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Last update 08 May 2025

SAHH

Last update 08 May 2025

Basic Info

Synonyms

Adenosylhomocysteinase, AdoHcyase, AHCY

+ [3]

Introduction

Catalyzes the hydrolysis of S-adenosyl-L-homocysteine to form adenosine and homocysteine (PubMed:10933798). Binds copper ions (By similarity).

Drugs associated with SAHH

Deoxyeritadenine methyl ester

Target

SAHH

Mechanism

SAHH inhibitors

Active Org.

Shanghai Institute of Materia Medica Chinese Academy of Sci [+1]

Originator Org.

Shanghai Institute of Materia Medica Chinese Academy of Sci

Active Indication

Psoriasis [+1]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

3-deazaneplanocin A

Target

PRC2 x SAHH

Mechanism

Polycomb repressive complex 2 inhibitors [+1]

Active Org.

Kawasaki Medical School [+1]

Originator Org.

National Cancer Institute

Active Indication

Melanoma [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MDL-28842

Target

SAHH

Mechanism

SAHH inhibitors

Active Org.-

Originator Org.

Hoechst Marion Roussel, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SAHH

CTR20180681

/ Not yet recruitingPhase 1

健康受试者口服脱氧菇嘌甲酯片单中心、随机、双盲、安慰剂对照、剂量递增的单次和多次给药Ⅰ期临床研究

[Translation] A single-center, randomized, double-blind, placebo-controlled, dose-escalating, single and multiple-dose phase I clinical study of oral deoxycholate tablets in healthy subjects

本研究目的评价DZ2002及其代谢产物（DZA）在健康受试者的安全性、耐受性和药代动力学研究，为后续临床研究提供指导剂量。

[Translation]

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of DZ2002 and its metabolite (DZA) in healthy subjects and provide dosage guidance for subsequent clinical studies.

Start Date-

Sponsor / Collaborator

Ningbo Ziyuan Pharmaceuticals Inc

[+1]

CTR20240702

/ Not yet recruitingPhase 1

DZ2002 乳膏在健康受试者中单次、多次局部给药的安全性、耐受性及药代动力学 I 期临床研究

[Translation] Phase I clinical study on the safety, tolerability and pharmacokinetics of single and multiple topical administration of DZ2002 cream in healthy subjects

主要目的：评价DZ2002乳膏在健康受试者中单次、多次局部给药的安全性和耐受性；探索性目的：评价DZ2002乳膏在健康受试者中的药代动力学特征。

[Translation]

Main purpose: To evaluate the safety and tolerability of single and multiple topical administrations of DZ2002 cream in healthy subjects; Exploratory purpose: To evaluate the pharmacokinetic characteristics of DZ2002 cream in healthy subjects.

Start Date-

Sponsor / Collaborator

Ningbo Ziyuan Pharmaceuticals Inc

100 Clinical Results associated with SAHH

100 Translational Medicine associated with SAHH

0 Patents (Medical) associated with SAHH

1,116

Literatures (Medical) associated with SAHH

01 Jun 2025·Journal of Oral Biosciences

Impact of DLX3/SAHH axis on osteogenic differentiation of BMSCs in alveolar bone

Article

Author: Chen, Xinyi ; Chen, Kang ; Jiang, Yuxi ; Sun, Haipeng ; Chai, Jinyou ; Sun, Shichen

OBJECTIVESBone marrow mesenchymal stem cells (BMSCs) promote alveolar bone formation and repair. Distal-less homeobox 3 (DLX3) plays a key regulatory role in BMSC osteogenesis. However, the precise pathway by which it mediates osteogenesis in BMSCs remains unclear. In this study, we investigated the potential epigenetic mechanisms underlying DLX3-mediated BMSCs osteogenesis.METHODSBMSCs were isolated from the alveolar bone. DLX3 overexpression and knockdown cell lines were established using lentivirus-mediated gene transfer. Osteogenic differentiation was evaluated using alkaline phosphatase expression, alizarin red staining, real-time quantitative polymerase chain reaction, western blotting, chromatin immunoprecipitation, RNA immunoprecipitation, and S-adenosyl-homocysteine hydrolase (SAHH) activity measurements.RESULTSDLX3 enhanced the osteogenic differentiation of BMSCs, positively regulated SAHH, and enhancer of zeste homolog 2 (EZH2) activity. In addition, the long non-coding RNA H19 (H19) bound to SAHH in BMSCs. DLX3 regulated the expression of H19, and rescue experiments showed that H19 knockdown increased SAHH activity, thereby promoting osteogenic differentiation in the DLX3-overexpression group.CONCLUSIONSThe DLX3/SAHH axis may regulate the activity of EZH2 involved in the osteogenic differentiation of BMSCs.

01 Apr 2025·Journal of Biological Chemistry

Methionine cycle inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival

Article

Author: D'Antuono, Matthew ; Ayad, Nagi G ; Jermakowicz, Anna M ; Rowland, Emma C

Glioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with a fatal prognosis. This is due in part to metabolic reprogramming that allows tumors to evade treatment. Therefore, we must uncover the pathways mediating these adaptations to develop novel and effective treatments. We searched for genes that are essential in GBM cells as measured by a whole-genome pan-cancer CRISPR screen available from DepMap and identified the methionine metabolism genes MAT2A and AHCY. We conducted genetic knockdown, evaluated mitochondrial respiration, and performed targeted metabolomics to study the function of these genes in GBM. We demonstrate that MAT2A or AHCY knockdown induces oxidative stress, hinders cellular respiration, and reduces the survival of GBM cells. Furthermore, selective MAT2a or AHCY inhibition reduces GBM cell viability, impairs oxidative metabolism, and shifts the cellular metabolic profile towards oxidative stress and cell death. Mechanistically, MAT2a and AHCY regulate spare respiratory capacity, the redox buffer cystathionine, lipid and amino acid metabolism, and prevent oxidative damage in GBM cells. Our results point to the methionine metabolic pathway as a novel vulnerability point in GBM.

28 Mar 2025·Journal of Natural Products

Biochemical and Structural Insights of the N-Methyltransferase CyaF in Cyanogramide Biosynthesis

Article

Author: Zhu, Hanning ; Zhang, Qingbo ; Fang, Chunyan ; Chen, Ruijie ; Zhu, Yiguang ; Zhang, Liping ; Zhu, Weiming ; Zhang, Changsheng

N-Methyltransferases involved in indole methylation have seldom been discovered in natural product biosynthesis. This study focuses on the enzyme CyaF, which catalyzes a critical N-methylation step of indole in the β-carboline skeleton during cyanogramide biosynthesis. Seven β-carboline analogues (3-9) were isolated from the recombinant strain Streptomyces coelicolor YF11/cyaABC, including three new compounds (5-7). In vitro assays revealed CyaF's substrate flexibility. The crystal structure of the CyaF/S-adenosyl-L-homocysteine (SAH) complex, combined with the AlphaFold-predicted model and site-directed mutagenesis, elucidated the catalytic mechanism and structural features that enable CyaF to accommodate diverse substrates, highlighting its potential for biocatalytic applications.

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