Drug Research Strategy

Comprehensive drug investigation using 50+ ToolUniverse tools across chemical databases, clinical trials, adverse events, pharmacogenomics, and literature.

KEY PRINCIPLES

:

Report-first approach

- Create report file FIRST, then populate progressively

Compound disambiguation FIRST

- Resolve identifiers before research

Citation requirements

- Every fact must have inline source attribution

Evidence grading

- Grade claims by evidence strength (T1-T4)

Mandatory completeness

- All sections must exist, even if "data unavailable"

English-first queries

- Always use English drug/compound names in tool calls, even if the user writes in another language. Only try original-language terms as a fallback. Respond in the user's language

Workflow Overview

1. Report-First Approach (MANDATORY)

DO NOT

show the search process or tool outputs to the user. Instead:

Create the report file FIRST

-

[DRUG]_drug_report.md

with all 11 section headers and

[Researching...]

placeholders. See

REPORT_TEMPLATE.md

for the full template.

Progressively update the report

- Replace placeholders with findings as you query each tool.

Use ALL relevant tools

- Query multiple databases for each data type; cross-reference across sources.

2. Citation Requirements (MANDATORY)

Every piece of information MUST include its source. Use inline citations:

*

Source: PubChem via

PubChem_get_compound_properties_by_CID

(CID: 4091)

*

3. Progressive Writing Workflow

Step 1: Create report file with all section headers

Step 2: Resolve compound identifiers -> Update Section 1

Step 3: Query PubChem/ADMET-AI/DailyMed SPL -> Update Section 2 (Chemistry)

Step 4: Query FDA Label MOA + ChEMBL + DGIdb -> Update Section 3 (Mechanism)

Step 5: Query ADMET-AI tools -> Update Section 4 (ADMET)

Step 6: Query ClinicalTrials.gov -> Update Section 5 (Clinical)

Step 7: Query FAERS/DailyMed -> Update Section 6 (Safety)

Step 8: Query PharmGKB -> Update Section 7 (Pharmacogenomics)

Step 9: Query DailyMed/Orange Book -> Update Section 8 (Regulatory)

Step 10: Query PubMed/literature -> Update Section 9 (Literature)

Step 11: Synthesize findings -> Update Executive Summary & Section 10

Step 12: Document all sources -> Update Section 11 (Data Sources)

Compound Disambiguation (Phase 1)

CRITICAL

Establish compound identity before any research.

Identifier Resolution Chain

1. PubChem_get_CID_by_compound_name(compound_name)

-> Extract: CID, canonical SMILES, formula

2. ChEMBL_search_compounds(query=drug_name)

-> Extract: ChEMBL ID, pref_name

3. DailyMed_search_spls(drug_name)

-> Extract: Set ID, NDC codes (if approved)

4. PharmGKB_search_drugs(query=drug_name)

-> Extract: PharmGKB ID (PA...)

Handle Naming Ambiguity

Issue

Example

Resolution

Salt forms

metformin vs metformin HCl

Note all CIDs; use parent compound

Isomers

omeprazole vs esomeprazole

Verify SMILES; separate entries if distinct

Prodrugs

enalapril vs enalaprilat

Document both; note conversion

Brand confusion

Different products same name

Clarify with user

Research Paths Summary

Each path has detailed tool chains and output examples in

REPORT_GUIDELINES.md

.

PATH 1: Chemical Properties & CMC

Tools

PubChem properties -> ADMET-AI physicochemical -> ADMET-AI solubility -> DailyMed chemistry/description

Output

Physicochemical table, Lipinski assessment, QED score, salt forms, formulation comparison

PATH 2: Mechanism & Targets

Tools

DailyMed MOA -> ChEMBL activities (NOT

ChEMBL_get_molecule_targets

) -> ChEMBL target details -> DGIdb -> PubChem bioactivity

Critical

Derive targets from activities filtered to pChEMBL >= 6.0. Avoid

ChEMBL_get_molecule_targets

.

Output

FDA MOA text, target table with UniProt/potency, selectivity profile

PATH 3: ADMET Properties

Tools

ADMET-AI (bioavailability, BBB, CYP, clearance, toxicity)

Fallback

DailyMed clinical_pharmacology + pharmacokinetics + drug_interactions

Critical

If ADMET-AI fails, automatically use fallback. Never leave Section 4 empty.

PATH 4: Clinical Trials

Tools

search_clinical_trials -> compute phase counts -> extract outcomes/AEs -> fda_pharmacogenomic_biomarkers

Critical

Section 5.2 must show actual counts by phase/status in table format.

PATH 5: Post-Marketing Safety

Tools

FAERS (reactions, seriousness, outcomes, deaths, age) + DailyMed (DDI, dosing, warnings)

Critical

Include FAERS date window, seriousness breakdown, and limitations paragraph.

PATH 6: Pharmacogenomics

Tools

PharmGKB (search -> details -> annotations -> guidelines)

Fallback

DailyMed pharmacogenomics section + PubMed literature

PATH 7: Regulatory & Patents

Tools

FDA Orange Book (search, approval history, exclusivity, patents, generics) + DailyMed (special populations via LOINC codes)

Note

US-only data; document EMA/PMDA limitation.

PATH 8: Real-World Evidence

Tools

ClinicalTrials.gov (OBSERVATIONAL studies) + PubMed (real-world, registry, surveillance)

PATH 9: Comparative Analysis

Tools

Abbreviated tool chains for each comparator + head-to-head trial search + PubMed meta-analyses FDA Label Core Fields For approved drugs, retrieve these DailyMed sections early (after getting set_id): Batch Sections Maps to Report Phase 1 mechanism_of_action, pharmacodynamics, chemistry Sections 2-3 Phase 2 clinical_pharmacology, pharmacokinetics, drug_interactions Sections 4, 6.5 Phase 3 warnings_and_cautions, adverse_reactions, dosage_and_administration Sections 6, 8.2 Phase 4 pharmacogenomics, clinical_studies, description, inactive_ingredients Sections 5, 7 Fallback Chains Primary Tool Fallback Use When PubChem_get_CID_by_compound_name ChEMBL_search_compounds Name not in PubChem ChEMBL_get_molecule_targets Use ChEMBL_search_activities instead Always avoid this tool ChEMBL_get_bioactivity_by_chemblid PubChem_get_bioactivity_summary_by_CID No ChEMBL ID DailyMed_search_spls PubChem_get_drug_label_info_by_CID DailyMed timeout PharmGKB_search_drugs DailyMed PGx sections + PubMed PharmGKB unavailable PharmGKB_get_dosing_guidelines DailyMed pharmacogenomics section PharmGKB API error FAERS_count_reactions_by_drug_event Document "FAERS unavailable" + use label AEs API error ADMETAI_ (all tools) DailyMed clinical_pharmacology + pharmacokinetics Invalid SMILES or API error Quick Reference: Tools by Use Case Use Case Primary Tool Fallback Evidence Name -> CID PubChem_get_CID_by_compound_name ChEMBL_search_compounds T1 Properties PubChem_get_compound_properties_by_CID ADMET-AI physicochemical T1/T2 FDA MOA DailyMed_get_spl_sections_by_setid (mechanism_of_action) - T1 Targets ChEMBL_search_activities -> ChEMBL_get_target DGIdb_get_drug_info T1 ADMET ADMETAI_predict_ (5 tools) DailyMed PK sections T2/T1 Trials search_clinical_trials - T1 Trial outcomes extract_clinical_trial_outcomes - T1 FAERS FAERS_count_reactions_by_drug_event Label adverse_reactions T1 Dose mods DailyMed_get_spl_sections_by_setid (dosage, warnings) - T1 PGx PharmGKB_search_drugs DailyMed PGx + PubMed T2/T1 Label DailyMed_search_spls PubChem_get_drug_label_info_by_CID T1 Literature PubMed_search_articles EuropePMC_search_articles Varies Regulatory FDA_OrangeBook_* tools DailyMed label data T1 See TOOLS_REFERENCE.md for the complete tool listing with parameters and input format requirements. Type Normalization Many tools require string inputs. Always convert IDs before API calls: ChEMBL IDs, PubMed IDs, NCT IDs: convert int -> str SMILES for ADMET-AI: pass as list ["SMILES_STRING"] FAERS drug names: use UPPERCASE (e.g., "METFORMIN" ) ChEMBL IDs: full format "CHEMBL1431" not "1431" PharmGKB IDs: PA prefix "PA450657" not "450657" Common Use Cases Use Case Primary Sections Light Sections Approved Drug Profile All 11 sections None Investigational Compound 1, 2, 3, 4, 9 5, 6, 7, 8 Safety Review 1, 5, 6, 7, 9 2, 3, 4, 8 ADMET Assessment 1, 2, 4 3, 5, 6, 7, 8, 9 Clinical Development Landscape 1, 5, 9 2, 3, 4, 6, 7, 8 Always maintain all section headers but adjust depth based on query focus and data availability. When NOT to Use This Skill Target research -> Use target-intelligence-gatherer skill Disease research -> Use disease-research skill Literature-only -> Use literature-deep-research skill Single property lookup -> Call tool directly Structure similarity search -> Use PubChem_search_compounds_by_similarity directly Additional Resources Report template : REPORT_TEMPLATE.md - Initial file template, citation format, evidence grading, scorecard, audit template Report guidelines : REPORT_GUIDELINES.md - Detailed section-by-section instructions with output examples Tool reference : TOOLS_REFERENCE.md - Complete tool listing with parameters and input formats Verification checklist : CHECKLIST.md - Section-by-section pre-delivery verification Examples : EXAMPLES.md - Detailed workflow examples for different use cases