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Last update 08 May 2025

EphB4

Last update 08 May 2025

Basic Info

Synonyms

EPH receptor B4, EPHB4, Ephrin type-B receptor 4

+ [6]

Introduction

Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells.

Drugs associated with EphB4

sEphB4-HSA

Target

EphB4

Mechanism

EphB4 antagonists

Active Org.

VasGene Therapeutics, Inc.

Originator Org.

VasGene Therapeutics, Inc.

Active Indication

Metastatic urothelial carcinoma [+2]

Inactive Indication

Acute lymphoblastic leukemia recurrent [+28]

Drug Highest PhasePhase 2/3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NVP-BHG712

Target

CTSK x EphB4

Mechanism

CTSK inhibitors [+1]

Active Org.

Shandong University [+1]

Originator Org.

Novartis AG

Active Indication

Osteoporosis, Postmenopausal

Inactive Indication

Melanoma

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SA-VA

Target

EphB4 x VEGFR2

Mechanism

EphB4 antagonists [+1]

Active Org.

Xi'an Jiaotong University

Originator Org.

Xi'an Jiaotong University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with EphB4

NCT06493552

/ RecruitingPhase 2/3

A Modular, Open Label, Randomized Phase II/III Trial to Assess Efficacy of Combining sEphB4-HSA (EphrinB2 Inhibitor) With Immunotherapy Regimens in Patients With EphrinB2-High Solid Tumors

Patients with solid tumors that have high expression levels of EphrinB2 are treated with regimens that include EphrinB2 inhibitor, sEphB4-HSA. The primary objective of this study is to demonstrate additive therapeutic benefit for sEphB4-HSA. The secondary objectives are to determine whether the sEphB4-HSA containing regimen is safe and whether the oncological endpoints of importance in each cohort improve as a result of treatment with sEphB4-HSA containing regimen relative to a predefined threshold or to a control arm in the cohort where available. Treatment continues until progression of disease or unacceptable toxicities arise.

Start Date15 Mar 2025

Sponsor / Collaborator

VasGene Therapeutics, Inc.

NCT03552796

/ WithdrawnPhase 1IIT

A First-in-Human Phase I Study of Intravesical sEphB4-HSA in Patients With "BCG-Unresponsive" Bladder Carcinoma In Situ (CIS), Completely Resected High Grade Ta/T1, to Establish the Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D)

This phase I trial studies the side effects and best dose of recombinant EphB4-HSA fusion protein (sEphB4-HSA), and to see how well it works in treating participants with bladder cancer that has come back or that isn't responding to bacillus Calmette-Guerin (BCG) vaccine treatment. sEphB4-HAS prevents tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor. Giving sEphB4-HSA may work better in treating participants with bladder cancer.

Start Date01 Aug 2023

Sponsor / Collaborator

University of Southern California

[+1]

NCT03993106

/ RecruitingPhase 2

A Phase II Study of sEphB4-HSA in Kaposi Sarcoma

sEphB-HSA may prevent tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor. The purpose of this study is to learn if sEphB4-HSA will decrease the number or size of Kaposi sarcoma lesions in people.

Start Date17 Sep 2020

Sponsor / Collaborator

VasGene Therapeutics, Inc.

100 Clinical Results associated with EphB4

100 Translational Medicine associated with EphB4

0 Patents (Medical) associated with EphB4

864

Literatures (Medical) associated with EphB4

01 Jun 2025·Journal of Oral Biosciences

Alendronate inhibits bone-specific blood vessels in the femoral metaphyses of mice

Article

Author: Ishizu, Hotaka ; Hasegawa, Tomoka ; Yoshino, Hirona ; Li, Weisong ; Amizuka, Norio ; Shi, Yan ; Liu, Xuanyu ; Yamamoto, Tomomaya ; Sekiguchi, Tamaki ; Sakakibara, Mako ; Cui, Jiaxin ; Haraguchi-Kitakamae, Mai ; Shimizu, Tomohiro ; Haoyu, Wang

To determine whether alendronate affects vascular endothelial cells and regulates the interactions between blood vessels and osteoblasts, we have examined the femoral metaphyses of alendronate-administered mice. Following administration, the bone-specific blood vessels exhibited significantly reduced luminal diameters and rough luminal surfaces with numerous small protrusions and vesicles. Although the osteoclast distribution remained unchanged in ALN-treated mice, osteoblasts were inactivated in the metaphyseal regions where blood vessels had shrunk. Additionally, the expression of genes such as Ephb4/Efnb2, which mediate vascular endothelial cell-osteoblast interactions, was diminished. Therefore, alendronate may primarily affect bone-specific blood vessels, thus leading to osteoblast inactivation.

