Development of first-in-class antagonists of the retinoid pathway as novel oral therapies for type 2 diabetes
Ended Project Grant Awarded Last action
- Award ID
- R43DK136420
- Recipient
-
Kayothera, Inc. UEI RPZEUH63MQA3
- Awarding agency
-
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $337,609
Award facts
- Assistance listing
- 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
- Completion date
- Originally
- Place of performance
- New Jersey, USA
Award details come from USAspending.gov.
Description
- Abstract
- The retinoid pathway is a central regulatory pathway in human biology that has been considered undruggable for the last 20 years. IT is activated when dietary vitamin a is transported to target tissues, is oxidized to all-trans retinoic acid (atra), and then binds the rara/SS/ nuclear receptors. This binding results in transcriptional regulation that is best known to influence the differentiation state of various cells and tissues. In metabolic disorders, ALDH1A3 is a key enzyme responsible for the final synthetic step of the retinoid ligand, and has also been identified as one of the principal pancreatic SS cell markers for type 2 diabetes. Numerous studies have shown that ALDH1A3 protein levels or enzymatic activity is a specific marker for failing/dedifferentiated SS cells that lose the ability to produce insulin in type 2 diabetics. Whereas retinoid signaling has long been a pathway of interest in both rodent and human diabetes, published studies have not established whether or not retinoid signaling and thus ALDH1A3 are drivers of type 2 diabetes. Our initial discovery work suggests that ALDH1A3 is a driver of the SS cell dedifferentiation observed in type 2 diabetes and thus may offer a target whose inhibition can offer durable treatment effects for diabetics. Discussions with stakeholders across the type 2 diabetes community have demonstrated considerable interest in disease-modifying therapies that restore pancreatic function as there is broad recognition that current therapies are limited in activity to controlling blood glucose levels and insulin sensitivity rather than affecting pancreatic health. Thus, to reverse the projected rise of type 2 diabetics across the world, next generation drug combinations are needed that restore pancreatic SS cells to their normal differentiation status. Utilizing proprietary chemistry platforms, kayothera is the first group to have developed lead inhibitors against ALDH1A3 that show exceptional potency and specificity while avoiding the pharmacologic liabilities of other drug development programs in the retinoid pathway. Our therapies show strong potency in inhibiting the retinoid pathway (
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $337,609 |
Quick answers
Who received award R43DK136420?
R43DK136420 was awarded to Kayothera, Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on May 24, 2023.
How much is award R43DK136420 worth?
$337,609 has been obligated on R43DK136420.
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