Avutometinib

Avutometinib
	Skeletal formula and ball-and-stick model of avutometinib
Clinical data
Other names	RO-5126766; CH-5126766; CKI-27; R-7304; RG-7304
Pharmacokinetic data
Elimination half-life	60 h (45.8–93.7 h)
Identifiers
	IUPAC name 3-[[3-fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]-4-methyl-7-pyrimidin-2-yloxychromen-2-one;
CAS Number	946128-88-7;
PubChem CID	16719221;
DrugBank	DB15254;
ChemSpider	17623621;
UNII	D0D4252V97;
KEGG	D12515;
ChEBI	CHEBI:78825;
ChEMBL	ChEMBL3264002;
PDB ligand	CHU (PDBe, RCSB PDB);
Chemical and physical data
Formula	C21H18FN5O5S
Molar mass	471.46 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C(=O)OC2=C1C=CC(=C2)OC3=NC=CC=N3)CC4=C(C(=NC=C4)NS(=O)(=O)NC)F;
	InChI InChI=1S/C21H18FN5O5S/c1-12-15-5-4-14(31-21-25-7-3-8-26-21)11-17(15)32-20(28)16(12)10-13-6-9-24-19(18(13)22)27-33(29,30)23-2/h3-9,11,23H,10H2,1-2H3,(H,24,27); Key:LMMJFBMMJUMSJS-UHFFFAOYSA-N;

Avutometinib (INN; codenamed RO-5126766, CH-5126766, CKI-27, R-7304, RG-7304, and VS-6766 at various stages of its development) is an inhibitor of Ras-Raf-MEK-ERK signaling being developed as a potential treatment for cancer.

It was discovered by Chugai Pharmaceutical Co. (a subsidiary of Roche) through derivatization of a hit compound identified by high-throughput screening.^[1] It was licensed by Verastem Oncology in 2020 for clinical trials.^[2]^[3]

The co-packaged medication avutometinib/defactinib was approved for medical use in the United States in May 2025.^[4]^[5]

References

^ Ishii N, Harada N, Joseph EW, Ohara K, Miura T, Sakamoto H, Matsuda Y, Tomii Y, Tachibana-Kondo Y, Iikura H, Aoki T, Shimma N, Arisawa M, Sowa Y, Poulikakos PI, Rosen N, Aoki Y, Sakai T (July 2013). "Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity". Cancer Res. 73 (13): 4050–4060. doi:10.1158/0008-5472.CAN-12-3937. PMC 4115369. PMID 23667175.
^ Adams, Ben (8 January 2020). "Verastem pens KRAS-focused drug licensing deal with Chugai". Fierce Biotech. Retrieved 5 June 2022.
^ "Drug Profile: Avutometinib" (PDF). AdisInsight. 23 May 2022. Retrieved 5 June 2022.
^ "FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer". U.S. Food and Drug Administration. 8 May 2025. Archived from the original on 8 May 2025. Retrieved 16 May 2025. This article incorporates text from this source, which is in the public domain.
^ "FDA Approves the Avmapki Fakzynja Combination Therapy as the First-Ever Treatment for Adult Patients with KRAS-mutated Recurrent Low-Grade Serous Ovarian Cancer". Verastem (Press release). Retrieved 16 May 2025.

[1] Ishii N, Harada N, Joseph EW, Ohara K, Miura T, Sakamoto H, Matsuda Y, Tomii Y, Tachibana-Kondo Y, Iikura H, Aoki T, Shimma N, Arisawa M, Sowa Y, Poulikakos PI, Rosen N, Aoki Y, Sakai T (July 2013). "Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity". Cancer Res. 73 (13): 4050–4060. doi:10.1158/0008-5472.CAN-12-3937. PMC 4115369. PMID 23667175.

[2] Adams, Ben (8 January 2020). "Verastem pens KRAS-focused drug licensing deal with Chugai". Fierce Biotech. Retrieved 5 June 2022.

[AdisInsight-3] "Drug Profile: Avutometinib" (PDF). AdisInsight. 23 May 2022. Retrieved 5 June 2022.

[FDA_Avmapki_Fakzynja-4] "FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer". U.S. Food and Drug Administration. 8 May 2025. Archived from the original on 8 May 2025. Retrieved 16 May 2025. This article incorporates text from this source, which is in the public domain.

[Verastem_PR-5] "FDA Approves the Avmapki Fakzynja Combination Therapy as the First-Ever Treatment for Adult Patients with KRAS-mutated Recurrent Low-Grade Serous Ovarian Cancer". Verastem (Press release). Retrieved 16 May 2025.

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