cambinol reduced tumor growth ( Fig. 6E) relative to mice treated with vehicle alone. These findings suggest that cambinol is active in the xenograft model and that concentrations of cambinol in vivo are high enough to obtain the antitumor effect without inducing obvious toxicity to animals. Reference: Cancer Res. 2006 Apr 15;66(8):4368-77. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16618762

	Solvent	mg/mL	mM
Solubility
	DMSO	21.0	58.26

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 360.43 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

Formulation protocol:

In vitro protocol:

1. Dykes SS, Friday E, Pruitt K, Cardelli JA. The histone deacetylase inhibitor cambinol prevents acidic pHe-induced anterograde lysosome trafficking independently of sirtuin activity. Biochem Biophys Rep. 2015 Jul 26;3:83-93. doi: 10.1016/j.bbrep.2015.07.015. PMID: 29124170; PMCID: PMC5668693. 2. Figuera-Losada M, Stathis M, Dorskind JM, Thomas AG, Bandaru VV, Yoo SW, Westwood NJ, Rogers GW, McArthur JC, Haughey NJ, Slusher BS, Rojas C. Cambinol, a novel inhibitor of neutral sphingomyelinase 2 shows neuroprotective properties. PLoS One. 2015 May 26;10(5):e0124481. doi: 10.1371/journal.pone.0124481. PMID: 26010541; PMCID: PMC4444023.

In vivo protocol:

1. Heltweg B, Gatbonton T, Schuler AD, Posakony J, Li H, Goehle S, Kollipara R, Depinho RA, Gu Y, Simon JA, Bedalov A. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77. doi: 10.1158/0008-5472.CAN-05-3617. PMID: 16618762.

