VHLL

Last update 08 May 2025

Basic Info

Synonyms

VHL like, VHL-like protein, VHLL

+ [3]

Introduction

Functions as a dominant-negative VHL to serve as a protector of HIFalpha.

100 Clinical Results associated with VHLL

100 Translational Medicine associated with VHLL

0 Patents (Medical) associated with VHLL

1,138

Literatures (Medical) associated with VHLL

01 Jul 2025·European Journal of Medicinal Chemistry

Discovery of the first-in-class DOT1L PROTAC degrader

Article

Author: Xie, Ling ; Cao, Tao ; Xu, Zhongli ; Chen, Xian ; Sun, Renhong ; Kaniskan, H Ümit ; Kim, Minjeong ; Jin, Jian ; Kim, Huen Suk ; Yim, Hyerin

DOT1L is the lysine methyltransferase responsible for histone H3 lysine 79 (H3K79) methylation and plays a crucial role in leukemia progression. Furthermore, DOT1L has biological functions that are independent of its methyltransferase activity. Therefore, targeting and degrading DOT1L with PROteolysis TArgeting Chimeras (PROTACs) could represent a promising therapeutic strategy. Here, we report the discovery of the first-in-class DOT1L PROTAC degrader, compound 13 (MS2133), which potently induces DOT1L degradation in a concentration- and time-dependent manner, without affecting DOT1L mRNA expression. The DOT1L degradation induced by 13 requires binding to the E3 ligase von Hippel-Lindau (VHL) and DOT1L and occurs through the ubiquitin-proteasome system. 13 is selective for DOT1L over other methyltransferases and effectively inhibits the growth of mixed lineage leukemia-rearranged (MLL-r) leukemia cells while having no toxicity on normal cells. Overall, 13 is a valuable chemical biology tool for further studying functions of DOT1L and a potential therapeutic for DOT1L-dependent cancers.

24 Apr 2025·Journal of Medicinal Chemistry

Discovery of a Potent and Selective Protein Arginine Methyltransferase 5 (PRMT5) PROTAC Degrader

Article

Author: Xie, Ling ; Qian, Chao ; Guccione, Ernesto ; Xiong, Yan ; Chen, Xian ; Shen, Yudao ; Jin, Jian ; Chen, Matthew ; Hu, Jacqueline ; Kim, Huensuk ; Zhong, Yue

Protein arginine methyltransferase 5 (PRMT5) plays crucial roles in the regulation of various biological processes through the mono- and symmetric dimethylation of protein substrates. PRMT5 is overexpressed in various human cancers and its overexpression is associated with poor prognosis. We previously reported the first-in-class PRMT5 degrader, MS4322, which is also the only von Hippel-Lindau (VHL)-recruiting PRMT5 degrader to date. Here, we performed structure-activity relationship (SAR) studies exploring various linkers and ligands of VHL and PRMT5, which resulted in the best-in-class PRMT5 degrader, MS115 (compound 10). Compound 10 potently and selectively degraded PRMT5 and its coactivator, MEP50, in concentration-, time-, and ubiquitin-proteasome system-dependent manners. It displayed much improved PRMT5/MEP50 degradation potency over MS4322, which translated to better antiproliferative effect in both breast and prostate cancer cells. Overall, we discovered a highly potent and selective PRMT5/MEP50 complex degrader, which is an invaluable chemical biology tool and a potential cancer therapeutic.

01 Apr 2025·Zhonghua wai ke za zhi [Chinese journal of surgery]

[Diagnosis and treatment of pancreatic tumors in children:a retrospective study in a single center].

Article

Author: Li, M ; Liu, D H ; Li, Y ; Tang, X L

Objective: To summarize the clinical traits, diagnostic and therapeutic experiences of pancreatic tumors in children. Methods: This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 35 children with primary pancreatic tumors who were treated at the Department of General Surgery, the Children's Hospital Affiliated to Xiangya School of Medicine, Central South University were collected from January 2010 to June 2023. There were 17 male and 18 female patients, aging from 3 months to 15 years and 1 month, with a median age of 9 years and 2 months. The presenting symptoms included 16 patients who had abdominal mass, 13 had clinical symptoms of abdominal pain and vomiting, 4 cases were detected on the physical examination, and 7 cases were discovered on abdominal trauma examinations. Results: Among the 35 cases, 16 cases of tumors were located in the pancreatic head. Among them, 9 cases underwent open pancreaticoduodenal surgery, 2 cases received duodenum-preserving pancreatic cephalectomy, 4 cases underwent pancreatic tumor resection, and 1 case underwent laparotomy for pancreatic tumor biopsy. Seventeen cases had tumors located in the body and tail of the pancreas, including 13 patients who underwent laparoscopic splenic-sparing caudectomy and 4 patients who underwent pancreatic tumors resection. Two cases of von Hippel-Lindau(VHL) with diffuse cystic pancreatic degeneration were continuously observed and followed up. Postoperative pathological examinations revealed that there were 20 cases of solid pseudopapillary neoplasm(SPN), 6 cases of pancreaticoblastoma(PBL), 2 cases of insulinoma, 2 cases of serous cystadenoma, 2 cases of mature teratoma and 1 case of lipoma. Four patients with PBL were completely resected after 4 cycles of induction chemotherapy due to their large tumors. All PBL patients received standardized systematic treatment including surgery and chemotherapy. Postoperative complications included 4 cases(12.1%) of biochemical leakage, 1 case(3.0%) of grade B pancreatic fistula complicated with massive bleeding, 2 cases(6.1%) of elevated platelet count, and 2 cases(6.1%) of intestinal obstruction. One case of grade B pancreatic fistula complicated with massive bleeding underwent emergency surgery, and other cases with complications were cured through conservative treatment. Two patients with SPN recurred at 36 and 33 months and were treated with reoperation. One patient with obstructive jaundice with high-grade transformed SPN was abandoned after diagnosis, and one patient with PBL died. The follow-up period of the patients was 1 to 7 years. The tumor size of 2 VHL patients with diffuse cystic pancreatic degeneration did not change after regular visits, and tumor survival was not observed in other children. Conclusions: There are no specific clinical manifestations of pancreatic tumors in children and there are various pathological types, with the majority being SPN and PBL. Radical surgery for preservation of organ and functions is the preferred treatment for pediatric pancreatic tumors, and most have a favorable prognosis.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

VHLL

Basic Info

Related

Analysis