ADMET Lead Desk -- frozen database

Score matrix used for IBM Fez job d9lpnanbupns73e7qujg (schema admet_lead_desk_v1). Values are desirability in [0, 1]: higher means more favorable for advancing an oral small-molecule lead under that logic.

Public-proxy panel for architecture comparison. Not a claim that every cell is a TDC experimental assay label for that compound. Endpoint names follow the Therapeutics Data Commons ADMET Benchmark Group (17 of 22). Source overview: tdcommons.ai

Compounds (assets)

ID	Name	Class	Role in the conflict
1	caffeine	cns_tool	Generally favorable oral / CNS tool profile
2	propranolol	cardiovascular	Lipophilic beta-blocker; CYP / P-gp tension
3	digoxin	cardiovascular	P-gp substrate / narrow therapeutic index
4	ibuprofen	nsaid	Strong oral NSAID; moderate DILI tension
5	cisplatin	oncology	Poor oral ADME; high toxicity
6	doxorubicin	oncology	Cardiotoxicity / poor BBB
7	fluoxetine	cns	CNS exposure with CYP2D6 liability
8	terfenadine	withdrawn	hERG / CYP3A4 poster child
9	acetaminophen	analgesic	Strong ADME; DILI risk at overdose (filter trap)

Seventeen contextures (columns)

#	Column	Family	TDC-aligned meaning	Desirability
0	caco2	Absorption	Caco-2 permeability	Higher permeability better
1	hia	Absorption	Human intestinal absorption	Absorbed better
2	pgp	Absorption	P-gp liability	Low P-gp risk better
3	bioavailability	Absorption	Oral bioavailability	Higher F better
4	lipophilicity	Absorption	Drug-like lipophilicity	Balanced better
5	solubility	Absorption	Aqueous solubility	Higher better
6	bbb	Distribution	BBB permeation	Permeant higher (panel mixes intents)
7	ppbr	Distribution	Plasma protein binding balance	Moderate preferred
8	vdss	Distribution	Volume of distribution balance	Moderate preferred
9	cyp2c9_inh	Metabolism	CYP2C9 inhibition	Non-inhibitor better
10	cyp2d6_inh	Metabolism	CYP2D6 inhibition	Non-inhibitor better
11	cyp3a4_inh	Metabolism	CYP3A4 inhibition	Non-inhibitor better
12	half_life	Excretion	Half-life balance	Moderate preferred
13	cl_hepa	Excretion	Hepatocyte clearance balance	Moderate preferred
14	herg	Toxicity	hERG blockade	Non-blocker better
15	ames	Toxicity	Ames mutagenicity	Non-mutagen better
16	dili	Toxicity	DILI risk	Low risk better

Frozen desirability matrix (IBM job table)

ID	Name	caco2	hia	pgp	F	lipo	sol	bbb	ppbr	vdss	2c9	2d6	3a4	t1/2	CLh	hERG	Ames	DILI
1	caffeine	0.88	0.92	0.85	0.90	0.78	0.82	0.90	0.75	0.70	0.88	0.85	0.80	0.72	0.70	0.88	0.90	0.85
2	propranolol	0.80	0.85	0.55	0.78	0.70	0.55	0.82	0.60	0.65	0.70	0.45	0.55	0.68	0.60	0.72	0.88	0.75
3	digoxin	0.35	0.40	0.15	0.30	0.45	0.50	0.20	0.55	0.40	0.80	0.75	0.70	0.55	0.50	0.65	0.85	0.55
4	ibuprofen	0.85	0.90	0.80	0.88	0.72	0.48	0.55	0.50	0.60	0.55	0.70	0.60	0.65	0.55	0.80	0.88	0.60
5	cisplatin	0.10	0.08	0.70	0.05	0.25	0.70	0.05	0.70	0.35	0.85	0.85	0.80	0.40	0.35	0.55	0.45	0.15
6	doxorubicin	0.20	0.15	0.35	0.10	0.40	0.45	0.08	0.40	0.45	0.65	0.60	0.55	0.50	0.40	0.25	0.50	0.20
7	fluoxetine	0.75	0.82	0.50	0.80	0.68	0.40	0.88	0.45	0.70	0.60	0.20	0.50	0.75	0.55	0.70	0.85	0.70
8	terfenadine	0.70	0.78	0.40	0.65	0.55	0.35	0.45	0.40	0.55	0.50	0.55	0.15	0.60	0.50	0.08	0.80	0.55
9	acetaminophen	0.90	0.95	0.88	0.92	0.80	0.85	0.70	0.78	0.65	0.90	0.88	0.85	0.70	0.65	0.90	0.88	0.35

Classical sequential gates used on this table

Survivors require: hERG ≥ 0.55, Ames ≥ 0.55, DILI ≥ 0.50, P-gp ≥ 0.45, bioavailability ≥ 0.45. On this matrix that keeps caffeine, propranolol, ibuprofen, fluoxetine -- and drops acetaminophen despite a high equal-weight score.