<i>In-silico</i>evidence of ADAM metalloproteinase pathology in cancer signaling networks

Sen, Plaboni; Kandasamy, Thirukumaran; Ghosh, Siddhartha Sankar

doi:10.1080/07391102.2021.1964602

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…ADAM17 is a member of the adamalysins subfamily of metzincin metalloproteinases consisting of 824 amino acids with zinc-dependent catalytic activities (29). The human ADAM17 protein sequence contains an N-terminal signal sequence (SS), a prodomain (PD), a catalytic metalloprotease domain (MD), a disintegrin domain (DD), a membraneproximal protein domain (MPD), a conserved ADAM17 interaction sequence (CANDIS), a transmembrane domain (TM), and a C-terminal cytoplasmic domain (CD), which are located at amino acid residues 1-17, 18-216, 217-474, 480-559, 581-642, 643-666, 672-694, and 695-824, respectively (7,30) (Figure 1A).…”

Section: Structure Of Adam17mentioning

confidence: 99%

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

et al. 2022

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ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.

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Section: Structure Of Adam17mentioning

confidence: 99%

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

et al. 2022

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“…127 Moreover, an in silico study conducted by our group demonstrates the various binding affinities of the different classes of molecules and their functional derivatives (obtained from PubChem) against the ADAM protease. 128 Through molecular docking studies, it was ascertained that the derivatives of the γ-lactam hydroxamate IK862 exhibit superior binding properties, followed by ZLDI8, a competitive and irreversible lymphoid tyrosine phosphatase inhibitor, in comparison to the derivatives of the other class of molecules. However, the in vitro assessment of TMI-1, a thiomorpholine sulfonamide hydroxamate bearing novel propargylic P1 group, endowed us with the efficacy of the compound in inhibiting the EMT, along with incorporating differentiated epithelial phenotype (CD44 + /CD24 + ).…”

Section: Modification Ofmentioning

confidence: 99%

“…Moreover, an in silico study conducted by our group demonstrates the various binding affinities of the different classes of molecules and their functional derivatives (obtained from PubChem) against the ADAM protease . Through molecular docking studies, it was ascertained that the derivatives of the γ-lactam hydroxamate IK862 exhibit superior binding properties, followed by ZLDI8, a competitive and irreversible lymphoid tyrosine phosphatase inhibitor, in comparison to the derivatives of the other class of molecules.…”

Section: Implications Of Notch In Cancermentioning

confidence: 99%

The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer

Sen

Ghosh

2023

ACS Pharmacol. Transl. Sci.

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The Notch pathway is remarkably simple without the interventions of secondary messengers. It possesses a unique receptor−ligand interaction that imparts signaling upon cleavage of the receptor followed by the nuclear localization of its cleaved intracellular domain. It is found that the transcriptional regulator of the Notch pathway lies at the intersection of multiple signaling pathways that enhance the aggressiveness of cancer. The preclinical and clinical evidence supports the pro-oncogenic function of Notch signaling in various tumor subtypes. Owing to its oncogenic role, the Notch signaling pathway assists in enhanced tumorigenesis by facilitating angiogenesis, drug resistance, epithelial to mesenchymal transition, etc., which is also attributed to the poor outcome in patients. Therefore, it is extremely vital to discover a suitable inhibitor to downregulate the signal-transducing ability of Notch. The Notch inhibitory agents, such as receptor decoys, protease (ADAM and γ-secretase) inhibitors, and monoclonal/bispecific antibodies, are being investigated as candidate therapeutic agents. Studies conducted by our group exemplify the promising results in ablating tumorigenic aggressiveness by inhibiting the constituents of the Notch pathway. This review deals with the detailed mechanism of the Notch pathways and their implications in various malignancies. It also bestows us with the recent therapeutic advances concerning Notch signaling in the context of monotherapy and combination therapy.

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