8-Chloroadenosine

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

MedKoo CAT#: 527728

CAS#: 34408-14-5

Description: 8-Chloroadenosine, also known as NSC-354258 and 8-Cl-Ado, is an 5' AMP-activated protein kinase (AMPK) agonist potentially for the treatment of chronic lymphocytic leukemia. 8-Chloroadenosine has shown to deplete ATP and inhibit tumor growth in hematological malignancies as well as in lung and breast cancer cell lines. 8-chloroadenosine activity is associated with inhibition of the mTOR pathway, and that phospho RPS6 and PI3K pathway activation status may determine resistance.


Price and Availability

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8-Chloroadenosine (NSC-354258, 8-Cl-Ado) is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 527728
Name: 8-Chloroadenosine
CAS#: 34408-14-5
Chemical Formula: C10H12ClN5O4
Exact Mass: 301.0578
Molecular Weight: 301.687
Elemental Analysis: C, 39.81; H, 4.01; Cl, 11.75; N, 23.21; O, 21.21


Synonym: 8-Chloroadenosine; 8 Chloroadenosine; 8Chloroadenosine; NSC-354258; NSC 354258; NSC354258; 8-Cl-Ado; 8 Cl Ado; 8ClAdo

IUPAC/Chemical Name: (2R,3R,4S,5R)-2-(6-amino-8-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol

InChi Key: MHDPPLULTMGBSI-UUOKFMHZSA-N

InChi Code: InChI=1S/C10H12ClN5O4/c11-10-15-4-7(12)13-2-14-8(4)16(10)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,13,14)/t3-,5-,6-,9-/m1/s1

SMILES Code: OC[C@@H]1[C@H]([C@H]([C@H](N2C(Cl)=NC3=C(N=CN=C32)N)O1)O)O


Technical Data

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).

Harmonized System Code:
293490


References

1: Dicitore A, Grassi ES, Caraglia M, Borghi MO, Gaudenzi G, Hofland LJ, Persani L, Vitale G. The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines. Endocrine. 2016 Jan;51(1):101-12. doi: 10.1007/s12020-015-0597-7. PubMed PMID: 25863490.

2: Kearney AY, Fan YH, Giri U, Saigal B, Gandhi V, Heymach JV, Zurita AJ. 8-Chloroadenosine Sensitivity in Renal Cell Carcinoma Is Associated with AMPK Activation and mTOR Pathway Inhibition. PLoS One. 2015 Aug 27;10(8):e0135962. doi: 10.1371/journal.pone.0135962. PubMed PMID: 26313261; PubMed Central PMCID: PMC4552467.

3: Stellrecht CM, Vangapandu HV, Le XF, Mao W, Shentu S. ATP directed agent, 8-chloro-adenosine, induces AMP activated protein kinase activity, leading to autophagic cell death in breast cancer cells. J Hematol Oncol. 2014 Mar 14;7:23. doi: 10.1186/1756-8722-7-23. PubMed PMID: 24628795; PubMed Central PMCID: PMC4007639.

4: Han YY, Zhou Z, Cao JX, Jin YQ, Li SY, Ni JH, An GS, Zhang YX, Jia HT. E2F1-mediated DNA damage is implicated in 8-Cl-adenosine-induced chromosome missegregation and apoptosis in human lung cancer H1299 cells. Mol Cell Biochem. 2013 Dec;384(1-2):187-96. doi: 10.1007/s11010-013-1797-1. PubMed PMID: 24037421.

5: Jiao YY, Wang XQ, Lu WL, Yang ZJ, Zhang Q. A novel approach to improve the pharmacokinetic properties of 8-chloro-adenosine by the dual combination of lipophilic derivatisation and liposome formulation. Eur J Pharm Sci. 2013 Jan 23;48(1-2):249-58. doi: 10.1016/j.ejps.2012.10.026. PubMed PMID: 23159667.

6: Gao WL, Liu H, Li N, Zong MH. Regioselective enzymatic undecylenoylation of 8-chloroadenosine and its analogs with biomass-based 2-methyltetrahydrofuran as solvent. Bioresour Technol. 2012 Aug;118:82-8. doi: 10.1016/j.biortech.2012.04.104. PubMed PMID: 22705510.

7: Duan HY, Cao JX, Qi JJ, Wu GS, Li SY, An GS, Jia HT, Cai WW, Ni JH. E2F1 enhances 8-chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells. Biochemistry (Mosc). 2012 Mar;77(3):261-9. doi: 10.1134/S0006297912030042. PubMed PMID: 22803943.

8: McBrayer SK, Yarrington M, Qian J, Feng G, Shanmugam M, Gandhi V, Krett NL, Rosen ST. Integrative gene expression profiling reveals G6PD-mediated resistance to RNA-directed nucleoside analogues in B-cell neoplasms. PLoS One. 2012;7(7):e41455. doi: 10.1371/journal.pone.0041455. PubMed PMID: 22848499; PubMed Central PMCID: PMC3407247.

