Table 3 Potential molecules targeting RAS directly in preclinical or clinical trials
From: Emerging strategies to target RAS signaling in human cancer therapy
Target RAS directly | ||||||
|---|---|---|---|---|---|---|
DACI | HEK-293Â T | KRAS Mut | Pre | NA | Inhibit SOS-Ras interaction | [88] |
BAY-293 | NSCLC cell lines | KRAS G12C | Pre | NA | Inhibit SOS-Ras interaction | [90] |
BI 3406 | Cell lines | KRAS Mut lnc | Pre | NA | Inhibit SOS-Ras interaction | [226] |
BI 1701963 | Solid tumors | KRAS Mut | Clinical I | Recruiting | Inhibit SOS-Ras interaction Single agent or comb Trametinib | NCT04111458 |
SML-10-70-1 | NSCLC cell lines | KRAS G12C | Pre | NA | Inhibit GN binding | |
KRA-533 | NSCLC xenografts | KRAS K117A | Pre | NA | Inhibit GN binding | [103] |
Rigosertib | PanIN; CRC NSCLC xenograft models | KRAS G12D G13D G12S | Pre | NA | Inhibit Ras effectors interaction | [94] |
Kobe2602 Kobe0065 | CRC xenograft models | KRAS G12V | Pre | NA | Inhibit Ras effectors interaction | [104] |
ARS853 | NSCLC cell lines | KRAS G12C | Pre | NA | Target inactive Ras | |
ARS1620 | NSCLC xenograft models | KRAS G12C | Pre | NA | Target inactive Ras | [93] |
LY3537982 | NSCLC PDX | KRAS G12C | Pre | NA | Target inactive Ras | [227] |
MRTX1133 | PDAC xenograft | KRAS G12D | Pre | NA | Target inactive Ras | [100] |
2C07 | NA | HRAS M72C | Pre | NA | Target inactive Ras | [96] |
BI-2852 | NCI-H358 cell | KRAS G12D | Pre | NA | Target surface pocket of RAS | [97] |
AMG510 | Mut solid tumors | KRAS G12C | Clinical I/II | Recruiting | Target inactive Ras Single agent | NCT03600883() (CodeBreaK 100) |
| Â | Mut solid tumors | KRAS G12C | Clinical I | Recruiting | Target inactive Ras Single agent | NCT04380753 (CodeBreaK105) |
| Â | NSCLC | KRAS G12C | Clinical III | Not yet recruiting | Target inactive Ras Compare with Docetaxel | NCT04303780 (CodeBreaK200) |
|  | Advanced solid tumors | KRAS G12C | Clinical Ib/II | Recruiting | Targeting inactive Ras Comb with MEKi, PD1i, PDL1i, SHP2i Pan-ErbBi, EGFRi + chemotherapy | NCT04185883 (CodeBreaK101) |
MRTX849 | Advanced solid tumors | KRAS G12C | Clinical I/II | Recruiting | Target inactive Ras Single agent and comb With Pembrolizumab/Cetuximab/Afatinib | NCT03785249 |
| Â | Advanced solid tumors | KRAS G12C | Clinical I/II | Recruiting | Comb with TNO155 | NCT04330664 |
LY3499446 | Solid tumors NSCLC, CRC | KRAS G12C | Clinical I/II | Terminated | Target inactive Ras Single agent or comb Single agent or comb with Abemaciclib/Cetuximab Erlotinib/Docetaxel | NCT04165031 |
JNJ-74699157 | Solid tumors NSCLC, CRC Neoplasms | KRAS G12C | Clinical I | Completed | Target inactive Ras | NCT04006301 |