Sovateltide (IRL-1620) | CAS 142569-99-1 | ETB Receptor Agonist | Research Grade

Product Overview

Sovateltide (IRL-1620), CAS 142569-99-1, is a synthetic 14-amino-acid peptide analogue of endothelin-1, engineered as a highly selective endothelin-B (ETB) receptor agonist. The peptide is N-terminally modified with a succinyl (Suc) group and carries substitutions at positions 9 and 11 relative to the native endothelin-1 sequence.

Sequence (1-letter): Suc-DEEAVYFAHLDIIW

Sequence (3-letter): Suc-Asp-Glu-Glu-Ala-Val-Tyr-Phe-Ala-His-Leu-Asp-Ile-Ile-Trp

Two molecular forms circulate in commercial catalogues and must be distinguished. The free peptide has the formula C86H117N17O27 and a molecular weight of approximately 1820.95. The trifluoroacetate (TFA) salt has the formula C88H118F3N17O29 and a molecular weight of 1934.97. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Salt Form Clarification

CAS 142569-99-1 is the identifier applied to Sovateltide across major chemical databases and is used in commercial listings for both the free peptide and the TFA salt. The formula and molecular weight declared on the lot COA determine which form is supplied:

• Free peptide: C86H117N17O27 / approximately 1820.95

• TFA salt: C88H118F3N17O29 / 1934.97

The 114 g/mol mass difference between the two forms is material for molarity calculations. The salt form, counter-ion content and peptide content are specified per lot on the COA. Buyers should confirm the declared formula and molecular weight before procurement rather than relying on the CAS number alone.

Naming note: Sovateltide has been referred to by the development codes IRL-1620, PMZ-1620 and SPI-1620. These are synonyms for the same molecular entity.

Structural and Mechanistic Note

Sovateltide binds ETB receptors, a class A GPCR expressed on vascular endothelium, neurons and other cell types. Its pharmacological signature is defined by two features: exceptionally high ETB selectivity and a downstream effect profile that converges on neurovascular repair.

The N-terminal succinyl group and the Ala9/Ala11 substitutions are the structural determinants of the ETB selectivity, which is approximately 120,000-fold over the ETA receptor (Ki ratio ETA/ETB). The peptide contains a single tryptophan (Trp14) and a single tyrosine (Tyr6), which provide UV chromophores for detection, and no cysteine or methionine, which removes disulfide scrambling and methionine sulfoxide formation as principal degradation pathways.

Product Parameters

Packaging and MOQ

Product Details

1. Overview

Sovateltide is a synthetic analogue of endothelin-1 designed as a potent and highly selective agonist of the endothelin-B receptor. Endothelin-1 is one of the most potent endogenous vasoconstrictors known, and it signals through two receptor subtypes: ETA, which mediates vasoconstriction and smooth muscle proliferation, and ETB, which mediates vasodilation, clearance of endothelin-1, and neurogenesis, angiogenesis and neurovascular remodeling.

Sovateltide was engineered to isolate the ETB-mediated repair and cytoprotective actions from the ETA-mediated vasoconstrictor actions of the native hormone. The peptide has been investigated clinically as a neuroprotective and neurorestorative agent in acute ischemic stroke and is being developed under the brand name TYVALZI in India. The material supplied under this specification is research-grade and is not intended for human administration.

2. Receptor Pharmacology and Selectivity

Sovateltide binds the ETB receptor with sub-nanomolar affinity and displays one of the highest selectivity ratios reported for any endothelin receptor ligand.

In functional systems, the peptide increases cytosolic calcium in vascular endothelium and relaxes norepinephrine-stimulated tone with minimal effect on resting muscle tone, consistent with an endothelium-dependent vasodilatory mechanism. In the guinea pig trachea, Sovateltide produces contraction at 1-100 nM, with an effective concentration of approximately 28 nM for 30% of the contraction induced by 60 mM KCl.

The selectivity data across independent sources are internally consistent and converge on a Ki of approximately 16 pM at ETB, which is the defining pharmacological constant for this compound. These values are assay- and system-dependent and are provided for scientific reference only.

3. Research Applications and Clinical Context

Published pharmacological characterizations and clinical trial protocols describe the following research applications:

• Endothelin-B (ETB) receptor binding and functional agonist assays (calcium mobilization, vascular relaxation)

• ETB-mediated neurogenesis and angiogenesis research in stroke and brain injury models

• Neuronal progenitor cell differentiation and mitochondrial function studies

• Neurovascular remodeling and cerebral blood flow research

• Alzheimer's disease and cognitive impairment models (A-beta-induced oxidative stress and cognitive deficits)

• Hypoxic-ischemic encephalopathy (HIE) models in neonatal animals

• Acute cerebral ischemic stroke research (clinical trial contexts)

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

Preclinical studies document that Sovateltide activates neuronal differentiation and prevents mitochondrial dysfunction in adult mammalian brains following stroke, with improved neurological and motor function and higher neuronal progenitor cell counts relative to control animals. In neonatal rat models of hypoxic-ischemic encephalopathy, Sovateltide attenuates oxidative stress and neural injury and promotes repair and regeneration in the brain. In Alzheimer's disease models, the peptide suppresses pro-inflammatory cytokine release and inhibits BACE1 activity through modulation of MAPK, NF-kB, PI3K/Akt/mTOR, Notch, Wnt/beta-catenin and NLRP3 inflammasome pathways. In normal and diabetic rats, Sovateltide prevents A-beta-induced oxidative stress and cognitive impairment.

In clinical development, Sovateltide has been evaluated in acute cerebral ischemic stroke under the development code PMZ-1620 and is the subject of multiple registered trials, including a Phase III study (RESPECT-ETB) and a Phase IV study (NCT05955326) evaluating safety and efficacy in patients with acute cerebral ischemic stroke. The Phase IV study is designed to randomize 160 patients to Sovateltide plus standard treatment versus normal saline plus standard treatment, with efficacy assessed by NIHSS, mRS and Barthel index scores and safety assessed by adverse event monitoring.

The proposed mechanism in this context is enhancement of neuronal progenitor cell activity and angiogenesis, promotion of new mature neuron and blood vessel formation, anti-apoptotic activity, and increased cerebral blood flow when administered after ischemia. These data are from early- and mid-stage clinical research and do not establish efficacy or safety for any therapeutic indication; they are provided for scientific context only.

Quality Control

Solubility and Handling

Solubility

Sovateltide solubility data are reported for both the TFA salt and the free peptide, and the values are consistent in indicating good DMSO solubility.

Aqueous solubility data were not identified in the sourced literature, and given the peptide's hydrophobic Trp-Phe-Ile-Ile segment, aqueous stock preparation should be approached empirically. 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 tryptophan (Trp14) and tyrosine (Tyr6) residues are oxidation-sensitive; protect from prolonged exposure to air and light, and store under an inert atmosphere where practical.

• The peptide contains no cysteine or methionine, so reducing agents and methionine-oxidation protection measures are not required.

Storage and Stability

The -20C powder condition is the most widely supported archival temperature; -80C is the conservative choice for extended storage of either powder or solutions. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening to prevent condensation. The product is stable at ambient temperature for a few days during ordinary shipping and customs transit.

Documentation Support

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

Compliance StatementFOR 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. Sovateltide is under clinical investigation for acute cerebral ischemic stroke and other neurological conditions 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.