Discovery of highly potent V600E-B-RAF kinase inhibitors: Molecular modeling study

Tarazi, Hamadeh; El‐Gamal, Mohammed I.; Oh, Chang‐Hyun

doi:10.1016/j.bmc.2019.01.004

Cited by 9 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequently, they further investigated the effect of other derivatives on the V600E-B-RAF kinase. 28 Compound 2 in which R 2 was substituted with 4-chloro-3-trifluoromethyl and R 1 was hydrogen showed a significant kinase inhibitory effect with an IC 50 value of 7 nM. The molecular docking results showed that its binding to V600E-B-RAF kinase was based on hydrogen bonds established with Cys-532 and Glu-501 residues (Fig.…”

Section: Pyrazolesmentioning

confidence: 94%

Research and development ofN,N′-diarylureas as anti-tumor agents

et al. 2023

View full text Add to dashboard Cite

show abstract

Section: Pyrazolesmentioning

confidence: 94%

Research and development ofN,N′-diarylureas as anti-tumor agents

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In addition, a urea linker is more favorable than amide as the two NH groups of urea form hydrogen bonds as donors with the αC-helix Glu501amino acid residue ( Figure 74 ). In addition, the pyrazole ring forms a hydrophobic interaction with the Phe595 residue, and the urea oxygen interacts with Asp594 residue ( Figure 75 ) [ 84 ]. Moreover, compound 71 was tested for anticancer activity over the NCI-60 cancer cell lines of nine cancer types and showed promising activity.…”

Section: Pyrazole-based Raf Kinase Inhibitorsmentioning

confidence: 99%

“… V600E-B-RAF-compound 71 binding interactions throughout the 50 ns simulation period; ( A ) the fractions of interaction happened between compound 71 and V600E-B-RAF kinase. ( B ) 2D interaction diagram of compound 71 within V600E-B-RAF active site [ 84 ]. …”

Section: Figurementioning

confidence: 99%

Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011–2020): Current Status and Future Prospects

et al. 2022

Self Cite

View full text Add to dashboard Cite

Pyrazole has been recognized as a pharmacologically important privileged scaffold whose derivatives produce almost all types of pharmacological activities and have attracted much attention in the last decades. Of the various pyrazole derivatives reported as potential therapeutic agents, this article focuses on pyrazole-based kinase inhibitors. Pyrazole-possessing kinase inhibitors play a crucial role in various disease areas, especially in many cancer types such as lymphoma, breast cancer, melanoma, cervical cancer, and others in addition to inflammation and neurodegenerative disorders. In this article, we reviewed the structural and biological characteristics of the pyrazole derivatives recently reported as kinase inhibitors and classified them according to their target kinases in a chronological order. We reviewed the reports including pyrazole derivatives as kinase inhibitors published during the past decade (2011–2020).

show abstract

Section: Introductionmentioning

confidence: 99%

“…Vemurafenib (Figure 1), marketed as Zelboraf ® , is an FDA-approved pyridine derivative designed to treat advanced melanoma. It is a selective inhibitor of the V600E-mutated BRAF kinase [38][39][40]. In a recent publication [41], we described the antiproliferative activity of a novel series of cyanopyridine compounds as dual EGFR/BRAF V600E inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel 3-Cyanopyridone/Pyrazoline Hybrids as Potential Apoptotic Antiproliferative Agents Targeting EGFR/BRAFV600E Inhibitory Pathways

Al-Wahaibi,

Abou-Zied,

Hisham

et al. 2023

Molecules

View full text Add to dashboard Cite

A series of novel 3-cyanopyridone/pyrazoline hybrids (21–30) exhibiting dual inhibition against EGFR and BRAFV600E has been developed. The synthesized target compounds were tested in vitro against four cancer cell lines. Compounds 28 and 30 demonstrated remarkable antiproliferative activity, boasting GI50 values of 27 nM and 25 nM, respectively. These hybrids exhibited dual inhibitory effects on both EGFR and BRAFV600E pathways. Compounds 28 and 30, akin to Erlotinib, displayed promising anticancer potential. Compound 30 emerged as the most potent inhibitor against cancer cell proliferation and BRAFV600E. Notably, both compounds 28 and 30 induced apoptosis by elevating levels of caspase-3 and -8 and Bax, while downregulating the antiapoptotic Bcl2 protein. Molecular docking studies confirmed the potential of compounds 28 and 30 to act as dual EGFR/BRAFV600E inhibitors. Furthermore, in silico ADMET prediction indicated that most synthesized 3-cyanopyridone/pyrazoline hybrids exhibit low toxicity and minimal adverse effects.

show abstract

Discovery of highly potent V600E-B-RAF kinase inhibitors: Molecular modeling study

Cited by 9 publications

References 19 publications

Research and development ofN,N′-diarylureas as anti-tumor agents

Research and development ofN,N′-diarylureas as anti-tumor agents

Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011–2020): Current Status and Future Prospects

Design, Synthesis, and Biological Evaluation of Novel 3-Cyanopyridone/Pyrazoline Hybrids as Potential Apoptotic Antiproliferative Agents Targeting EGFR/BRAFV600E Inhibitory Pathways

Contact Info

Product

Resources

About