About Ace Therapeutics
Ace Therapeutics combines scientific expertise in iron metabolism and chelation chemistry with extensive experience in preclinical drug development. Our focus is on providing a comprehensive service with high-quality data and strategic insights to accelerate the advancement of promising innovative treatment towards clinical evaluation.
Iron overload, or hemosiderosis, is characterized by excessive iron accumulation beyond the body's needs, depositing in vital organs. Normal serum transferrin saturation (TS) is ~30%; overload is indicated by TS >45% in females or >50% in males, with cellular damage occurring when TS exceeds 60%. It's classified as primary (hereditary hemochromatosis, often genetic mutations like HFE C282Y) or secondary (from factors like multiple blood transfusions or increased absorption). Excess iron first accumulates in the liver, then affects endocrine organs and the heart, causing tissue damage and complications such as liver fibrosis, cirrhosis, heart failure, and diabetes, significantly impacting patient survival.
Hereditary hemochromatosis is the most common genetic disorder in North America, especially among those of Northern European ancestry, with C282Y homozygosity around 0.4-0.5% in European/North American whites. Secondary overload is common in transfusion-dependent patients as the body lacks effective iron excretion. Diagnosis primarily uses serum ferritin (SF) and transferrin saturation (TS). SF >300 ng/mL (men) or >200 ng/mL (women) with TS >45% suggests HH. Non-invasive MRI T2* is preferred for quantifying organ iron (e.g., liver T2* <4 ms indicates moderate/severe overload). Treatment involves iron chelators like deferoxamine, deferiprone, and deferasirox to reduce iron burden.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight | Launched Year |
|---|---|---|---|---|---|
|
deferasirox (Rec INN; USAN) | 201530-41-8 | C21 H15 N3 O4 | 373.362 | 2005 |
|
deferiprone (Rec INN; USAN) | 30652-11-0 | C7 H9 N O2 | 139.152 | 1995 |
|
deferoxamine (USAN) | 70-51-9 | C25 H48 N6 O8 | 560.684 | 1963 |
| Target Name | Gene Symbol |
|---|---|
| amyloid beta precursor protein | APP |
| hepcidin antimicrobial peptide | HAMP |
| solute carrier family 40 member 1 | SLC40A1 |
| transmembrane serine protease 6 | TMPRSS6 |
Hepcidin antimicrobial peptide (HAMP), homeostatic iron regulator (HFE), solute carrier family 11 member 2 (SLC11A2), solute carrier family 40 member 1 (SLC40A1), and transmembrane serine protease 6 (TMPRSS6) are directly involved in the regulation of iron absorption, utilization, and storage. Mutations or dysregulation of these genes can lead to iron-overload conditions.
Endothelial PAS domain protein 1 (EPAS1), hepatocyte nuclear factor 4 alpha (HNF4A), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B influence iron homeostasis through regulation of gene expression and signaling pathways that modulate hepcidin levels and iron metabolism.
We provide expert in vitro assay development and screening services against a panel of critical biomolecules in iron overload occurrence and progression. These methods include, but are not limited to: ELISA, luciferine/luciferase assay, FRET assays, radioactivity assay, chemiluminescence analysis.
Our service employs a suite of advanced biochemical and cell-based assay methodologies tailored to the specific properties of each biological target included or not included in the table below.
| Dihydroorotate Dehydrogenase | Endothelial PAS Domain Protein 1 |
| Glutathione Peroxidase 4 | Solute Carrier Family 11 Member 2 |
| Solute carrier Family 40 Member 1 | ST14 Transmembrane Serine Protease Matriptase |
| Synuclein Alpha | Transferrin Receptor |
| Transmembrane Serine Protease 6 |
Developing novel therapies for iron overload disorders demands not only rigorous preclinical execution but also a deep, specialized understanding of iron metabolism, pathophysiology, and the unique challenges inherent in this field. At Ace Therapeutics, we are not just a general preclinical service provider; we are your dedicated experts, focused specifically on advancing therapies to address the critical unmet needs of patients with iron overload.
Q: What specific expertise does your team possess in the iron overload preclinical research?
A: Our team comprises scientists and toxicologists with deep, specialized knowledge in iron metabolism, the pathophysiology of iron overload disorders (including hemochromatosis, thalassemia, and other transfusion-dependent anemias), and the mechanisms of iron chelation and regulation. We have extensive hands-on experience designing, executing, and interpreting preclinical studies specifically for compounds targeting excess iron, understanding the unique challenges and relevant biological endpoints in this field. Our expertise allows us to provide insightful guidance tailored to your compound and target indication.
Q: What preclinical models for iron overload do you offer or commonly utilize to evaluate drug candidates?
A: We leverage and have significant experience with several well-established and clinically relevant preclinical models of iron overload. These commonly include:
Dietary iron loading models: Inducing iron overload through diet to mimic certain conditions.
Transfusion-induced iron overload models: Simulating overload seen in patients receiving chronic blood transfusions.
Genetic models: Utilizing specific strains that predispose to iron accumulation. We work closely with you to select and/or adapt the most appropriate model(s) that best reflect the specific iron overload condition you are targeting and the mechanism of action of your therapeutic candidate, ensuring the data generated is highly translatable. We also utilize relevant in vitro systems.
Q: How do you accurately assess and quantify iron overload and evaluate the efficacy of test compounds in your studies?
A: Accurate assessment is key in iron overload research. We employ a range of precise analytical methods to quantify iron burden and evaluate therapeutic impact. This includes quantitative measurement of total and non-heme iron content in key tissues (e.g., liver, heart, spleen, pancreas) using validated biochemical assays. We also measure serum iron parameters such as ferritin, transferrin saturation, and unbound iron, as well as relevant biomarkers of oxidative stress and organ damage associated with iron toxicity. Our pathology services include expert assessment of iron deposition using histochemical staining (e.g., Prussian blue) and evaluation of associated tissue pathology.
Q: What quality control and quality assurance measures are in place to ensure the reliability and integrity of the data from your preclinical iron overload studies?
A: Reliability is paramount in all our studies. We operate under a robust quality management system that includes strict internal Standard Operating Procedures (SOPs) developed based on industry best practices and principles aligned with GLP standards, where applicable to preclinical research. Every study involves meticulous protocol adherence, rigorous training of personnel, robust data capture and management systems with built-in checks, and comprehensive Quality Control (QC) and Quality Assurance (QA) oversight throughout the study lifecycle. This ensures the accuracy, integrity, and reproducibility of the data generated, providing a solid foundation for your regulatory submissions.
Q: Can you assist with tailoring a preclinical study design specifically for my novel iron overload therapeutic candidate and its unique properties?
A: Absolutely. We are a collaborative partner. Based on our specialized expertise in iron overload, we don't just run standard protocols; we work closely with your team to design preclinical studies that are optimally tailored to your compound's specific mechanism of action, pharmacokinetic profile, and the intended clinical indication. We provide strategic scientific input on model selection, study endpoints, dosing regimens, and study duration to ensure the design is scientifically sound, ethically responsible, and most likely to yield the critical data needed to advance your promising therapy.
Ace Therapeutics is a preclinical research leader specializing in obesity and metabolic disorders, offering validated models and advanced analytics to accelerate anti-obesity drug development. With a decade of expertise, we deliver end-to-end solutions, empowering biopharma innovators to transform therapies from concept to preclinical success.