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XL01126 | XL01126 : Degrader (PROTAC) of LRRK2
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
LRRK2 (Mutant:WT, G2019S)
  • IC50:12.4 nM
  • DC50:32 nM
  • DC50:14 nM
  • EC50:54 nM
  • EC50:15 nM
  • IC50:1.4 µM
Degrader (PROTAC)
up to 300 nM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
To assess the degradation selectivity of XL01126 and identify potential off-targets at the proteome ...

Potency
Cellular
In Vitro

LRRK2 (Mutant:WT, G2019S)

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/jacs.2c05499

In Vivo Validations

Mouse
Dose: 5 mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.52 h
Systemic clearance: 0.208 L/h/Kg
Area Under the Curve:: 23981 h*ng/mL
Volume of Distribution at Steady-State: 0.511 L/Kg

DOI Reference: 10.1021/jacs.2c05499

Dose: 30 mg/Kg
Route of delivery: Intraperitoneal
Plasma half life: 5.2 h
Cmax: 7700 ng/mL
Tmax: 0.25 h
Area Under the Curve:: 64068 h*mg/mL
Bioavailability: 29.2%

DOI Reference: 10.1021/jacs.2c05499

Dose: 30 mg/Kg
Route of delivery: Oral
Plasma half life: 21.9 h
Cmax: 3620 ng/mL
Tmax: 2 h
Area Under the Curve:: 109 h*ng/mL
Bioavailability: 15%
Target engagement assay: First-time report of a VHL-based PROTAC that is both orally bioavailable (F = 15%) and BBB-permeable

DOI Reference: 10.1021/jacs.2c05499

Negative Control Compounds

CANSAR3935386
Notes: Cis-XL01126 showed no degradation of WT LRRK2 and G2019S LRRK2 and 7-fold less potency than XL01126 in inhibiting Rab10 phosphorylation.

Chemical Information

Molecular Formula C50H64ClFN10O6S2
SMILEs CNc1nc(Nc2ccc(C(=O)N3CCN(CC4CCC(CSC(C)(C)[C@H](NC(=O)C5(F)CC5)C(=O)N5C[C@H](O)C[C@H]5C(=O)NCc5ccc(-c6scnc6C)cc5)CC4)CC3)cc2OC)ncc1Cl
InChI InChI=1S/C50H64ClFN10O6S2/c1-30-41(69-29-56-30)34-12-10-31(11-13-34)24-54-44(64)39-23-36(63)27-62(39)46(66)42(58-47(67)50(52)16-17-50)49(2,3)70-28-33-8-6-32(7-9-33)26-60-18-20-61(21-19-60)45(65)35-14-15-38(40(22-35)68-5)57-48-55-25-37(51)43(53-4)59-48/h10-15,22,25,29,32-33,36,39,42,63H,6-9,16-21,23-24,26-28H2,1-5H3,(H,54,64)(H,58,67)(H2,53,55,57,59)/t32?,33?,36-,39+,42-/m1/s1
Molecular weight 1018.41 Da
AlogP 0.0
HBond acceptors 16
HBond donors 5
Atoms 134

Vendors

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Expert Reviews

by SERP+
(on 6 Feb 2026 )
Cellular Use Rating
In Model Organisms
XL01126 is a well-validated, selective degrader with demonstrated ternary complex formation and target engagement, supported by generally high-quality data and a clear phenotypic effect.
by SERP+
(on 6 Feb 2026 )
Cellular Use Rating
In Model Organisms
XL01126 is a highly recommend compound for degradation of LRRK2 alongside its negative control compound cis-XL01126. Care should be taken above 500 nM due to solubility issues with the compound.
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria