Peptide and peptidomimetic ligands for CXC chemokine receptor 4 (CXCR4)

Oishi, Shinya; Fujii, Nobutaka

doi:10.1039/c2ob25107h

Cited by 31 publications

(31 citation statements)

References 157 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it did not achieve maximal pharmacodynamics effect in human based on the elevation of white blood cells (28). Alternatively, many peptide antagonists have been identified for CXCR4, and include T22, T140 and its analogues, a cyclic pentapeptide FC131 and its analogues, CTCE-9908 and BKT140 (17)(18)(19). Some of them, such as CTCE-9908 and BKT140, were moved into clinic studies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of LY2510924, a Novel Cyclic Peptide CXCR4 Antagonist That Exhibits Antitumor Activities in Solid Tumor and Breast Cancer Metastatic Models

Peng

Zhang

Paul

et al. 2015

Molecular Cancer Therapeutics

123

129

View full text Add to dashboard Cite

Emerging evidence demonstrates that stromal cell-derived factor 1 (SDF-1) and CXCR4, a chemokine and chemokine receptor pair, play important roles in tumorigenesis. In this report, we describe a small cyclic peptide, LY2510924, which is a potent and selective CXCR4 antagonist currently in phase II clinical studies for cancer. LY2510924 specifically blocked SDF-1 binding to CXCR4 with IC 50 value of 0.079 nmol/L, and inhibited SDF-1-induced GTP binding with Kb value of 0.38 nmol/L. In human lymphoma U937 cells expressing endogenous CXCR4, LY2510924 inhibited SDF-1-induced cell migration with IC 50 value of 0.26 nmol/L and inhibited SDF-1/ CXCR4-mediated intracellular signaling. LY2510924 exhibited a concentration-dependent inhibition of SDF-1-stimulated phospho-ERK and phospho-Akt in tumor cells. Biochemical and cellular analyses revealed that LY2510924 had no apparent agonist activity. Pharmacokinetic analyses suggested that LY2510924 had acceptable in vivo stability and a pharmacokinetic profile similar to a typical small-molecular inhibitor in preclinical species. LY2510924 showed dose-dependent inhibition of tumor growth in human xenograft models developed with non-Hodgkin lymphoma, renal cell carcinoma, lung, and colon cancer cells that express functional CXCR4. In MDA-MB-231, a breast cancer metastatic model, LY2510924 inhibited tumor metastasis by blocking migration/homing process of tumor cells to the lung and by inhibiting cell proliferation after tumor cell homing. Collectively, the preclinical data support further investigation of LY2510924 in clinical studies for cancer. Mol Cancer Ther; 14(2); 480-90. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Alternatively, many potent peptide antagonists for CXCR4 have been identified (17). However, these peptide antagonists generally have a short in vivo half-life.…”

Section: Introductionmentioning

confidence: 99%

Identification of LY2510924, a Novel Cyclic Peptide CXCR4 Antagonist That Exhibits Antitumor Activities in Solid Tumor and Breast Cancer Metastatic Models

Peng

Zhang

Paul

et al. 2015

Molecular Cancer Therapeutics

123

129

View full text Add to dashboard Cite

show abstract

“…Oishi et al 17 reported a compilation of different peptides and peptidomimetic ligands of CXCR4. Among them, pepducins 18 are a representative family of intracellular regulators of GPCR signaling 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Studying the binding interactions of allosteric agonists and antagonists of the CXCR4 receptor

Planesas

Pérez‐Nueno

Borrell

et al. 2015

Journal of Molecular Graphics and Modelling

View full text Add to dashboard Cite

“…These compounds have no structural resemblance with known peptide ligands and can be considered as functional (type--II) mimetics. reviewed by Oishi and Fujii [47].…”

Section: Cxcr4: Biology and Pharmacologymentioning

confidence: 99%

Progress Toward Rationally Designed Small-Molecule Peptide and Peptidomimetic CXCR4 Antagonists

Våbenø

Haug

2015

Future Med. Chem.

View full text Add to dashboard Cite

Over the last five years, X--ray structures of CXC chemokine receptor 4 (CXCR4) in complex with three different ligands (the small--molecule antagonist IT1t, the polypeptide antagonist CVX15, and the viral chemokine antagonist vMIP--II) have been released. In addition to the inherent scientific value of these specific X--ray structures, they (i) provide a reliable structural foundation for studies of the molecular interactions between CXCR4 and its key peptide ligands (CXCL12 and HIV--1 gp120); and (ii) serve as valuable templates for further development of small--molecule CXCR4 antagonists with therapeutic potential. We here review recent computational studies of the molecular interactions between CXCR4 and its peptide ligands -based on the X--ray structures of CXCR4 -and the current status of small--molecule peptide and peptidomimetic CXCR4 antagonists. 2) Isostere: In the context of this review, an isostere is defined as any functional group or moiety that is included in a peptide sequence as a replacement of an amide bond.3) Scaffold: The term scaffold is used for rigid (normally cyclic) structures onto which the functional groups of amino acid side chains can be introduced. 4) Structure--based and ligand--based design:In structure--based design, the 3D structure of the target is known and guides the design of active compounds. When the 3D structure of the target is unknown, indirect information has to be used in order to design/optimize compounds that bind to the target. This information is normally obtained through SAR studies and pharmacophore modeling, and the overall approach is known as ligand--based design. 5) 7TM receptors: As signalling via G proteins is a common feature for seven--

show abstract

Peptide and peptidomimetic ligands for CXC chemokine receptor 4 (CXCR4)

Abstract: This article is dedicated to the lOth anniversary of Organic & Biomolecular Chemistry.

Cited by 31 publications

References 157 publications

Identification of LY2510924, a Novel Cyclic Peptide CXCR4 Antagonist That Exhibits Antitumor Activities in Solid Tumor and Breast Cancer Metastatic Models

Identification of LY2510924, a Novel Cyclic Peptide CXCR4 Antagonist That Exhibits Antitumor Activities in Solid Tumor and Breast Cancer Metastatic Models

Studying the binding interactions of allosteric agonists and antagonists of the CXCR4 receptor

Progress Toward Rationally Designed Small-Molecule Peptide and Peptidomimetic CXCR4 Antagonists

Contact Info

Product

Resources

About