Pim-1 kinase as cancer drug target: An update

Tursynbay, Yernar; Zhang, Jinfu; Li, Zhi; Tokay, Tursonjan; Zhumadilov, Zhaxybay; Wu, Denglong; Xie, Yingqiu

doi:10.3892/br.2015.561

Cited by 101 publications

(75 citation statements)

References 69 publications

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“…Pim1 kinase is part of the serinethreonine protein kinases that play a role in apoptosis, metabolism, cycles, and migration of cells in tumor growth. Pim1 kinase is also overexpressed in several types of human cancers and it's activity also reported as a promoter of carcinogenesis, so that it is postulated as a potential target of cancer therapy (Tursynbay et al, 2016;Matthew et al, 2015;Weirauch et al, 2013). Pim1 downloaded from PDB with ID code of 5 wdr selected due to has a resolution of 2Å, descended from Homo sapiens and complexes with a small molecule ligand of [N-4-(1R,3S,5S)-3-amino-5-methylcyclohexylpyridine-3-yl-6-(2,6-difluorophenyl)-5fluoropicolinamide (5H7_401(A)].…”

Section: Resultsmentioning

confidence: 99%

“…Pim1 kinase is overexpressed in many human cancer diseases and has been associated with metastasis and overall treatment response. The experimental model study reported that inhibition of Pim1 kinase suppressed proliferation and migration cell, induced apoptotic cell death, and synergized with other chemotherapeutic agents so that Pim1 kinase is the preferential target for inhibition of the mitotic processing and can be chosen as drug target for the treatment of cancer (Gisele et al, 2016;Tursynbay et al, 2016;Matthew et al, 2015;Weirauch et al, 2013). Some compounds were reported to inhibit the activity of serine/threonine kinases of Pim1, such as imidazopyridazine, benzoimidazol, acylhydrazone, triazolopyridine, thiazolidine-2,4-dione, pyridone, staurosporin, and bisindolylmaleimide (Merkel et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer

Widiyarti

Firdayani²,

Hanafi

et al. 2019

Valensi

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The proviral insertion site in Moloney murine leukemia virus-1 (Pim1) kinase is overexpressed in many human cancer diseases. Inhibition of Pim1 kinase has been reported can suppress cell proliferation and induce apoptotic cell death, so that the protein could be chosen as drug target for the treatment of cancer. Citronellol and geraniol mainly contained in citronella oil that's one of Indonesian natural products have bioactivity as antitumor agents, so that both of the compounds can be used as guiding compound to be developed as chemoprevention and chemotherapeutic agent compounds for cancer especially for leukemia cancer. In this research, sixteen citronellol and geraniol esters as an inhibitor of leukemia cancer designed were docked based on their interaction with leukemia receptor target of Pim1 kinase by using Molegro Virtual Docker (MVD). The result showed that the binding citronellol and geraniol esters to Pim1 kinase are more stable and better affinity than the binding between citronellol and geraniol, indicated by rerank score were lower than rerank score of citronellol/geraniol-Pim1 kinase. The docking resulted in the four top-ranked compounds, namely, citronellyl caproate, citronellyl caprylate, geranyl caproate and geranyl caprylate with rerank score value from -182.560 to -189.822 KJ/mol. These compounds have hydrogen bonding with amino acid residues of Lys 67 and Asp 186 of an active site of Pim1 kinase. Based on Lipinski's rule of five, among of the four top-ranked compounds, citronellyl caproate and geranyl caproate were predicted have potency as new chemopreventive and chemotherapeutic agents for leukemia anticancer candidates.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer

Widiyarti

Firdayani²,

Hanafi

et al. 2019

Valensi

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“…Upregulation of PIM 1 expression has been shown in prostate cancer following inhibition of AKT [20], providing further evidence for the idea of crosstalk between both PIM kinase and PI3K/AKT/mTOR pathways [21]. Inhibition of AKT can also induce increased expression of several different receptor tyrosine kinases such as HER2 through PIM 1-mediated regulation [2,22].…”

Section: Introductionmentioning

confidence: 82%

“…In this study, we have determined that elevated expression of PIM 1 is significantly associated with elevated sensitivity to IBL-302 in both TNBC and HER2+/ER+ cell lines. PIM 1 has been highlighted as a therapeutic target in TNBC [12,14,60] and as a result, not much focus has been placed on HER2+/ER+ cells, especially those with acquired resistance to HER2 targeted therapies. Interestingly, there is high PIM 1 expression in the HER2+ HCC-1954 cells, whilst the PIK3CA mutant BT-474 cells, which have low expression of PIM 1, are also sensitive to IBL-302.…”

Section: Discussionmentioning

confidence: 99%

“…The PIM (proviral integration of Moloney virus) family of serine/threonine protein kinases were first discovered in experimental lymphomas [1]. The PIM kinase family is made up of three members; PIM 1, PIM 2 and PIM 3 [2]. Functions of the PIM kinase family vary, from cell cycle regulation, proliferation, apoptosis, invasion, metastasis and senescence [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer

Kennedy

O’Neill²,

Cunningham³

et al. 2020

Oncogene

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The proviral integration of Moloney virus (PIM) family of protein kinases are overexpressed in many haematological and solid tumours. PIM kinase expression is elevated in PI3K inhibitor-treated breast cancer samples, suggesting a major resistance pathway for PI3K inhibitors in breast cancer, potentially limiting their clinical utility. IBL-302 is a novel molecule that inhibits both PIM and PI3K/AKT/mTOR signalling. We thus evaluated the preclinical activity of IBL-302, in a range of breast cancer models. Our results demonstrate in vitro efficacy of IBL-302 in a range of breast cancer cell lines, including lines with acquired resistance to trastuzumab and lapatinib. IBL-302 demonstrated single-agent, anti-tumour efficacy in suppression of pAKT, pmTOR and pBAD in the SKBR-3, BT-474 and HCC-1954 HER2+/PIK3CA-mutated cell lines. We have also shown the in vivo single-agent efficacy of IBL-302 in the subcutaneous BT-474 and HCC-1954 xenograft model in BALB/c nude mice. The combination of trastuzumab and IBL-302 significantly increased the anti-proliferative effect in HER2+ breast cancer cell line, and matched trastuzumab-resistant line, relative to testing either drug alone. We thus believe that the novel PIM and PI3K/mTOR inhibitor, IBL-302, represents an exciting new potential treatment option for breast cancer, and that it should be considered for clinical investigation.

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Emerging Trends in Quinoxaline‐Based Analogs as Protein Kinase Inhibitors: Structural Developments and SAR Insights

Shivani,

Mahajan,

Chaudhary

2024

ChemMedChem

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Cancer remains a leading cause of mortality and has been recognized as a significant global health concern. Although numerous effective anticancer agents are available; most of the current drugs lack specificity, leading to common side‐effects associated with chemotherapy. Recent research, however, offers promise for developing more targeted and safer anticancer therapies through protein kinase inhibition. Quinoxaline derivatives represent a notable class of heterocyclic compounds. The extensive spectrum of biological activities demonstrated by quinoxalines has garnered substantial research interest. Quinoxaline and its derivatives have emerged as a novel class of chemotherapeutic agents with significant activity against various tumors through protein kinase inhibition. This review aims to elucidate recent advancements in the quinoxaline derivatives targeting protein kinase along with structural developments and structure‐activity relationships associated with these compounds.

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Pim-1 kinase as cancer drug target: An update

Cited by 101 publications

References 69 publications

Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer

Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer

Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer

Emerging Trends in Quinoxaline‐Based Analogs as Protein Kinase Inhibitors: Structural Developments and SAR Insights

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