XPro1595
Also known as: DN-TNF, dominant-negative TNF, dTNF, pegipanermin, XPro-1595, XPro1595
Source XPro1595 at Peptiology
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Summary
XPro1595 is an engineered soluble form of tumor necrosis factor that acts as a dominant‑negative inhibitor of soluble TNF. By selectively neutralizing soluble TNF activity, it aims to reduce neuroinflammation without impairing the protective functions of transmembrane TNF, and is being evaluated for neurodegenerative and traumatic brain injury indications.
Mechanism of Action
Forms heterotrimers with native soluble TNF, preventing its binding to TNF receptors while preserving transmembrane TNF signaling
Routes of Administration
Goals & Uses
- Treatment-resistant depressionPsychiatryLow
- Mild cognitive impairment (MCI) treatmentCognitive DeclineLow
- Neuroprotection in CNS diseaseNeuroprotectionLow
- ALS (amyotrophic lateral sclerosis)NeurodegenerationLow
- Alzheimer's disease neuroinflammation reductionNeurodegenerationModerate
- Multiple SclerosisAutoimmune DiseaseLow
- Traumatic brain injuryNeuroprotectionModerate
- Parkinson's diseaseNeurodegenerationModerate
- Alzheimer's diseaseNeurodegenerationModerate
Contraindications
- Demyelinating disease (e.g., multiple sclerosis)NeurologicalModerate
- Active serious infectionsInfectiousHigh
- Active tuberculosisInfectiousHigh
- Known hypersensitivity to XPro1595 or any excipientsAllergyHigh
- Active severe infectionInfectiousHigh
- Known hypersensitivity to XPro1595 or excipientsAllergy/HypersensitivityHigh
Adverse Effects
- Anti‑drug antibodiesImmunogenicityUnknown
- Injection site reactionsLocalCommon
- HeadacheNeurologicUncommonPain in the head or upper neck
- Upper respiratory tract infectionInfectiousUncommon
- FatigueGeneralUncommonLow energy or tiredness
- Injection site erythemaLocalCommonRedness at the injection site
- Anti-drug antibodiesImmunologicUnknownAntibodies formed against the therapeutic agent
- Infection susceptibilityImmunologicUncommon
Drug Interactions
- Immunosuppressants (e.g., methotrexate, azathioprine)Moderate
- Other TNF inhibitors (e.g., etanercept, adalimumab)High
- Live attenuated vaccinesHigh
- Live vaccinesHigh
- Immunosuppressive agents (e.g., azathioprine, methotrexate)Moderate
- Other biologic TNF inhibitors (e.g., etanercept, infliximab)High
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patientsAgeRelative
- Pediatric patients (<18 y)AgeRelative
- Pregnant womenReproductiveRelative
- Patients with History of MalignancyOncologyRelative
- Elderly patients with multiple comorbiditiesAge / ComorbidityRelative
Regulatory Status
- European UnionInvestigationalClinical trial authorization obtained in several member states
- United StatesInvestigationalIND holder: Xencor; Phase 1/2 trials ongoing
- United KingdomInvestigationalMHRA clinical trial permission; no marketing authorization
Currently under IND in the United States and similar clinical‑trial authorizations in the EU and UK; not approved for any therapeutic indication.
Evidence & Sources
No sources recorded yet.
Frequently Asked Questions
What is XPro1595?
XPro1595 is an engineered soluble form of tumor necrosis factor that acts as a dominant‑negative inhibitor of soluble TNF. By selectively neutralizing soluble TNF activity, it aims to reduce neuroinflammation without impairing the protective functions of transmembrane TNF, and is being evaluated for neurodegenerative and traumatic brain injury indications.
What is XPro1595 used for?
XPro1595 is educationally associated with: Treatment-resistant depression, Mild cognitive impairment (MCI) treatment, Neuroprotection in CNS disease, ALS (amyotrophic lateral sclerosis), Alzheimer's disease neuroinflammation reduction, Multiple Sclerosis, Traumatic brain injury, Parkinson's disease, Alzheimer's disease. Educational only — not medical advice.
How is XPro1595 administered?
Recorded routes of administration: Intravenous, Subcutaneous.
What are the potential side effects of XPro1595?
Reported adverse effects include: Anti‑drug antibodies, Injection site reactions, Headache, Upper respiratory tract infection, Fatigue, Injection site erythema, Anti-drug antibodies, Infection susceptibility. This list is not exhaustive — consult a qualified clinician.
Who should avoid XPro1595?
Recorded contraindications: Demyelinating disease (e.g., multiple sclerosis), Active serious infections, Active tuberculosis, Known hypersensitivity to XPro1595 or any excipients, Active severe infection, Known hypersensitivity to XPro1595 or excipients. Consult a qualified clinician before use.