Icatibant Acetate | CAS 138614-30-9 / 130308-48-4 | Bradykinin B2 Receptor Antagonist (Research Use Only) | Knowlux

Product Description

Icatibant Acetate, CAS 138614-30-9 (acetate salt) / 130308-48-4 (free base), is a synthetic decapeptide peptidomimetic bradykinin B2 receptor antagonist supplied by Knowlux for laboratory research use. The peptide sequence is H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH, incorporating five non-proteinogenic residues: D-arginine at position 1, trans-4-hydroxy-L-proline (Hyp) at position 4, L-3-(2-thienyl)alanine (Thi) at position 6, D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (D-Tic) at position 8, and octahydroindole-2-carboxylic acid (Oic) at position 9. The acetate salt molecular formula and molecular weight are addressed in the CAS and Salt Form Clarification below. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Salt Form Clarification: Icatibant presents one of the more complex salt-form landscapes among the peptide APIs in this catalogue, with four distinct registries relevant to procurement. CAS 130308-48-4 is the free base (net Icatibant), corresponding to formula C59H89N19O13S and a molecular weight of 1304.52. CAS 138614-30-9 is the acetate salt registry most widely applied in commercial listings, including ChemicalBook, Selleck, MedChemExpress, and DailyMed. Two additional acetate registries appear in the primary literature and supplier documentation: CAS 1622305-64-9 (monoacetate) and CAS 2802398-98-5 (triacetate), with CAS 2378734-44-0 also listed as a tetraacetate variant in one supplier catalogue. The molecular formula and weight associated with CAS 138614-30-9 diverge across authoritative sources: NCATS Inxight reports C59H89N19O13S.C2H4O2 with a molecular weight of 1364.574 (consistent with a monoacetate); DrugBank reports C61H93N19O15S with an average weight of 1364.59 and a monoisotopic mass of 1363.68; Sigma-Aldrich and Carl Roth list C59H89N19O13S.xC2H4O2 with the free base molecular weight of 1304.52; MedChemExpress and ChemScene list C61H93N19O15S with MW 1364.57. The most chemically coherent reading is that 1304.52 is the free peptide, 1364.57 is the monoacetate (1304.52 + 60.05), and the C61H93N19O15S formula is a condensed representation of the monoacetate stoichiometry. The DailyMed prescribing information corroborates this relationship: each mL of the commercial solution contains 10 mg of icatibant (free base) equivalent to 11.38 mg of icatibant acetate, a ratio consistent with a monoacetate. Knowlux specifies the salt stoichiometry, acetate content, and water content per lot on the COA. Buyers should confirm whether the quoted material is reported on a free-base, monoacetate, or higher-acetate basis before procurement, as the counter-ion load shifts the mass balance.

Structural Note: Icatibant is a decapeptide with a C-terminal free arginine carboxylate and a free N-terminal D-arginine amine; unlike the terminally blocked peptides in the Semax and Melanotan families, neither terminus is acetylated or amidated. The five non-proteinogenic residues are the structural basis for its resistance to bradykinin-degrading enzymes and its higher potency relative to earlier B2 antagonists. The peptide contains no cysteine residues or disulfide bonds, distinguishing its handling profile from the disulfide-constrained peptides in the Plecanatide and Ziconotide families. The thienyl side chain of Thi6 is sulfur-containing but not a thioether in the methionine sense; oxidation liability is lower than for methionine-containing peptides.

Product Parameters

Product Details

1. Overview

Icatibant is a synthetic decapeptide that functions as a potent, selective, and competitive antagonist at the bradykinin B2 receptor (B2R). It was designed as a peptidomimetic of bradykinin, with non-natural amino acid substitutions that confer resistance to bradykinin-degrading enzymes and increase potency relative to earlier B2 antagonists. B2R is a class A GPCR that couples to Gq/11 and mediates bradykinin-driven vasodilation, vascular permeability, and nociceptor sensitization. In hereditary angioedema (HAE), deficiency or dysfunction of C1-esterase inhibitor leads to excessive bradykinin production and episodic swelling; Icatibant blocks bradykinin binding at B2R and thereby interrupts this pathophysiological cascade. In clinical medicine, Icatibant Acetate is approved for the treatment of acute HAE attacks (FDA approval 2011; EMA approval 2008). The material supplied under this specification is research-grade and is not intended for human administration. Knowlux supplies this compound strictly for laboratory investigation of bradykinin B2 receptor pharmacology, kinin-mediated inflammation, and vascular permeability.

