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. 2022 Feb 15;13(3):358-364.
doi: 10.1021/acsmedchemlett.1c00600. eCollection 2022 Mar 10.

GPCR Inhibition in Treating Lymphoma

Marilia Barreca  1 , Virginia Spanò  1 , Maria V Raimondi  1 , Roberta Bivacqua  1 , Stefano Giuffrida  1 , Alessandra Montalbano  1 , Andrea Cavalli  2   3 , Francesco Bertoni  4   5 , Paola Barraja  1
Affiliations

GPCR Inhibition in Treating Lymphoma

Marilia Barreca et al. ACS Med Chem Lett. .

Abstract

G protein-coupled receptors (GPCRs) are important classes of cell surface receptors involved in multiple physiological functions. Aberrant expression, upregulation, and mutation of GPCR signaling pathways are frequent in many types of cancers, promoting hyperproliferation, angiogenesis, and metastasis. Recent studies showed that alterations of GPCRs are involved in different lymphoma types. Herein, we review the synthetic strategies to obtain GPCR inhibitors, focusing on CXCR4 inhibitors which represent most of the GPCR inhibitors available in the market or under preclinical investigations for these diseases.

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Conflict of interest statement

The authors declare the following competing financial interest(s): Francesco Bertoni: institutional research funds from Acerta, ADC Therapeutics, Bayer AG, Cellestia, CTI Life Sciences, EMD Serono, Helsinn, ImmunoGen, Menarini Ricerche, NEOMED Therapeutics 1, Nordic Nanovector ASA, Oncology Therapeutic Development, Polyphor, PIQUR Therapeutics AG; consultancy fee from Helsinn, Menarini; expert statements provided to HTG; travel grants from Amgen, Astra Zeneca, Jazz Pharmaceuticals, PIQUR Therapeutics AG. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Structures of nonpeptidic GPCR inhibitors.
Scheme 1
Scheme 1. Synthetic Route for Plerixafor Using Cr(CO)6
Scheme 2
Scheme 2. Synthetic Route for Plerixafor Using P(NMe2)3 or B(NMe2)3
Scheme 3
Scheme 3. Synthetic Route for GENZ-644494
Scheme 4
Scheme 4. Synthetic Route for AMD070
Scheme 5
Scheme 5. Synthetic Route for WK1
Scheme 6
Scheme 6. Synthetic Route for IQS-01.01RS
Figure 2
Figure 2
Structures of peptidic GPCR inhibitors.
See this image and copyright information in PMC

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