RWJ-800088
Source RWJ-800088 at Peptiology
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Summary
RWJ-800088 is a synthetic, polyethylene‑glycol‑conjugated peptide that mimics thrombopoietin (TPO). It has been investigated as a vascular radioprotectant and as a means to raise platelet counts in thrombocytopenia. Early human studies used a single intravenous dose in healthy volunteers, while pre‑clinical work examined its ability to limit radiation‑induced vascular leakage and inflammation in rodents.
Mechanism of Action
The peptide binds the TPO receptor (c‑Mpl) on megakaryocyte progenitors, activating the JAK/STAT pathway that drives megakaryocyte proliferation, maturation and platelet production. In addition, TPO signalling has endothelial‑protective effects, reducing radiation‑triggered increases in vascular permeability and leukocyte‑endothelial adhesion, likely through preservation of endothelial integrity and anti‑inflammatory signaling.
What the Research Shows
A double‑blind, placebo‑controlled phase I study in healthy adults showed that single intravenous doses of RWJ‑800088 (≥0.75 µg/kg) produced dose‑related rises in platelet counts without detectable anti‑drug antibodies. Pharmacokinetic profiling was performed for 2.5–3.0 µg/kg doses, although a full dose‑exposure relationship was not defined. In rodents, a single dose given 10 minutes after localized prostate irradiation protected penile arterial vasodilation and prevented radiation‑induced changes in artery size, but did not avert erectile dysfunction, indicating nerve injury remained. In a murine ear‑vein model, RWJ‑800088 reduced radiation‑induced vascular leakage and leukocyte rolling, supporting its role as a vascular radioprotectant. Non‑clinical repeat‑dose toxicity studies revealed dose‑dependent platelet elevation, reversible myelofibrosis and hyperostosis in rats when platelet levels exceeded three‑fold, but not in dogs, and no antibody formation.
Reported Benefits
Evidence indicates RWJ‑800088 can increase circulating platelet numbers in a dose‑dependent manner, offering potential utility for treating thrombocytopenia. In animal models, it attenuates early radiation‑induced vascular permeability and inflammatory leukocyte adhesion, suggesting a role in reducing radiotherapy‑related microvascular toxicity. The peptide was well tolerated after a single intravenous administration in healthy volunteers.
Limitations of the Evidence
Human data are limited to a single‑dose phase I trial in healthy subjects; efficacy in patients with thrombocytopenia or undergoing radiotherapy has not been demonstrated. The vascular protective effect did not translate into functional preservation of erectile function in a rat prostate‑irradiation model, highlighting incomplete protection of nerve injury. Long‑term safety, especially bone‑related effects observed at high platelet levels in rats, remains uncharacterized, and no regulatory approval status is provided.
Safety Considerations
Single‑dose administration in healthy volunteers was well tolerated, with no serious adverse events or anti‑drug antibody formation reported. In repeat‑dose animal studies, excessive platelet elevation (>3‑fold) was associated with reversible myelofibrosis and hyperostosis in rats, underscoring the need for platelet monitoring and dose limits. No immunogenicity was observed in the human study, but bone‑marrow effects warrant caution in prolonged or high‑dose regimens.
How It Is Administered
RWJ‑800088 has been administered intravenously as a single bolus injection in both human phase I and animal studies. The peptide is formulated as a PEG‑conjugated solution suitable for IV infusion. No oral or other routes have been reported in the literature.
Routes of Administration
No administration routes recorded yet.
Goals & Uses
No goal associations recorded yet.
Contraindications
No contraindications recorded yet.
Adverse Effects
No adverse effects recorded yet.
Drug Interactions
No drug interactions recorded yet.
Population Constraints
No population constraints recorded yet.
Regulatory Status
No regulatory status recorded yet.
Evidence & Sources
- Journal ArticleLowAshcraft KA, et al.2019-01-01T00:00:00.000000Z
- Journal ArticleLowLiem-Moolenaar M, et al.2008-01-01T00:00:00.000000Z
- Journal ArticleLowAshcraft KA, et al.2018-01-01T00:00:00.000000Z
- Journal ArticleLowKnight E, et al.2011-01-01T00:00:00.000000Z
Frequently Asked Questions
What condition is RWJ‑800088 being studied for?
The peptide is investigated as a thrombopoietin mimetic to raise platelet counts in thrombocytopenia and as a vascular radioprotectant to limit radiation‑induced endothelial damage in pre‑clinical models.
Has RWJ‑800088 been approved for clinical use?
No regulatory approval has been reported. The available data consist of early‑phase human safety studies and animal research, without an approved therapeutic indication.
What are the main safety concerns?
In rats, high platelet levels caused reversible myelofibrosis and bone overgrowth (hyperostosis). Human single‑dose studies showed good tolerability and no antibody formation, but long‑term safety has not been established.
How is the drug given?
All reported studies used intravenous administration of a PEG‑conjugated peptide solution, typically as a single bolus injection.
Does it protect against all radiation‑induced damage?
Animal data show protection of vascular permeability and leukocyte adhesion, but a rat prostate‑irradiation model demonstrated that vascular protection alone did not prevent erectile dysfunction, indicating nerve injury remains unaddressed.
What is RWJ-800088?
RWJ-800088 is a synthetic, polyethylene‑glycol‑conjugated peptide that mimics thrombopoietin (TPO). It has been investigated as a vascular radioprotectant and as a means to raise platelet counts in thrombocytopenia. Early human studies used a single intravenous dose in healthy volunteers, while pre‑clinical work examined its ability to limit radiation‑induced vascular leakage and inflammation in rodents.