Icon representing a puzzle

2745: LRH-1 Round 6

Closed since 3 days ago

Intermediate Overall Small Molecule Design

Summary

Created
March 27, 2026
Expires
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. Avatar for Anthropic Dreams
    1. Anthropic Dreams
    100 pts. 20,617
  2. Avatar for VeFold 2. VeFold 63 pts. 19,014
  3. Avatar for Go Science 3. Go Science 37 pts. 18,956
  4. Avatar for Australia 4. Australia 21 pts. 17,978
  5. Avatar for L'Alliance Francophone 5. L'Alliance Francophone 11 pts. 17,696
  6. Avatar for Contenders 6. Contenders 5 pts. 17,489
  7. Avatar for FamilyBarmettler 7. FamilyBarmettler 2 pts. 16,517
  8. Avatar for Void Crushers 8. Void Crushers 1 pt. 13,096
  9. Avatar for fold me 9. fold me 1 pt. 9,349
  10. Avatar for Eὕρηκα! Heureka! 10. Eὕρηκα! Heureka! 1 pt. 9,347
  1. Avatar for Arlind1 41. Arlind1 Lv 1 1 pt. 11,368
  2. Avatar for rinze 42. rinze Lv 1 1 pt. 10,859
  3. Avatar for roarshock 43. roarshock Lv 1 1 pt. 10,206
  4. Avatar for Jimmalas 44. Jimmalas Lv 1 1 pt. 10,042
  5. Avatar for Momuro 45. Momuro Lv 1 1 pt. 9,561
  6. Avatar for Mohoernchen 46. Mohoernchen Lv 1 1 pt. 9,544
  7. Avatar for Painture 47. Painture Lv 1 1 pt. 9,470
  8. Avatar for Stas Gunko 48. Stas Gunko Lv 1 1 pt. 9,448
  9. Avatar for hada 49. hada Lv 1 1 pt. 9,411
  10. Avatar for mengzach 50. mengzach Lv 1 1 pt. 9,395

Comments

Sciren Staff Lv 1

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.)