| DC58063 |
HG106
|
HG106 is a potent SLC7A11 inhibitor and enhances ROS generation, ER stress, and ultimately growth arrest specifically in KRAS-mutant lung adenocarcinoma (LUAD). |
| DC74365 |
RMC-4998
|
RMC-4998 (RMC4998) is a tricomplex inhibitor that targets the active state or GTP-bound state of KRAS G12C, selectively inhibits the proliferation of KRASG12C mutant cells with mean IC50 of 0.28 nM. |
| DC70730 |
Ras binder 2C07
|
Ras binder 2C07 is a switch-II binding ligand which binds Ras GDP and GTP states. |
| DC70578 |
LY-3537982
|
LY-3537982 (LY3537982) is a highly selective and potent KRAS-G12C inhibitor, selectively inhibits growth of KRAS G12C mutant cells (IC50=1-60 nM).LY-3537982 does not inhibit growth of KRAS G12S/G13C/G12D mutant cells and WT KRAS cells (CI50>10 uM).LY-3537982 displays high selectivity for proteome-wide cysteine residues was evaluated using competitive chemical proteomics (8866 peptides).LY3537982 inhibits the growth of subcutaneous EL3187 NSCLC PDX tumors in nude mice in a dose dependent manner.LY3537982 demonstrates robust tumor regression in combination with other agents in KRAS G12C in vivo models.LY3537982 is a promising KRAS G12C inhibitor predicted to deliver >90% KRAS G12C target occupancy in the clinic. |
| DC70535 |
KAL-21404358
|
KAL-21404358 (KAL21404358) is a small-molecule, allosteric inhibitor of K-Ras(G12D), binds to K-Ras(G12D) P110 site with KD of 88 uM in MST assay;
KAL-21404358 disrupts the K-RasG12D-B-Raf interaction using a NanoBiT split luciferase assay, and to impair the Raf-MEK-ERK and the PI3K-AKT signaling pathways.
KAL-21404358 exhibited specificity for K-RasG12D over K-RasWT, H-RasWT, Rap1a, R-Ras and R-Ras2. |
| DC70371 |
DW0254
|
DW0254 (DW-0254,DW 0254) is a small molecules capable of inhibiting RAS-related C3 botulinum toxin substrate (RAC) small GTPase activation in ALL cell lines, directly binds to the hydrophobic pocket of PDE6D (Kd=436 nM, ITC), a RAS chaperone protein.DW0254 demonstrated dose-dependent RAC inhibition, arrest of proliferation and induced apoptosis in human leukemic cell lines (RS4;11 IC50=1.5-1.8 uM), also showed promising anti-leukemic activity in RAS-mutated cells (CCRF-CEM NRAS G12D, IC50=3.3-4.2 uM).DW0254 disrupted the interaction between PDE6D and RAS, disturbing RAS subcellular localization.DW0254 demonstrated anti-leukemic activity, decreased tumor progression in a murine xenograft model. |
| DC70046 |
MRTX 0902
|
MRTX0902 is a potent SOS1 inhibitor with an IC50 of 46 nM (WO2021127429A1; Example 12-10). |
| DC47351 |
ASP2453
|
ASP2453 is a potent, selective and covalent KRAS G12C inhibitor. ASP2453 inhibits the Son of Sevenless (SOS)-mediated interaction between KRAS G12C and Raf with an IC50 value of 40 nM. |
| DC47210 |
JDQ-443
|
JDQ443 (example 1a) is a covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1). |
| DC46924 |
MRTX849 acid
|
MRTX849 acid, a derivative of MRTX849, can be used in the synthesis of PROTAC LC-2. LC-2 is a potent and first-in-class PROTAC capable of degrading endogenous KRAS G12C (DC50s between 0.25 and 0.76 μM).
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