2745: LRH-1 Round 6

Open for the next 3 days

Summary

• Created: March 27, 2026
• Expires: April 03, 2026 at 23:00 UTC
• Max points: 100

Description

LRH-1 (liver receptor homologue-1) is a nuclear receptor that helps control how the body balances fat and sugar metabolism by turning specific genes on and off. Because of this central role, tuning LRH-1 activity has shown therapeutic promise: synthetic compounds that modulate LRH-1 can reduce symptoms of inflammatory bowel disease and diabetes in mouse models. LRH-1 is also implicated in multiple cancers, making it an important, but notoriously difficult, drug target.

Your creativity could help “drug the undruggable.” Build from what’s known, explore bold new possibilities, and design binders that could help become the next generation of LRH-1 therapeutics! For more information check out the blog post.

Note form the collaborator: This compound was found to bind to lrh1 in an in vitro screen and activate lrh1 gene expression in cells in this study.  However we do not know the actual binding mode. This pose is from extensive structure-based docking against the target pocket where we expect synthetic ligands to bind and as suggested by the in vitro screen. There are some favorable interactions, but also steric clashes in this docked pose. Exploring how the various groups of these compounds which are chemically dissimilar to the known binders can help probe patterns of lrh1 binding.

Top groups

• 1. Go Science 17,892
• 2. Anthropic Dreams 16,592
• 3. Australia 16,090
• 4. Contenders 15,560
• 5. VeFold 14,688
• 6. L'Alliance Francophone 14,002
• 7. 凌云 9,349

Top soloists

• 21. DScott 10,408
• 22. junzhe1135 9,349
• 23. zbp 9,329

Comments

[Sciren]

Objectives

Maximum bonus: +9000

Compound Library (max +2000)
Gives a bonus if your current compound is in the library. This uses a local cached version of the Compound Library search results to determine if the compound is in the library. If you manually create a compound that happens to be in the library (or if you load a shared solution with an on-library compound), you may need to submit the compound to the compound library search and wait to get the results back before the objective can properly recognize that the compound is in the library. (If the objective is not updating, try wiggling the structure. See this forum post for more discussion.)

Torsion Quality (max +1000)
Keeps bond rotations in a good range. Using Wiggle or Tweak Ligand can fix bad torsions. (Show highlights torsions to be rotated.)

Number of Rotatable Bonds (max +1000)
Intended to keep the ligand from getting too big and floppy. You can reduce rotatable bonds by deleting groups or forming rings. (Show highlights rotatable bonds.)

Ligand TPSA (max +1000)
Topological Polar Surface Area - Keeps the polar surface area (including buried polar surface) low. To improve, try removing oxygens and nitrogens. (Show highlights atoms contributing to higher TPSA.)

Ligand cLogP (max +1000)
A measure of polarity - Keeps the molecule from getting too hydrophobic. To improve, try adding polar oxygens and nitrogens. (Show highlights atoms contributing to higher cLogP.)

Bad Groups (max +1000)
Gives a bonus for avoiding groups that interfere with assays, which are far from the compounds in the library, or which otherwise have issues. (Show highlights groups at issue.)

Molecular Weight (max +1000)
Keeps the ligand within a reasonable size limit.

Synthetic Accessibility (max +1000)
Keeps the ligand from going too far from the compounds in the library. (Show highlights parts of the molecule at issue.)