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Last update 08 May 2025

ZFP91

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase ZFP91, PZF, RING-type E3 ubiquitin transferase ZFP91

+ [8]

Introduction

Atypical E3 ubiquitin-protein ligase that mediates 'Lys-63'-linked ubiquitination of MAP3K14/NIK, leading to stabilize and activate MAP3K14/NIK. It thereby acts as an activator of the non-canonical NF-kappa-B2/NFKB2 pathway. May also play an important role in cell proliferation and/or anti-apoptosis.

Drugs associated with ZFP91

BPHY-08

Target

IKZF1 x IKZF3 x ZFP91

Mechanism

IKZF1 inhibitors [+2]

Active Org.

Baiji Hongye (Nantong) Pharmaceutical Technology Co., Ltd.

Originator Org.

Baiji Hongye (Nantong) Pharmaceutical Technology Co., Ltd.

Active Indication

Multiple Myeloma

Inactive Indication-

Drug Highest PhaseIND Approval

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AEV-003

Target

ZFP91

Mechanism

ZFP91 gene modulators

Active Org.

AevisBio, Inc.

Originator Org.

AevisBio, Inc.

Active Indication

Alzheimer Disease [+1]

Inactive Indication

Craniocerebral Trauma

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SRT-152

Target

ZFP91

Mechanism

ZFP91 gene modulators

Active Org.

Smart Therapeutics, Inc.

Originator Org.

Smart Therapeutics, Inc.

Active Indication

Myotonic Dystrophy

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ZFP91

100 Translational Medicine associated with ZFP91

0 Patents (Medical) associated with ZFP91

101

Literatures (Medical) associated with ZFP91

01 Feb 2025·Journal of Pharmaceutical Sciences

A population pharmacokinetic analysis to evaluate the impact of renal impairment on the pharmacokinetics of iberdomide

Article

Author: Lin, Hongxia ; Wang, Alice ; Xue, Yongjun ; Thomas, Mark ; Li, Yan ; Cheng, Yiming ; Chen, Ping

Iberdomide, a novel potent cereblon E3 ligase modulator, is under investigation for multiple myeloma. This study assessed how renal impairment (RI) affects iberdomide pharmacokinetics (PK). Twenty-six subjects with varying renal function, including those with severe renal impairment and those requiring intermittent hemodialysis (IHD), received a single oral 1 mg dose of iberdomide. Plasma, urine, and dialysate samples were analyzed to evaluate the PK of iberdomide and its major active metabolite, M12. Data were subsequently pooled with PK data from four other clinical trials involving 354 patients to develop a parent - metabolite population PK model using nonlinear mixed-effects modeling to assess the impact of various degrees of RI on drug exposure. The population PK model effectively described the PK of iberdomide and M12, showing that normal, mild, and moderate RI had no significant impact on iberdomide PK exposure, whereas severe RI reduced total clearance and increased PK exposure of iberdomide and M12. Subjects with kidney failure on IHD had comparable total clearance and PK exposure to those with normal renal function. These findings systematically examined the effects of various degrees of RI on iberdomide PK and provide a basis for informing iberdomide dosing in patients with varying degrees of renal impairment.

01 Jan 2025·International Immunopharmacology

Mollugin inhibits IL-1β production by reducing zinc finger protein 91-regulated Pro-IL-1β ubiquitination and inflammasome activity

Article

Author: Li, Jia Xuan ; Song, Lei ; Zuo, Hong Xiang ; Tai, Yi ; Jin, Xuejun ; Xing, Yue ; Han, Jing ; Cao, Shen ; Ma, Juan ; Liu, Xin Zhe ; Cao, Sheng ; Li, Ming Yue

BACKGROUNDRubia cordifolia L. has been formally included in the Chinese Pharmacopoeia and utilized for centuries as a traditional Chinese medicine. Mollugin, a quinone compound, is a major active compound extracted from Rubia cordifolia L. Mollugin was reported has multiple pharmacological activity, including anti-inflammatory, anti-tumor effects. However, the anti-inflammatory mechanism is not yet clear. In this study, we explored the anti-inflammatory activity and potential mechanism of mollugin in vitro and in vivo.MATERIALS AND METHODSWe explored the mechanisms that mollugin suppressed IL-1β expression through ZFP91 using various assays, including western blot, immunofluorescence, immunoprecipitation, MTT, RT-PCR, and ELISA assays in vitro. In vivo, oral administration of DSS induced colitis in mice and intraperitoneal injection of alum induced peritonitis in mice.RESULTSFirst, the results demonstrated that mollugin dramatically suppressed IL-1β secretion through reducing ZFP91 in macrophages. Crucially, we proved that mollugin inhibited K63-linked Pro-IL-1β ubiquitination through ZFP91 and limitated Pro-IL-1β cleavage efficacy. In addition, ZFP91-mediated Caspase-8 inflammasome component expression was inhibited by mollugin. Furthermore, mollugin inhibited the assembly of the Caspase-8 inflammasome complex by downregulating ZFP91. In vivo studies further revealed that mollugin improved DSS-induced colitis and alum-induced peritonitis in mice by reducing ZFP91. Notely, mollugin significantly altered the abundance of gut flora in DSS-induced colitis mice, which in turn ameliorated the colitis.CONCLUSIONWe present a novel finding that mollugin inhibition of ZFP91 is a crucial regulatory step, preventing undue inflammatory responses and thereby maintaining immune homeostasis. The current study offers new insight into the development of anti-inflammatory therapeutics targeting ZFP91.

01 Nov 2024·Clinical Lymphoma Myeloma and Leukemia

Cereblon E3 Ligase Modulators Mezigdomide and Iberdomide in Multiple Myeloma

Review

Author: Al Hadidi, Samer ; Patel, Tanvi H ; van Rhee, Frits

Multiple Myeloma (MM) remains a challenging hematological malignancy despite significant advancements made during the past 2 decades. Outcomes have improved by incorporating immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies into treatment algorithms that include high dose chemotherapy and autologous hematopoietic stem cell transplantation. However, many patients may eventually relapse despite these innovations. Newer therapies targeting B-Cell Maturation Antigen (BCMA) offer promise for patients with relapsed or refractory disease. BCMA-targeted therapies carry notable side effects, necessitating vigilant monitoring and proactive infection prevention measures. They can also induce considerable immunosuppression, attributed to lower levels of immunoglobulins and increased susceptibility to infections. There is still a need for alternative treatment options with different mechanisms of action that can be easily administered and have a better safety profile. In addition, pomalidomide only overcomes lenalidomide refractoriness in a subset of patients. This review aims to explore 2 next-generation cereblon E3 ligase modulators (CELMoDs), Mezigdomide (CC92480), and Iberdomide (CC-220). We will discuss the biological aspects of these agents, including their mechanisms of action, efficacy, and toxicity profile, and provide a comprehensive review of current literature. Special attention will be paid to ongoing and future clinical trials that provide insights into the potential of these novel therapies in the management of MM.

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