The chemical biology of apoptosis: Revisited after 17 years

Yang, Shu; Mao, Yujia; Zhang, Huijun; Xu, Yan; An, Jing; Huang, Ziwei

doi:10.1016/j.ejmech.2019.05.019

Cited by 26 publications

(14 citation statements)

References 112 publications

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“…519 It is undergoing evaluation in several phase I clinical trials in patients with relapsed/refractory AML or MDS (NCT02979366), and relapsed/refractory MM or lymphoma (NCT02992483). Two other MCL-1 inhibitors AZD-5991 520 and AMG-176 521 have also entered clinical trials to evaluate their safety, PKs, and antitumor response in patients with hematological malignancies (NCT03218683 and NCT02675452). Neither efficacy nor safety data of MCL-1 inhibitors are currently available.…”

Section: Bcl-2 Inhibitorsmentioning

confidence: 99%

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Zhong

Xiong

et al. 2021

Sig Transduct Target Ther

716

490

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Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.

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Section: Bcl-2 Inhibitorsmentioning

confidence: 99%

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Zhong

Xiong

et al. 2021

Sig Transduct Target Ther

716

490

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“…It has been almost 30 years since the identification of BCL-2 and its family members in regulating cell apoptosis (anti-apoptosis: BCL-2, BCL-lnctnXL, and MCL-1; pro-apoptosis: BIM, BID, BAX, and BAK). The anti-apoptosis proteins of the BCL-2 family execute their function by sequestering pro-apoptosis proteins and preventing the creation of pores in the mitochondrial outer membrane via protein-protein interactions ( Ashkenazi et al, 2017 ; Huang et al, 2019 ; Yang et al, 2019 ). Repressing the expression of anti-apoptosis protein via gene silencing or inhibiting such protein-protein interaction via BH3 mimetics are therefore emerging as novel targeting treatments for cancer, including several hematological malignancies in which BCL-2 and/or MCL-1 are aberrantly activated in leukemic stem cells (LSCs) or leukemic blasts.…”

Section: Introductionmentioning

confidence: 99%

Targeting Bim via a lncRNA Morrbid Regulates the Survival of Preleukemic and Leukemic Cells

et al. 2020

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SUMMARY Inhibition of anti-apoptotic proteins BCL-2 and MCL-1 to release pro-apoptotic protein BIM and reactivate cell death could potentially be an efficient strategy for the treatment of leukemia. Here, we show that a lncRNA, MORRBID , a selective transcriptional repressor of BIM , is overexpressed in human acute myeloid leukemia (AML), which is associated with poor overall survival. In both human and animal models, MORRBID hyperactivation correlates with two recurrent AML drivers, TET2 and FLT3 ITD . Mice with individual mutations of Tet2 or Flt3 ITD develop features of chronic myelomonocytic leukemia (CMML) and myeloproliferative neoplasm (MPN), respectively, and combined presence results in AML. We observe increased levels of Morrbid in murine models of CMML, MPN, and AML. Functionally, loss of Morrbid in these models induces increased expression of Bim and cell death in immature and mature myeloid cells, which results in reduced infiltration of leukemic cells in tissues and prolongs the survival of AML mice.

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“…Upon a cytotoxic stimulus, mitochondrial outer membrane integrity was damaged (also known as MOMP) which results in cytochrome c release into the cytosol. The release of cytochrome c activates caspase-9 which activates effector caspases (caspase-3, caspase-6, and caspase-7), finally resulting in apoptosis [10]. MOMP is enhanced by proapoptotic proteins Bcl-2-associated X (BAX) and Bcl-2 antagonist killer (BAK); meanwhile, it is suppressed by antiapoptotic Bcl-2 family proteins (Bcl-2, Bcl-XL) [11,12].…”

Section: Introductionmentioning

confidence: 99%

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

Wang

Song

et al. 2020

BioMed Research International

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Background. Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound 9i and also investigated the underlying molecular mechanism. Methods. Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound 9i. Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot. Results. Compound 9i suppressed HeLa cell viability in a time- and dose-dependent manner. Compound 9i induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis. Conclusion. Compound 9i induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that 9i could be a potential lead compound to be developed as a cancer therapeutic molecule.

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The chemical biology of apoptosis: Revisited after 17 years

Cited by 26 publications

References 112 publications

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Targeting Bim via a lncRNA Morrbid Regulates the Survival of Preleukemic and Leukemic Cells

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

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