# Development of novel Amadorins for Diabetic Peripheral Neuropathy

> **NIH NIH R42** · PRAETEGO, INC. · 2020 · $874,423

## Abstract

PROJECT SUMMARY
Diabetic peripheral neuropathy (DPN) is the most common diabetic complication. DPN is a leading cause for
disability due to foot ulceration and amputation, gait disturbance, and fall-related injury. There is no FDA-
approved disease modifying treatment for DPN, a condition affecting up to 50% of the estimated 30 million
diabetic patients in the US. Neuropathy occurs in patients with both type 1 and type 2 diabetes but the only
current recommendation for preventing or slowing progression of neuropathy is to maintain close glycemic
control. Multiple drugs are available to treat hyperglycemia itself, but no drugs that treat the pathogenesis of DPN
or the other complications have succeeded in advanced clinical trials. Praetego Inc. plans to advance new
chemical entities in the class of “Amadorins” for the treatment of DPN pathogenesis. Hyperglycemia is the key
common factor linking all diabetic complications. Direct reaction of proteins with glucose leads to formation of
so-called advanced glycation endproducts (AGEs). Praetego Inc. and others believe that AGE formation
underlies, at least in part, all the major microvascular complications of diabetes. In diabetic patients, these
glucose-mediated reactions damage the microvascular blood vessels that nourish nerves, the retina and kidney
glomeruli. Our present focus is the preclinical drug development of two novel Amadorin AGE inhibitors that
emerged in our Phase I SBIR study. We will advance the drug development of a lead Amadorin candidate, PTG-
630, and, as a de-risking strategy, secondary studies will be carried out on a back-up Amadorin PTG-641, with
distinguishing properties from the lead. In our Phase I SBIR grant, we studied the in vitro AGE inhibition potency
of several novel Amadorins, and the in vitro and in vivo safety of the most promising candidates, PTG-630 and
PTG-640. Both demonstrated the predicted potent AGE inhibition and also exhibited the hoped for improved
margin of safety in maximum tolerated dose (MTD) studies and in in vitro off-target screening panels. PTG-630
was the most potent AGE inhibitor and proved safer than our previous lead. We designate it as our lead
candidate. PTG-640 demonstrated an extremely high MTD, likely due to limited absorption, and no hits in the in
vitro off-target panel screen. However, our preferred back-up is its precursor methyl ester PTG-641. It is deemed
the better drug candidate for development: it should hydrolyze in the body to the safe PTG-640, it is a 3-fold
stronger AGE inhibitor, and it should have better bioavailability. Thus, in this Phase II STTR we will: (1)
characterize and optimize the chemical properties, stability and bioavailability of these two drug candidates, and
(2) advance the best forms of these two leads into long-term preclinical efficacy in multiple DPN rodent models
of Type 1 and Type 2 diabetes. A key objective will be obtaining central nervous system and small and large
fiber measurements that translate ...

## Key facts

- **NIH application ID:** 10079227
- **Project number:** 2R42DK120063-02
- **Recipient organization:** PRAETEGO, INC.
- **Principal Investigator:** RAJA G KHALIFAH
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $874,423
- **Award type:** 2
- **Project period:** 2018-09-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079227

## Citation

> US National Institutes of Health, RePORTER application 10079227, Development of novel Amadorins for Diabetic Peripheral Neuropathy (2R42DK120063-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10079227. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*