ADMET Profile Report

2026-05-04T23:28:20Z

In-silico ADMET risk and developability triage for CNS-oriented human small-molecule lead candidates.

Molecule IDAmiodarone
Input SMILESCCCCC1=C(C2=CC=CC=C2O1)C(=O)C3=CC(=C(C(=C3)I)OCCN(CC)CC)I
Standardized SMILESCCCCc1oc2ccccc2c1C(=O)c1cc(I)c(OCCN(CC)CC)c(I)c1
i Scores and progression labels reflect a CNS small-molecule lead-optimization framework and should be interpreted as prioritization guidance, not experimental truth.
Tier F
Fails Current Program Fit
Blocking hard-gate failure present.
Rationale: Weak CNS exposure (0.19), weak PK/distribution (0.33), and weak developability (0.23). Primary liability is CNS program fit. Secondary liability is hERG. At least one hard gate is incompatible with CNS program progression.
Recommended action: Fail for current CNS program fit unless program goals or evidence changes.

Pillar Scores

Safety Liability
0.23
High safety liability
  • hERG safety score is below 0.50; cardiac liability follow-up is recommended.
  • At least one major CYP isoform has safety score below 0.50; potential DDI liability signal.
  • Composite CYP/DDI score is below 0.45 after worst-isoform penalty.
CNS Exposure
0.19
Poor CNS exposure profile
  • Extreme PK/developability liability profile (size/lipophilicity burden) was detected.
PK / Distribution
0.33
Concerning PK / distribution profile
  • Very high PPB may substantially limit free drug exposure and increase risk of over-sequestration.
Developability
0.23
Poor developability
  • Solubility profile is concerning for practical formulation.
  • High logD7.4 may increase lipophilic developability burden (stickiness, nonspecific binding, and formulation pain).

Hard Gates

Cardiac Safety (hERG)
major red flag / strong escalation
hERG safety score is below the strong-escalation threshold (0.10).
herg safety score0.06
CYP / DDI Safety
requires justification
CYP/DDI score is below 0.50 and needs explicit DDI-risk justification.
cyp ddi score0.45
CNS Access BLOCKING
fail for CNS program
BBB and P-gp scores are compatible with CNS exposure requirements, but physicochemical profile falls outside practical CNS lead space.
bbb score0.69
pgp score0.52
blood/brain ratio1.13
efflux ratio2.30
PK Sanity
program-fit red flag / low prioritization signal
PPB score is very low.
vdss score0.4
ppb score0.14
half life score0.5
vdss l/kg12.7
ppb percent99.64
half life hour12.9
Developability Floor
program-fit red flag / low prioritization signal
Solubility score is concerning. logD7.4 value is extreme for practical developability.
solubility score0.23
logd74 score0.24
solubility logs-6.07
logd74 value4.91

Endpoint Predictions

hERG — Cardiac Safety
Prediction sourceLeak-safe prediction (exact isomeric match, reduced quality)
Predicted IC500.241 µM (pIC50: 6.62)
10× reliability74% (≈0.0241–2.41 µM)
3× precision45% (≈0.0802–0.722 µM)
LabelLikely high hERG risk
hERG safety score0.06 (model max: 0.88)
CYP3A4 Inhibition
Prediction sourceFull model prediction
Predicted IC502.67 µM (pIC50: 5.57)
10× reliability87% (≈0.267–26.7 µM)
3× precision55% (≈0.89–8.01 µM)
LabelLikely moderate inhibitor
CYP3A4 safety score0.41 (model max: 0.77)
CYP2D6 Inhibition
Prediction sourceFull model prediction
Predicted IC506.14 µM (pIC50: 5.21)
10× reliability89% (≈0.614–61.4 µM)
3× precision58% (≈2.05–18.4 µM)
LabelLikely moderate inhibitor
CYP2D6 safety score0.52 (model max: 0.88)
CYP2C9 Inhibition
Prediction sourceFull model prediction
Predicted IC502.14 µM (pIC50: 5.67)
10× reliability91% (≈0.214–21.4 µM)
3× precision53% (≈0.713–6.41 µM)
LabelLikely strong to moderate inhibitor
CYP2C9 safety score0.42 (model max: 0.63)
BBB Permeability
Prediction sourceLeak-safe prediction (exact isomeric match, reduced quality)
Target range (LogBB)0.00 to 0.50
Predicted logBB0.0534
Brain/Blood ratio1.1308
LogBB labelGood (likely within target range)
LogBB score0.69 (model max: 0.75)
P-gp Substrate Likelihood
Prediction sourceFull model prediction
Predicted log10(ER)0.3626
Predicted efflux ratio2.305
P-gp substrate labelBorderline substrate
P-gp substrate score0.52 (model max: 0.95)
Aqueous Solubility
Prediction sourceFull model prediction
Target range (LogS)-4.00 to -2.50
Predicted solubility (LogS)-6.0662
Solubility labelLow solubility (below target)
Solubility score0.23 (model max: 0.81)
Plasma Protein Binding
Prediction sourceFull model prediction
Calibrated target84-98% binding rate
Predicted log10(fu)-2.4431
Predicted fu fraction0.0036
Predicted PPB (%)99.6395
PPB labelLikely too high
PPB score0.14 (model max: 0.76)
Volume of Distribution (Vdss)
Prediction sourceFull model prediction
Calibrated target range0.58-6.4 L/kg
Predicted log10(Vdss L/kg)1.1046
Predicted Vdss (L/kg)12.7221
Vdss labelUncertain (mid to very high, requires secondary signals)
Vdss score0.40 (model max: 0.66)
Half-Life (t½)
Prediction sourceFull model prediction
Target range3-24 hours
Predicted log10(half-life hr)1.1119
Predicted half-life (hr)12.9376
Half-life labelGood (likely within target range)
Half-life score0.50 (model max: 0.50)
logD7.4
Prediction sourceLeak-safe prediction (exact isomeric match, reduced quality)
Calibrated target1.90-3.55
Predicted logD7.44.9128
logD7.4 labelLikely extremely high
logD7.4 score0.24 (model max: 0.81)

Notes