KIRHub: Kinase Inhibitor Repurposing Hub

1. Choose a module: Use the three large buttons on the top of the app to open either Wild-Type Kinases, Mutant Kinases, or Cancer Lineages.
2. Search/select: Start typing a kinase/mutation; the list filters dynamically. Exact matches are best (e.g., ABL1; BRAF(V600D); FGFR1OP/FGFR1).
3. Review ranked drugs: The table shows the top candidates by % inhibition (and selectivity via Gini Scores). Use column headers to sort; use the download button to export results.
4. Open visuals: Radar plots display per-drug inhibition distribution; KISS vs Inhibition scatters highlight drugs balancing on-target inhibition and off-target burden.
5. Dual targets (optional): Add a second kinase/mutation to see drugs that score highly for both (intersection of top candidates).

Goal: Prioritize inhibitors for a wild-type kinase (or dual kinase or paralog pair).

1. Select a kinase (e.g., P38A/MAPK14, ABL2/ARG, AURKA).
2. Optionally select a second kinase/paralog to co-prioritize.
3. Review ranked drugs by % inhibition and Gini. Download table as CSV; download Radar/KISS figures as PNG.
4. KISS vs Inhibition: Points in the upper-right (higher KISS and higher % inhibition) are favorable.

Goal: Find clinically approved inhibitors with high inhibition for a selected mutant kinase (optionally a combination).

1. Select a mutant (e.g., BRAF(V599E), ALK/TFG Fusion, FGFR1(V561M)).
2. Optionally select a second mutant to prioritize drugs effective on both.
3. Interpret the table: Inhibition (%) is computed as 100 − residual activity at 1 μM. Gini approximates selectivity (higher is more selective).
4. Use the download button to export ranked results (CSV).
5. Open Radar Plot(s) for a quick visual of drug inhibition patterns across candidates.

Goal: See where a kinase is essential across primary and nested lineages (DepMap-derived). “Essential” is a kinase that has a gene effect score of less than -0.5 in a particular cancer lineage and its sub-lineages. These gene effect scores data are obtained from the DepMap Portal website.

1. Select a kinase; the table lists lineage counts and percentages where it’s essential.
2. Use the bar chart to compare total essential counts by Lineage 1.
3. Export the table or bar chart (CSV/PNG).

These files describe assay setup for each kinase used in biochemical profiling: whether the full-length protein or a domain fragment (with residue range when available) was assayed; the expression system (e.g., baculovirus/Sf21) and affinity tag (e.g., His/GST); and the general substrate (e.g., Abltide, Crosstide, Casein+Mn, etc.). This context addresses concerns about regulatory domains affecting activity/folding and substrate choice shaping readouts.

• Inhibition (%): Higher is better and equals 100 − residual activity at 1 μM.
• Radar Plot: Each spoke is a candidate drug; longer spokes = greater inhibition. The concentric inhibition guides (≤25/50/75/100%) help judge magnitude quickly.
• KISS Score: Balances on-target effect (geometric-mean inhibition on the chosen kinase set) against off-target burden. Use alongside % inhibition to find selective, potent options.
• Gini Score: Higher score suggests more selective inhibition profile across kinases.

If you have a kinase inhibition dataset or compound screen that you would like to see included in KIRHub, please follow the steps below.

Step 1 — Validate Dataset Format

Upload a .csv or .xlsx file to check whether it matches the required KIRHub format. No data are stored or analyzed automatically.

Step 2 — Contact the Authors to Submit a New Dataset

Once your file passes validation, please submit it by contacting the authors directly either via email or using the citation link below. Include a short description of the dataset and its source.

Citation:

Required File Format

• Column 1: Compound (aliases in parentheses allowed; e.g. Lapatinib (GW572016))
• Column 2: CAS (or other unique compound identifier; e.g. 231277-92-2)
• Column 3: Dose (e.g. 0.5, 1uM; no spaces) in uM only
• Columns 4+: HGNC kinase names (all caps, no whitespace; e.g. AURKA, MAPK1, EGFR). Same for mutants; eg. FGFR3(V555M), EGFR(D746_750_C797S)
• Values: Numeric residual activity values (0–100) or NA only, where 0 indicates complete inhibition and 100 indicates no inhibition relative to control.
• Characters: Standard US keyboard characters only (e.g. use u instead of Greek μ)

• Search strategy: Prefer exact names first (e.g., P38A/MAPK14) before abbreviations. For variants, include mutation (e.g., BRAF(V599E)) or '/' fusion tag.
• Dual-target logic: By default, the app intersects top-ranked lists per target; if the intersection seems too strict, try each target separately to see near-misses.
• Units: Inhibition values are computed at 1 μM experimental dose.
• Downloads: Look for the Download Table and Download Plot buttons below each output.
• Empty/NA results: If no values appear, try a different spelling or a broader kinase family member (paralog).