RS6077 induces mitotic arrest and selectively activates cell death in human cancer cell lines and in a lymphoma tumor in vivo

Sebastiani, Jessica; Puxeddu, Michela; Nalli, Marianna; Bai, Ruoli; Altieri, Ludovica; Rovella, Paola; Gaudio, Eugenio; Trisciuoglio, Daniela; Spriano, Filippo; Lavia, Patrizia; Fionda, Cinzia; Masci, Domiziana; Urbani, Andrea; Bigogno, Chiara; Dondio, Giulio; Hamel, Ernest; Bertoni, Francesco; Silvestri, Romano; Regina, Giuseppe La

doi:10.1016/j.ejmech.2022.114997

Cited by 7 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[46] Mechanistically, hybrid 32 280 nM), arrest cancer cells in the G2/M phase as well as induce apoptosis. [47] In the TMD8 xenografted mice model, RS6077 (100 mg/kg, oral administration) suppressed 43.8% tumor growth without obvious toxicity. In addition, RS6077 also showed promising metabolic stability in human liver microsomes with t 1/2 of 50.5 min and CL of 28.0 µL/min/mg.…”

Section: Quinazoline Derivativesmentioning

confidence: 97%

“…Pyrrolo[2,3‐ d ]pyrimidine‐pyrrole hybrid 33 (RS6077, IC 50 : 16.3–63.1 nM, MTT assay) was highly potent against AHH‐1, MCF‐7, HeLa, FARAGE, KARPAS‐422, U2932, Z138, MAVER1 and TMD8 cancer cell lines and could inhibit tubulin polymerization (IC 50 : 280 nM), arrest cancer cells in the G2/M phase as well as induce apoptosis. [ 47 ] In the TMD8 xenografted mice model, RS6077 (100 mg/kg, oral administration) suppressed 43.8% tumor growth without obvious toxicity. In addition, RS6077 also showed promising metabolic stability in human liver microsomes with t 1/2 of 50.5 min and CL of 28.0 µL/min/mg.…”

Section: Pyrrolo[23‐d]pyrimidine/pyrrolo[32‐d]pyrimidine Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Xu,

Wang,

2024

Archiv der Pharmazie

View full text Add to dashboard Cite

Cancer, characterized by uncontrolled cell growth and metastasis, is responsible for nearly one in six deaths and represents a severe threat to public health worldwide. Chemotherapy can substantially improve the quality of life and survival of patients with cancer, but anticancer chemotherapeutics are associated with a range of adverse effects. Moreover, almost all currently available anticancer chemotherapeutics could develop drug resistance over a period of time of application in cancer patients and ultimately lead to cancer relapse and death in 90% of patients, creating an urgent need to develop new anticancer agents. Fused pyrimidines trait the inextricable part of DNA and RNA and are vital in numerous biological processes. Fused pyrimidines can act on various biological cancer targets and have the potential to address drug resistance. In addition, more than 20 fused pyrimidines have already been approved for clinical treatment of different cancers and occupy a prominent place in the current therapeutic arsenal, revealing that fused pyrimidines are privileged scaffolds for the development of novel anticancer chemotherapeutics. The purpose of this review is to summarize the current scenario of fused pyrimidines with in vivo anticancer therapeutic potential along with their acute toxicity, metabolic profiles as well as pharmacokinetic properties, toxicity and mechanisms of action developed from 2020 to the present to facilitate further rational exploitation of more effective candidates.

show abstract

Section: Quinazoline Derivativesmentioning

confidence: 97%

Section: Pyrrolo[23‐d]pyrimidine/pyrrolo[32‐d]pyrimidine Derivativesmentioning

confidence: 99%

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Xu,

Wang,

2024

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

“…The authors have cited additional references within the Supporting Information (Ref. [27][28][29][30][31]).…”

Section: Supporting Informationmentioning

confidence: 99%

Synthesis of (Hetero)biaryls via Nickel Catalyzed Reductive Cross‐Electrophile Coupling Between (Hetero)aryl Iodides and Bromides

Surgenor,

Lee

2024

Chemistry A European J

View full text Add to dashboard Cite

(Hetero)biaryls are fundamental building blocks in the pharmaceutical industry and rapid access to these scaffolds is imperative for the success of numerous medicinal chemistry campaigns. Herein, a highly general, mild, and chemoselective reductive cross‐electrophile coupling between (hetero)aryl iodides and heteroaryl bromides is reported. By employing more reactive (hetero)aryl halides, a broad range of successful substrates (45 examples) were identified. The reaction was also found to be chemoselective for C(sp2)–C(sp2) bond formation between (hetero)aryl iodides and bromides over (hetero)aryl chlorides, which were generally inert under the described reaction conditions. The efficiency of the procedure is also further demonstrated in parallel synthesis library format, on gram scale, as well as in the formal synthesis of Ruxolitinib, a potent JAK inhibitor. As such, we anticipate this method will find widespread utility in the assembly of (hetero)biaryls for medicinal chemistry efforts.

show abstract

“…The major protein component found in microtubules is tubulin. Microtubule-targeting agents (MTAs) inhibit the function of cellular microtubules by promoting polymerization and depolymerization, resulting in the arrest of cell cycle progression and induction of cell death [113,114].…”

Section: Microtubulesmentioning

confidence: 99%

Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment

Masci,

Naro,

Puxeddu

et al. 2023

Molecules

Self Cite

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is one of the most heterogeneous and aggressive breast cancer subtypes with a high risk of death on recurrence. To date, TNBC is very difficult to treat due to the lack of an effective targeted therapy. However, recent advances in the molecular characterization of TNBC are encouraging the development of novel drugs and therapeutic combinations for its therapeutic management. In the present review, we will provide an overview of the currently available standard therapies and new emerging therapeutic strategies against TNBC, highlighting the promises that newly developed small molecules, repositioned drugs, and combination therapies have of improving treatment efficacy against these tumors.

show abstract

RS6077 induces mitotic arrest and selectively activates cell death in human cancer cell lines and in a lymphoma tumor in vivo

Cited by 7 publications

References 21 publications

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential

Synthesis of (Hetero)biaryls via Nickel Catalyzed Reductive Cross‐Electrophile Coupling Between (Hetero)aryl Iodides and Bromides

Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment

Contact Info

Product

Resources

About