MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 205788 | Name: Avutometinib
Featured

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Avutometinib, also known as RO5126766 and CH5126766, is a protein kinase inhibitor specific for the Raf and MEK mitogen-activated protein kinases (MAPKs) with potential anti-neoplastic activity. Raf/MEK dual kinase Inhibitor RO5126766 specifically inhibits the kinase activities of Raf and MEK, resulting in the inhibition of of target gene transcription that promotes malignant transformation of cells. Both Raf and MEK are serine/threonine-specific kinases that respond to extracellular stimuli, such as mitogens, and are involved in the regulation of cellular processes, such as gene expression, mitosis, differentiation, and apoptosis.

Chemical Structure

Avutometinib
Avutometinib
CAS#946128-88-7 (free)

Theoretical Analysis

MedKoo Cat#: 205788

Name: Avutometinib

CAS#: 946128-88-7 (free)

Chemical Formula: C21H18FN5O5S

Exact Mass: 471.1013

Molecular Weight: 471.46

Elemental Analysis: C, 53.50; H, 3.85; F, 4.03; N, 14.85; O, 16.97; S, 6.80

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
10mg USD 550.00 2 Weeks
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
946128-90-1 (potassium) 946128-88-7 (free) 946128-89-8 (sodium)
Synonym
Avutometinib; VS-6766; VS 6766; VS-6766; RO5126766; RO 5126766; RO5126766; CH5126766; CH5126766; CH 5126766.
IUPAC/Chemical Name
3-[[2-[(Methylaminosulfonyl)amino]-3-fluoropyridin-4-yl]methyl]-4-methyl-7-[(pyrimidin-2-yl)oxy]-2H-1-benzopyran-2-one
InChi Key
LMMJFBMMJUMSJS-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C1C(CC2=C(F)C(NS(=O)(NC)=O)=NC=C2)=C(C)C3=CC=C(OC4=NC=CC=N4)C=C3O1
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Phase I study of RO5126766: RO5126766 is a first-in-class, dual Raf/MEK inhibitor, which was tested in a phase I study. The results showed that  RO5126766 had a manageable safety profile. MTD was defined for all regimens and RP2D is 2.7 mg 4/3. Favorable PK/PD profile with encouraging biological and antitumor activity were demonstrated.  (source: J Clin Oncol 29: 2011 (suppl; abstr 3006).      
Product Data
Product Data
Instruction
View handling instruction
Biological target:
RO5126766 is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAFV600E, CRAF, MEK, and BRAF (IC50: 8.2, 56, 160 nM, and 190 nM, respectively).
In vitro activity:
RO5126766 is an attractive RAF/MEK inhibitor in RAS-mutated malignant tumor cells including melanoma. RO5126766 induced G1 cell cycle arrest in two melanoma cell lines with the BRAF V600E or NRAS mutation. In the RAS-mutated cells, RO5126766 suppressed the MEK reactivation caused by a MEK inhibitor. RO5126766 suppressed the tumor growth in SK-MEL-2 xenograft model. Reference: PLoS One. 2014 Nov 25;9(11):e113217. https://pubmed.ncbi.nlm.nih.gov/25422890/
In vivo activity:
RO5126766 is an effective RAF/MEK inhibitor in RAS-mutated rhabdomyosarcoma (RMS). RO5126766 inhibited the proliferation and growth in all of the RAS-mutated RMS cell lines and induced G1 cell cycle arrest in two of them. RO5126766 also suppressed the in vivo growth of RAS-mutated RMS tumor, and the mice showed improved survival. Reference: Biochem Biophys Res Commun. 2019 May 7;512(3):524-530. https://pubmed.ncbi.nlm.nih.gov/30904164/
Solvent mg/mL mM
Solubility
DMSO 125.0 265.13
