Acetylenic inhibitors of ADAM10 and ADAM17: In silico analysis of potency and selectivity

Healy, Eamonn F.; Romano, P.; Mejia, Moises; Lindfors, Gunnar

doi:10.1016/j.jmgm.2010.08.006

Cited by 11 publications

(5 citation statements)

References 32 publications

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“…Existing structural and modeling studies reveal the presence of a large S 3 Ј cleft in the ADAM17 structure that can potentially accommodate a bulky disaccharide (␤Gal-1,3-␣GalNAc) (59 -61). Alignment of ADAM10 and -17 sequences shows that residues forming the ADAM17 S 3 Ј pocket are not conserved between ADAM10 and -17 ( 189 EADLV versus 189 VSHIT for ADAM17 and -10, respectively) (60). Interestingly, the ADAM10 I192L/T193V double mutant cleavage specificity profile was indistinguishable from that of ADAM17 WT (38).…”

Section: Resultsmentioning

confidence: 96%

Discovery of Novel Inhibitors of a Disintegrin and Metalloprotease 17 (ADAM17) Using Glycosylated and Non-glycosylated Substrates

Minond

Čudić

Bionda

et al. 2012

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 96%

Discovery of Novel Inhibitors of a Disintegrin and Metalloprotease 17 (ADAM17) Using Glycosylated and Non-glycosylated Substrates

Minond

Čudić

Bionda

et al. 2012

Journal of Biological Chemistry

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“…ADAM metalloproteinase domain 10 (ADAM10, CDw156 or CD156c, EC 3.4.24.81) has a broad specificity for peptide hydrolysis, including TNF-α, ephrin, APP, CD44, HER2, and Notch. , The ADAM10 inhibitor GI254023X ( 8 , Figure ) is potent and selective as it displays over 100-fold higher potency for ADAM10 compared to ADAM17 (IC 50 = 5.3 nM for ADAM10 versus 541 nM for ADAM17/TACE) and blocks the constitutive shedding of cell surface proteins in cells. In combination with low doses of the anti-HER2 herceptin, selective ADAM10 inhibitors decrease proliferation of HER2-overexpressing tumor cells.…”

Section: Therapeutic Interventions Targeting Notchmentioning

confidence: 99%

Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases

2016

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Notch is a key player in various developmental processes during the embryonic stage as well as in regulating tissue homeostasis, cell differentiation, and stem cell maintenance in adult life. Activation of Notch signaling occurs following Notch receptor-ligand interaction and subsequent enzymatic proteolysis by the gamma-secretase complex, resulting in the cytoplasmic release of a Notch intracellular domain, which translocates to the nucleus to initiate the downstream transcriptional machinery. Notch activation and its aberrant signaling have been broadly linked to the pathogenesis of cancer and some chronic inflammatory diseases resulting in pathologic fibrotic processes. This review focuses on the molecular basis of Notch-induced signaling and its interaction with other pathways to identify therapeutic targets. We also highlight current efforts to pharmacologically intervene in Notch signaling and discuss promising ongoing experimental and clinical studies.

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“…ADAMs (a Disintegrin and Metalloproteinase) hücre yapışması, hücresel göç, hücresel sinyalleme ve proteoliz gibi fizyolojik işlemlerde önemli transmembran proteinler ailesidir [178,179]. Bu protein ailesinden olan ADAM10, alzheimer, prion hastalığı, alerjik reaksiyonlar, glioblastoma ve pankreas kanseri gibi hastalıkların tedavisi için umut verici bir hedeftir [180][181][182][183].…”

Section: De Novo İlaç Tasarımında Yapay Zeka Uygulamasıunclassified

İlaç Tasariminda Yapay Zekâ Uygulamalari

TARI,

ARPACI

2023

Ankara Ecz. Fak. Derg.

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Amaç: Yapay zekâ üzerindeki çalışmaların giderek artması, her alanda olduğu gibi ilaç endüstrisinin de bu çalışmalardan faydalanmasına sebep olmaktadır. Bu çalışmada, yapay zeka uygulamalarının ilaç tasarımı ve geliştirilmesi üzerinde nasıl bir rol aldığının incelenmesi amaçlanmıştır. Sonuç ve Tartışma: Yeni biyolojik olarak aktif bileşiklere ihtiyacın giderek arttığı günümüzde, yapay zekada sürekli yeni algoritmaların ortaya çıkması, güçlü hesaplama yeteneği, elde edilen kimyasal ve biyolojik verilerin birikmesi, ilaç tasarımında yapay zekâ kullanımına olanak sunmaktadır. İlaç tasarım aşamalarının neredeyse tüm basamaklarında uygulanabilen yapay zekâ yöntemleriyle, yeni ilaç geliştirilmesindeki uzun zaman gereksinimi ve yüksek maliyet gibi zorluklar azaltılmaya çalışılmaktadır. Bu çalışma sonucunda, yapay zekâ teknolojisinin ilaç tasarım sürecindeki uygulamaları ve geleneksel yöntemlere göre avantajları kapsamlı bir şekilde analiz edilerek karşılaştırılmıştır.

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Acetylenic inhibitors of ADAM10 and ADAM17: In silico analysis of potency and selectivity

Cited by 11 publications

References 32 publications

Discovery of Novel Inhibitors of a Disintegrin and Metalloprotease 17 (ADAM17) Using Glycosylated and Non-glycosylated Substrates

Discovery of Novel Inhibitors of a Disintegrin and Metalloprotease 17 (ADAM17) Using Glycosylated and Non-glycosylated Substrates

Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases

İlaç Tasariminda Yapay Zekâ Uygulamalari

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