Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

The JAK-STAT Signaling Pathway

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

Protein Kinases and Phosphatases

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...

Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Riding toward Selectivity: Optimization of Covalent 7-Azaindole-Based BMX Kinase Inhibitors.

Journal of medicinal chemistry·2026

Same author

USP22 is a novel vulnerability regulating MEIS1 protein abundance and gene transcription in KMT2Ar acute leukemia.

Blood·2026

Same author

AURORA A interacts with DICER and SETD2 to promote S-phase progression.

EMBO reports·2026

Same author

On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.

Journal of medicinal chemistry·2026

Same author

p21-Activated Kinase (PAK) Group I-Targeting Inhibitors Promote the Dimeric Conformation in Live Cells.

ACS chemical biology·2026

Same author

The structural basis for LRRK2's activation and autoinhibition.

bioRxiv : the preprint server for biology·2026

Search research articles

Related Experiment Video

Updated: May 26, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor

Published on: September 13, 2018

Small-molecule modulators of HIPK4 activity and proteostasis.

Zaile Zhuang¹, Riley K Togashi^1,2, Patrick Kearney³

¹Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.

Biorxiv : the Preprint Server for Biology

|May 25, 2026

Summary

Researchers discovered new cyanoquinoline inhibitors for Homeodomain-interacting protein kinase 4 (HIPK4), a key protein in sperm development. These compounds show promise for nonhormonal male contraceptives and probing HIPK4 biology.

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Related Experiment Videos

Last Updated: May 26, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor

Published on: September 13, 2018

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Area of Science:

Biochemistry
Molecular Biology
Reproductive Biology

Background:

Homeodomain-interacting protein kinase 4 (HIPK4) is crucial for sperm development, particularly during spermiogenesis.
HIPK4 regulates the acroplaxome structure essential for sperm head shaping.
Understanding HIPK4's molecular targets is vital for developing nonhormonal male contraceptives.

Purpose of the Study:

To discover and characterize novel small-molecule inhibitors of HIPK4.
To explore the potential of these inhibitors as tools for studying HIPK4 function.
To evaluate HIPK4 inhibitors as leads for nonhormonal male contraceptive development.

Main Methods:

High-throughput screening to identify HIPK4 inhibitors.
Biochemical assays to determine inhibitor potency and selectivity.
Cell-based assays to investigate compound effects on HIPK4 proteostasis and spermatid biology.

Main Results:

Discovery of a novel series of cyanoquinoline-based HIPK4 inhibitors with nanomolar potency.
Demonstrated selectivity of lead compounds for HIPK4 over other kinases.
Observed that a subset of inhibitors induces HIPK4 aggregation and interacts with TAX1BP1 in spermatids, affecting proteostasis.

Conclusions:

Cyanoquinoline derivatives represent a new chemical class for HIPK4 inhibition.
These compounds serve as valuable chemical probes for investigating HIPK4-related biological processes.
The findings support the advancement of HIPK4 inhibitors for nonhormonal male contraceptive research.