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 471.46 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Wang C, Xi D, Wang H, Niu Y, Liang L, Xu F, Peng Y, Xu P. Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs. Eur J Med Chem. 2020 Jun 15;196:112271. doi: 10.1016/j.ejmech.2020.112271. Epub 2020 Apr 9. PMID: 32305784. 2. Wada M, Horinaka M, Yamazaki T, Katoh N, Sakai T. The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells. PLoS One. 2014 Nov 25;9(11):e113217. doi: 10.1371/journal.pone.0113217. PMID: 25422890; PMCID: PMC4244135. 3. Nakagawa N, Kikuchi K, Yagyu S, Miyachi M, Iehara T, Tajiri T, Sakai T, Hosoi H. Mutations in the RAS pathway as potential precision medicine targets in treatment of rhabdomyosarcoma. Biochem Biophys Res Commun. 2019 May 7;512(3):524-530. doi: 10.1016/j.bbrc.2019.03.038. Epub 2019 Mar 21. PMID: 30904164. 4. Honda K, Yamamoto N, Nokihara H, Tamura Y, Asahina H, Yamada Y, Suzuki S, Yamazaki N, Ogita Y, Tamura T. Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Sep;72(3):577-84. doi: 10.1007/s00280-013-2228-4. Epub 2013 Jul 17. PMID: 23860959.
In vitro protocol:
1. Wang C, Xi D, Wang H, Niu Y, Liang L, Xu F, Peng Y, Xu P. Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs. Eur J Med Chem. 2020 Jun 15;196:112271. doi: 10.1016/j.ejmech.2020.112271. Epub 2020 Apr 9. PMID: 32305784. 2. Wada M, Horinaka M, Yamazaki T, Katoh N, Sakai T. The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells. PLoS One. 2014 Nov 25;9(11):e113217. doi: 10.1371/journal.pone.0113217. PMID: 25422890; PMCID: PMC4244135.
In vivo protocol:
1. Nakagawa N, Kikuchi K, Yagyu S, Miyachi M, Iehara T, Tajiri T, Sakai T, Hosoi H. Mutations in the RAS pathway as potential precision medicine targets in treatment of rhabdomyosarcoma. Biochem Biophys Res Commun. 2019 May 7;512(3):524-530. doi: 10.1016/j.bbrc.2019.03.038. Epub 2019 Mar 21. PMID: 30904164. 2. Honda K, Yamamoto N, Nokihara H, Tamura Y, Asahina H, Yamada Y, Suzuki S, Yamazaki N, Ogita Y, Tamura T. Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Sep;72(3):577-84. doi: 10.1007/s00280-013-2228-4. Epub 2013 Jul 17. PMID: 23860959.
1: Qamar F, Sharif Z, Idrees J, Wasim A, Haider S, Salman S. SARS-CoV-2-induced phosphorylation and its pharmacotherapy backed by artificial intelligence and machine learning. Future Sci OA. 2024 May 15;10(1):FSO917. doi: 10.2144/fsoa-2023-0112. PMID: 38827795; PMCID: PMC11140666. 2: Yoshimura A, Horinaka M, Yaoi T, Ono H, Itoh K, Yamada T, Takayama K, Sakai T. Epithelial-mesenchymal transition status is a remarkable biomarker for the combination treatment with avutometinib and defactinib in KRAS-mutated non-small cell lung cancer. Br J Cancer. 2024 May 31. doi: 10.1038/s41416-024-02727-2. Epub ahead of print. PMID: 38822146. 3: Sakai T. "RB-reactivator screening" as a novel cell-based assay for discoveries of molecular targeting agents including the first-in-class MEK inhibitor trametinib (trade name: Mekinist). Pharmacol Ther. 2022 Aug;236:108234. doi: 10.1016/j.pharmthera.2022.108234. Epub 2022 Jun 19. PMID: 35732246. 4: Roskoski R Jr. Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS. Pharmacol Res. 2021 Oct;172:105806. doi: 10.1016/j.phrs.2021.105806. Epub 2021 Aug 24. PMID: 34450320. 5: Tomida A, Yagyu S, Nakamura K, Kubo H, Yamashima K, Nakazawa Y, Hosoi H, Iehara T. Inhibition of MEK pathway enhances the antitumor efficacy of chimeric antigen receptor T cells against neuroblastoma. Cancer Sci. 2021 Oct;112(10):4026-4036. doi: 10.1111/cas.15074. Epub 2021 Aug 24. PMID: 34382720; PMCID: PMC8486218. 6: Ono H, Horinaka M, Sukeno M, Morita M, Yasuda S, Nishimoto E, Konishi E, Sakai T. Novel RAF/MEK inhibitor CH5126766/VS-6766 has efficacy in combination with eribulin for the treatment of triple-negative breast cancer. Cancer Sci. 2021 Oct;112(10):4166-4175. doi: 10.1111/cas.15071. Epub 2021 Aug 1. PMID: 34288272; PMCID: PMC8486178. 7: Dual RAF-MEK Inhibitor Assessed. Cancer Discov. 2021 Jan;11(1):5-6. doi: 10.1158/2159-8290.CD-NB2020-101. Epub 2020 Nov 13. PMID: 33188055. 8: Guo C, Chénard-Poirier M, Roda D, de Miguel M, Harris SJ, Candilejo IM, Sriskandarajah P, Xu W, Scaranti M, Constantinidou A, King J, Parmar M, Turner AJ, Carreira S, Riisnaes R, Finneran L, Hall E, Ishikawa Y, Nakai K, Tunariu N, Basu B, Kaiser M, Lopez JS, Minchom A, de Bono JS, Banerji U. Intermittent schedules of the oral RAF-MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study. Lancet Oncol. 