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-293 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 | [101, 102] |
| 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 | [91, 92] |
| 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) |
| Mut solid tumors | KRAS G12C | Clinical I | Recruiting |
Target inactive Ras Single agent |
NCT04380753 (CodeBreaK105) | |
| 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 |
| 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 |