ISS-1018

Identification

Name
ISS-1018
Accession Number
DB05463
Description

ISS 1018 is a short, synthetic, unmethylated CpG oligodeoxynucleotide (CpG ODN) with immunostimulatory activity. ISS 1018 signals through Toll-like receptor 9 (TLR9) to induce the production of immunoglobulin by B cells and interferon (IFN) -alpha, IFN-beta, interleukin-12 (IL-12), and tumor necrosis factor - alpha (TNF-alpha) by plasmacytoid dendritic cells (pDC). ISS 1018 CpG ODN promotes antigen presentation and co-stimulatory molecule expression. ISS 1018 is currently being investigated in combination with HBsAg vaccine as a prophylactic treatment for to prevent Hepatitis B in adults. It is also being investigated in combination with rituximab for treatment of b-cell or non-hodgkin's lymphoma.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available
External IDs
  • 1018 ISS
  • CPG 1018
  • CPG-1018
  • ISS 1018
  • ISS 1018 CpG ODN
  • ISS-1018

Pharmacology

Pharmacology
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Indication

Investigated for use/treatment in colorectal cancer, hepatitis (viral, B), and lymphoma (non-hodgkin's). ISS 1018 is currently being investigated in combination with HBsAg vaccine as a prophylactic treatment for to prevent Hepatitis B in adults. It has also been investigated in combination with rituximab for treatment of b-cell or non-hodgkin's lymphoma.

Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

ISS 1018 is a short, synthetic CpG oligodeoxynucleotide (CpG ODN) with immunostimulatory activity. ISS 1018 is an unmethylated CpG motifs in which regions of genomic DNA containing the cytosine-guanine dinucleotide does not show methylation of cytosine. ISS 1018 signals through Toll-like receptor 9 (TLR9) to induce the production of immunoglobulin by B cells and interferon (IFN) -alpha, IFN-beta, interleukin-12 (IL-12), and tumor necrosis factor - alpha (TNF-alpha) by plasmacytoid dendritic cells (pDC). ISS 1018 CpG ODN also promotes antigen presentation and co-stimulatory molecule expression.

Mechanism of action

ISS 1018 signals through Toll-like receptor 9 (TLR9) to induce the production of immunoglobulin by B cells and interferon (IFN) -alpha, IFN-beta, interleukin-12 (IL-12), and tumor necrosis factor - alpha (TNF-alpha) by plasmacytoid dendritic cells (pDC). pDC and IFN-alpha and -beta then induce natural killer (NK) cell proliferation, NK cell production of IFN-gamma, and NK cell-mediated cytotoxicity. Secreted IFNs also stimulate bystander T cell activation and differentiation of naive CD4+ T cells into T-helper 1 cells on specific antigen challenge.

TargetActionsOrganism
UToll-like receptor 9Not AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Medicalerrors
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Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
25DT549L0G
CAS number
937402-51-2

References

General References
  1. Ponzio NM, Cutro S, Hu J, Marzouk A, Marshall JD: CpG oligodeoxynucleotide-induced immunity prevents growth of germinal center-derived B lymphoma cells. Int Immunopharmacol. 2006 Dec 20;6(13-14):2057-68. Epub 2006 Sep 18. [PubMed:17161362]
  2. Authors unspecified: Immunostimulatory DNA--Dynavax. AIC, Amb a 1 immunostimulatory conjugate, HBV-ISS, ISS 1018, ISS DNA, ISS DNA--dynavax, ISS1, ISS2. Drugs R D. 2002;3(3):193-6. [PubMed:12099166]
  3. Halperin SA, Van Nest G, Smith B, Abtahi S, Whiley H, Eiden JJ: A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. Vaccine. 2003 Jun 2;21(19-20):2461-7. [PubMed:12744879]
PubChem Substance
347910152

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2TerminatedPreventionViral Hepatitis B1
2, 3Not Yet RecruitingPreventionCoronavirus Disease 2019 (COVID‑19)1
1Active Not RecruitingPreventionCoronavirus Disease 2019 (COVID‑19)1
1CompletedPreventionViral Hepatitis B1
1RecruitingPreventionHuman Immunodeficiency Virus (HIV) Infections1
1TerminatedTreatmentNeoplasms, Colorectal1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 i...
Gene Name
TLR9
Uniprot ID
Q9NR96
Uniprot Name
Toll-like receptor 9
Molecular Weight
115858.665 Da

Drug created on November 18, 2007 18:25 / Updated on June 12, 2020 16:52