Novel thiole di-oxide derivative targeting LAMP-1 for PET imaging of lysosomal storage diseases
Computationally designed small molecule ligand that binds LAMP-1, a key lysosomal membrane protein. Developed through pharmacophore modeling and screening of 19M synthetic compounds, the lead candidate shows strong Caco-2 permeability and bioavailability, positioning it as a promising PET tracer for diagnosing lysosomal storage diseases.
Overview
This solution is a novel thiole di-oxide small molecule designed to bind Lysosomal-Associated Membrane Protein 1 (LAMP-1), the most abundant protein component of lysosome membranes. The compound was developed using an in-silico workflow that began with a pharmacophore model based on previously reported NAG–LAMP-1 interactions. The model was used to screen a database of 19 million synthetic compounds and 10,000 phyto-actives, followed by side-chain enumeration and lead optimization. The resulting candidate has a molecular weight of 265.29 Da and is being advanced as a potential PET (Positron Emission Tomography) ligand for imaging LAMP-1 in the context of lysosomal storage diseases.
Technical specifications
- Target: LAMP-1, a lysosomal membrane protein relevant to lysosomal storage disorders
- Pharmacophore model: Built from four interaction features derived from NAG–LAMP-1 binding templates
- Screening scale: 19 million synthetic compounds and 10,000 phyto-actives evaluated against the pharmacophore
- Lead optimization: Side-chain enumeration using a thiole di-oxide fragment, followed by iterative optimization to enhance activity
- ADME profile: Promising results in Caco-2 permeability and bioavailability assays; impermeable to the blood–brain barrier, which is favorable for peripheral imaging applications
- Binding behavior: Non-saturable interaction observed, reducing complexity for PET ligand design and target saturation studies
Technology readiness level
The compound has been validated through in-silico design and in-vitro ADME assays, demonstrating favorable permeability and bioavailability. Current readiness is at a preclinical stage. Future validation requires radiolabeling of the lead compound and target saturation studies in animal models, including dosage-dependent evaluation. The research team is actively seeking a collaboration partner to support animal model development and radiolabeling workflows to advance the candidate toward PET imaging applications.
About R.V. College of Engineering
RV College of Engineering (RVCE) is an autonomous, self‑financing engineering institution in Bengaluru, affiliated to Visvesvaraya Technological University and accredited NAAC A+. It connects to industry through an active Industry Institute Interaction Cell, 150+ MoUs, and co‑located, industry‑sponsored labs and Centers of Excellence that enable joint training, prototyping, and upskilling on campus. Proximity to Bengaluru’s technology cluster supports internships, capstone co‑supervision, and consultancy engagements throughout the year. Research here is supported by competitive national programs and industry, including DRDO/NRB, AICTE, and ISRO collaborations. An IP Coordination Cell, together with incubation resources and a student‑run Entrepreneurship Development Cell, assists with patenting, licensing, and venture formation.
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