Loading
MRTX1133 was the first potent chemical tool against KRAS G12D, and proved the mutation could be drugged even though it lacks the reactive handle G12C has.
MRTX1133 is a non-covalent small molecule that binds the switch-II pocket of KRAS G12D and inhibits both the ON and OFF states; because G12D lacks the reactive cysteine that G12C drugs exploit, it needed a different, high-affinity chemistry. It was the first potent chemical tool against KRAS G12D, a common driver in pancreatic cancer, and it produced striking regressions in pancreatic patient-derived xenograft models (Nature 2023). Poor oral bioavailability forced intravenous dosing in the phase 1/2 trial, and development slowed after Bristol Myers Squibb acquired Mirati, while covalent RAS(ON) competitors advanced. Its lasting importance is as proof that G12D can be drugged, opening the door to oral and pan-RAS successors. For a newcomer, it showed that a KRAS mutation once thought undruggable can be hit.
Non-covalent binder to the switch-II pocket of KRAS G12D, inhibiting both ON and OFF states. Connects to KRAS.
1.MRTX1133 slips into a pocket on KRAS.
| Date | Deal | Type | Upfront | Total | Source |
|---|---|---|---|---|---|
| 2023-10-08 | Mirati Therapeutics to Bristol Myers Squibb Adagrasib (Krazati) and MRTX1133 (KRAS G12D) | Acquisition | not disclosed | $4.8bn (plus a contingent value right of up to $1.0bn) | source |
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Query for this drug: (TITLE:"MRTX1133" OR ABSTRACT:"MRTX1133") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MRTX1133, not a curated reading list.
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, KRAS & RAS inhibitors, The undruggable drivers.
Shares Pancreatic cancer: the failed and stopped programmes and why, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, The undruggable drivers, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares KRAS & RAS inhibitors, The undruggable drivers, RAS / RAF / MEK / ERK (MAPK), KRAS.
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, KRAS & RAS inhibitors, The undruggable drivers, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, KRAS & RAS inhibitors, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, RAS / RAF / MEK / ERK (MAPK).
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, KRAS & RAS inhibitors, The undruggable drivers, RAS / RAF / MEK / ERK (MAPK).
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, RAS / RAF / MEK / ERK (MAPK), KRAS.
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, KRAS & RAS inhibitors, The undruggable drivers.