Icon representing a puzzle

2730: SF-1 Round 3

Closed since 15 days ago

Intermediate Overall Small Molecule Design

Summary

Created
February 20, 2026
Expires
Max points
100
Description

SF-1 (steroidogenic factor-1) is a nuclear receptor that helps control hormone balance by regulating genes involved in steroid production. Because SF-1 sits at the center of these pathways, adjusting its activity has strong therapeutic potential: SF-1 has been linked to obesity and metabolic dysfunction, plays important roles in reproduction, and is a proposed therapeutic target for endometriosis. SF-1 is also associated with several cancers—including the rare and aggressive adrenocortical carcinoma—making it a compelling but challenging 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 SF-1 therapeutics! For more information check out the blog post.

Note: The starting ligand in this puzzle includes an orthocarbonate group. Orthocarbonates are generally chemically unstable and are not typical medicinal-chemistry functional groups. We use it here as a phosphate surrogate: it helps reproduce key polar interaction geometry similar to a phospholipid headgroup, while avoiding the practical difficulty of editing a true phosphate in Foldit. Phospholipids are known to bind LRH-1 and SF-1 and can modulate their activity, so this starting scaffold is meant to encourage exploration of phospholipid-like binding modes rather than represent a directly drug-like compound.

Top groups

  1. Avatar for Anthropic Dreams
    1. Anthropic Dreams
    100 pts. 27,408
  2. Avatar for VeFold 2. VeFold 60 pts. 25,273
  3. Avatar for Go Science 3. Go Science 33 pts. 24,669
  4. Avatar for Contenders 4. Contenders 17 pts. 23,314
  5. Avatar for FamilyBarmettler 5. FamilyBarmettler 8 pts. 22,755
  6. Avatar for Australia 6. Australia 4 pts. 22,700
  7. Avatar for L'Alliance Francophone 7. L'Alliance Francophone 2 pts. 21,894
  8. Avatar for Void Crushers 8. Void Crushers 1 pt. 17,002
  9. Avatar for Foldit Staff 9. Foldit Staff 1 pt. 16,804
  10. Avatar for SETI.Germany 10. SETI.Germany 1 pt. 15,746
  1. Avatar for TheGUmmer 41. TheGUmmer Lv 1 1 pt. 17,002
  2. Avatar for Jimmalas 42. Jimmalas Lv 1 1 pt. 16,961
  3. Avatar for rmoretti 43. rmoretti Lv 1 1 pt. 16,804
  4. Avatar for drumpeter18yrs9yrs 44. drumpeter18yrs9yrs Lv 1 1 pt. 16,654
  5. Avatar for rinze 45. rinze Lv 1 1 pt. 16,175
  6. Avatar for p.naka 46. p.naka Lv 1 1 pt. 15,917
  7. Avatar for dahast.de 47. dahast.de Lv 1 1 pt. 15,746
  8. Avatar for Swapper242 48. Swapper242 Lv 1 1 pt. 15,714
  9. Avatar for Tron 49. Tron Lv 1 1 pt. 15,712
  10. Avatar for hada 50. hada Lv 1 1 pt. 15,712

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.)