Request Demo

Last update 23 Jan 2025

CDK4 x CDK1 x CDK9

Last update 23 Jan 2025

Basic Info

Related Targets

CDK4CDK1CDK9

Drugs associated with CDK4 x CDK1 x CDK9

ZK-304709

Target

CDK1 x CDK2 x CDK4 x CDK7 x CDK9 x PDGFR x VEGFR

Mechanism

CDK1 inhibitors [+6]

Active Org.-

Originator Org.

Bayer AG

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Riviciclib

Target

CDK1 x CDK4 x CDK9

Mechanism

CDK1 inhibitors [+2]

Active Org.-

Originator Org.

Piramal Phytocare Ltd.

Active Indication-

Inactive Indication

Advanced cancer [+11]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with CDK4 x CDK1 x CDK9

NCT01903018

/ CompletedPhase 2

A Multicenter, Phase II/III Study to Assess Radiation Induced Mucositis in Subjects With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Administered Cisplatin and Radiation With or Without P276-00

A Clinical Study to Assess Radiation Induced Mucositis in Subjects with Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Start Date01 Jul 2012

Sponsor / Collaborator

Piramal Enterprises Ltd.

NCT01333137

/ TerminatedPhase 1

An Open-Label Randomized Phase II Trial Comparing Gemcitabine and Carboplatin With and Without P276-00 in Subjects With Metastatic Triple Negative Breast Cancer, With a Phase I Run-in of Escalating Dose of P276-00 Added to Gemcitabine and Carboplatin

P276-00 is a novel, potent, small-molecule, flavone-derived Cdk 4 D1, Cdk1 B, and Cdk9 T inhibitor, with potent cytotoxic effects against chemosensitive and chemoresistant cancer cell lines.This study is planned to compare efficacy of the standard chemotherapy regimen of gemcitabine and carboplatin when administered with or without P276-00 in subjects with advanced triple negative breast cancer.

Start Date01 Aug 2011

Sponsor / Collaborator

Piramal Enterprises Ltd.

100 Clinical Results associated with CDK4 x CDK1 x CDK9

100 Translational Medicine associated with CDK4 x CDK1 x CDK9

0 Patents (Medical) associated with CDK4 x CDK1 x CDK9

Literatures (Medical) associated with CDK4 x CDK1 x CDK9

01 Sep 2023·Bioorganic & medicinal chemistry letters

Discovery of SHR5428 as a selective and noncovalent inhibitor of CDK7.

Article

Author: Chen, Gang ; Mao, Yuchang ; Zhang, Ting ; Li, Jie ; Yin, Junzhao ; Jia, Minqiang ; He, Feng ; Li, Xun ; Wang, Weimin ; Zhou, Qian ; Wu, Ting ; Feng, Jun ; Hu, Min ; Li, Xin

Cyclin dependent kinase 7 (CDK7) is an attractive target in tumor indications via regulating both cell cycle and transcription. Here, SHR5428 was discovered as a selective and noncovalent CDK7 inhibitor with highly potent CDK7 enzymatic activity and triple negative breast cancer cellular activity on MDA-MB-468 cell. SHR5428 also displayed favorable pharmacokinetic properties in different preclinical species such as mouse, rat and dog, and showed high selectivity over CDK1, CDK2, CDK4, CDK6, CDK9, CDK12 in CDK family. Furthermore, the computational modeling has shed some light on this mechanism. Additionally the in vivo efficacy study in a breast cancer cell line (HCC70 cell) derived xenograft mouse model proved SHR5428 to be orally efficacious with dose-dependent tumor growth inhibition.

01 Dec 2022·Current Molecular PharmacologyQ4 · BIOLOGY

Promising Anticancer Activity of Multitarget Cyclin Dependent Kinase Inhibitors against Human Colorectal Carcinoma Cells

Q4 · BIOLOGY

Article

Author: Manohar, Sonal M. ; Joshi, Kalpana S.

Background:Colorectal cancer (CRC) is the third leading cause of cancer death worldwide, and its incidence is steadily rising in developing nations. Cell cycle aberrations due to deregulation of cyclin dependent kinases (CDKs) and cyclins are common events during colorectal carcinogenesis. Yet, efficacy of multitarget CDK inhibitors as therapeutic agents has not been much explored against CRC.Objective:The anticancer potential of multitarget CDK inhibitor riviciclib (also known as P276-00), was investigated against CRC cell lines of varied genetic background.Method:Cytotoxicity of riviciclib - potent CDK1, CDK4 and CDK9-specific inhibitor was evaluated in vitro. Further, its effect on clonogenic potential, cell cycle, apoptosis and transcription was tested using colony forming assay, flow cytometry and western blot analysis, respectively. Also, efficacy of riviciclib in combination with standard chemotherapeutic agents was assessed. Dependency of CRC cells on specific CDKs for their survival was confirmed using siRNA studies.Results:Riviciclib exerted significant cytotoxicity against CRC cells and inhibited their colony forming potential. It induced apoptosis along with inhibition of cell cycle CDKs and cyclins as well as transcriptional CDKs and cyclins. Moreover, dual combination of riviciclib with standard chemotherapeutic drugs exhibited synergism in CRC cells. siRNA studies indicated that CRC cells are dependent on specific CDKs for their survival which are targets of riviciclib.Conclusion:This study provides evidence that multitarget CDK inhibitors can serve as promising therapeutic agents against CRC alone or in combination.

10 Aug 2020·Angewandte Chemie International EditionQ1 · CHEMISTRY

Development of CDK2 and CDK5 Dual Degrader TMX‐2172

Q1 · CHEMISTRY

Article

Author: Teng, Mingxing ; Victor, Chiara ; Fischer, Eric S. ; Sorger, Peter K. ; Zhang, Tinghu ; Mills, Caitlin E. ; Jiang, Jie ; Donovan, Katherine A. ; Kwiatkowski, Nicholas P. ; Hatcher, John M. ; He, Zhixiang ; Gray, Nathanael S.

AbstractCyclin‐dependent kinase 2 (CDK2) is a potential therapeutic target for the treatment of cancer. Development of CDK2 inhibitors has been extremely challenging as its ATP‐binding site shares high similarity with CDK1, a related kinase whose inhibition causes toxic effects. Here, we report the development of TMX‐2172, a heterobifunctional CDK2 degrader with degradation selectivity for CDK2 and CDK5 over not only CDK1, but transcriptional CDKs (CDK7 and CDK9) and cell cycle CDKs (CDK4 and CDK6) as well. In addition, we demonstrate that antiproliferative activity in ovarian cancer cells (OVCAR8) depends on CDK2 degradation and correlates with high expression of cyclin E1 (CCNE1), which functions as a regulatory subunit of CDK2. Collectively, our work provides evidence that TMX‐2172 represents a lead for further development and that CDK2 degradation is a potentially valuable therapeutic strategy in ovarian and other cancers that overexpress CCNE1.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis