Novel CDK12/13 Inhibitors AU-15506 and AU-16770 Are Potent Anti-Cancer Agents in EGFR Mutant Lung Adenocarcinoma with and without Osimertinib Resistance

Maity, Tapan K.; Kim, Eun Young; Cultraro, Constance M.; Venugopalan, Abhilash; Khare, Leena; Poddutoori, Ramulu; Marappan, Sivapriya; Doheri, Samiulla; Telford, William G.; Samajdar, Susanta; Ramachandra, Murali; Guha, Udayan

doi:10.3390/cancers15082263

Cited by 3 publications

(1 citation statement)

References 30 publications

(42 reference statements)

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“…The therapies can be targeted towards cyclic-dependent kinase and RNA polymerases [ 40 ]. Enzymes are another important group of potential targets for the development of new cancer therapeutics [ 41 , 42 ]. Aromatase enzyme is a potential target for breast cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

In Silico Analysis of Novel Bacterial Metabolites with Anticancer Activities

Maumela,

Serepa-Dlamini

2024

Metabolites

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Resistance to anticancer therapeutics is a major global concern. Thus, new anticancer agents should be aimed against novel protein targets to effectively mitigate the increased resistance. This study evaluated the potential of secondary metabolites from a bacterial endophyte, as new anticancer agents, against a novel protein target, fibroblast growth factor. In silico genomic characterization of the Bacillus sp. strain MHSD_37 was used to identify potential genes involved in encoding secondary metabolites with biological activity. The strain was also exposed to stress and liquid chromatography–mass spectrometry used for the identification and annotation of secondary metabolites of oligopeptide class with anticancer activity. Selected metabolites were evaluated for their anticancer activity through molecular docking and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties analysis. Phylogenetic analysis revealed that strain MHSD_37 shared close evolutionary relationships with Bacillus at the species level, with no identified relationships at the sub-species level. Both in silico genomic characterization and spectrometry analysis identified secondary metabolites with potential anticancer activity. Molecular docking analysis illustrated that the metabolites formed complexes with the target protein, fibroblast growth factor, which were stabilized by hydrogen bonds. Moreover, the ADMET analysis showed that the metabolites passed the toxicity test for use as a potential drug. Thereby, Bacillus sp. strain MHSD_37 is a potential novel strain with oligopeptide metabolites that can be used as new anticancer agents against novel protein targets.

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Section: Introductionmentioning

confidence: 99%

In Silico Analysis of Novel Bacterial Metabolites with Anticancer Activities

Maumela,

Serepa-Dlamini

2024

Metabolites

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AI-enabled cancer target prioritization with optimal profiles balancing novelty, confidence and commercial tractability

Long,

Steurer,

Wong

et al. 2024

Future Medicine AI

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The identification of new biological targets is crucial to advance cancer therapy, but deciphering the fiendishly complex processes that drive and sustain disease can be tedious and resource intensive. To optimize and accelerate the drug discovery process, artificial intelligence (AI) platforms are emerging that enable fast and cost-effective identification and prioritization of novel and disease-specific therapeutic targets with optimal target profiles, balancing confidence, novelty and commercial tractability. AI-streamlined target profiling has the potential to significantly improve the commercial burden of traditional drug development, and provides an unbiased approach for novel target identification. Here, we discuss the AI-assessed target profile and clinical relevance of genes recently identified by our AI-driven target discovery platform as top priority cancer targets.

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Intellectual developmental disorder with hypertelorism and distinctive facies (IDDHDF) A case study with literature review

Nget,

Min

2024

J. Health. Science. Med. Therapy.

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The research aims to investigate the clinical manifestations of neurodevelopmental problems in children with different facies and CCNK gene mutant characteristics. A literature study was carried out to identify the role of CCNK mutations in IDDHDF. Chinese and international search engines like PubMed, MEDLINE, Wanfang Data Knowledge, and Google Scholar were used to search. The search phrases "CCNK", "intellectual developmental disorder", "hypertelorism", and "distinctive facies" were used. A total of 5 studies were found, 11 cases were presented, 3 were thoroughly discussed, and 1 case was presented in this study. The clinical signs and genetic characteristics of children with intellectual developmental disorders with hypertelorism and unique facies were summarized. A male child was 1 year 4 months old. Last 1 year, he appeared of motor and cognitive lag, unable to crawl or stand. He had a large forehead head, wide eye spacing, and cognitive deficiencies, and he was clinically diagnosed with global developmental delay. C.437(exon5) T>C was not found in any of the child's parents and represents a de novo mutation. The main clinical signs were impairments in intellectual development, wide eye spacing, and facial feature features. The findings of the studies discussed here imply that mutations in the CCNK gene may cause IDDHDF. This is a very new kind of study in China to uncover the clinical aspects of a case of Intellectual developmental disorder with hypertelorism and distinctive facies (IDDF). It's discovered that wild-type mRNA coding CCNK partially repaired early defects but not the mRNA with the identified likely pathogenic variation c.331A>G. This shows that CCNK variations are involved in IDDF. The researchers also discovered that the likely pathogenic mutation c.331A>G may induce IDDF via a haploinsufficiency mechanism.

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Novel CDK12/13 Inhibitors AU-15506 and AU-16770 Are Potent Anti-Cancer Agents in EGFR Mutant Lung Adenocarcinoma with and without Osimertinib Resistance

Cited by 3 publications

References 30 publications

In Silico Analysis of Novel Bacterial Metabolites with Anticancer Activities

In Silico Analysis of Novel Bacterial Metabolites with Anticancer Activities

AI-enabled cancer target prioritization with optimal profiles balancing novelty, confidence and commercial tractability

Intellectual developmental disorder with hypertelorism and distinctive facies (IDDHDF) A case study with literature review

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