How can AI models and chemistry robots help design a pan-TRK inhibitor that stays in the gut? We just submitted a US IND for KQTD-126, XtalPi’s internally developed, potential first-in-class candidate for chronic intestinal pain, designed through an AI and robotics loop. Preclinically, gut-to-blood exposure exceeds 1,000:1.
Made with AI
1
1
6
499
Chronic abdominal pain can persist even when IBD inflammation is controlled. In IBS, it is a defining symptom. TRK receptors amplify pain signals in the gut, but they function throughout the nervous system too. Where a drug acts matters as much as what it inhibits.

Sep 29, 2026 · 7:17 PM UTC

2
4
182
Potency alone was not enough. KQTD-126 had to inhibit all three TRK receptors, remain selective over other kinases, and stay largely confined to the gut. Each requirement shapes the molecule differently. The challenge was satisfying all three at once.
1
2
27
To tackle all three, we treated the search as one optimization problem at XtalPi. Generative models proposed structures, predictive models assessed them, and robots synthesized candidates for screening. The results then shaped which molecules we designed next.
1
2
44
The >1,000:1 figure compares exposure in gut tissue with exposure in blood. In preclinical studies, KQTD-126 also inhibited TRKA, TRKB, and TRKC at IC₅₀ <1 nM and showed high selectivity over other kinases.
1
2
40
KQTD-126 was designed to inhibit TRK activity in the gut while limiting systemic exposure. The next question is whether that profile translates in patients. The IND submission brings us one step closer to finding out. Full release: prnewswire.com/news-releases…

XtalPi Submits U.S. FDA IND Application for KQTD-126, a Potential First-in-Class, Gut-Restricted...

This milestone marks the first IND submission from XtalPi's proprietary pipeline, recently unveiled in its interim results, validating the company's AI and...

prnewswire.com
3
49
Sort replies: Relevant Recent Liked