Diabetic Nephropathy Drug Development Service
Diabetic nephropathy (DN), a severe complication of diabetes, currently can only be slowed by existing therapies (e.g., SGLT2 inhibitors, ACEIs/ARBs), but reversal of kidney damage remains elusive. As a preclinical CRO deeply involved in diabetes, Ace Therapeutics focuses on preclinical drug development for diabetic nephropathy. By integrating AI target prediction, cross-species disease modeling, multi-omics validation and translational medicine platforms, we provide our clients with one-stop solutions for target screening, efficacy assessment, mechanistic analysis and preclinical filing, which will help them to accelerate the development of innovative therapies.
Challenges in Diabetic Nephropathy Drug Development
Diabetic nephropathy is the leading cause of renal failure. Currently, available therapies can only relieve symptoms and do not treat the underlying pathophysiology of diabetic nephropathy.
- The target mechanism is not clear.
- Some traditional animal models have limited predictive translation to humans.
- Insufficient renal targeting.
Fig. 1 Timeline showing the landmark trials for diabetic nephropathy. (Sawaf, H.; et al., 2022)
Diabetic Nephropathy Drug Development Services at Ace Therapeutics
Ace Therapeutics provides one-stop preclinical drug discovery services to help clients discover novel antidiabetic nephropathy drugs.
Target Discovery and Validation Services
- Based on in-depth research on the pathological mechanisms of diabetic nephropathy, we combine bioinformatics analysis with high-throughput screening technology to uncover potential targets that are closely related to the onset and progression of diabetic nephropathy.
- We utilize gene editing technology, cell models and animal models to functionally validate the targets and determine their feasibility and effectiveness as therapeutic targets, laying a solid foundation for subsequent therapeutic development.
Drug Design and Optimization Services
- Based on validated targets, we utilize computer-aided drug design (CADD), structural biology and other technologies to design small molecule compounds, biomolecule drugs or gene therapy vectors.
- Through structure-activity relationship (SAR) studies and structural optimization, we help our clients to improve the activity, selectivity and pharmacokinetic properties of their drugs, and to reduce potential toxicity.
Preclinical Drug Evaluation Services
In the preclinical drug evaluation stage, we carry out comprehensive pharmacodynamics, pharmacokinetics and safety evaluation.
- Animal models of diabetic nephropathy are employed to evaluate drug-induced improvements in renal function and histopathological restoration.
- Pharmacokinetic studies are employed to characterize drug absorption, distribution, metabolism, and excretion (ADME) properties in vivo.
- Comprehensive toxicology experiments provide reliable data to support the entry of drugs into clinical trials.
Combination Therapy Development Services
In view of the complex pathogenesis of diabetic nephropathy, we help our clients to develop combination therapies. Combining drugs with different mechanisms of action, such as combining anti-inflammatory drugs with antioxidant drugs, and combining hypoglycemic drugs with renal protective drugs. We validate the synergistic effect of combination therapies through cell and animal experiments to provide more innovative therapies for diabetic nephropathy.
Why Choose Our Diabetic Nephropathy Drug Development Services
- Multi-target therapeutic development capability
Encompassing metabolic, anti-inflammatory, and anti-fibrotic pathways implicated in diabetic nephropathy.
| Metabolic regulatory agents |
| Renin-angiotensin system (RAS) blockades |
SGLT2 inhibitor |
GLP-1 agonist |
| Anti-inflammatory and immunomodulatory agents |
| JAK/STAT pathway inhibitors |
Ineralocorticoid receptor antagonists |
| Innovative anti-fibrotic therapies |
| TGF-β/Smad pathway antagonists |
Endothelin antagonist |
- Customized in vitro and in vivo diabetic nephropathy modeling
We customize the optimal diabetic nephropathy model based on the stage of drug development.
| In vitro cell models |
- High glucose-induced podocyte insulin resistance model
- Model of transdifferentiation of renal tubular epithelial cells stimulated by advanced glycosylation end products (AGEs)
|
| Animal models of diabetic nephropathy |
- STZ-induced rat model
- STZ + high-fat diet-induced rat model
- NOD mouse model
- KK-Ay mouse model
- db/db mouse model
- GK rat model
|
| Non-human primate models |
Assessment of long-term (>12 months) renal fibrosis progression and drug safety. |
- Multidimensional assay indicators
We establish multiple testing parameters to support comprehensive evaluation of drug efficacy and safety.
| Functional evaluation |
Classical renal function indicators |
Serum creatinine, cystatin C, 24-hour urine protein quantification (gold standard) |
| Novel biomarkers |
Urinary exosomal miRNA-21 (early injury), plasma IL-18 (inflammatory activation), KIM-1 (tubular injury) |
| Molecular biological analysis |
Proteomic analysis |
LC-MS to quantify the expression of target proteins such as AGEs, TGF-β, etc., combined with iTRAQ labeling technology to reveal the drug regulatory network. |
| Epigenetic analysis |
ChIP-seq detects the regulatory role of histone modifications (e.g. H3K27ac) in diabetic nephropathy. |
| Pathology and imaging analysis |
Super-resolution microscopy |
Quantification of pedicle width and basement membrane thickness |
| Immunofluorescence multiple staining |
Simultaneous detection of podocyte markers (nephrin), macrophages (CD68) and collagen deposition (Masson stain) |
Ace Therapeutics supports diabetic nephropathy therapeutics development through scientific R&D systems, innovative technology platforms, and a professional service team. Contact us now to access customized solutions.
References
- Sawaf, H.; et al. Therapeutic advances in diabetic nephropathy. Journal of Clinical Medicine. 2022, 11(2): 378.
- Lv, M.; et al. Therapeutic strategies of diabetic nephropathy: recent progress and future perspectives. Drug Discovery Today. 2015, 20(3): 332-346.
- Rao, V.; et al. Diabetic nephropathy: an update on pathogenesis and drug development. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019, 13(1): 754-762.
All of our services and
products are intended for preclinical research use only and cannot be used to diagnose, treat or
manage patients.
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