|
Back to products
Browse products
Approved anticancer agents
Anticancer agents in trials
Anticancer molecular libraries
Other drug agents
Drug intermediates
Bio-reagents and biochemicals
|
MedKoo product information:
Isatoribine
Descrpition of isatoribine: isatoribine (also known
as immunosine, or 7-thia-8-oxoguanosine) is a novel guanosine
analogue showing immunostimulatory activity both in vivo and in
vitro. This compound acts on different components of the immune
system including B cells, natural killer (NK) cells and
antigen-presenting cells (APC). It was found that immunosine
significantly stimulates proliferation of T cells. The effect was
dose-dependent and also depended on concentrations of specific
stimulators. Maximal stimulation was seen using 250 microM
immunosine. The stimulatory effect of immunosine on lymphocyte
proliferation triggered by Concanavalin A (Con A) correlated with
increased interleukin 2 (IL-2) production and upregulation of the
IL-2 receptor alpha (IL-2Ralpha) expression. (source: Fundam Clin
Pharmacol. 2000 May-Jun;14(3):209-17.)
Current developer:
Anadys Pharmaceuticals, Inc.
|
MedKoo Code#:
201590
|
|
Name:
Isatoribine
|
|
CAS#:
198832-38-1
Synonym:
ANA245;Immusine;Isatoribine hydrate;Isatoribine
monohydrate;D04619;7-thia-8-oxoguanosine.
IUPAC/Chemical name:
5-amino-3-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)thiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione
hydrate
|
|
Chemical structure: |
Theoretical analysis
|
|

|
Isatoribine monohydrate
Chemical Formula: C10H14N4O7S
Molecular Weight: 334.31
Elemental Analysis: C, 35.93; H, 4.22; N,
16.76; O, 33.50; S, 9.59
Isatoribine
Chemical Formula:
C10H12N4O6S
Exact Mass: 316.04775
Elemental Analysis: C,
37.97; H, 3.82; N, 17.71; O, 30.35; S, 10.14
|
|
Availability and price:
This product is available through custom synthesis
To inquire the quotation and lead time of custom synthesis for this agent, please send email to
sales@medkoo.com to describe your needs. A representative
will respond your email shortly. We offer big discount for orders of bulk quantities.
|
|
Quality control
data:
Product will be shipped with
supporting analytical data.
|
|
Information about this agent
|
Isatoribine is currently
developed by Anadys Pharmaceuticals, Inc. According to
Anadys's website, isatoribine is a
nucleoside analog currently in evaluating in ongoing clinical trials for
the treatment of HCV infections. Isatoribine represents one of a new
class of drugs being developed by Anadys to regulate innate immunity,
combat HCV infection, and overcome limitations of current anti-HCV
therapies. Anadys believes isatoribine interacts with a specific
receptor, Toll-like receptor 7, or TLR7, that is present on certain
immune system cells. Although results of initial clinical trials may not
be predictive of future results, interim results of the Phase 1B
clinical trial show that isatoribine is biologically active in adults
with chronic HCV infection and results from dosing a cohort of six HCV
infected patients with 800mg of isatoribine showed a statistically
significant reduction of viral load (p=0.03) at the end of one week,
with a median change in viral load from baseline of -0.94 log10 units.
Anadys is currently enrolling patients for an isatoribine Phase I/II
study.
Current developer:
Anadys Pharmaceuticals, Inc.
1: Xiang AX, Webber SE, Kerr BM, Rueden EJ,
Lennox JR, Haley GJ, Wang T, Ng JS, Herbert MR, Clark DL, Banh VN, Li W,
Fletcher SP, Steffy KR, Bartkowski DM, Kirkovsky LI, Bauman LA, Averett
DR. Discovery of ANA975: an oral prodrug of the TLR-7 agonist
isatoribine. Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):635-40.
PubMed PMID: 18066870.
2: Jin G, Wu CC, Carson DA, Cottam HB. Guanosine analog in the pyrido[2,3-d]pyrimidine
ring system as a potential toll-like receptor agonist. Nucleosides
Nucleotides Nucleic Acids. 2006;25(12):1391-7. PubMed PMID: 17067960.
3: Fletcher S, Steffy K, Averett D. Masked oral prodrugs of toll-like
receptor 7 agonists: a new approach for the treatment of infectious
disease. Curr Opin Investig Drugs. 2006 Aug;7(8):702-8. Review. PubMed
PMID: 16955681.
4: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods
Find Exp Clin Pharmacol. 2005 Nov;27(9):665-77. PubMed PMID: 16357953.
5: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods
Find Exp Clin Pharmacol. 2005 Oct;27(8):569-612. PubMed PMID: 16273137.
6: Horsmans Y, Berg T, Desager JP, Mueller T, Schott E, Fletcher SP,
Steffy KR, Bauman LA, Kerr BM, Averett DR. Isatoribine, an agonist of
TLR7, reduces plasma virus concentration in chronic hepatitis C
infection. Hepatology. 2005 Sep;42(3):724-31. PubMed PMID: 16116638.