2. Receptor Pharmacology and Selectivity

Icatibant binds the human bradykinin B2 receptor with sub-nanomolar affinity and produces competitive antagonism of bradykinin-mediated signaling. MedChemExpress reports an IC50 of 1.07 nM and a Ki of 0.798 nM at the B2 receptor, values that have been widely cited in the pharmacological literature. BindingDB's curated dataset includes a Ki of 0.060 nM for human cloned B2 receptor expressed in CHO cells, measured by [3H]bradykinin displacement, alongside a second entry reporting a Ki of 0.064 nM and an IC50 of 0.090 nM in the same system. An independent study in human synovial fibroblasts reported a Ki of 4.6 nM and an IC50 of approximately 3 nM, consistent with earlier published values. The spread in reported constants (0.06 nM to 4.6 nM) reflects differences in assay format, receptor density, radioligand concentration, and species; the nanomolar-to-subnanomolar range is the consensus for high-affinity B2 binding. Selectivity for B2 over the B1 receptor is a defining pharmacological property of Icatibant and distinguishes it from des-Arg9-bradykinin and other B1-preferring ligands. These values are assay- and system-dependent and are provided for scientific reference only.

3. Research Applications

Published pharmacological characterizations and documented protocols describe the following research applications:

• Bradykinin B2 receptor binding and functional antagonist assays (radioligand displacement, calcium mobilization, vasodilation models)

• Hereditary angioedema and kinin-mediated angioedema pathophysiology research

• Bradykinin-induced inflammation, vascular permeability, and nociception studies

• Comparative pharmacology of B1 versus B2 receptor antagonists

• Peptidomimetic stability and enzyme-resistance studies (Icatibant as a protease-resistant bradykinin analogue)

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

These descriptions are derived from published research and are provided for scientific reference only. They do not constitute clinical guidance or dosing recommendations.

Quality Control

Solubility and Handling

Solubility: Icatibant Acetate is freely soluble in water, DMSO, and ethanol, with solubility values that are more consistent across sources than for most peptides in this catalogue. Selleck's batch-tested experimental data reports DMSO 100 mg/mL (73.28 mM), water 100 mg/mL, and ethanol 100 mg/mL, with the note that moisture-contaminated DMSO may reduce solubility and that freshly opened anhydrous DMSO should be used. TargetMol reports H2O 100 mg/mL (73.28 mM) and DMSO 122.5 mg/mL (89.77 mM), both with sonication recommended, and lists a 10% DMSO + 90% saline vehicle achieving 10 mg/mL. MyBioSource lists DMSO 100 mg/mL with ultrasonic assistance. The EMA-approved commercial formulation is an aqueous solution at pH approximately 5.5 containing 10 mg/mL icatibant (free base) equivalent to 11.38 mg/mL icatibant acetate, which provides a practical confirmation of aqueous solubility in the clinically relevant concentration range. For stock preparation, water, DMSO, or ethanol are all viable at 100 mg/mL; Selleck recommends a 10 mM DMSO stock as a working concentration. Selleck's technical note on DMSO stock precipitation in aqueous media recommends preheating the media to 37C, mixing rapidly upon addition, and adding the aqueous phase last for complex mixtures. 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 is not classified as a potent toxin, but good laboratory hygiene practices for peptide APIs should be followed. Follow institutional chemical hygiene plans for research peptides.

Storage and Stability

Documentation Support

Per lot: COA, MSDS, certificate of origin, HPLC chromatogram, and mass spectrometry data. Acetate content, water content, peptide content, and counter-ion stoichiometry 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. Icatibant Acetate is an approved medicinal product in certain jurisdictions for the treatment of acute hereditary angioedema attacks; however, 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 sequence H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH is confirmed by DailyMed, Sigma-Aldrich, and the IUPAC name in the BOC Sciences listing. The free base molecular formula C59H89N19O13S and molecular weight 1304.52 are confirmed by NCATS Inxight, Sigma-Aldrich, Carl Roth, and XIANGLONG. The monoacetate molecular formula and weight (C61H93N19O15S, 1364.57) are confirmed by DrugBank, MedChemExpress, ChemScene, and NCATS Inxight (which reports C59H89N19O13S.C2H4O2, MW 1364.574). The additional acetate registries (1622305-64-9 monoacetate, 2802398-98-5 triacetate, 2378734-44-0 tetraacetate, 148699-92-7 deleted CAS) are from the BOC Sciences catalogue. The B2R affinity data span 0.06 nM to 4.6 nM across BindingDB, MedChemExpress, and the human synovial fibroblast study; this range is reported as-is rather than reconciled into a single value because the underlying assays differ in receptor source, radioligand, and incubation conditions. Solubility values (water 100 mg/mL, DMSO 100-122.5 mg/mL, ethanol 100 mg/mL) are from Selleck batch-tested data and TargetMol and are consistent across the principal research-grade suppliers. Storage shelf-life divergence (-20C versus -80C for powder) is reported as-is; the -20C 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. Hyp, Thi, D-Tic, and Oic are rendered as standard three-letter abbreviations without Greek or superscript characters. 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.