9: Stellrecht CM, Ayres M, Arya R, Gandhi V. A unique RNA-directed nucleoside analog is cytotoxic to breast cancer cells and depletes cyclin E levels. Breast Cancer Res Treat. 2010 Jun;121(2):355-64. doi: 10.1007/s10549-009-0481-3. PubMed PMID: 19641990.

10: Dennison JB, Ayres ML, Kaluarachchi K, Plunkett W, Gandhi V. Intracellular succinylation of 8-chloroadenosine and its effect on fumarate levels. J Biol Chem. 2010 Mar 12;285(11):8022-30. doi: 10.1074/jbc.M109.085803. PubMed PMID: 20064937; PubMed Central PMCID: PMC2832953.

11: Dennison JB, Balakrishnan K, Gandhi V. Preclinical activity of 8-chloroadenosine with mantle cell lymphoma: roles of energy depletion and inhibition of DNA and RNA synthesis. Br J Haematol. 2009 Nov;147(3):297-307. doi: 10.1111/j.1365-2141.2009.07850.x. PubMed PMID: 19709085; PubMed Central PMCID: PMC2778754.

12: Chen LS, Nowak BJ, Ayres ML, Krett NL, Rosen ST, Zhang S, Gandhi V. Inhibition of ATP synthase by chlorinated adenosine analogue. Biochem Pharmacol. 2009 Sep 15;78(6):583-91. doi: 10.1016/j.bcp.2009.05.019. PubMed PMID: 19477165; PubMed Central PMCID: PMC2763632.

13: Jia XZ, Yang SY, Zhou J, Li SY, Ni JH, An GS, Jia HT. Inhibition of CHK1 kinase by Gö6976 converts 8-chloro-adenosine-induced G2/M arrest into S arrest in human myelocytic leukemia K562 cells. Biochem Pharmacol. 2009 Mar 1;77(5):770-80. doi: 10.1016/j.bcp.2008.11.008. PubMed PMID: 19059218.

14: Zhang HJ, Li WJ, Yang SY, Li SY, Ni JH, Jia HT. 8-Chloro-adenosine-induced E2F1 promotes p14ARF gene activation in H1299 cells through displacing Sp1 from multiple overlapping E2F1/Sp1 sites. J Cell Biochem. 2009 Feb 15;106(3):464-72. doi: 10.1002/jcb.22033. PubMed PMID: 19115249.

15: Yang SY, Jia XZ, Feng LY, Li SY, An GS, Ni JH, Jia HT. Inhibition of topoisomerase II by 8-chloro-adenosine triphosphate induces DNA double-stranded breaks in 8-chloro-adenosine-exposed human myelocytic leukemia K562 cells. Biochem Pharmacol. 2009 Feb 1;77(3):433-43. doi: 10.1016/j.bcp.2008.10.022. PubMed PMID: 19014910.

16: Li WJ, Gu YY, Zhang HJ, Zhou J, Jia HT. Induction of p14ARF by E2F1 contributes to 8-chloro-adenosine-induced apoptosis in human lung cancer H1299 cells. Chemotherapy. 2009;55(5):335-43. doi: 10.1159/000230697. PubMed PMID: 19641316.

17: Robinson-White AJ, Hsiao HP, Leitner WW, Greene E, Bauer A, Krett NL, Nesterova M, Stratakis CA. Protein kinase A-independent inhibition of proliferation and induction of apoptosis in human thyroid cancer cells by 8-Cl-adenosine. J Clin Endocrinol Metab. 2008 Mar;93(3):1020-9. PubMed PMID: 18073299; PubMed Central PMCID: PMC2266951.

18: Stellrecht CM, Phillip CJ, Cervantes-Gomez F, Gandhi V. Multiple myeloma cell killing by depletion of the MET receptor tyrosine kinase. Cancer Res. 2007 Oct 15;67(20):9913-20. PubMed PMID: 17942923.

19: Gu YY, Zhang HY, Zhang HJ, Li SY, Ni JH, Jia HT. 8-Chloro-adenosine inhibits growth at least partly by interfering with actin polymerization in cultured human lung cancer cells. Biochem Pharmacol. 2006 Aug 28;72(5):541-50. PubMed PMID: 16844099.

20: Janković D, Pesić M, Marković J, Kanazir S, Marković I, Rakić L, Ruzdijić S. The combination of sulfinosine and 8-Cl-cAMP induces synergistic cell growth inhibition of the human neuroblastoma cell line in vitro. Invest New Drugs. 2006 Jan;24(1):15-25. PubMed PMID: 16379041.