03 May 2025·British Journal of Cancer

EphB4-ephrin-B2 are targets in castration resistant prostate cancer

Article

Author: Ma, Binyun ; El-Khoueiry, Anthony ; Sadeghi, Sarmad ; Zhang, Shaobing ; Siddiqi, Imran N ; Liu, Ren ; Salhia, Bodour ; Gill, Parkash S ; Sali, Akash ; Gross, Mitchell ; Li, Grace Xiuqing

AbstractBackgroundPI3K pathway activation is a common and early event in prostate cancer, from loss of function mutations in PTEN, or activating mutations in PIK3Ca or AKT leading to constitutive activation, induction of growth factor-receptors kinase EphB4 and its ligand ephrin-B2. We hypothesized that induction of EphB4 is an early event required for tumor initiation. Secondly, we hypothesized that EphB4 remains relevant when prostate cancer becomes androgen independent.MethodsGenetic mouse model of conditional PTEN deletion in prostate epithelium induces tumor in all mice. We tested this model against EPHB4 wild type and deleted in prostate epithelium. This allowed us to test its role in tumor initiation. We also tested an orthogonal approach by using decoy soluble EphB4 to block bidirectional signaling resulting from EphB4-ephrin-B2 interaction. Role of EphB4-ephrin-B2 in androgen deprived mice was tested for role in refractory cancer model.ResultsPTEN deletion induces EphB4 and ephrin-B2 in prostate cancer which was substantially reduced when EPHB4 is deleted in the same prostate epithelial cells. sEphB4-alb fusion protein with improved pharmacokinetics similarly inhibited tumor formation, thus establishing the role in tumor initiation. sEphB4-alb retained the efficacy in castration resistant androgen independent prostate cancer. We have thus observed that induction of EphB4 is required for the initiation of prostate cancer in PTEN null mouse and that signaling downstream from EphB4 is required in androgen deprivation and thus castration resistant prostate cancer. Pharmacological inhibition of EphB4 pathway reproduced the results. Targeting EphB4 should be tested in prostate cancer especially those resistant to androgen deprivation therapy.ConclusionsEphB4 and ephrin-B2 receptor ligand pair is induced in PTEN null prostate cancer, which significantly contributes to the tumor initiation. Secondly, EphB4-ephrin-B2 pathway continue to promote tumor progression even in androgen deprivation and thus hormone refractory tumor. EphB4-ephrin-B2 may be candidates for precision medicine with biomarker-based patient selection with and without concurrent standard of care.

15 Apr 2025·ACS Omega

Discovery of Novel Multiangiogenic Agents Targeting VEGFR2, EphB4, FGFR-1, and TIE-2: Receptor-Based Pharmacophore Modeling, Virtual Screening, and Molecular Modeling Studies

Article

Author: Keshari, Amit K. ; Patra, Jeevan ; Bhandare, Richie R. ; Parrot, Madison ; Lin, Shiru ; Shaik, Afzal B.

The angiogenesis phenomenon is crucial for the formation of new blood vessels in cancer cells. The cancerous cells' progress hampers other healthy cells. The main objective of this study is to explore and decipher multimodal natural compounds against VEGFR2, EphB4, FGFR-1, and TIE-2 drug targets to arrest angiogenesis and progression. The receptor-based pharmacophore modeling of VEGFR2, EphB4, FGFR-1, and TIE-2 was developed and validated through enrichment parameters. Further, the validated hypothesis allowed for screening druglike natural product databases such as SuperNatural 3.0, COCONUT, and LOTUS. The common pharmacophoric featured natural compounds were assessed for binding affinities using absolute end-point methods. Finally, density functional theory has been studied to understand the chemical reactivity and stability of the protein complexes. Among all of the screened natural compounds, 17 natural compounds were found to align accurately against validated pharmacophore models having higher fitness scores and align scores. Taking reference drugs sorafenib (VEGFR2), NVP-BHG712 (EphB4), pemiganitib (FGFR-1), and DP1919 (TIE-2), three promising natural compounds CNP0003920, CNP0243075, and CNP0211397 were concluded based on their end-point binding energies, binding interactions, molecular dynamics, and optimal pharmacokinetic and toxicity profiles. The density functional theory (DFT) results suggested that the identified compounds bound with protein complexes are stable. Our findings can represent a promising starting point for developing multimodal analogues VEGFR2, EphB4, FGFR-1, and TIE-2 proteins.

News (Medical) associated with EphB4

16 Sep 2019

·elevartherapeutics.com

Elevar Therapeutics Announces Appointment of New Member to the Board of Directors

SALT LAKE CITY, USA, September 16, 2019 Elevar Therapeutics is pleased to announce the addition of a new member to the Board of Directors, Paul Chen. “We are very excited to have Paul join our Board of Directors,” said Alex Kim, Elevar Therapeutics’ CEO, “Paul is a serial entrepreneur with multiple successful hits with new molecules, most notably as the inventor of rivoceranib.” Mr. Chen has over 36 years of experience in the pharmaceutical industry with hands-on experience from discovery to preclinical to clinical development. As an inventor, he has authored almost 30 patents covering novel compounds and derivatives, including rivoceranib (commonly known as apatinib). Mr. Chen has worked at a variety of companies from small startups to established pharmaceutical companies such as Amgen. He also founded his own company, Advenchen Laboratories in Southern California which is the licensor of rivoceranib to Jiangsu Hengrui (China) and Elevar Therapeutics (rest of world). About Elevar Therapeutics Elevar Therapeutics (formerly LSK BioPharma) is a privately held biopharmaceutical company with offices in Utah, California, and South Korea. The Company aims to provide patients and their caregivers with exceptional choices for effective and well-tolerated therapies. Elevar Therapeutics’ lead proprietary drug candidate is rivoceranib, a selective VEGFR-2 inhibitor which has demonstrated clinical efficacy in a variety of solid tumors. Elevar Therapeutics can be found on the web at www.elevartherapeutics.com. Contact: Jenna Choi jenna.choi@elevartherapeutics.com###

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