{
 "updated": "2026-09-04",
 "pipeline": "ChEMBL activity + drug max_phase join (repurpose_screen.py)",
 "pchembl_cutoff": 6.0,
 "note": "Approved drugs (max_phase 4) with measured potency (pchembl>=6) against a novel endometriosis target. Hypothesis-generation only; direction of effect requires mechanism review.",
 "per_target": {
  "ABCC4": {
   "chembl": "CHEMBL1743128",
   "potent_actives": 2,
   "candidates": []
  },
  "ACKR3": {
   "chembl": "CHEMBL2010631",
   "potent_actives": 82,
   "candidates": []
  },
  "ACVR1B": {
   "chembl": "CHEMBL5310",
   "potent_actives": 84,
   "candidates": [
    {
     "molecule": "CHEMBL601719",
     "name": "CHEMBL601719",
     "pchembl": 6.07,
     "phase": 4.0
    },
    {
     "molecule": "CHEMBL2028663",
     "name": "CHEMBL2028663",
     "pchembl": 6.22,
     "phase": 4.0
    }
   ]
  },
  "AOC3": {
   "chembl": "CHEMBL3265",
   "potent_actives": 7,
   "candidates": []
  },
  "CCR6": {
   "chembl": "CHEMBL4423",
   "potent_actives": 67,
   "candidates": []
  },
  "CCR8": {
   "chembl": "CHEMBL4596",
   "potent_actives": 92,
   "candidates": []
  },
  "CMKLR1": {
   "chembl": "CHEMBL3540",
   "potent_actives": 73,
   "candidates": []
  },
  "CX3CR1": {
   "chembl": "CHEMBL4843",
   "potent_actives": 62,
   "candidates": []
  },
  "ENTPD1": {
   "chembl": "CHEMBL2766",
   "potent_actives": 0,
   "candidates": []
  },
  "ENTPD2": {
   "chembl": "CHEMBL5049",
   "potent_actives": 0,
   "candidates": []
  },
  "F2RL1": {
   "chembl": "CHEMBL5963",
   "potent_actives": 61,
   "candidates": []
  },
  "FKBP4": {
   "chembl": "CHEMBL4050",
   "potent_actives": 16,
   "candidates": [
    {
     "molecule": "CHEMBL160",
     "name": "CHEMBL160",
     "pchembl": 7.8,
     "phase": 4.0
    },
    {
     "molecule": "CHEMBL413",
     "name": "CHEMBL413",
     "pchembl": 8.38,
     "phase": 4.0
    },
    {
     "molecule": "CHEMBL269732",
     "name": "CHEMBL269732",
     "pchembl": 7.64,
     "phase": 4.0
    }
   ]
  },
  "FPR1": {
   "chembl": "CHEMBL3359",
   "potent_actives": 69,
   "candidates": []
  },
  "FPR2": {
   "chembl": "CHEMBL4227",
   "potent_actives": 86,
   "candidates": []
  },
  "GPER1": {
   "chembl": "CHEMBL5872",
   "potent_actives": 87,
   "candidates": [
    {
     "molecule": "CHEMBL135",
     "name": "CHEMBL135",
     "pchembl": 9.52,
     "phase": 4.0
    }
   ]
  },
  "GPX4": {
   "chembl": "CHEMBL4295754",
   "potent_actives": 31,
   "candidates": []
  },
  "HPGD": {
   "chembl": "CHEMBL1293255",
   "potent_actives": 94,
   "candidates": []
  },
  "HTRA1": {
   "chembl": "CHEMBL4523419",
   "potent_actives": 100,
   "candidates": []
  },
  "ILK": {
   "chembl": "CHEMBL5247",
   "potent_actives": 100,
   "candidates": []
  },
  "KLRK1": {
   "chembl": "CHEMBL5483005",
   "potent_actives": 20,
   "candidates": []
  },
  "METTL3": {
   "chembl": "CHEMBL4106140",
   "potent_actives": 100,
   "candidates": []
  },
  "MRGPRX2": {
   "chembl": "CHEMBL5849",
   "potent_actives": 22,
   "candidates": [
    {
     "molecule": "CHEMBL1200490",
     "name": "CHEMBL1200490",
     "pchembl": 6.21,
     "phase": 4.0
    }
   ]
  },
  "NGFR": {
   "chembl": "CHEMBL4762",
   "potent_actives": 1,
   "candidates": []
  },
  "PDK3": {
   "chembl": "CHEMBL3893",
   "potent_actives": 23,
   "candidates": []
  },
  "PFKFB3": {
   "chembl": "CHEMBL2331053",
   "potent_actives": 93,
   "candidates": []
  },
  "PLAUR": {
   "chembl": "CHEMBL4883",
   "potent_actives": 16,
   "candidates": []
  },
  "S1PR2": {
   "chembl": "CHEMBL2955",
   "potent_actives": 76,
   "candidates": []
  },
  "S1PR3": {
   "chembl": "CHEMBL3892",
   "potent_actives": 87,
   "candidates": []
  },
  "SLC7A11": {
   "chembl": "CHEMBL1075149",
   "potent_actives": 17,
   "candidates": [
    {
     "molecule": "CHEMBL421",
     "name": "CHEMBL421",
     "pchembl": 6.8,
     "phase": 4.0
    }
   ]
  },
  "SLCO2A1": {
   "chembl": "CHEMBL2073680",
   "potent_actives": 25,
   "candidates": [
    {
     "molecule": "CHEMBL815",
     "name": "CHEMBL815",
     "pchembl": 7.35,
     "phase": 4.0
    }
   ]
  },
  "SPHK1": {
   "chembl": "CHEMBL4394",
   "potent_actives": 86,
   "candidates": []
  },
  "SUCNR1": {
   "chembl": "CHEMBL2150838",
   "potent_actives": 74,
   "candidates": []
  },
  "TPSAB1": {
   "chembl": "CHEMBL2617",
   "potent_actives": 96,
   "candidates": []
  },
  "TRPM3": {
   "chembl": "CHEMBL3559708",
   "potent_actives": 0,
   "candidates": []
  },
  "YAP1": {
   "chembl": "CHEMBL3334415",
