Last update 01 Nov 2024

CDK3

Last update 01 Nov 2024

Basic Info

Synonyms

CDK3, CDKN3, Cell division protein kinase 3

+ [2]

Introduction

Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1-independent manner.

Drugs associated with CDK3

CDK3 inhibitors(Senex)

Target

CDK3

Mechanism

CDK3 inhibitors

Active Org.

Senex Biotechnology, Inc.

Originator Org.

Senex Biotechnology, Inc.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NEOS-518

Target

CDK1 x CDK2 x CDK3 x CDK9

Mechanism

CDK1 inhibitors [+3]

Active Org.-

Originator Org.

Neosome Life Sciences LLCStartup

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NVP-LCQ195

Target

CDK1 x CDK2 x CDK3 x CDK5 x CDK9

Mechanism

CDK1 inhibitors [+4]

Active Org.-

Originator Org.

Astex Therapeutics Ltd.

Active Indication-

Inactive Indication

Multiple Myeloma

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CDK3

100 Translational Medicine associated with CDK3

0 Patents (Medical) associated with CDK3

145

Literatures (Medical) associated with CDK3

01 Sep 2024·Cellular Signalling

MicroRNA-1205 promotes breast cancer cell metastasis by regulating epithelial-to-mesenchymal transition via targeting of CDK3

Article

Author: Zheng, Duo ; Hou, Wulei ; Guo, Wenjun ; Chen, Cheng ; Zhu, Lizhi ; Zou, Yongdong ; Yang, Heng ; Ye, Linhui ; Xiang, Qin ; Li, Shuaihu ; Xiao, Tian

Metastasis poses a huge obstacle to the survival of breast cancer patients. The microRNA miR-1205 acts as a tumor suppressor in various cancers, but its roles in breast cancer and metastasis remain unclear. To elucidate its function in breast cancer progression, we analyzed miR-1205 expression in human tumor samples and carried out a series of functional studies in in vitro and in vivo. miR-1205 was expressed more highly in metastatic breast tumor samples than in non-metastatic samples and was associated with lymph node metastasis, clinical stage, and poor prognosis. Moreover, miR-1205 promoted breast cancer cell invasiveness in vitro and metastasis in mice by directly targeting CDK3 and reducing CDK3 protein levels. We also showed that CDK3 interacts with Snail protein, inducing Snail degradation via the ubiquitin-proteasome system and potentially affecting epithelial-to-mesenchymal transition. Furthermore, analysis of clinical tissue samples indicated that CDK3 and miR-1205 levels were inversely correlated in lymph node metastasis-positive primary tumors. This study demonstrated the pro-metastatic role of miR-1205 in breast cancer, mediated via a novel miR-1205/CDK3/Snail axis. Moreover, we identified miR-1205 and CDK3 as potential markers of invasion and progression in breast cancer.

02 Dec 2023·Molecular and Cellular Biology

A PTP1B-Cdk3 Signaling Axis Promotes Cell Cycle Progression of Human Glioblastoma Cells through an Rb-E2F Dependent Pathway

Article

Author: Patiño-López, Genaro ; Terrazas, Luis Ignacio ; Loza-Mejía, Marco Antonio ; Chernoff, Jonathan ; Vivar-Sierra, Alonso ; Villamar-Cruz, Olga ; Olguín, Jonadab Efraín ; Ávila-Moreno, Federico ; Saha, Sayanti ; Saldivar-Cerón, Héctor Iván ; Arias-Romero, Luis Enrique ; Armas-López, Leonel ; Camacho-Arroyo, Ignacio

PTP1B plays a key role in developing different types of cancer. However, the molecular mechanism underlying this effect is unclear. To identify molecular targets of PTP1B that mediate its role in tumorigenesis, we undertook a SILAC-based phosphoproteomic approach, which allowed us to identify Cdk3 as a novel PTP1B substrate. Substrate trapping experiments and docking studies revealed stable interactions between the PTP1B catalytic domain and Cdk3. In addition, we observed that PTP1B dephosphorylates Cdk3 at tyrosine residue 15 in vitro and interacts with it in human glioblastoma cells. Next, we found that pharmacological inhibition of PTP1B or its depletion with siRNA leads to cell cycle arrest with diminished activity of Cdk3, hypophosphorylation of Rb, and the downregulation of E2F target genes Cdk1, Cyclin A, and Cyclin E1. Finally, we observed that the expression of a constitutively active Cdk3 mutant bypasses the requirement of PTP1B for cell cycle progression and expression of E2F target genes. These data delineate a novel signaling pathway from PTP1B to Cdk3 required for efficient cell cycle progression in an Rb-E2F dependent manner in human GB cells.

01 Oct 2023·Investigational new drugs

Development of novel palbociclib-based CDK4/6 inhibitors exploring the back pocket behind the gatekeeper.

Article

Author: Li, Lina ; Xue, Xia ; Chen, Fengquan ; Liao, Yongxiang ; Li, Mengzhe ; Luan, Yun ; Wang, Yongjie ; Jiang, Wen

CDK4/6 inhibitors plus endocrine therapy is a standard therapy for HR+/HER2- breast cancer. Herein, using structure-based drug design strategy, a novel series of palbociclib derivatives were designed and synthesized as CDK4/6 inhibitors, among which compound 17m exhibited more potent CDK4/6 inhibitory activity and in vitro antiproliferative activity against the phosphorylated Rb-positive cell line MDA-MB-453 than the approved drug palbociclib. Moreover, compound 17m possessed remarkable CDK4/6 selectivity over other CDK family members including CDK1, CDK2, CDK3, CDK5, CDK7 and CDK9. The potent and selective CDK4/6 inhibitory activity endowed compound 17m with robust G1 cell cycle arrest ability in MDA-MB-453 cells. The intracellular inhibition of CDK4/6 by 17m was confirmed by western blot analysis of the levels of phosphorylated Rb in MDA-MB-453 cells. With respect to the metabolic stability, compound 17m possessed longer half-life (t_1/2) in mouse liver microsome than palbociclib.

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CDK3

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