Development of pyrolo[2,3-c]pyrazole, pyrolo[2,3-d]pyrimidine and their bioisosteres as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological evaluation and molecular dynamics investigations

Article Oncology

Cyclin-dependent kinase 7/9 inhibitor SNS-032 induces apoptosis in diffuse large B-cell lymphoma cells

Liling Jiang et al.

Summary: The study found that SNS-032 shows potential for treating DLBCL by inhibiting cell growth, inducing apoptosis, and suppressing tumor growth in mouse models.

CANCER BIOLOGY & THERAPY (2022)

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Review Chemistry, Medicinal

A patent review of anticancer CDK2 inhibitors (2017-present)

Mohamed A. Said et al.

Summary: Developing selective CDK2 inhibitors is challenging, but ongoing efforts by Incyte Corporation and Pfizer Inc. may bring novel information critical for the development of CDK2 inhibitors.

EXPERT OPINION ON THERAPEUTIC PATENTS (2022)

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Article Chemistry, Multidisciplinary

Synthesis, molecular docking, and in silico ADME prediction of some fused pyrazolo[1,5-a]pyrimidine and pyrazole derivatives as potential antimicrobial agents

Ashraf S. Hassan et al.

Summary: Twenty compounds of pyrazolo[1,5-a]pyrimidines 14a-j and pyrazole derivatives as Schiff bases 16a-j have been synthesized and evaluated for their antimicrobial inhibitory activity. Some products showed broad-spectrum activity, with certain compounds exhibiting acceptable bioactivity scores through in silico prediction of physicochemical properties, drug-likeness model score, ADME, and toxicity properties. Additionally, molecular docking studies demonstrated lower binding energy with different types of binding mode, suggesting potential as antimicrobial agents.

JOURNAL OF THE IRANIAN CHEMICAL SOCIETY (2022)

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Article Chemistry, Physical

Design and synthesis of novel urea derivatives of pyrimidine-pyrazoles as anticancer agents

Purna Koteswara Rao Cherukumalli et al.

Summary: A series of novel urea derivatives of pyrimidine-pyrazole were designed and synthesized, showing promising anticancer activity by targeting tubulin. Molecular docking studies indicated that these compounds could interact effectively with the tubulin interface, suggesting their potential as tubulin inhibitors.

JOURNAL OF MOLECULAR STRUCTURE (2022)

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Review Biochemistry & Molecular Biology

A Review of the Recent Development in the Synthesis and Biological Evaluations of Pyrazole Derivatives

Oluwakemi Ebenezer et al.

Summary: Pyrazoles are nitrogen-containing five-membered heterocyclic compounds that are important for drug development and exhibit diverse biological activities. This review summarizes published research on the synthesis and biological activities of pyrazole derivatives.

BIOMEDICINES (2022)

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Article Biochemistry & Molecular Biology

Synthesis, biological evaluation, and in silico studies of new CDK2 inhibitors based on pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffold with apoptotic activity

Asmaa A. Mandour et al.

Summary: A series of novel pyrazolopyrimidine derivatives were designed and synthesized as CDK2 inhibitors, showing promising anticancer activity against breast and colon cancer cells. Compound 15 exhibited the most significant inhibitory activity, causing alterations in cell cycle progression and apoptosis. Furthermore, compound 15 demonstrated low cytotoxicity in normal cells, indicating its potential therapeutic value.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2022)

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Review Pharmacology & Pharmacy

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy

Dorina Amariucai-Mantu et al.

Summary: This review presents the latest advances in hybrid azine derivatives with antimicrobial activity, which have shown promising results in overcoming microbial drug resistance.

PHARMACEUTICS (2022)

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Review Medicine, Research & Experimental

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

Kun Pang et al.

Summary: Protein phosphorylation is an important post-transcriptional modification involved in a wide range of intracellular signaling pathways. Many drugs targeting protein phosphorylation have been developed for the treatment of various diseases. This review analyzed small-molecule protein phosphorylation kinase inhibitors and classified them into different groups and families, providing insights into their regulatory network and roles in disease intervention.

MEDCOMM (2022)

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Article Chemistry, Multidisciplinary

Discovery of pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives as novel CDK2 inhibitors: synthesis, biological and molecular modeling investigations

Ibrahim F. Nassar et al.

Summary: CDK2 inhibition is a promising target for cancer treatment, and a new set of small molecules have been designed and synthesized as potential CDK2 targeting compounds. These compounds showed superior cytotoxic activities against certain cancer cell lines and demonstrated significant inhibitory activity against CDK2.

RSC ADVANCES (2022)

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Article Chemistry, Medicinal

Design and Synthesis of New CDK2 Inhibitors Containing Thiazolone and Thiazolthione Scafold with Apoptotic Activity

Nour E. A. Abd El-Sattar et al.

Summary: Inhibition of CDK2 has been established as an effective strategy for cancer treatment. Novel thiazolone and fused thiazolthione derivatives showed potent inhibitory effects on CDK2 and exhibited potential antitumor activity against breast and colon cancer cell lines. Further studies involved flow cytometry analysis and molecular modeling, demonstrating the compounds' potential as therapeutic agents for cancer treatment.

CHEMICAL & PHARMACEUTICAL BULLETIN (2021)

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Article Biochemistry & Molecular Biology

3-Methyl-imidazo[2,1-b]thiazole derivatives as a new class of antifolates: Synthesis, in vitro/in vivo bio-evaluation and molecular modeling simulations

Menna A. Ewida et al.

Summary: In this study, novel series of 3-methyl-imidazo [2,1-b] thiazole-based analogs targeting DHFR were synthesized and evaluated for their inhibitory profile. Compounds 22 and 23 showed potent inhibition towards DHFR, promising cytotoxicity against breast cancer cell lines, and significant therapeutic effects in animal models. Molecular modeling simulations supported the high affinity binding potential of these compounds towards DHFR, while ADMET study suggested favorable pharmacokinetic properties for further development as DHFR inhibitors.

BIOORGANIC CHEMISTRY (2021)

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Review Chemistry, Medicinal

An Overview of the Biological Activity of Pyrrolo[3,4-c]pyridine Derivatives

Anna Wojcicka et al.

Summary: Pyrrolo[3,4-c]pyridine derivatives have broad pharmacological properties, mainly used in analgesic, sedative, and treatment of diseases related to the nervous and immune systems. They also show activities against diabetes, mycobacterial infections, viruses, and tumors.

PHARMACEUTICALS (2021)

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Article Chemistry, Medicinal

Nanomolar potency of imidazo[2,1-b]thiazole analogs as indoleamine 2,3-dioxygenase inhibitors

Menna A. Ewida et al.

Summary: A series of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole analogs were synthesized and evaluated for their inhibitory effects on IDO1, with several compounds showing promising activity. Molecular modeling simulations suggested that these analogs can chelate iron(III) within the IDO1 binding pocket and have better binding affinity through hydrophobic interactions.

ARCHIV DER PHARMAZIE (2021)

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Article Chemistry, Medicinal

Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax

Hannah M. King et al.

Summary: CDK9, a member of the cyclin-dependent kinase family, is involved in transcriptional regulation. Researchers developed PROTAC 2, a compound that selectively degrades CDK9, sensitizing cells to growth inhibition by Venetoclax.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2021)

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Article Biochemistry & Molecular Biology

Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Adel A-H Abdel-Rahman et al.

Summary: A variety of new pyridine, pyrazolopyridine, and furopyridine derivatives were synthesized and evaluated for their inhibition of CDK2 enzyme and cytotoxicity against human cancer cell lines. Several compounds showed promising inhibition of the enzyme and cytotoxic effects on cancer cells in vitro.

MOLECULES (2021)

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Review Pharmacology & Pharmacy

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Aastha Mahapatra et al.

Summary: Cancer is a global health challenge with resistance to existing drugs, prompting research on novel anticancer agents such as pyrimidine derivatives. This review focuses on the structure-activity relationship of pyrimidine derivatives as anticancer agents in the past decade, aiming to assist in the development of more potent and efficacious drugs.

FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES (2021)

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Review Chemistry, Medicinal