2. Apoptosis
  3. TNF Receptor
  4. ISIS 104838

ISIS 104838 is an antisense oligonucleotide targeting TNF-α. ISIS 104838 specifically binds to human TNF-α mRNA via Watson-Crick base pairing to form a DNA:RNA hybrid duplex, thereby recruiting the ubiquitously expressed intracellular enzyme RNase H to degrade the target mRNA and inhibit TNF-α protein synthesis at the transcriptional level. ISIS 104838 induces moderate, self-limiting thrombocytopenia in cynomolgus monkeys. ISIS 104838 can be used for the study of inflammatory diseases.

For research use only. We do not sell to patients.

DNA, d(P-thio)([2′-O-(2-methoxyethyl)]rG-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]rG-[2′-O-(2-methoxyethyl)]rA-T-T-A-G-A-G-A-G-A-G-[2′-O-(2-methoxyethyl)]rG-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rC)

ISIS 104838 Chemical Structure

CAS No. : 250755-32-9

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Based on 1 publication(s) in Google Scholar

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ISIS 104838 Related Antibodies

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Description

ISIS 104838 is an antisense oligonucleotide targeting TNF-α. ISIS 104838 specifically binds to human TNF-α mRNA via Watson-Crick base pairing to form a DNA:RNA hybrid duplex, thereby recruiting the ubiquitously expressed intracellular enzyme RNase H to degrade the target mRNA and inhibit TNF-α protein synthesis at the transcriptional level. ISIS 104838 induces moderate, self-limiting thrombocytopenia in cynomolgus monkeys. ISIS 104838 can be used for the study of inflammatory diseases[1][2].

In Vitro

ISIS 104838 (30-300 nM, 6 h) potently inhibits TNF-α protein production in PMA-activated human neonatal epidermal keratinocytes, reducing its secretion level to 15% of the baseline at the concentration of 300 nM[2].
ISIS 104838 (1-30 μM, 7 h) potently and selectively inhibits TNF-α mRNA in LPS-activated human THP-1 monocytes, with an IC50 value of < 1 μM[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ISIS 104838 Related Antibodies

ELISA Assay[2]

Cell Line: neonatal human epidermal keratinocytes (PMA-activated)
Concentration: 30, 100 and 300 nM
Incubation Time: 4 h pretreatment; 12 h PMA activation
Result: Reduced secreted TNF-α protein levels to 15% of the levels produced in the absence of oligonucleotide, representing 85% suppression of TNF-α protein at 300 nM.

Real Time qPCR[2]

Cell Line: human THP-1 monocytic cells (LPS-activated)
Concentration: 1, 3, 10 and 30 μM
Incubation Time: 5 h recovery; 2 h LPS activation
Result: Inhibited TNF-α mRNA with an IC50 value < 1 μM, reducing TNF-α mRNA levels to < 10% of untreated levels at tested concentrations.
Showed no suppression of IL-1β mRNA levels, confirming target specificity.
In Vivo

ISIS 104838 (30 mg/kg, subcutaneous injection; 1-2 times per week for 80 days) induces dose-dependent, self-limiting (phenotype 1) or severe (phenotype 2) thrombocytopenia in cynomolgus monkeys by increasing platelet sequestration in the liver and spleen[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Chinese origin (female, 4-6 years old)[1]
Dosage: 30 mg/kg (loading dose on Days 1,4,7); 30 mg/kg twice weekly (Days 10-35); 30 mg/kg once weekly (Days 38-80); total weekly dose of 60 mg/kg
Administration: s.c.; loading dose on Days 1, 4, 7; twice weekly from Days 10 to 35; once weekly from Days 38 to 80
Result: Reduced platelet counts relative to baseline by Day 30 (baseline: 396-551 ×103 cells/μL).
Induced moderate 50% platelet count decrease (to ~150 ×103 cells/μL, Phenotype 1) in four monkeys and severe thrombocytopenia (as low as 16 ×103 cells/μL, Phenotype 2) in one monkey.
Increased mean platelet volume most significantly in the severely affected monkey.
Increased platelet sequestration in the liver and/or spleen by 25-45% relative to baseline at Day 55/56.
Increased total serum IgM by 2-4.5-fold, anti-platelet factor 4 (PF4) IgM by 2-5-fold, and anti-platelet IgM by 2-3-fold in all monkeys.
Increased monocyte chemoattractant protein 1 (MCP-1) levels by 2-9-fold and monocyte-derived extracellular vesicles by 2-6-fold in all monkeys.
Increased von Willebrand factor (VWF) antigen by 2-3-fold in all monkeys with no clear decrease in ADAMTS13 activity.
Showed correlation between IL-8 levels and platelet counts, with IL-8 levels decreasing parallel to platelet count reductions and rebounding as platelet counts recovered in the severely affected monkey.
Normalized platelet counts and mean platelet volume in the severely affected monkey after corticosteroid treatment, but had little effect in the four monkeys with moderate thrombocytopenia.
Molecular Weight

7283.90

CAS No.
Appearance

Solid

Color

White to off-white

Sequence

DNA, d(P-thio)([2′-O-(2-methoxyethyl)]rG-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]rG-[2′-O-(2-methoxyethyl)]rA-T-T-A-G-A-G-A-G-A-G-[2′-O-(2-methoxyethyl)]rG-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rC)
SMILES

[ISIS 104838]
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Purity & Documentation
References
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ISIS 104838 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

ISIS 104838250755-32-9ISIS104838ISIS-104838TNF ReceptorTumor Necrosis Factor ReceptorTNFRkeratinocytesRNase Hvon Willebrand factor antigenneonatal human epidermal keratinocytesperipheral blood leukocytesTNF-α mRNAcynomolgus monkeysTHP-1 monocytic cellsmonocytesextracellular vesiclesInhibitorinhibitorinhibit

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