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ATC161 exposure and alpha-synuclein aggregate degradation

A reduced AUTOTAC PK/PD model linking ATC161 exposure to concentration-dependent degradation and recovery of alpha-synuclein aggregates.

Targeted degradation of ⍺-synuclein aggregates in Parkinson’s disease using the AUTOTAC technology ↗

Molecular Neurodegeneration

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MODEL IN MOTION 18 sec

How does ATC161 exposure connect to the modeled aggregate response?

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Starting example

PO 20 mg/kg first-order PK/degradation

PO 20 mg/kg first-order PK/degradation

How does ATC161 exposure control the time course and recovery of alpha-synuclein aggregate reduction? Explore this biological starting configuration through Plasma ATC161, ATC161 molar concentration, Aggregate degradation effect, Alpha-synuclein aggregate fraction.

0–24 h

Scenario details

PO 20 mg/kg first-order PK/degradation

How does ATC161 exposure control the time course and recovery of alpha-synuclein aggregate reduction? Explore this biological starting configuration through Plasma ATC161, ATC161 molar concentration, Aggregate degradation effect, Alpha-synuclein aggregate fraction.

Readouts

Plasma ATC161 concentration · ng/mL
Plasma ATC161 concentration over the selected simulation window.
ATC161 molar concentration · Unit unavailable
ATC161 molar concentration over the selected simulation window.
Aggregate degradation effect · Unit unavailable
Aggregate degradation effect over the selected simulation window.
Alpha synuclein aggregate fraction · dimensionless
Alpha synuclein aggregate fraction over the selected simulation window.

Study purpose

  • How does ATC161 exposure control the time course and recovery of alpha-synuclein aggregate reduction?

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

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Model parameter

Oral ATC161 half-life controlling the time required for the corresponding quantity to decrease by half.

h

Suggested: 1.85–5.55. You can explore beyond this range.

3.7 → —

Half-maximal degradation concentration at which the corresponding modeled effect reaches half of its maximum.

nM

Suggested: 50–150. You can explore beyond this range.

100 → —

Aggregate degradation rate governing loss, degradation, or removal in the modeled biological process.

1/h

Suggested: 0.02–0.06. You can explore beyond this range.

0.04 → —

Aggregate recovery rate coefficient used by the released system of model equations.

1/h

Suggested: 5.00e-4–0.0015. You can explore beyond this range.

0.001 → —

Baseline aggregate fraction represented as a dimensionless fraction in the released equations.

—

Suggested: 0.5–1.5. You can explore beyond this range.

1 → —
Simulation time
h
h
24 → 168

Time between reported samples.

h
0.1 → 1

2 changes · Variation 1

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Biology

A scenario initializes plasma ATC161, which declines by first-order loss and generates a saturable aggregate-degradation drive. The aggregate fraction falls through exposure-driven degradation and recovers toward its baseline, while ATC161 exposure accumulates.

How does ATC161 exposure shift alpha-synuclein aggregate degradation and recovery?A scenario initializes plasma ATC161, which declines by first-order loss and generates a saturable aggregate-degradation drive. The aggregate fraction falls through exposure-driven degradation and recovers toward its baseline, while ATC161 exposure accumulates.BIOLOGY OVERVIEWHow does ATC161 exposure shift alpha-synuclein aggregate degradation and recovery?Plasma ATC161: Scenario-initialized exposurePlasma ATC161Scenario-initialized exposureATC161 loss: Half-life-driven decayATC161 lossHalf-life-driven decayDegradation drive: Saturable concentration effectDegradation driveSaturable concentration effectAggregate fraction: Alpha-synuclein aggregate stateAggregate fractionAlpha-synuclein aggregatestateBaseline recovery: Restores aggregate fractionBaseline recoveryRestores aggregate fractionCumulative exposure: ATC161 concentration integralCumulativeexposureATC161 concentration integralPRIMARY READOUTSPlasma ATC161Plasma ATC161ATC161 concentrationATC161 concentrationDegradation effectDegradation effectAggregate fractionAggregate fraction

Solid arrows show modeled movement or change; two-headed arrows show reversible exchange; dashed arrows show modulation without material transfer.

Model scope: Oral absorption, brain distribution, p62 recruitment, autophagosome or lysosome states, ternary-complex binding, aggregate species, and neuronal outcomes are not represented.

Modeled relationships (6)
  • Plasma ATC161 → ATC161 loss: first-order (loss)
  • Plasma ATC161 → Degradation drive: saturable effect (modulation)
  • Degradation drive → Aggregate fraction: aggregate loss (loss)
  • Aggregate fraction → Baseline recovery: baseline deficit (modulation)
  • Baseline recovery → Aggregate fraction: restoration (production)
  • Plasma ATC161 → Cumulative exposure: integrates C (production)

Modeled relationships: Plasma ATC161 to ATC161 loss: first-order (loss); Plasma ATC161 to Degradation drive: saturable effect (modulation); Degradation drive to Aggregate fraction: aggregate loss (loss); Aggregate fraction to Baseline recovery: baseline deficit (modulation); Baseline recovery to Aggregate fraction: restoration (production); Plasma ATC161 to Cumulative exposure: integrates C (production).

Primary readouts: Plasma ATC161; ATC161 concentration; Degradation effect; Aggregate fraction.

Model details

6 parameters · 3 states · 3 equations · 8 derived outputs

Classification & API access
Therapeutic
ATC161
Modality
Targeted protein degrader
Target
alpha-synuclein aggregates, SNCA aggregates, p62, SQSTM1
Disease / scope
Preclinical Parkinson disease and synucleinopathy models
ParameterDefaultUnitDescription
Aggregate degradation rateaggregate_degradation_k_h0.041/hAggregate degradation rate governing loss, degradation, or removal in the modeled biological process.
Aggregate recovery rateaggregate_recovery_k_h0.0011/hAggregate recovery rate coefficient used by the released system of model equations.
ATC161 mw gatc161_mw_g_mol624.274823533379g/molATC161 mw g coefficient used by the released system of model equations.
Oral ATC161 half-lifeatc161_po_half_life_h3.7hOral ATC161 half-life controlling the time required for the corresponding quantity to decrease by half.
Baseline aggregate fractionbaseline_aggregate_fraction1—Baseline aggregate fraction represented as a dimensionless fraction in the released equations.
Half-maximal degradation concentrationdc50_nM100nMHalf-maximal degradation concentration at which the corresponding modeled effect reaches half of its maximum.

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