Synthesis and evaluation of 2,5 and 2,6 pyridine-based CXCR4 inhibitors

Gaines, Theresa; Camp, Davita; Bai, Renren; Liang, Zhongxing; Yoon, Younghyoun; Shim, Hyunsuk; Mooring, Suazette Reid

doi:10.1016/j.bmc.2016.08.018

Cited by 20 publications

(12 citation statements)

References 26 publications

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“…All of the prepared compounds were first screened with a binding affinity assay as described in our previous publications [18][19][20][21][22][23]. The screening protocol is a competitive CXCR4 binding assay between biotinylated TN14003, a potent CXCR4 peptidic antagonist, and the target compounds Ia-b, IIa-c, and IIIa-o at concentrations of 1, 10, 100, and 1000 nM.…”

Section: Preliminary Binding Affinity Screeningmentioning

confidence: 99%

Development of CXCR4 modulators based on the lead compound RB-108

Bai

Jie

Sun

et al. 2019

European Journal of Medicinal Chemistry

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The CXCR4/CXCL12 axis plays prominent roles in tumor metastasis and inflammation. CXCR4 has been shown to be involved in a variety of inflammation-related diseases. Therefore, CXCR4 is a promising potential target to develop novel anti-inflammatory agents. Taking our previously discovered CXCR4 modulator RB-108 as the lead compound, a series of derivatives were synthesized structurally modifying and optimizing the amide and sulfamide side chains. The derivatives successfully maintained potent CXCR4 binding affinity. Furthermore, compounds Ilb, IIc, IIIg, IIIj, and IIIm were all efficacious in inhibiting the invasion of CXCR4-positive cells, displaying a much more potent effect than the lead compound RB-108. Notably, compound IIIm significantly decreased carrageenan-induced swollen volume and paw thickness in a mouse paw edema model. More importantly, IIIm exhibited satisfying PK profiles with a half-life of 4.77 h in an SD rat model. In summary, we have developed compound IIIm as a new candidate for further investigation based on the lead compound RB-108.

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Section: Preliminary Binding Affinity Screeningmentioning

confidence: 99%

Development of CXCR4 modulators based on the lead compound RB-108

Bai

Jie

Sun

et al. 2019

European Journal of Medicinal Chemistry

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“…This study was stopped in phase II clinical tests, because of non‐clinical reports of hepatotoxicity (cytochrome P450 2D6 inhibition) and histologic findings. Some other CXCR4 inhibitors have been introduced with non‐anti‐HIV‐1 effects that are not related to the present review …”

Section: Hiv‐1 Entry Inhibitorsmentioning

confidence: 99%

HIV‐1 Entry Inhibitors: A Review of Experimental and Computational Studies

Rad

Saghaie

Fassihi

2018

Chemistry & Biodiversity

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The HIV-1 life cycle consists of different events, such as cell entry and fusion, virus replication, assembly and release of the newly formed virions. The more logical way to inhibit HIV transmission among individuals is to inhibit its entry into the immune host cells rather than targeting the intracellular viral enzymes. Both viral and host cell surface receptors and co-receptors are regarded as potential targets in anti-HIV-1 drug design process. Because of the importance of this topic it was decided to summarize recent reports on small-molecule HIV-1 entry inhibitors that have not been considered in the latest released reviews. All the computational studies reported in the literature regarding HIV-1 entry inhibitors since 2014 was also considered in this review.

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“…A serial of novel small molecule modulators of the CXCR4 receptor have been developed these years. These new compounds may potentially open up new therapeutics for CXCR4 related pulmonary firbrosis 81,82 .…”

Section: Potential Therapy Targeted On Circulating Fibrocyte and Cxcr4mentioning

confidence: 99%

Role of CXCL12/CXCR4-Mediated Circulating Fibrocytes in Pulmonary Fibrosis

Xie¹,

Zhao²

2017

J. Biomed

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Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix (ECM) and remodeling of the lung architecture, with clinically irreversible loss of lung function. The exact molecular and cellular mechanisms of pulmonary fibrosis are complicated. Many types of cells are involved in the pathogenic processes. The chemokine (C-X-C motif) ligand 12 (CXCL12) can attract circulating fibrocytes trafficking into lungs via chemokine (C-X-C motif) receptor 4 (CXCR4) to promote tissue repair or impertinently worsen fibrotic lesions. In this review, we briefly summarize the existing experimental and clinical findings about fibrocytes in pulmonary fibrosis and discuss the potential therapeutic target CXCL12/CXCR4 biological axis.

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Synthesis and evaluation of 2,5 and 2,6 pyridine-based CXCR4 inhibitors

Cited by 20 publications

References 26 publications

Development of CXCR4 modulators based on the lead compound RB-108

Development of CXCR4 modulators based on the lead compound RB-108

HIV‐1 Entry Inhibitors: A Review of Experimental and Computational Studies

Role of CXCL12/CXCR4-Mediated Circulating Fibrocytes in Pulmonary Fibrosis

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