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ACBI3 | ACBI3 : panKRAS Degrader (PROTAC)
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
KRAS (Mutant:pan variants)
  • Kd:6 nM
  • DC50:2 nM
  • DC50:7 nM
  • IC50:5 nM
  • IC50:15 nM
Degrader (PROTAC)
up to 100 nM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
The degradation selectivity of ACBI3 was assessed by whole cell proteomics MS analysis of GP2d cells ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
Proliferation inhibition data was assessed for 240 cancer cell lines for ACBI3

Potency
Cellular
In Vitro

KRAS (Mutant:pan variants)

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? No

DOI Reference: 10.1126/science.adm8684

In Vivo Validations

Mouse
Dose: 2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 0.67 h MRT
Systemic clearance: 39 mL/L*h
Area Under the Curve:: 857 nmol/L*h
Volume of Distribution at Steady-State: 1.6 L/Kg

DOI Reference: 10.1126/science.adm8684

Dose: 30 mg/Kg
Route of delivery: Subcutaneous
Cmax: 70 nM
Tmax: 2 h
Area Under the Curve:: 9040 nM/L*h

DOI Reference: 10.1126/science.adm8684

Negative Control Compounds

cis-ACBI3
Notes: Cis-ACBI3 is a stereoisomer of ACBI3 displaying deficient binding to VHL, and hence can be used as a negative control for KRAS degradation. Note, however, that cis-ACBI3 still binds KRAS and acts as a non-covalent KRAS inhibitor
SMILES: CC(C)[C@H](N1C=C(OCCCCN2CCCN([C@@H](C)C2)C2=NC(=CC=N2)C2=NOC(=N2)[C@@]2(C)CCCC3=C2C(C#N)=C(N)S3)N=N1)C(=O)N1C[C@@H](O)C[C@H]1C(=O)N[C@@H](CO)C1=CC=C(C=C1)C1=C(C)N=CS1

Chemical Information

Molecular Formula C50H62N14O6S2
SMILEs Cc1ncsc1-c1ccc([C@H](CO)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@H](C(C)C)n2cc(OCCCCN3CCCN(c4nccc(-c5noc([C@@]6(C)CCCc7sc(N)c(C#N)c76)n5)n4)[C@@H](C)C3)nn2)cc1
InChI InChI=1S/C50H62N14O6S2/c1-29(2)42(47(68)63-25-34(66)22-38(63)46(67)55-37(27-65)32-11-13-33(14-12-32)43-31(4)54-28-71-43)64-26-40(58-60-64)69-21-7-6-18-61-19-9-20-62(30(3)24-61)49-53-17-15-36(56-49)45-57-48(70-59-45)50(5)16-8-10-39-41(50)35(23-51)44(52)72-39/h11-15,17,26,28-30,34,37-38,42,65-66H,6-10,16,18-22,24-25,27,52H2,1-5H3,(H,55,67)/t30-,34+,37-,38-,42-,50-/m0/s1
Molecular weight 1018.44 Da
AlogP 0.0
HBond acceptors 20
HBond donors 5
Atoms 134

Expert Reviews

by SERP
(on 10 Oct 2025 )
Cellular Use Rating
In Model Organisms
ACBI3 is a very well characterized pan KRAS degrader, developed by leaders in the field of targeted protein degradation. Sparing HRAS and NRAS, this probe is useful for addressing specific KRAS mutants...
by SERP
(on 13 Oct 2025 )
Cellular Use Rating
In Model Organisms
While there is strong evidence of KRAS degradation, ternary complex, and pathway inhibition, data supporting direct cellular engagement of KRAS was not provided.
by SERP+
(on 6 Feb 2026 )
Cellular Use Rating
In Model Organisms
Highly selective pan-KRAS degrader shown through proteomics data, broadly active across cancer cell lines containing mutant KRAS versus wild-type. High efflux could be mitigated with the use of zosuquidar....
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