Cibinetide (ARA290) | CAS 1208243-50-8 | Innate Repair Receptor Agonist (Research Use Only) | Knowlux

Product Description

Cibinetide (ARA290), CAS 1208243-50-8, is a synthetic 11-amino-acid peptide engineered to mimic the three-dimensional structure of the helix B surface domain of erythropoietin (EPO), supplied by Knowlux for laboratory research use. The peptide is an EPO derivative designed to bind selectively to the non-hematopoietic EPO receptor, commonly referred to as the innate repair receptor (IRR). Unlike EPO, Cibinetide does not stimulate erythropoiesis and is not a hematopoietic agent; its pharmacological activity is directed toward tissue protection and resolution of inflammation. The molecular formula is C51H84N16O21 and the molecular weight is 1257.31–1257.32 g/mol on a free-peptide basis. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Naming Clarification: CAS 1208243-50-8 is the registry for the free peptide Cibinetide and is the identifier applied across the FDA UNII database, PeptideDB, MedChemExpress, InvivoChem, Adooq, and the Guide to Pharmacology. The UNII is 9W5677JKDA, and the WHO drug number is 10264. The acetate salt circulates under the same CAS in many commercial listings and is represented as C51H84N16O21.xC2H4O2 without a discrete acetate registry, so the counter-ion basis must be confirmed on the lot COA. A trifluoroacetate (TFA) form also appears in supplier catalogues and is analytically distinct from the acetate salt. The compound is also known by the research codes ARA 290, ARA-290, PHBSP, and helix B surface peptide (HBSP); these are synonyms for the same molecular entity and do not represent separate products. Knowlux specifies the salt form, counter-ion identity, and peptide content per lot on the COA. Buyers should confirm whether the quoted material is free peptide, acetate salt, or TFA salt before procurement.

Structural and Mechanistic Note: The sequence is {Glp}-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (pEQLERALNSS), with a pyroglutamate (Glp) at the N-terminus and a free C-terminal serine carboxylate. The peptide is linear, contains no cysteine, and has no intramolecular cross-link. It is highly hydrophilic, with a computed LogP of -6.59 and a hydrogen bond donor count of 20, which places it among the more polar peptides in this catalogue and distinguishes its solvent profile from the DMSO-favoring, hydrophobic peptides such as Pentagastrin and PNC-27. The absence of methionine and tryptophan removes methionine sulfoxide and tryptophan oxidation as principal degradation pathways. Cibinetide is not a conventional receptor agonist in the G-protein-coupled receptor sense; it acts through the IRR, a heterodimer of EPOR and the cytokine family beta common receptor (betaCR, CD131). This receptor architecture is the structural basis for its non-hematopoietic, tissue-protective pharmacology.

Product Parameters

Item	Specification
Product Name	Cibinetide (ARA290)
Synonyms	ARA 290; ARA-290; PHBSP; Helix B Surface Peptide (HBSP); Pyroglutamate HBSP
CAS No.	1208243-50-8 (free peptide; applied to salt forms in commercial listings)
UNII	9W5677JKDA
WHO Drug Number	10264
Molecular Formula	C51H84N16O21 (free peptide); C51H84N16O21.xC2H4O2 (acetate salt)
Molecular Weight	1257.31–1257.32 g/mol (free peptide)
Sequence (1-letter)	pEQLERALNSS
Sequence (3-letter)	H-Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser-OH
Sequence Length	11 amino acids, linear
Key Structural Features	N-terminal pyroglutamate (Pyr/Glp); C-terminal free Ser-OH; no cysteine, disulfide, methionine, or tryptophan; highly hydrophilic (LogP -6.59)
InChIKey	WZTIQQBMSJTRBR-WYKNNRPVSA-N
Appearance	White to off-white powder or solid
Solubility	DMSO: >=34 mg/mL (27.04 mM); Water: 50 mg/mL (with pH adjustment to 8 using NH3.H2O); 0.1 M NaOH: 50 mg/mL (see Solubility section)
Purity	>=95.0% to >=98.0% (HPLC); batch-level values of 96.055% and >98% reported
Identity	Confirmed by LC-MS and HPLC
Grade	Research grade
Counter-ion	Free peptide, acetate, or TFA (lot-specific, declared on COA)
Storage	See Storage and Stability section
Packaging	1 mg / 5 mg / 10 mg / 25 mg / 50 mg / 100 mg vial; bulk on request
Application	Laboratory research use only
Origin	China