7: Colić M, Jandrić D, Gasić S, Vucević D, Popović P, Medić-Mijacević L,
Rakić L. Immunosine (7-thia-8-oxoguanosine) acts as a cofactor for
proliferation of T cells. Fundam Clin Pharmacol. 2000
May-Jun;14(3):209-17. PubMed PMID: 15602797.
8: Lee J, Chuang TH, Redecke V, She L, Pitha PM, Carson DA, Raz E,
Cottam HB. Molecular basis for the immunostimulatory activity of guanine
nucleoside analogs: activation of Toll-like receptor 7. Proc Natl Acad
Sci U S A. 2003 May 27;100(11):6646-51. Epub 2003 May 8. PubMed PMID:
12738885; PubMed Central PMCID: PMC164501.
9: Colić M, Gasić S, Vucević D, Pavicić L, Popović P, Jandrić D,
Medić-Mijacević L, Rakić L. Modulatory effect of 7-thia-8-oxoguanosine
on proliferation of rat thymocytes in vitro stimulated with concanavalin
A. Int J Immunopharmacol. 2000 Mar;22(3):203-12. PubMed PMID: 10685003.
10: Colic M, Vucevic D, Vasilijic S, Popovic L, Pejanovic V, Jandric D,
Medic-Mijacevic L, Rakic L. Proliferation of spleen cells in culture
stimulated by 7-thia-8-oxoguanosine: evidence that both B- and T-cells
are the targets of its action. Methods Find Exp Clin Pharmacol. 1999
Nov;21(9):583-90. PubMed PMID: 10669901.
11: Colić M, Gasić S, Vasilijić S, Pejanović V, Jandrić D,
Medić-Mijacević L, Rakić L. A nucleoside analogue, 7-thia-8-oxoguanosine
stimulates proliferation of thymocytes in vitro. Immunol Lett. 1999 Sep
1;69(3):293-300. PubMed PMID: 10528791.
12: Black PL, McKinnon KM, Wooden SL, Ussery MA. Antiviral activity of
biological response modifiers in a murine model of AIDS. Requirement for
augmentation of natural killer cell activity and synergy with oral AZT.
Int J Immunopharmacol. 1996 Nov;18(11):633-50. PubMed PMID: 9089007.
13: Smee DF, Alaghamandan HA, Ramasamy K, Revankar GR. Broad-spectrum
activity of 8-chloro-7-deazaguanosine against RNA virus infections in
mice and rats. Antiviral Res. 1995 Mar;26(2):203-9. PubMed PMID:
7605116.
14: Lewis AF, Drach JC, Fennewald SM, Huffman JH, Ptak RG, Sommadossi
JP, Revankar GR, Rando RF. Inhibition of human cytomegalovirus in
culture by alkenyl guanine analogs of the thiazolo[4,5-d]pyrimidine ring
system. Antimicrob Agents Chemother. 1994 Dec;38(12):2889-95. PubMed
PMID: 7695278; PubMed Central PMCID: PMC188302.
15: Sidwell RW, Huffman JH, Barnard DL, Smee DF, Warren RP, Chirigos MA,
Kende M, Huggins J. Antiviral and immunomodulating inhibitors of
experimentally-induced Punta Toro virus infections. Antiviral Res. 1994
Oct;25(2):105-22. PubMed PMID: 7847873.
16: Sidwell RW, Huffman JH, Smee DF, Gilbert J, Gessaman A, Pease A,
Warren RP, Huggins J, Kende M. Potential role of immunomodulators for
treatment of phlebovirus infections of animals. Ann N Y Acad Sci. 1992
Jun 16;653:344-55. PubMed PMID: 1385686.
17: Sharma BS, Mhaskar S, Balazs L, Siaw M. Immunomodulatory activity of
a novel nucleoside, 7-thia-8-oxoguanosine: I. Activation of natural
killer cells in mice. Immunopharmacol Immunotoxicol. 1992;14(1-2):1-19.
PubMed PMID: 1597650.
18: Sharma BS, Mhaskar S, Balazs L, Jin A, Smee DF. Immunomodulatory
activity of a novel nucleoside, 7-thia-8-oxoguanosine. II.
Characterization of induced effector cells and the mechanism of
induction. Immunopharmacol Immunotoxicol. 1992;14(1-2):21-38. PubMed
PMID: 1375956.
19: Kini GD, Anderson JD, Sanghvi YS, Lewis AF, Smee DF, Revankar GR,
Robins RK, Cottam HB. Synthesis and antiviral activity of certain
guanosine analogues in the thiazolo[4,5-d]pyrimidine ring system. J Med
Chem. 1991 Oct;34(10):3006-10. PubMed PMID: 1656042.
