Solnatide | CAS 259206-53-6 | ENaC Activator / TIP Peptide (Research Use Only) | Knowlux

Product Description

Solnatide (AP301, TIP peptide), CAS 259206-53-6, is a synthetic 17-amino-acid cyclic peptide engineered to mimic the lectin-like domain (ILD) of human tumor necrosis factor-alpha (TNF-alpha), supplied by Knowlux for laboratory research use. The peptide is constrained by a single intramolecular disulfide bridge between the N-terminal Cys1 and C-terminal Cys17, and carries a free C-terminal tyrosine carboxylate. The molecular formula is C82H119N23O27S2 and the molecular weight is 1923.1 g/mol on a free-peptide basis. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Salt Form Clarification: CAS 259206-53-6 is the free peptide registry for Solnatide and is the identifier applied across ChemicalBook, CPhI, BenchChem, TargetMol, Biorbyt, and NCATS Inxight. Commercial listings frequently supply the acetate salt under this CAS without declaring a separate acetate registry, and the CPhI quality specification explicitly includes an acetate content limit of 5.0% to 12.0%. The molecular formula C82H119N23O27S2 and molecular weight 1923.1 correspond to the free-peptide basis; if supplied as the monoacetate, the mass balance shifts by approximately 60 g/mol. Knowlux declares the salt form, acetate content, and peptide content per lot on the COA. Buyers should confirm the declared counter-ion basis before procurement, particularly when converting between mass and molar concentrations.

Structural and Mechanistic Note: Solnatide is a cyclic TIP peptide with a compact hydrophobic core and two electrostatically charged poles in solution, as characterized by NMR. It is the only TIP peptide reported to retain full ENaC-activating activity after nebulization into droplets of 4 micrometers or smaller, a property that underpins its investigation as an inhaled therapeutic. The peptide contains a single tryptophan (Trp14) and a single tyrosine (Tyr16), which provide UV chromophores for detection. The disulfide bridge is the principal structural liability under reducing conditions, and the tryptophan is the principal oxidation liability.

Product Parameters

Product Details

1. Overview

Solnatide is a synthetic cyclic peptide derived from the lectin-like domain of TNF-alpha. Unlike the receptor-binding sites of TNF that drive inflammation and cell death, the ILD is a spatially distinct region that interacts with glycoproteins and activates the amiloride-sensitive epithelial sodium channel (ENaC). By activating ENaC on the apical surface of alveolar epithelial cells, Solnatide promotes sodium and water reabsorption from the alveolar space, thereby accelerating alveolar fluid clearance. This mechanism is the pharmacological rationale for its investigation in pulmonary permeability edema, acute respiratory distress syndrome (ARDS), and primary graft dysfunction following lung transplantation. Solnatide has received Orphan Drug Designation from the FDA for primary graft dysfunction following lung transplantation and for pseudohypoaldosteronism type 1B. The material supplied under this specification is research-grade and is not intended for human administration.

2. Receptor Pharmacology and Mechanism

Solnatide binds specifically to the C-terminal domain of the alpha-subunit of ENaC, and this interaction requires precedent binding to glycosylated extracellular loops of the channel. In patch-clamp studies, Solnatide restores mutant PHA1B ENaC currents to at least wild-type levels. Downstream of ENaC activation, Solnatide restores alveolar-capillary barrier function by mitigating protein kinase C-alpha activation and myosin light chain phosphorylation, and it increases expression of the tight junction protein occludin, thereby improving barrier stability. The peptide also exerts an inhibitory effect on pro-inflammatory signaling. These mechanisms are distinct from the receptor-mediated G-protein signaling of the GPCR agonists in this catalogue; Solnatide acts as a channel-activating peptide ligand rather than a classical receptor agonist.

