ISTH0036 

ISTH0036 is a phosphorothioate LNA-modified antisense oligonucleotide gapmer that selectively targets and downregulates TGF-β2 mRNA. ISTH0036 suppresses TGF-β2 expression, reduces choroidal neovascularization and vascular leakage, inhibits fibrosis, blocks epithelial-to-mesenchymal transition, and inhibits angiogenesis while promoting bleb survival. ISTH0036 exhibits long-lasting, dose-dependent ocular tissue distribution and target engagement in rabbit and non-human primate eyes. ISTH0036 can be used for the study of various ocular disorders, such as glaucoma and neovascular retinal diseases^[1][2][3].

ISTH0036 potently and specifically suppresses TGF-β2 mRNA (IC₅₀ = 0.4 μM) and protein (IC₅₀ = 0.7 μM) in human A172, human Panc1, human trabecular meshwork cells, and murine astrocytes^[1].
ISTH0036 potently downregulates TGF-β2 mRNA in a dose-dependent manner in relevant ocular cell-based assays^[3].

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

ISTH0036 (intravitreal; single dose) suppresses ocular TGF-β2 mRNA and protein levels for up to 8 weeks in New Zealand White rabbit eyes^[1].
ISTH0036 (intravitreal; single dose) preserves bleb size and survival in a mouse glaucoma filtration surgery model^[1].
ISTH0036 exhibits potent anti-fibrotic and antiangiogenic activity in a mouse choroidal neovascularization model^[1].
ISTH0036 (intravitreal; single dose, repeated doses) induces pronounced, long-lasting dose- and time-dependent target engagement in rabbit and non-human primate ocular tissues, with target engagement lasting up to 4 months in non-human primates after a single intravitreal dose^[2].
ISTH0036 exhibits potent activity in murine choroidal neovascularization models by reducing neovascularization, vascular leakage, fibrotic development, and blocking epithelial-to-mesenchymal transition^[2].
ISTH0036 (intracameral; day 0, day 14; until day 28) significantly increases bleb area and prolongs bleb survival in a murine glaucoma filtration surgery model^[3].
ISTH0036 (intravitreal; single dose post laser procedure) significantly reduces angiogenesis with no effect on early inflammation in a murine laser-induced choroidal neovascularization model^[3].

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

2179222-27-4

Solid

White to off-white

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Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Pfeiffer N, Voykov B, Renieri G, et al. First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery. PLoS One. 2017;12(11):e0188899.  [Content Brief]

  [2]. Ruckert R, et al. Long-term safety and efficacy of ISTH0036 - a selective TGF-β2 blocking antisense oligonucleotide in preclinical and Phase 1 clinical studies. Invest Ophthalmol Vis Sci. 2021 Jun;62(8):321.

  [3]. Janicot M. Selective Antisense Oligonucleotide Targeting Transforming Growth Factor beta 2 (TGF-β2) Isoform, in Different Ocular Disease Preclinical Models. Invest Ophthalmol Vis Sci. 2015 Jun;56(7):1278.