1: Lugrin J, Ciarlo E, Santos A, Grandmaison G, dos Santos I, Le Roy D, Roger T. The sirtuin inhibitor cambinol impairs MAPK signaling, inhibits inflammatory and innate immune responses and protects from septic shock. Biochim Biophys Acta. 2013 Jun;1833(6):1498-510. doi: 10.1016/j.bbamcr.2013.03.004. Epub 2013 Mar 13. PubMed PMID: 23499872. 2: Figuera-Losada M, Stathis M, Dorskind JM, Thomas AG, Bandaru VV, Yoo SW, Westwood NJ, Rogers GW, McArthur JC, Haughey NJ, Slusher BS, Rojas C. Cambinol, a novel inhibitor of neutral sphingomyelinase 2 shows neuroprotective properties. PLoS One. 2015 May 26;10(5):e0124481. doi: 10.1371/journal.pone.0124481. eCollection 2015. PubMed PMID: 26010541; PubMed Central PMCID: PMC4444023. 3: Mahajan SS, Scian M, Sripathy S, Posakony J, Lao U, Loe TK, Leko V, Thalhofer A, Schuler AD, Bedalov A, Simon JA. Development of pyrazolone and isoxazol-5-one cambinol analogues as sirtuin inhibitors. J Med Chem. 2014 Apr 24;57(8):3283-94. doi: 10.1021/jm4018064. Epub 2014 Apr 15. PubMed PMID: 24697269; PubMed Central PMCID: PMC4002067. 4: Medda F, Russell RJ, Higgins M, McCarthy AR, Campbell J, Slawin AM, Lane DP, Lain S, Westwood NJ. Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J Med Chem. 2009 May 14;52(9):2673-82. doi: 10.1021/jm8014298. PubMed PMID: 19419202; PubMed Central PMCID: PMC2691587. 5: Lautz TB, Naiditch JA, Clark S, Chu F, Madonna MB. Efficacy of class I and II vs class III histone deacetylase inhibitors in neuroblastoma. J Pediatr Surg. 2012 Jun;47(6):1267-71. doi: 10.1016/j.jpedsurg.2012.03.039. PubMed PMID: 22703804. 6: Heltweg B, Gatbonton T, Schuler AD, Posakony J, Li H, Goehle S, Kollipara R, Depinho RA, Gu Y, Simon JA, Bedalov A. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77. PubMed PMID: 16618762. 7: Portmann S, Fahrner R, Lechleiter A, Keogh A, Overney S, Laemmle A, Mikami K, Montani M, Tschan MP, Candinas D, Stroka D. Antitumor effect of SIRT1 inhibition in human HCC tumor models in vitro and in vivo. Mol Cancer Ther. 2013 Apr;12(4):499-508. doi: 10.1158/1535-7163.MCT-12-0700. Epub 2013 Jan 21. PubMed PMID: 23339189. 8: Marshall GM, Liu PY, Gherardi S, Scarlett CJ, Bedalov A, Xu N, Iraci N, Valli E, Ling D, Thomas W, van Bekkum M, Sekyere E, Jankowski K, Trahair T, Mackenzie KL, Haber M, Norris MD, Biankin AV, Perini G, Liu T. SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability. PLoS Genet. 2011 Jun;7(6):e1002135. doi: 10.1371/journal.pgen.1002135. Epub 2011 Jun 16. PubMed PMID: 21698133; PubMed Central PMCID: PMC3116909. 9: Giammona LM, Panuganti S, Kemper JM, Apostolidis PA, Lindsey S, Papoutsakis ET, Miller WM. Mechanistic studies on the effects of nicotinamide on megakaryocytic polyploidization and the roles of NAD+ levels and SIRT inhibition. Exp Hematol. 2009 Nov;37(11):1340-1352.e3. doi: 10.1016/j.exphem.2009.08.004. Epub 2009 Aug 26. PubMed PMID: 19715739; PubMed Central PMCID: PMC2763937. 10: Preyat N, Leo O. Complex role of nicotinamide adenine dinucleotide in the regulation of programmed cell death pathways. Biochem Pharmacol. 2016 Feb 1;101:13-26. doi: 10.1016/j.bcp.2015.08.110. Epub 2015 Sep 3. PubMed PMID: 26343585. 11: Stenzinger A, Endris V, Klauschen F, Sinn B, Lorenz K, Warth A, Goeppert B, Ehemann V, Muckenhuber A, Kamphues C, Bahra M, Neuhaus P, Weichert W. High SIRT1 expression is a negative prognosticator in pancreatic ductal adenocarcinoma. BMC Cancer. 2013 Oct 2;13:450. doi: 10.1186/1471-2407-13-450. PubMed PMID: 24088390; PubMed Central PMCID: PMC3850795. 12: Simmons GE Jr, Pandey S, Nedeljkovic-Kurepa A, Saxena M, Wang A, Pruitt K. Frizzled 7 expression is positively regulated by SIRT1 and β-catenin in breast cancer cells. PLoS One. 2014 Jun 4;9(6):e98861. doi: 10.1371/journal.pone.0098861. eCollection 2014. PubMed PMID: 24897117; PubMed Central PMCID: PMC4045932. 13: Laemmle A, Lechleiter A, Roh V, Schwarz C, Portmann S, Furer C, Keogh A, Tschan MP, Candinas D, Vorburger SA, Stroka D. Inhibition of SIRT1 impairs the accumulation and transcriptional activity of HIF-1α protein under hypoxic conditions. PLoS One. 2012;7(3):e33433. doi: 10.1371/journal.pone.0033433. Epub 2012 Mar 30. PubMed PMID: 22479397; PubMed Central PMCID: PMC3316573. 14: Ghosh A, Sengupta A, Seerapu GPK, Nakhi A, Shivaji Ramarao EVV, Bung N, Bulusu G, Pal M, Haldar D. A novel SIRT1 inhibitor, 4bb induces apoptosis in HCT116 human colon carcinoma cells partially by activating p53. Biochem Biophys Res Commun. 2017 May 17. pii: S0006-291X(17)30963-4. doi: 10.1016/j.bbrc.2017.05.089. [Epub ahead of print] PubMed PMID: 28526414. 15: Fernandes CA, Fievez L, Neyrinck AM, Delzenne NM, Bureau F, Vanbever R. Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages. Biochem Biophys Res Commun. 2012 Apr 20;420(4):857-61. doi: 10.1016/j.bbrc.2012.03.088. Epub 2012 Mar 24. PubMed PMID: 22469470. 16: Moscardó A, Vallés J, Latorre A, Jover R, Santos MT. The histone deacetylase sirtuin 2 is a new player in the regulation of platelet function. J Thromb Haemost. 2015 Jul;13(7):1335-44. doi: 10.1111/jth.13004. Epub 2015 Jun 11. PubMed PMID: 25960087. 17: Liang Z, Yang Y, Wang H, Yi W, Yan X, Yan J, Li Y, Feng Y, Yu S, Yang J, Jin Z, Duan W, Chen W. Inhibition of SIRT1 signaling sensitizes the antitumor activity of silybin against human lung adenocarcinoma cells in vitro and in vivo. Mol Cancer Ther. 2014 Jul;13(7):1860-72. doi: 10.1158/1535-7163.MCT-13-0942. Epub 2014 May 5. PubMed PMID: 24798868. 18: Holloway KR, Barbieri A, Malyarchuk S, Saxena M, Nedeljkovic-Kurepa A, Cameron Mehl M, Wang A, Gu X, Pruitt K. SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression. Mol Endocrinol. 2013 Mar;27(3):480-90. doi: 10.1210/me.2012-1347. Epub 2013 Jan 22. PubMed PMID: 23340254; PubMed Central PMCID: PMC3589668. 19: Gerhauser C. Cancer chemoprevention and nutriepigenetics: state of the art and future challenges. Top Curr Chem. 2013;329:73-132. doi: 10.1007/128_2012_360. Review. PubMed PMID: 22955508. 20: Huang J, Plass C, Gerhauser C. Cancer chemoprevention by targeting the epigenome. Curr Drug Targets. 2011 Dec;12(13):1925-56. Review. PubMed PMID: 21158707.