Product Details

1. Overview

Cibinetide is a first-in-class peptide agonist of the innate repair receptor (IRR), a heterodimeric receptor complex composed of EPOR and CD131 (the cytokine family beta common receptor). It was engineered from the helix B surface domain of EPO to isolate the tissue-protective and anti-inflammatory actions of EPO from its erythropoietic actions. In preclinical models, Cibinetide activates the IRR on innate immune cells and produces anti-inflammatory effects that are dependent on CD131 and JAK2 functionality and are mediated through inhibition of NF-kB subunit p65 activity. The peptide has been investigated clinically in sarcoidosis-associated small fiber neuropathy (SFN), type 2 diabetic neuropathy, and other neuropathic and inflammatory conditions. The material supplied under this specification is research-grade and is not intended for human administration.

2. Receptor Pharmacology and Anti-Inflammatory Mechanism

Cibinetide binds the EPOR/CD131 heteroreceptor (IRR) rather than the homodimeric EPOR that drives erythropoiesis. This selectivity is the defining pharmacological feature of the molecule and is the basis for its non-hematopoietic profile. Activation of the IRR engages JAK2-dependent signaling and suppresses NF-kB p65 activity, reducing the production of pro-inflammatory mediators in myeloid cells. In experimental colitis models, Cibinetide dampens innate immune cell functions, reduces disease activity, and lowers mortality, with the effects abolished when CD131 or JAK2 function is disrupted. The IRR is also proposed to function as an integration point between the immune system and pain signaling via nociception. This mechanism distinguishes Cibinetide from the GLP-1 receptor agonists, opioid receptor agonists, and calcitonin receptor agonists in this catalogue: its primary pharmacology is cytoprotective and immunomodulatory rather than secretory or analgesic in the classical sense.

3. Research Applications and Clinical Context

Published preclinical and clinical characterizations describe the following research applications:

• Innate repair receptor (EPOR/CD131) signaling and JAK2/NF-kB pathway studies

• Anti-inflammatory and innate immune cell function research (macrophage polarization, cytokine suppression)

• Small fiber neuropathy (SFN) and neuropathic pain research models (sarcoidosis-associated SFN, type 2 diabetic neuropathy)

• Tissue protection and cytoprotection studies in injury and inflammation models

• Corneal nerve fiber density and skin biopsy nerve morphology endpoints

• Metabolic control and diabetic complications research (diabetic macular edema, albuminuria)

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

In an open-label proof-of-concept study in patients with sarcoidosis (n=10) and type 2 diabetes (n=10) with moderate-to-severe neuropathic pain, three intravenous injections of ARA290 (2 mg) over one week produced maximal pain relief on the day of the third injection, with a 25% reduction in pain score in the type 2 diabetes group and a 40% reduction in the sarcoidosis group. In the first placebo-controlled sarcoidosis trial (n=22), ARA290 (2 mg intravenously three times weekly for one month) produced greater improvements in the Small Fiber Neuropathy Screening List at week 4, with a responder rate of 83% versus 60% for a 1- to 5-point reduction and 42% versus 0% for a >15-point reduction, alongside significant quality-of-life improvement. The NERVARA phase 2 trial (n=38) evaluated subcutaneous ARA290 at 4 mg daily for four weeks, focusing on small fiber morphology by skin biopsy and corneal confocal microscopy. These data are from early-phase clinical studies and do not establish efficacy or safety for any therapeutic indication; they are provided for scientific context only.

Quality Control

Test Item	Method	Acceptance Criteria
Purity	RP-HPLC	>=95.0% (entry grade); >=98.0% (standard research grade); batch-level 96.055% (TFA-removed lot) and >98% reported
Identity	LC-MS and HPLC	Consistent with structure (1257.31 +/- 1 for free peptide)
Single Impurity	RP-HPLC	<=2.0% (entry grade); <=1.0% (higher grade)
Peptide Content	Nitrogen analysis or AAA	>=80.0% (reference grade)
Water Content	Karl Fischer	<=8.0% (supplier specification)
Appearance	Visual	White to off-white powder

Purity specifications for Cibinetide span the 95% to 98% range depending on supplier and grade. A NovoPro Certificate of Analysis for a TFA-removed lot reports HPLC purity of 96.055%. TargetMol lists 98.00% purity for its catalogue item. ProbeChem specifies >98% by HPLC. Anjiechem specifies >98% with DMSO solubility of >=34 mg/mL (27.04 mM). The principal quality consideration is the salt-form ambiguity: a lot reported at MW 1257.31 is on a free-peptide basis, and the acetate or TFA counter-ion will shift the mass balance and the solubility profile. Researchers preparing molar solutions should use the peptide content value and the declared salt basis rather than the HPLC purity figure alone. Cibinetide is highly hydrophilic and has no aromatic residue, so HPLC methods require 214 nm detection or an equivalent peptide-bond detection strategy; buyers should confirm the detection wavelength on the lot COA.

Solubility and Handling

Solubility: Cibinetide solubility is solvent- and pH-dependent, and the reported values cluster around two practical conditions. In DMSO, ProbeChem, Anjiechem, and ChemicalBook supplier listings report solubility of >=34 mg/mL (27.04 mM). In aqueous media, solubility is limited at neutral pH but can be achieved with pH adjustment: AbMole reports water solubility of 50 mg/mL after adjusting to pH 8 with NH3.H2O, and 0.1 M NaOH solubility of 50 mg/mL. The need for alkaline pH adjustment is consistent with the peptide's two acidic residues (Glu2, Glu5) and its computed LogP of -6.59; at neutral pH the free peptide may be only moderately soluble, while the acetate salt and alkaline conditions improve dissolution. For practical stock preparation, DMSO at >=34 mg/mL is the most consistently supported organic condition, and aqueous stocks at 50 mg/mL are achievable with pH adjustment to approximately pH 8. For in vivo formulation where a purely aqueous vehicle is required, the pH-adjusted aqueous stock should be neutralized and diluted promptly before use. 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 peptide contains no cysteine, methionine, or tryptophan, so reducing agents and oxidation-protection measures are not required. The principal handling consideration is the pH-dependent aqueous solubility; avoid assuming that a neutral-pH aqueous stock will reach the same concentration as a pH-adjusted stock. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening.

Storage and Stability

Format	Temperature	Shelf Life
Lyophilized Powder	-20C, sealed, desiccated	3 years (InvivoChem, ChemicalBook/TargetMol); 12 months (ProbeChem); 2 years (one ChemicalBook supplier)
Lyophilized Powder	4C, sealed, desiccated	2 years (InvivoChem); 6 months (ProbeChem)
Reconstituted Solution	-80C, aliquoted, sealed	6 months (InvivoChem)
Reconstituted Solution	-20C, aliquoted, sealed	1 month (InvivoChem)

Storage guidance for Cibinetide converges on -20C for the lyophilized powder as the standard long-term condition, with desiccation and protection from moisture. InvivoChem specifies 3 years at -20C and 2 years at 4C for powder, with solutions stable for 6 months at -80C or 1 month at -20C, and notes that the product is stable at ambient temperature for a few days during ordinary shipping. ProbeChem specifies 12 months at -20C and 6 months at 4C for powder, with the same solution windows. One ChemicalBook supplier lists a 2-year shelf life at -20C for a 10 mM solution format. The -20C powder condition is the most widely supported archival temperature across suppliers; -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.

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.

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. Cibinetide has been investigated in clinical trials for sarcoidosis-associated small fiber neuropathy and diabetic neuropathy 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 C51H84N16O21 and molecular weight 1257.31–1257.32 are confirmed across the FDA UNII database, PeptideDB, MedChemExpress, InvivoChem, and Adooq. The sequence {Glp}-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser is confirmed by the FDA UNII preferred substance name and PeptideDB. The UNII 9W5677JKDA and InChIKey WZTIQQBMSJTRBR-WYKNNRPVSA-N are from the FDA UNII database. The EPOR/CD131 heterodimer (IRR) mechanism is from the Guide to Pharmacology and MedChemExpress. The JAK2/NF-kB p65 anti-inflammatory mechanism is from the PubMed-indexed colitis study. The clinical data (2 mg IV three times weekly in the open-label study and first RCT; 4 mg SC daily in NERVARA) are from the PAIN Reports review. Solubility values are reported with their source and pH conditions rather than reconciled into a single figure because the DMSO and aqueous data reflect different pH environments and salt forms. Storage shelf-life divergence (1 year versus 3 years at -20C for powder) is reported as-is; the -20C powder condition is the most widely supported archival temperature, and -80C is presented as the conservative option.

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.