Cilengitide | CAS 188968-51-6 | Integrin alpha-v beta3 / alpha-v beta5 Antagonist (Research Use Only) | Knowlux

Product Description

Cilengitide (EMD 121974), CAS 188968-51-6, is a synthetic cyclic pentapeptide integrin antagonist supplied by Knowlux for laboratory research use. The peptide is a head-to-tail cyclized RGD motif analogue incorporating a D-phenylalanine at position 4 and an N-methylated valine at position 5. The sequence is cyclo(Arg-Gly-Asp-D-Phe-NMeVal). The molecular formula is C27H40N8O7 and the molecular weight is 588.66 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: Cilengitide circulates in commercial catalogues as three distinct chemical forms, and the distinction is material for molecular weight, solubility, and assay design. CAS 188968-51-6 is the free peptide (free base), with formula C27H40N8O7 and MW 588.66, as confirmed by ChemicalBook, Tocris, ChemBlink, Adooq, and Xcess Biosciences. A trifluoroacetate (TFA) salt is registered under CAS 199807-35-7, with a molecular weight of approximately 702.68 for the TFA salt form, as listed by Selleck. A hydrochloride salt is registered under CAS 188969-00-8, with formula C27H41ClN8O7 and MW 625.12, as listed by MedChemExpress. The free base is the reference basis for the 588.66 molecular weight. 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 base, TFA salt, or hydrochloride salt before procurement, as the counter-ion shifts the mass balance and affects molarity calculations.

Structural and Mechanistic Note: Cilengitide is a cyclic RGD pentapeptide, and the cyclization is essential for its biological activity. The RGD motif is the minimal recognition sequence for several integrin heterodimers, and the D-Phe and N-Me-Val substitutions confer selectivity for the alpha-v beta3 and alpha-v beta5 subtypes over the platelet GP IIb/IIIa receptor. Unlike linear RGD peptides that are susceptible to rapid proteolytic degradation, the head-to-tail cyclic structure of Cilengitide confers metabolic stability and a defined bioactive conformation. The peptide contains no cysteine, methionine, or tryptophan, which removes disulfide scrambling, methionine sulfoxide formation, and tryptophan oxidation as principal degradation pathways. The sole aromatic residue is the D-phenylalanine at position 4.

Product Parameters

Product Details

1. Overview

Cilengitide is a cyclic RGD pentapeptide developed as a selective antagonist of the alpha-v beta3 and alpha-v beta5 integrins. These integrins are upregulated on activated endothelial cells during angiogenesis and on the surface of several tumor cell types, where they mediate cell adhesion to extracellular matrix proteins such as vitronectin and fibronectin. By blocking integrin-ligand engagement, Cilengitide disrupts the outside-in signaling that supports endothelial cell survival, migration, and tube formation, and it has been investigated clinically as an anti-angiogenic and anti-tumor agent, most notably in glioblastoma. The material supplied under this specification is research-grade and is not intended for human administration.

2. Receptor Pharmacology and Selectivity

Cilengitide binds the alpha-v beta3 and alpha-v beta5 integrins with high affinity and exhibits a defined selectivity profile across the integrin family. Potency values reported in the literature vary depending on the salt form and assay format. For the free base, MedChemExpress reports IC50 values of 0.61 nM (alpha-v beta3), 8.4 nM (alpha-v beta5), 14.9 nM (alpha5 beta1), 2050 nM (alpha-v beta6), 2350 nM (alpha-v beta8), and 5400 nM (alpha-IIb beta3). Selleck, reporting on the TFA salt, lists IC50 values of 4.1 nM (alpha-v beta3) and 79 nM (alpha-v beta5) in cell-free assays, with approximately 10-fold selectivity against GP IIb/IIIa. TargetMol and the ScienceDirect overview report IC50 values of 4 nM (alpha-v beta3) and 79 nM (alpha-v beta5) for inhibition of vitronectin binding. Creative Enzymes reports IC50 values of 2.3 nM (alpha-v beta3) and 37 nM (alpha-v beta5). The spread across these sources reflects differences in radioligand, integrin source, and whether the assay measures direct binding or cell adhesion. A key selectivity feature, consistent across sources, is the substantially weaker activity at alpha-IIb beta3 (GP IIb/IIIa), which distinguishes Cilengitide from non-selective RGD peptides. A Ki of 1.0 nM has also been reported for the human alpha-v beta3 receptor in a protein complex binding format.

3. Research Applications

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

• Integrin alpha-v beta3 and alpha-v beta5 binding and functional antagonist assays (radioligand displacement, cell adhesion inhibition)

• Integrin selectivity profiling across alpha-v beta3, alpha-v beta5, alpha5 beta1, alpha-IIb beta3, alpha-v beta6, and alpha-v beta8

• Angiogenesis and endothelial cell migration/tube formation studies

• Glioblastoma and melanoma tumor biology research models (viability, apoptosis, colony formation, autophagy)

• Integrin-mediated signaling pathway studies (FAK, Src, Akt, mTOR, STAT3 phosphorylation; PD-L1 modulation)

• Blood-brain barrier permeability and CNS tumor targeting research

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

MedChemExpress documents in vitro activity in B16 and A375 melanoma cells: time- and dose-dependent inhibition of viability (1-1000 microg/mL, 24-72 h), inhibition of colony formation (5-10 microg/mL, two weeks), induction of apoptosis (5-10 microg/mL, 12 h), and reduction of PD-L1 expression, with decreased phosphorylation of AKT and mTOR. Selleck documents inhibition of FAK, Src, and Akt phosphorylation in G28 and HMEC-1 cells, and dose-dependent impairment of adhesion to vitronectin in glioma cell lines (LNT-229, T98G, LN-18, LN-308, U87MG) at 0.1-10 microM. These descriptions are derived from published research and are provided for scientific reference only.