2020 Nov;21(11):1478-1488. doi: 10.1016/S1470-2045(20)30464-2. Epub 2020 Oct 28. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. doi: 10.1016/S1470-2045(21)00014-0. PMID: 33128873. 9: Acar A, Nichol D, Fernandez-Mateos J, Cresswell GD, Barozzi I, Hong SP, Trahearn N, Spiteri I, Stubbs M, Burke R, Stewart A, Caravagna G, Werner B, Vlachogiannis G, Maley CC, Magnani L, Valeri N, Banerji U, Sottoriva A. Exploiting evolutionary steering to induce collateral drug sensitivity in cancer. Nat Commun. 2020 Apr 21;11(1):1923. doi: 10.1038/s41467-020-15596-z. PMID: 32317663; PMCID: PMC7174377. 10: Wang C, Xi D, Wang H, Niu Y, Liang L, Xu F, Peng Y, Xu P. Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs. Eur J Med Chem. 2020 Jun 15;196:112271. doi: 10.1016/j.ejmech.2020.112271. Epub 2020 Apr 9. PMID: 32305784. 11: Umemura S, Sowa Y, Iizumi Y, Kitawaki J, Sakai T. Synergistic effect of the inhibitors of RAF/MEK and AXL on KRAS-mutated ovarian cancer cells with high AXL expression. Cancer Sci. 2020 Jun;111(6):2052-2061. doi: 10.1111/cas.14414. Epub 2020 May 17. PMID: 32291856; PMCID: PMC7293078. 12: Nakagawa N, Kikuchi K, Yagyu S, Miyachi M, Iehara T, Tajiri T, Sakai T, Hosoi H. Mutations in the RAS pathway as potential precision medicine targets in treatment of rhabdomyosarcoma. Biochem Biophys Res Commun. 2019 May 7;512(3):524-530. doi: 10.1016/j.bbrc.2019.03.038. Epub 2019 Mar 21. PMID: 30904164. 13: Takeuchi Y, Tanaka T, Higashi M, Fumino S, Iehara T, Hosoi H, Sakai T, Tajiri T. In vivo effects of short- and long-term MAPK pathway inhibition against neuroblastoma. J Pediatr Surg. 2018 Dec;53(12):2454-2459. doi: 10.1016/j.jpedsurg.2018.08.026. Epub 2018 Sep 1. PMID: 30266481. 14: Knauf JA, Luckett KA, Chen KY, Voza F, Socci ND, Ghossein R, Fagin JA. Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers. J Clin Invest. 2018 Aug 31;128(9):4086-4097. doi: 10.1172/JCI120966. Epub 2018 Aug 20. PMID: 29990309; PMCID: PMC6118575. 15: Bhatt MH, Prajapati CK, Reddy MN. In silico docking studies of Lupeol with MAPK pathway proteins- Raf-1, MEK & ERK. J Exp Ther Oncol. 2017 Nov;12(2):137-140. PMID: 29161781. 16: Tanaka T, Higashi M, Kimura K, Wakao J, Fumino S, Iehara T, Hosoi H, Sakai T, Tajiri T. MEK inhibitors as a novel therapy for neuroblastoma: Their in vitro effects and predicting their efficacy. J Pediatr Surg. 2016 Dec;51(12):2074-2079. doi: 10.1016/j.jpedsurg.2016.09.043. Epub 2016 Sep 16. PMID: 27686482. 17: Ueyama A, Ban N, Fukazawa M, Hirayama T, Takeda M, Yata T, Muramatsu H, Hoshino M, Yamamoto M, Matsuo M, Kawashima Y, Iwase T, Kitazawa T, Kushima Y, Yamada Y, Kawabe Y. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. J Diabetes Res. 2016;2016:8264830. doi: 10.1155/2016/8264830. Epub 2015 Dec 28. PMID: 26839898; PMCID: PMC4709921. 18: Van Dort ME, Galbán S, Wang H, Sebolt-Leopold J, Whitehead C, Hong H, Rehemtulla A, Ross BD. Dual inhibition of allosteric mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) oncogenic targets with a bifunctional inhibitor. Bioorg Med Chem. 2015 Apr 1;23(7):1386-94. doi: 10.1016/j.bmc.2015.02.053. Epub 2015 Mar 6. PMID: 25766633; PMCID: PMC4370322. 19: Wada M, Horinaka M, Yamazaki T, Katoh N, Sakai T. The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells. PLoS One. 2014 Nov 25;9(11):e113217. doi: 10.1371/journal.pone.0113217. PMID: 25422890; PMCID: PMC4244135. 20: Aoki T, Hyohdoh I, Furuichi N, Ozawa S, Watanabe F, Matsushita M, Sakaitani M, Morikami K, Takanashi K, Harada N, Tomii Y, Shiraki K, Furumoto K, Tabo M, Yoshinari K, Ori K, Aoki Y, Shimma N, Iikura H. Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning. ACS Med Chem Lett. 2014 Jan 22;5(4):309-14. doi: 10.1021/ml400379x. PMID: 24900832; PMCID: PMC4027752.