C1632 inhibits ovarian cancer cell growth and migration by inhibiting LIN28 B/let-7/FAK signaling pathway and FAK phosphorylation

Zhang, Qian; Zheng, Ruiling; Han, Haoyi; Zhang, Xin; Lin, Feng

doi:10.1016/j.ejphar.2023.175935

Cited by 4 publications

(2 citation statements)

References 63 publications

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“…Like DNA-binding proteins, small-molecule inhibition of RBPs is difficult, although recent high-throughput approaches have generated candidates ( Wu, 2020 ). The most promising LIN28(A/B) inhibitor is C1632, which targets LIN28B + cell lines both by disruption of LIN28B–let-7 interaction ( Franses et al, 2020 ; Zhang Q. et al, 2023 ; Shahab et al, 2023 ) and in Ewing sarcoma by disruption of the interaction between EWS-FLI1 mRNA and LIN28B ( Keskin et al, 2020 ). Other molecules such as LI71 bind the cold shock domain and have efficacy against LIN28B + cancer cell lines ( Wang L. et al, 2018 ).…”

Section: Targeting Aberrant Stem Cell Programs In Leukemia For Therapymentioning

confidence: 99%

Aberrant stem cell and developmental programs in pediatric leukemia

Ling,

Cross,

Roy

2024

Front. Cell Dev. Biol.

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Hematopoiesis is a finely orchestrated process, whereby hematopoietic stem cells give rise to all mature blood cells. Crucially, they maintain the ability to self-renew and/or differentiate to replenish downstream progeny. This process starts at an embryonic stage and continues throughout the human lifespan. Blood cancers such as leukemia occur when normal hematopoiesis is disrupted, leading to uncontrolled proliferation and a block in differentiation of progenitors of a particular lineage (myeloid or lymphoid). Although normal stem cell programs are crucial for tissue homeostasis, these can be co-opted in many cancers, including leukemia. Myeloid or lymphoid leukemias often display stem cell-like properties that not only allow proliferation and survival of leukemic blasts but also enable them to escape treatments currently employed to treat patients. In addition, some leukemias, especially in children, have a fetal stem cell profile, which may reflect the developmental origins of the disease. Aberrant fetal stem cell programs necessary for leukemia maintenance are particularly attractive therapeutic targets. Understanding how hijacked stem cell programs lead to aberrant gene expression in place and time, and drive the biology of leukemia, will help us develop the best treatment strategies for patients.

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Section: Targeting Aberrant Stem Cell Programs In Leukemia For Therapymentioning

confidence: 99%

Aberrant stem cell and developmental programs in pediatric leukemia

Ling,

Cross,

Roy

2024

Front. Cell Dev. Biol.

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“…With this knowledge, much research has been carried out to nd the small molecule inhibitors of LIN28 to subside tumors [4][5][6][7][8][9][10][11][12][13], but to note that LIN28 is not only involved in the cell cycle but also in other metabolic process like glucose metabolism which will be affected if LIN28 is affected [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Identification of small molecule inhibitors against Lin28/let-7 to suppress tumor progression and its alleviation role in LIN28-dependent glucose metabolism

Raja,

Sundararaj,

Kandasamy

2024

Med Oncol

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The reciprocal suppression of an RNA binding protein LIN28 (human abnormal cell lineage 28) and miRNA Let-7 (Lethal 7) is considered to have a prime role in hepatocellular carcinoma (HCC). Though targeting this inhibition interaction is effective for therapeutics, it causes other unfavorable effects on glucose metabolism and increased insulin resistance. Hence, this study aims to identify small molecules targeting Lin28/let-7 interaction along with additional potency to improve insulin sensitivity. Of 22,14,996 small molecules screened by high throughput virtual screening, 6 molecules, namely 41354, 1558, 12437, 23837, 15710, and 8319 were able to block the LIN28 interaction with let-7 and increase the insulin sensitivity via interacting with PPARγ (peroxisome proliferator-activated receptors γ). MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) analysis is used to re-score the binding a nity of docked complexes. Upon further analysis, it is also seen that these molecules have superior ADME (Absorption, Distribution, Metabolism and Excretion) properties and form stable complexes with the targets for a signi cant period in a biologically simulated environment (Molecular Dynamics simulation) for 100 ns. From our results, we hypothesize that these identi ed 6 small molecules can be potential candidates for HCC treatment and the glucose metabolic disorder caused by the HCC treatment.

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