Last update 01 Nov 2024

LEDGF

Last update 01 Nov 2024

Basic Info

Synonyms

CLL-associated antigen KW-7, Dense fine speckles 70 kDa protein, DFS 70

+ [10]

Introduction

Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.

Drugs associated with LEDGF

Pirmitegravir

Target

LEDGF

Mechanism

LEDGF inhibitors

Active Org.

ST Pharm Co., Ltd.

Originator Org.

ST Pharm Co., Ltd.

Active Indication

HIV Infections

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

BDM-2

Target

LEDGF

Mechanism

LEDGF inhibitors

Active Org.-

Originator Org.

Hivih

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

OCU-100

Target

LEDGF

Mechanism

LEDGF stimulators

Active Org.-

Originator Org.

CU Anschutz Medical Campus

Active Indication-

Inactive Indication

Retinitis Pigmentosa

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with LEDGF

NCT05869643 / RecruitingPhase 2

A Phase 2a, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Investigate the Antiviral Effect, Safety, Tolerability, and Pharmacokinetics of STP0404 in Adults With HIV-1 Infection

The purpose of this study is to evaluate the antiviral effect, safety, tolerability, and pharmacokinetics of STP0404 in adult participants living with Human Immunodeficiency Virus Type 1 (HIV-1) infection.

Start Date23 May 2023

Sponsor / Collaborator

ST Pharm Co., Ltd.

NCT03634085 / CompletedPhase 1

A Single Ascending Dose Trial Investigating the Safety, Tolerability and Pharmacokinetics of Orally Administered BDM-2 in Healthy Male Subjects

This is a first-in-human (FIH), double-blind, placebo-controlled, randomized trial in healthy adult male subjects, to evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending oral doses of BDM-2. The effect of food on the PK of a single dose of BDM-2 will also be evaluated.

Start Date17 May 2018

Sponsor / Collaborator

Hivih

[+1]

100 Clinical Results associated with LEDGF

100 Translational Medicine associated with LEDGF

0 Patents (Medical) associated with LEDGF

526

Literatures (Medical) associated with LEDGF

01 Oct 2024·Cancer Science

N‐acetylgalactosaminyltransferase GALNT6 is a potential therapeutic target of clear cell renal cell carcinoma progression

Article

Author: Li, Zeyu ; Lu, Min ; Sun, Luhaoran ; Shu, Peng

AbstractHigh expression of truncated O‐glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N‐acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues. The current study aimed to determine the role of GALNT6 in ccRCC, and whether GALNT6‐mediated O‐glycosylation aggravates malignant behaviors. Gain‐ and loss‐of‐function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC‐derived xenograft tumor growth and lung metastasis. In line with this, silencing of GALNT6 yielded the opposite results. Mechanically, high expression of GALNT6 led to the accumulation of Tn antigen in ccRCC cells. By undertaking immunoprecipitation coupled with liquid chromatography/mass spectrometry, vicia villosa agglutinin blot, and site‐directed mutagenesis assays, we found that O‐glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6‐induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium‐derived growth factor (LEDGF) as a key regulator of GALNT6 transcriptional induction in ccRCC growth and an upstream contributor to ccRCC aggressive behavior. Collectively, our findings indicate that GALNT6‐mediated abnormal O‐glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development.

01 Oct 2024·FEBS Letters

Fragment‐based discovery of small molecule inhibitors of the HDGFRP2 PWWP domain

Article

Author: Li, Shuju ; Gao, Jia ; Wang, Lei ; Fan, Weiwei ; Ruan, Ke ; Li, Zihuan ; Wei, Xiaoli

The PWWP domain of hepatoma‐derived growth factor‐related protein 2 (HDGFRP2) recognizes methylated histones to initiate the recruitment of homologous recombination repair proteins to damaged silent genes. The combined depletion of HDGFRP2 and its paralog PSIP1 effectively impedes the onset and progression of diffuse intrinsic pontine glioma (DIPG). Here, we discovered varenicline and 4‐(4‐bromo‐1H‐pyrazol‐3‐yl) pyridine (BPP) as inhibitors of the HDGFRP2 PWWP domain through a fragment‐based screening method. The complex crystal structures reveal that both Varenicline and BPP engage with the aromatic cage of the HDGFRP2 PWWP domain, albeit via unique binding mechanisms. Notably, BPP represents the first single‐digit micromolar inhibitor of the HDGFRP2 PWWP domain with a high ligand efficiency. As a dual inhibitor targeting both HDGFRP2 and PSIP1 PWWP domains, BPP offers an exceptional foundation for further optimization into a chemical tool to dissect the synergetic function of HDGFRP2 and PSIP1 in DIPG pathogenesis.

30 Sep 2024·Annals of Laboratory Medicine

Rare Non-Cryptic NUP98 Rearrangements Associated With Myeloid Neoplasms and Their Poor Prognostic Impact

Article

Author: Kim, Boram ; Kim, Hee-Jin ; Jung, Chul Won ; Kim, Hyun-Young ; Park, Min-Seung ; Jang, Jun Ho

BackgroundNUP98 rearrangements (NUP98r), associated with various hematologic malignancies, involve more than 30 partner genes. Despite their clinical significance, reports on the clinicopathological characteristics of rare NUP98r remain limited. We investigated the characteristics of patients with myeloid neoplasms harboring NUP98r among those identified as having 11p15 translocation in chromosomal analysis.MethodsWe retrospectively reviewed results from bone marrow chromosomal analyses conducted between 2011 and 2023 and identified 15 patients with 11p15 translocation. Subsequently, NUP98r were evaluated using FISH and/or reverse transcription PCR, and clinical and laboratory data of the patients were analyzed.ResultsNUP98r were identified in 11 patients initially diagnosed as having AML (N=8), myelodysplastic syndrome (N=2), or chronic myelomonocytic leukemia (N=1), with a median age of 44 yrs (range, 4-77 yrs). Three patients had a history of chemotherapy. In total, five NUP98 fusions were identified: NUP98::DDX10 (N=3), NUP98::HOXA9 (N=2), NUP98::PSIP1 (N=2), NUP98::PRRX1 (N=1), and NUP98::HOXC11 (N=1). Patients with NUP98r exhibited a poor prognosis, with a median overall survival of 12.0 months (95% confidence interval [CI], 3.4-29.6 months) and a 5-yr overall survival rate of 18.2% (95% CI, 5.2%-63.7%).ConclusionsOur study revealed the clinical and genetic characteristics of patients with myeloid neoplasms harboring rare and non-cryptic NUP98r. Given its association with poor prognosis, a comprehensive evaluation is crucial for identifying previously underdiagnosed NUP98r in patients with myeloid neoplasms.

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