3. Research Applications and Clinical Context

Published preclinical and clinical characterizations describe the following research applications:

• ENaC activation and alveolar fluid clearance studies in lung epithelial cell models and isolated lung preparations

• Pulmonary permeability edema and ARDS research models (including high-altitude pulmonary edema and infection-associated ARDS)

• Primary graft dysfunction following lung transplantation research

• Pseudohypoaldosteronism type 1B (PHA1B) ENaC rescue studies

• Aerosol formulation and nebulization stability research (post-nebulization bioactivity)

• Anti-inflammatory and alveolar-capillary barrier function studies

• Reference standard development for HPLC and LC-MS analytical methods

In a randomized controlled pilot trial in SARS-CoV-2-positive patients with moderate-to-severe ARDS (n=30), Solnatide inhalation did not improve ventilator-free days (VFDs) or survival compared with placebo over seven days; 11 of 15 patients (73.3%) in the Solnatide group survived to day 28 versus 9 of 15 in the placebo group, a difference that did not reach statistical significance. The study authors noted that Solnatide reversed the SARS-CoV-2 receptor-binding-domain-induced inactivation of ENaC and improved endothelial barrier function in experimental systems, but the clinical endpoints were not met in this small pilot cohort. These data are from an early-phase clinical study and do not establish efficacy or safety for any therapeutic indication; they are provided for scientific context only.

Quality Control

Solubility and Handling

Solubility: Solnatide solubility is supplier-declared as H2O/DMSO without a published numeric limit in most catalogue entries. BenchChem lists the material as soluble in DMSO, and TargetMol provides reconstitution guidance for a 20 mg/mL DMSO stock solution from 2 mg of peptide in 100 microliters of DMSO. The cyclic structure and the presence of multiple charged residues (Arg, Glu, Lys) support aqueous dissolution, and the hydrophobic Trp-Pro segment contributes to the compound's amphipathic character. For practical stock preparation, DMSO at 20 mg/mL is the most specifically supported condition across the sourced data, and aqueous buffers may be evaluated empirically on the specific lot. Prepare solutions fresh and aliquot to avoid repeated freeze-thaw cycles.

Handling Precautions: Use powder-handling containment (glove box or fume hood with particulate control). Avoid inhalation of fine powder. Wear nitrile gloves, lab coat, and eye protection. The Cys1-Cys17 disulfide bridge is sensitive to reducing agents; avoid contact with dithiothreitol (DTT) or mercaptoethanol. The Trp14 residue is susceptible to oxidation; protect from prolonged exposure to air and light.

Storage and Stability

Documentation Support

Per lot: COA, MSDS, HPLC chromatogram, and mass spectrometry data. Salt-form identity, acetate content, water content, peptide content, and endotoxin data available on request. Custom specifications and third-party inspection can be arranged on a project basis.

About Knowlux

Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.

Compliance Statement

FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.

This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. Solnatide is under clinical investigation for ARDS, pulmonary permeability edema, and primary graft dysfunction following lung transplantation but is not approved as a medicinal product in the United States or the European Union; the material offered under this specification is research-grade and is not intended for clinical use. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.

Data Verification Notes

The molecular formula C82H119N23O27S2 and molecular weight 1923.1 are confirmed across CPhI, ChemicalBook, BenchChem, TargetMol, Biorbyt, and PeptideDB. The sequence Cyclo(CGQRETPEGAEAKPWYC) with the Cys1-Cys17 disulfide bridge is confirmed by ChemicalBook, BenchChem, and the NMR structural study. The ENaC-activating mechanism and the requirement for glycosylated extracellular loop binding are from NCATS Inxight and the PMC structural study. The clinical trial data (no improvement in VFDs or survival; 11/15 survival in Solnatide group versus 9/15 in placebo) are from the ScienceDirect/PubMed-indexed pilot RCT in SARS-CoV-2 ARDS. The FDA Orphan Drug Designations are from NCATS Inxight. The quality specifications are from the CPhI and ChemicalBook reference listings and are corroborated by multiple Chinese supplier technical sheets. Solubility is reported as supplier-declared H2O/DMSO with the TargetMol 20 mg/mL DMSO stock as the only specifically supported numeric condition. Storage guidance is reported as specified by TargetMol, BenchChem, and CPhI and is consistent across those sources.

Formatting Note: All formulas, sequences, and comparison operators use plain ASCII notation to prevent character corruption on the platform. Section headings, table alignment, and spacing follow the approved product detail pattern. No trailing spaces or non-breaking characters are used; tables use consistent pipe alignment. No web links or hyperlinks are included in this document.