Quality Control

Purity specifications for Cilengitide span the 95% to 99.5% range depending on supplier and grade. ChemicalBook supplier listings offer 95%, 98%, and 99% HPLC grades, with one entry specifying single impurity <=2.0%, acetate content <=12.0%, and water content <=8.0%. Sigma-Aldrich specifies >=95% for its TFA salt. Selleck reports a batch purity of 99.50% for its TFA salt. MedChemExpress reports a peptide content of 91.30% for its free base batch and 79.85% for its hydrochloride batch, illustrating the impact of counter-ion mass on the peptide content figure. The principal quality consideration is the salt-form ambiguity: a lot reported at MW 588.66 is on a free-base basis, whereas a hydrochloride lot at MW 625.12 or a TFA lot at approximately 702.68 will have a higher molecular weight and a proportionally lower peptide content. Researchers preparing molar solutions should use the peptide content value and the declared salt basis rather than the HPLC purity figure alone.

Solubility and Handling

Solubility: Cilengitide solubility is solvent-dependent, and the aqueous value requires careful interpretation. For DMSO, Selleck batch-tested data report solubility of 100 mg/mL (169.87 mM) at 25C, with the explicit caveat that moisture-contaminated DMSO reduces solubility and that fresh anhydrous DMSO should be used; the recommended stock concentration is 10 mM in DMSO. MedChemExpress corroborates DMSO solubility of 100 mg/mL. For water, reported values diverge substantially: Selleck lists 5 mg/mL with sonication and heating to 60C for 10 minutes; Sigma-Aldrich lists 20 mg/mL as a clear solution for its TFA salt; ChemicalBook lists >=22.56 mg/mL for one lot and soluble to 10 mg/mL for another; and a patent filing describes a free-base solubility range of 5-9 mg/mL. The divergence between the free-base and salt forms is a plausible contributor to these differences, as the TFA salt generally exhibits higher aqueous solubility than the free base. For practical stock preparation, DMSO at 100 mg/mL is the most consistently supported condition, and water at 5-20 mg/mL is achievable depending on the salt form and the application of heat and sonication. Selleck technical note on DMSO stock precipitation in aqueous media recommends preheating the aqueous phase to 37C, mixing rapidly upon addition, and adding the aqueous phase last for complex vehicles.

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. Because the peptide contains no cysteine or methionine, reducing agents and methionine-oxidation protection measures are not required. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening.

Storage and Stability

Storage guidance for Cilengitide converges on -20C for the lyophilized powder as the standard long-term condition, with desiccation and protection from moisture. Selleck, TargetMol, Adooq, and InvivoChem specify 3 years at -20C for powder, with solutions stable for 1 year at -80C or 1 month at -20C. MedChemExpress offers a more conservative tier of 2 years at -80C and 1 year at -20C for powder, with solutions stable for 6 months at -80C or 1 month at -20C under sealed, moisture-free conditions. One ChemicalBook supplier lists a 1-year shelf life at -20C, which is shorter than the 3-year claims from the principal suppliers and may reflect a specific lot history or a different stability-indicating method. The -20C powder condition is the most widely supported archival temperature; -80C is the conservative choice for extended storage. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening to prevent condensation. Protect from light and moisture throughout storage.

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. Cilengitide has been investigated in clinical trials for glioblastoma and other solid tumors 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 free-base formula C27H40N8O7 and MW 588.66 are confirmed across ChemicalBook, Tocris, ChemBlink, Adooq, Xcess Biosciences, MedChemExpress, and Selleck. The sequence cyclo(Arg-Gly-Asp-D-Phe-NMeVal) is confirmed by ChemicalBook, Tocris, Adooq, and MedChemExpress. The TFA salt CAS 199807-35-7 and MW approximately 702.68 are from Selleck. The hydrochloride CAS 188969-00-8, formula C27H41ClN8O7, and MW 625.12 are from MedChemExpress. The IC50 values are reported by salt form and source rather than reconciled into a single figure: 0.61 nM (alpha-v beta3) and 8.4 nM (alpha-v beta5) from MedChemExpress; 4.1 nM and 79 nM from Selleck (TFA salt); 4 nM and 79 nM from TargetMol and ScienceDirect; 2.3 nM and 37 nM from Creative Enzymes. The Ki of 1.0 nM for alpha-v beta3 is from the EBI/Guide to Pharmacology activity record. Solubility values are reported with their source and salt-form conditions because the aqueous data span 5-22.56 mg/mL across different lots 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. Greek integrin subunit names are rendered as alpha and beta in plain text. 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.