20: Sharma BS, Balazs L, Jin A, Jolley WB, Robins RK. Successful
immunotherapy of murine melanoma metastases with 7-thia-8-oxoguanosine.
Clin Exp Metastasis. 1991 Sep-Oct;9(5):429-39. PubMed PMID: 1914279.
21: Smee DF, Huffman JH, Gessaman AC, Huggins JW, Sidwell RW.
Prophylactic and therapeutic activities of 7-thia-8-oxoguanosine against
Punta Toro virus infections in mice. Antiviral Res. 1991
Mar-Apr;15(3):229-39. PubMed PMID: 1716090.
22: Sharma BS, Balazs L, Jin A, Wang JC, Jolley WB, Robins RK.
Potentiation of the efficacy of murine L1210 leukemia vaccine by a novel
immunostimulator 7-thia-8-oxoguanosine: increased survival after
immunization with vaccine plus 7-thia-8-oxoguanosine. Cancer Immunol
Immunother. 1991;33(2):109-14. PubMed PMID: 2036658.
23: Smee DF, Alaghamandan HA, Gilbert J, Burger RA, Jin A, Sharma BS,
Ramasamy K, Revankar GR, Cottam HB, Jolley WB, et al. Immunoenhancing
properties and antiviral activity of 7-deazaguanosine in mice.
Antimicrob Agents Chemother. 1991 Jan;35(1):152-7. PubMed PMID: 1707603;
PubMed Central PMCID: PMC244957.
24: Girgis NS, Michael MA, Smee DF, Alaghamandan HA, Robins RK, Cottam
HB. Direct C-glycosylation of guanine analogues: the synthesis and
antiviral activity of certain 7- and 9-deazaguanine C-nucleosides. J Med
Chem. 1990 Oct;33(10):2750-5. PubMed PMID: 2170645.
25: Bontems RJ, Anderson JD, Smee DF, Jin A, Alaghamandan HA, Sharma BS,
Jolley WB, Robins RK, Cottam HB. Guanosine analogues. Synthesis of
nucleosides of certain 3-substituted
6-aminopyrazolo[3,4-d]pyrimidin-4(5H)-ones as potential
immunotherapeutic agents. J Med Chem. 1990 Aug;33(8):2174-8. PubMed
PMID: 2165164.
26: Jin A, Mhaskar S, Jolley WB, Robins RK, Ojo-Amaize EA. A novel
guanosine analog, 7-thia-8-oxoguanosine, enhances macrophage and
lymphocyte antibody-dependent cell-mediated cytotoxicity. Cell Immunol.
1990 Apr 1;126(2):414-9. PubMed PMID: 2311125.
27: Smee DF, Alaghamandan HA, Cottam HB, Jolley WB, Robins RK. Antiviral
activity of the novel immune modulator 7-thia-8-oxoguanosine. J Biol
Response Mod. 1990 Feb;9(1):24-32. PubMed PMID: 2156954.
28: Smee DF, Alaghamandan HA, Jin A, Sharma BS, Jolley WB. Roles of
interferon and natural killer cells in the antiviral activity of
7-thia-8-oxoguanosine against Semliki Forest virus infections in mice.
Antiviral Res. 1990 Feb;13(2):91-102. PubMed PMID: 1693058.
29: Ojo-Amaize EA, Rubalcava B, Avery TL, Cottam HB, Matsumoto SS,
Jolley WB, Robins RK. Activation of the respiratory burst in murine
phagocytes by certain guanine ribonucleosides modified at the 7 and 8
positions: possible involvement of a pertussis toxin-sensitive
G-protein. Immunol Lett. 1990 Jan;23(3):173-8. PubMed PMID: 2106487.
30: Parandoosh Z, Ojo-Amaize E, Robins RK, Jolley WB, Rubalcava B.
Stimulation of phosphoinositide signaling pathway in murine B
lymphocytes by a novel guanosine analog, 7-thia-8-oxoguanosine. Biochem
Biophys Res Commun. 1989 Sep 29;163(3):1306-11. PubMed PMID: 2551285.
31: Smee DF, Alaghamandan HA, Cottam HB, Sharma BS, Jolley WB, Robins
RK. Broad-spectrum in vivo antiviral activity of 7-thia-8-oxoguanosine,
a novel immunopotentiating agent. Antimicrob Agents Chemother. 1989
Sep;33(9):1487-92. PubMed PMID: 2817849; PubMed Central PMCID:
PMC172688.
32: Robins RK, Ojo-Amaize E, Parandoosh Z, Cottam HB, Matsumoto SS,
Revankar GR, Smee DF, Fujitaki JM, Willis RC, Rubalcava B, et al.
Nucleoside and nucleotide modulation of genetic expression--a new
approach to chemotherapy. Adv Enzyme Regul. 1989;29:97-121. PubMed PMID:
2517379.
|
Contact MedKoo:
Email:
sales@medkoo.com
(Keyword; CAS#; MedKoo code#)
|