   "potent_actives": 17,
   "candidates": []
  }
 },
 "candidates": [
  {
   "target": "ACVR1B",
   "target_chembl": "CHEMBL5310",
   "molecule": "CHEMBL601719",
   "name": "Crizotinib",
   "pchembl": 6.07,
   "phase": 4.0,
   "status": "watchlist",
   "status_detail": "WATCHLIST \u2014 LOW: real ACVR1B/activin\u2192aromatase mechanism; cancer-TKI fertility/off-target baggage makes drug fit poor.",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "ACVR1B",
   "target_chembl": "CHEMBL5310",
   "molecule": "CHEMBL2028663",
   "name": "Dabrafenib",
   "pchembl": 6.22,
   "phase": 4.0,
   "status": "watchlist",
   "status_detail": "WATCHLIST \u2014 LOW: real ACVR1B/activin\u2192aromatase mechanism; cancer-TKI fertility/off-target baggage makes drug fit poor.",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "FKBP4",
   "target_chembl": "CHEMBL4050",
   "molecule": "CHEMBL160",
   "name": "Cyclosporine",
   "pchembl": 7.8,
   "phase": 4.0,
   "status": "watchlist",
   "status_detail": "WATCHLIST: rat-model efficacy but chronic immunosuppression heavy for benign disease; ChEMBL FKBP4 hit = promiscuity (clinical pharmacology via FKBP12/calcineurin).",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "FKBP4",
   "target_chembl": "CHEMBL4050",
   "molecule": "CHEMBL413",
   "name": "Sirolimus (rapamycin)",
   "pchembl": 8.38,
   "phase": 4.0,
   "status": "top-tier",
   "status_detail": "TOP TIER: independent mTOR endometriosis evidence + chronic-use safety; FKBP4/FKBP52 engagement plausible (PR-chaperone hypothesis; Phase 1.0 docking rapamycin\u2192FKBP52 \u22126.38 vs FKBP12 \u22127.06, 2026-09-04).",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "FKBP4",
   "target_chembl": "CHEMBL4050",
   "molecule": "CHEMBL269732",
   "name": "Tacrolimus",
   "pchembl": 7.64,
   "phase": 4.0,
   "status": "watchlist",
   "status_detail": "WATCHLIST: rat-model efficacy but chronic immunosuppression/nephrotoxicity heavy for benign disease; FKBP4 hit = promiscuity (pharmacology via FKBP12/calcineurin).",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "GPER1",
   "target_chembl": "CHEMBL5872",
   "molecule": "CHEMBL135",
   "name": "Estradiol",
   "pchembl": 9.52,
   "phase": 4.0,
   "status": "wrong-direction",
   "status_detail": "WRONG DIRECTION \u2014 target-validating only: endogenous GPER agonist activating a proliferation-driving receptor in endometriosis.",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "MRGPRX2",
   "target_chembl": "CHEMBL5849",
   "molecule": "CHEMBL1200490",
   "name": "Cetrorelix",
   "pchembl": 6.21,
   "phase": 4.0,
   "status": "validated-axis",
   "status_detail": "VALIDATED AXIS \u2014 target-validating, not repurposing: measured MRGPRX2 agonism (pChEMBL 6.21/6.09) + already an endo treatment; MRGPRX2 antagonism is the drug-development lead. Docking deferred to Phase 2 (tool boundary).",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "SLC7A11",
   "target_chembl": "CHEMBL1075149",
   "molecule": "CHEMBL421",
   "name": "Sulfasalazine",
   "pchembl": 6.8,
   "phase": 4.0,
   "status": "watchlist",
   "status_detail": "WATCHLIST \u2014 LOW-MEDIUM: binds xCT as predicted (Phase 1.0 docking \u22128.52 vs native \u22129.35, 2026-09-04); direction resolved (lesion-cell ferroptosis induction therapeutic); selectivity/toxicity remain the blockers.",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  },
  {
   "target": "SLCO2A1",
   "target_chembl": "CHEMBL2073680",
   "molecule": "CHEMBL815",
   "name": "Dinoprostone (PGE2)",
   "pchembl": 7.35,
   "phase": 4.0,
   "status": "wrong-direction",
   "status_detail": "WRONG DIRECTION \u2014 target-validating only: dinoprostone IS PGE2; therapy would need SLCO2A1 blockade, not the agonist.",
   "validation_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md"
  }
 ],
 "validation": {
  "updated": "2026-09-04",
  "method": "M3 depth-check 9/9 (2026-09-02) \u2014 mechanism/evidence/safety/novelty + direction-of-effect review (ferroptosis-direction.md); Phase 1.0 docking + ADMET (2026-09-04); Phase 0.5 GEO lesion-expression corroboration (2026-09-03/04)",
  "shortlist_ref": "https://raw.githubusercontent.com/wckdboy/openendo/main/docs/research/evidence/m3-validation.md",
  "status_vocabulary": [
   "top-tier",
   "watchlist",
   "validated-axis",
   "wrong-direction"
  ],
  "note": "status reflects the M3 validated shortlist; wrong-direction/validated-axis entries remain target-validating evidence, not repurposing candidates."
 }
}