Rectify Pharmaceuticals Unveils RTY-406, an Oral Dual ABCB4/BSEP Modulator for Primary Sclerosing Cholangitis
核心洞察
Rectify Pharmaceuticals (搜索) presented the discovery of RTY-406 (搜索), an oral ABCB4 (搜索)/BSEP (搜索) dual-targeted Positive Functional Modulator, at the ACS Fall 2026 Meeting in Chicago.
In a mouse model of PSC, RTY-406 (搜索) produced dose-dependent reductions in ALP and cholesterol crystals alongside improvements in ductular reaction, inflammation and fibrosis.
Cryo-EM structures confirmed the compound series modulates ABCB4 (搜索) and BSEP (搜索) by directly binding the target proteins, supporting a disease-modifying mechanism.
Rectify Pharmaceuticals (搜索), Inc. announced the presentation of the discovery of RTY-406 (搜索), its clinical candidate and an oral, ABCB4 (搜索)/BSEP (搜索) dual-targeted Positive Functional Modulator (PFM), at the American Chemical Society (ACS) Fall 2026 Meeting, held August 22-27, 2026, in Chicago, Illinois. The presentation, titled "Discovery of RTY-406: A Positive Functional Modulator of ABCB4 and BSEP as a Disease-Modifying Therapy for the Treatment of Primary Sclerosing Cholangitis (搜索)," was delivered during the Division of Medicinal Chemistry (MEDI) First Time Disclosures session by Nate Fuller, PhD, VP, Chemistry at Rectify Pharmaceuticals.
RTY-406 (搜索) is an orally administered, once-daily investigational therapy in clinical development for primary sclerosing cholangitis (搜索) (PSC). According to the company, its dual mechanism of action uniquely targets abnormal bile composition and reduced bile flow, described as two core pathophysiological drivers of PSC. The candidate is currently being evaluated in a phase 1 clinical study.
Preclinical Profile in a PSC Mouse Model
The ACS presentation detailed the identification of RTY-406 (搜索) as a potent dual PFM of ABCB4 (搜索) and BSEP (搜索) with what the company characterized as an excellent pharmacokinetic profile. In a mouse model of PSC, the compound demonstrated ABCB4 and BSEP target modulation, dose-dependent decreases in alkaline phosphatase (ALP) and cholesterol crystals — described as common clinical features of PSC progression — and dose-dependent improvements in key markers of ductular reaction, inflammation and fibrosis.
"By modulating ABCB4 (搜索) and BSEP (搜索) to restore normal bile composition and flow, we are directly addressing key pathophysiologic drivers of hepatobiliary disease," said Rajesh Devraj, PhD, President and Chief Executive Officer of Rectify Pharmaceuticals (搜索). "The meaningful improvements observed in bile composition, inflammation and fibrosis in an in vivo model give us confidence in this approach and its potential to become the first disease modifying therapy for PSC."
Devraj added that the data presented at ACS demonstrate RTY-406 (搜索) represents an entirely novel approach for the treatment of PSC, with pipeline-in-a-pill potential across multiple hepatobiliary diseases.
Platform Discovery and Structural Confirmation
The presentation outlined the application of Rectify's Positive Functional Modulator platform, which yielded a series of dual ABCB4 (搜索)/BSEP (搜索) PFMs. The company reported rapid optimization of this series to deliver compounds with improved potency on ABCB4 and BSEP and improved drug-like properties. High-resolution cryo-EM structures confirmed that the series modulates ABCB4 and BSEP function by directly binding to the target proteins.
Per the company, RTY-406 (搜索) demonstrated efficacy across multiple disease-relevant endpoints in a preclinical model of PSC, including inflammation, cholangitis, cholestasis and fibrosis. The abstract accompanying the presentation is available on the publications page of the Rectify website.
Broader Platform Context
Rectify is advancing Positive Functional Modulators, a class of oral small molecules designed to restore and enhance membrane protein function to address the underlying cause of serious diseases. The company states that its PFMs have the potential to modulate the activity of wild-type and mutated membrane-bound proteins, a historically difficult challenge with a small molecule approach. The platform is intended to enable efficient and rapid discovery of first- and best-in-class small molecule therapies with potential applications across rare and common diseases, including liver, cardio-renal-metabolic and neurodegenerative diseases.