Diabetes Drug R&D Services ace

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* 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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SGLT2-Targeted Drug Development for Diabetes

Pharmacological inhibition of sodium-glucose cotransporter protein 2 (SGLT2) is recognized as a promising therapeutic target for type 2 diabetes. Ace Therapeutics provides one-stop SGLT2 inhibitor development services from target validation to preclinical evaluation. With rich diabetes animal models, AI-driven molecular optimization platform, and multi-dimensional efficacy evaluation system, we accelerate discovery of highly selective, translational SGLT2 inhibitors.

Overview of SGLT2 and SGLT2 Inhibitors

SGLT2 is a key glucose transport mediator in renal proximal tubular epithelial cells and is responsible for the reabsorption of glucose in approximately 90% of glomerular filtrate. By inhibiting SGLT2 activity, this reabsorption process can be blocked, triggering multiple physiological effects:

Glucosuria: Improvement in glucose control.
Natriuresis: Improvement in blood pressure and reversal of tubuloglomerular feedback.
Improvement in albuminuria.
Weight loss and lipid metabolism shift.
Improvement in proximal tubular work and oxygen consumption.
Improved oxygen delivery and anemia.

As a novel class of antidiabetic agents, SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) represent a therapeutic breakthrough beyond conventional glucose-lowering medications by demonstrating dual benefits of systemic metabolic modulation and clinically proven cardiorenal protection. Therefore, the discovery and development of novel SGLT2 inhibitors could bring more therapeutic options for diabetes.

Mode of action of SGLT2-targeted therapeutic agents. Fig. 1 Mechanism of action of selective sodium-glucose cotransporter 2 (SGLT2) inhibitors. (Komaniecka, N.; et al., 2024)

Preclinical SGLT2 Inhibitor Development Services at Ace Therapeutics

As a preclinical contract research specialist with deep expertise in diabetes drug discovery, Ace Therapeutics focuses on the full process of SGLT2 inhibitor development, providing comprehensive solutions to clients worldwide. Our customized diabetes animal models and preclinical testing capabilities provide reliable data and clinical translational value to our clients' drug development programs.

Validation and mechanistic studies of SGLT2

Testing Program	Content
Gene/Protein expression assays	Construction of HEK293 cell models overexpressing humanized SLC5A2 gene involves target expression validation by qPCR and Western blot analysis. Validation of SGLT2-specific functions (e.g., glucose uptake inhibition rate) using CRISPR-Cas9 knockdown.
Functional activity verification	Measurement of SGLT2-mediated glucose transport activity employs either radiolabeled or fluorescent probe-based assays.
Diabetic nephropathy model	Verification of the correlation between upregulated SGLT2 expression and urinary albumin excretion rate (UACR) in STZ-induced diabetic rats.
Cardiovascular protection mechanism	Evaluation of SGLT2 inhibition on myocardial oxygen consumption (MVO₂) improvement using an ex vivo heart perfusion model.

Preclinical screening of SGLT-2 inhibitors

In vitro activity screening

Screening Platforms	Testing Indicators
Cellular glucose uptake	Fluorescent glucose analog (2-NBDG) uptake rate
Membrane protein binding assay	Surface plasmon resonance (SPR)
Enzyme activity inhibition	Recombinant human SGLT2 protein IC₅₀ assay

Computational chemistry-aided design

Virtual screening: molecular docking based on SGLT2 crystal structure.

ADMET Prediction: assessment of permeability and metabolic stability using ADMET Predictor.

Lead compound optimization

We provide SGLT2 lead compound optimization services supported by structure-activity relationship (SAR) analysis and structural biology studies. Through highly selective molecular design, drug-likeness enhancement, and preclinical validation, we assist clients in obtaining candidate SGLT2 inhibitors.

Preclinical efficacy and safety assessment

Testign Program	Content
Pharmacodynamic validation	Fasting blood glucose, glycosylated hemoglobin test. Urinary glucose excretion, insulin sensitivity testing. Oral glucose tolerance test.
Evaluation of organ-protective effects	Kidney protection Cardiovascular benefits
Safety assessment	Screening for off-target effects Toxicology studies Risk specificity assessment

Advantages of Our Preclinical SGLT-2 Inhibitor Development Services

Target-specific screening platforms

We use a humanized SGLT-2/GLUT2 co-expression system to ensure the selectivity of lead compounds for SGLT-2.

Cross-species PK/PD prediction modeling

We establish a translational efficacy prediction system from rodents to primates based on SGLT-2 glycosylation variants and renal glucose threshold differences.

Comprehensive renal protection efficacy assessment

We quantitatively assess the effects of drug candidates on renal tubular glucose transport and foot cell protection by modeling diabetic nephropathy.

Ace Therapeutics is committed to applying our expertise to accelerate the process of developing highly effective and safe SGLT-2 inhibitors. Please contact us for more information.

Reference

Komaniecka, N.; et al. Transporter Proteins as Therapeutic Drug Targets-With a Focus on SGLT2 Inhibitors. International Journal of Molecular Sciences. 25.13 (2024): 6926.

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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