ALDH Protein
ALDH (especially the mitochondrial isoform ALDH2) oxidizes the toxic acetaldehyde produced during ethanol metabolism into non-toxic acetic acid, thereby preventing the accumulation of acetaldehyde which can induce DNA damage, liver cirrhosis, and cancer risk. Meanwhile, ALDH is responsible for clearing endogenous aldehydes in cells, such as 4-hydroxynonenal (4-HNE) (a product of lipid peroxidation). This process reduces the toxic modification of proteins and nucleic acids by reactive aldehydes, protects cells from oxidative stress-induced damage, and maintains cellular homeostasis.
Beyond its core function in acetaldehyde metabolism, ALDH also possesses physiological regulatory roles. The ALDH1A family catalyzes the oxidation of retinal to retinoic acid, which regulates embryonic development, cell differentiation, and organ formation—playing a crucial role in the development of the nervous system and heart in particular. Acetic acid, generated by ALDH during acetaldehyde metabolism, also enters the tricarboxylic acid (TCA) cycle to supply energy, participating in cellular energy metabolism. During lipid metabolism, ALDH promotes high-density lipoprotein (HDL)-mediated reverse cholesterol transport. In mitochondria, ALDH2 can protect the integrity of mitochondrial membranes, maintain the efficiency of ATP synthesis, and counteract ischemia-reperfusion injury [1]. In the field of cancer and tumor regulation, high ALDH1 activity is a marker of cancer stem cells in cancers such as breast cancer and leukemia, and it is positively correlated with chemoresistance and recurrence risk [2]. Studies related to immune regulation and antiviral responses have shown that ALDH1B1 enhances the RIG-I receptor-mediated antiviral signaling pathway by aggregating the mitochondrial protein MAVS, thereby promoting interferon production and inhibiting the replication of RNA viruses such as influenza A and dengue virus [3].
Figure 1 The Pathway of ALDH2 catalyzes aldehyde metabolism
ALDH-Targeted Drugs
Currently, ALDH-targeted drugs are evolving from single detoxification functions to disease-modifying therapies. Their research and development mainly focus on chemical drugs, and the current types of ALDH-targeted drugs can be categorized as follows:
1. ALDH Activators: Restoring Mutant Enzyme Activity Alda Series Compounds (Cardiovascular Protection)
Alda-1: The first small-molecule allosteric activator. By filling the tetrameric interface cavity of the ALDH2*2 mutant (Glu487Lys), it restores 70-90% of the enzyme activity.
Alda-341 (Oral Modified Form): Phase II clinical trials in 2025 showed that the 24-hour myocardial necrosis area in patients with acute myocardial infarction was reduced by 32%.
Mirivadelgat (Pulmonary Arterial Hypertension Treatment)
An ALDH stimulant developed by Yida Biotech. It entered Phase II clinical trials in 2025 and improves vascular remodeling by enhancing the ALDH-mediated NO signaling pathway.
2. ALDH Inhibitors: Anticancer and Metabolic Disease Intervention Targeting ALDH1A1 (Overcoming Tumor Drug Resistance)
Novel Small-Molecule Inhibitors: Selectively inhibit ALDH1A1 enzyme activity, block retinoic acid synthesis and lipid droplet formation mediated by ALDH1A1, and increase the sensitivity of KRAS-mutant cancer cells to targeted drugs (e.g., Sotorasib) by 4-fold.
Key Mechanism: Reduce intracellular pH, inhibit the CREB1/GPX4 pathway, and enhance ferroptosis.
GS-548351 (Nicotine Dependence)
An ALDH inhibitor developed by Gilead. Its clinical development was terminated due to off-target effects, highlighting challenges in isoform-selective design.
3. Gene Therapy and RNA Intervention Lefelsiran Sodium (Chronic Disease Treatment)
An siRNA drug (developed by Dicerna/Novo Nordisk) that targets ALDH mRNA. It entered Phase I clinical trials for metabolic diseases and reduces enzyme expression through liver-targeted delivery.
ARO-INHBE (Obesity Treatment)
An RNAi therapy developed by Arrowhead Pharmaceuticals. It silences the INHBE gene and indirectly regulates the ALDH pathway, reducing fat mass and improving glucose homeostasis in animal models.
Our Capability
ALDH Experimental Results
Protein Purification Result(Period: In Stock/4 weeks)
Figure 2 Protein Purification Result
Crystallization and Structural Analysis(2-4 weeks)
Figure 3 Crystals under microscope
Figure 4 Diffraction Pattern