BI-2852
BI-2852 Basic information
- Product Name:
- BI-2852
- Synonyms:
-
- (S)-5-hydroxy-3-(2-(((1-((1-methyl-1H-imidazol-4-yl)methyl)-1H-indol-6-yl)methylamino)methyl)-1H-indol-3-yl)isoindolin-1-one
- BI-2852
- 1H-Isoindol-1-one, 2,3-dihydro-5-hydroxy-3-[2-[[[[1-[(1-methyl-1H-imidazol-4-yl)methyl]-1H-indol-6-yl]methyl]amino]methyl]-1H-indol-3-yl]-, (3S)-
- BI-2852,Ras,inhibit,BI 2852,Inhibitor,BI2852
- BI-2852, 10 mM in DMSO
- CAS:
- 2375482-51-0
- MF:
- C31H28N6O2
- MW:
- 516.59
- Mol File:
- 2375482-51-0.mol
BI-2852 Chemical Properties
- Boiling point:
- 906.5±65.0 °C(Predicted)
- Density
- 1.41±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO:77.5(Max Conc. mg/mL);150.02(Max Conc. mM)
Ethanol:23.0(Max Conc. mg/mL);44.52(Max Conc. mM) - form
- Solid
- pka
- 8.95±0.40(Predicted)
- color
- Off-white to light yellow
BI-2852 Usage And Synthesis
Uses
BI-2852 is a KRAS inhibitor for the switch I/II pocket (SI/II-pocket) by structure-based agent design with nanomolar affinity. BI-2852 is mechanistically distinct from covalent KRASG12C inhibitor (binds to switch II pocket) and binds ten-fold more strongly to active KRASG12D versus KRASwt (740 nM vs 7.5 μM). BI-2852 blocks GEF, GAP, and effector interactions with KRAS, leading to inhibition of downstream signaling and an antiproliferative effect in KRAS mutant cells.
Biological Activity
BI-2852 is a switch SI/II pocket KRAS inhibitor with nanomolar affinity through structure-based drug design. It is mechanistically distinct from covalent KRASG12C inhibitors (binding switch II), binding to active KRASG12D 10-fold more strongly than KRAS wt (740 nM vs 7.5 μM). BI-2852 blocks GEF, GAP and effector interactions with KRAS, resulting in inhibition of downstream signaling and antiproliferative effects in KRAS mutant cells.
in vitro
BI-2852 (Compound 1) (10 nM-10 μM; 2 hours) shows a dose-dependent pERK modulation and antiproliferative effect at EC 50 s of 5.8 μM and 6.7 μM in soft agar and low serum conditions in NCI-H358 cells.
target
| KRAS(G12C) 450 nM (IC 50 ) | KRAS(G12C) < p> 750 nM (Kd) |
IC 50
KRAS(G12C): 450 nM (IC50); KRAS(G12C): 750 nM (Kd)
References
[1] Kessler D, et al. Drugging an undruggable pocket on KRAS. Proc Natl Acad Sci U S A. 2019 Aug 6; 116(32):15823-15829. DOI:10.1073/pnas.1904529116
[2] Dirk Kessler, et al. Drugging all RAS isoforms with one pocket. FUTURE MEDICINAL CHEMISTRY
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