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Target-Gated Cargo QSP

Mechanistic QSP model for an intravenously dosed biologic designed to remain closed systemically and open after engaging a tumor-enriched gate. It connects three-compartment disposition, reversible cargo accessibility, tumor retention, and central-versus-tumor receptor occupancy using transparent UBI-authored equations and synthetic exploratory assumptions.

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MODEL IN MOTION 18 sec

How does removing the tumor gate change receptor occupancy?

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Balanced gate, 30 nmol IV

Nominal synthetic probe intended to produce low-to-moderate systemic cargo-receptor occupancy and substantially higher tumor occupancy.

0–336 hour

Scenario details

Balanced gate, 30 nmol IV

Nominal synthetic probe intended to produce low-to-moderate systemic cargo-receptor occupancy and substantially higher tumor occupancy.

Readouts

Systemic cargo receptor occupancy · %
Central occupancy predicted from assumed receptor capacity and synthetic kinetic priors; not a safety threshold or clinical biomarker.
Tumor cargo receptor occupancy · %
Tumor occupancy predicted from gate retention, opening, and cargo-receptor engagement; not a clinical efficacy claim.
Tumor gate target occupancy · %
Fraction of the assumed accessible gate capacity occupied by construct.
Total modeled construct · nmol
Mass ledger across free, gate-bound, and receptor-bound model states.

Study purpose

  • Can the assumed gate create a tumor-versus-systemic receptor-occupancy window?
  • How much tumor gate capacity is occupied during the two-week probe?

Assumptions

  • The 30 nmol input is illustrative.
  • Values are synthetic and uncalibrated.

Inputs changed since the displayed result. Run to update the comparison.

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Gating

First-order opening rate when construct is not bound to tumor gate target.

1/h

Suggested: 0.002–0.006. You can explore beyond this range.

0.004 → —
Gate target

Total accessible binding capacity of the generic tumor-enriched gate target.

nmol

Suggested: 0.075–0.225. You can explore beyond this range.

0.15 → —

Dissociation rate of gate-bound open construct.

1/h

Suggested: 0.015–0.045. You can explore beyond this range.

0.03 → —
Cargo receptor

Association rate shared by free-open and gate-retained open construct.

1/(nM·h)

Suggested: 0.2–0.6. You can explore beyond this range.

0.4 → —
Distribution

Symmetric concentration-driven exchange clearance between central plasma and accessible tumor space.

L/h

Suggested: 1.00e-5–3.00e-5. You can explore beyond this range.

0.00002 → —
Simulation time
h
h
336 → 168

Time between reported samples.

h
6 → 1

2 changes · Variation 1

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Biology

An 11-state, three-compartment model follows closed and open construct in central plasma, peripheral tissue, and tumor. Central open construct can bind a finite cargo-receptor capacity. In tumor, free closed or open construct can bind a finite gate capacity; gate-bound construct switches between closed and open states, and open free or gate-retained construct can engage tumor cargo receptor. The main outputs are central and tumor construct concentrations, receptor occupancy, and tumor gate occupancy.

An 11-state, three-compartment model follows closed and open construct in central plasma, peripheral tissue, and tumor. Central open construct can bind a finite cargo-receptor capacity. In tumor, free closed or open construct can bind a finite gate capacity; gate-bound construct switches between closed and open states, and open free or gate-retained construct can engage tumor cargo receptor. The main outputs are central and tumor construct concentrations, receptor occupancy, and tumor gate occupancy.

Model details

21 parameters · 11 states · 11 equations · 19 derived outputs

Classification & API access
Therapeutic
generic target-gated cargo
Modality
Other biologic or therapeutic modality
Target
configurable tumor gate target, configurable cargo receptor
Disease / scope
Solid tumors with an accessible tumor-enriched gate target
ParameterDefaultUnitDescription
Accessible tumor gate target capacitygate_capacity_tumor_nmol0.15nmolTotal accessible binding capacity of the generic tumor-enriched gate target.
Central peripheral exchange clearanceintercompartmental_clearance_peripheral_L_h0.012L/hSymmetric concentration-driven exchange clearance between central and peripheral spaces.
Central tumor exchange clearanceintercompartmental_clearance_tumor_L_h0.00002L/hSymmetric concentration-driven exchange clearance between central plasma and accessible tumor space.
Background closing ratek_close_background_h0.251/hFirst-order closing rate when construct is not bound to tumor gate target.
Gate bound closing ratek_close_gate_bound_h0.031/hEffective closing rate while construct remains gate-bound.
Cargo receptor complex internalizationk_internalize_receptor_complex_h0.061/hEffective loss rate for receptor-engaged construct; receptor capacity is assumed homeostatically replenished.
Gate bound construct lossk_loss_gate_bound_h0.0021/hSlow effective loss of gate-bound construct; gate-target capacity is assumed replenished.
Background opening ratek_open_background_h0.0041/hFirst-order opening rate when construct is not bound to tumor gate target.
Gate assisted opening ratek_open_gate_bound_h0.31/hEffective opening rate after construct binds the tumor gate target.
Cargo receptor dissociationkoff_cargo_receptor_h0.251/hDissociation rate shared by central and tumor cargo-receptor complexes.
Closed construct gate dissociationkoff_gate_closed_h0.251/hDissociation rate of gate-bound closed construct.
Open construct gate dissociationkoff_gate_open_h0.031/hDissociation rate of gate-bound open construct.
Cargo receptor associationkon_cargo_receptor_per_nM_h0.41/(nM·h)Association rate shared by free-open and gate-retained open construct.
Closed construct gate associationkon_gate_closed_per_nM_h0.081/(nM·h)Association rate between closed construct and free tumor gate target.
Open construct gate associationkon_gate_open_per_nM_h0.121/(nM·h)Association rate between open construct and free tumor gate target.
Central cargo receptor capacityreceptor_capacity_central_nmol0.015nmolHomeostatically maintained central capacity available for cargo engagement.
Tumor cargo receptor capacityreceptor_capacity_tumor_nmol0.0015nmolHomeostatically maintained tumor capacity available for cargo engagement.
Central construct clearancesystemic_clearance_L_h0.005L/hLinear clearance applied to free closed and open central construct.
Central plasma volumevolume_central_L3.5LNominal adult central volume used for exploratory concentration conversion.
Peripheral accessible volumevolume_peripheral_L10.5LNominal accessible peripheral volume.
Tumor extracellular accessible volumevolume_tumor_L0.004LNominal accessible tumor extracellular volume.

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