Binimetinib (MEK-162)
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MedKoo CAT#: 205531

CAS#: 606143-89-9

Description: Binimetinib, also known as MEK162 (ARRY-162), is an oral, highly selective MEK inhibitor. In preclinical studies, MEK162 showed significant antitumor activities in cell lines and animal models. MEK162 is the first targeted therapy to show activity in patients with NRAS -mutated melanoma and might offer a new option for a cancer with few effective treatments.


Chemical Structure

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Binimetinib (MEK-162)
CAS# 606143-89-9

Theoretical Analysis

MedKoo Cat#: 205531
Name: Binimetinib (MEK-162)
CAS#: 606143-89-9
Chemical Formula: C17H15BrF2N4O3
Exact Mass: 440.02956
Molecular Weight: 441.22681
Elemental Analysis: C, 46.28; H, 3.43; Br, 18.11; F, 8.61; N, 12.70; O, 10.88

Price and Availability

Size Price Availability Quantity
100.0mg USD 150.0 Ready to ship
200.0mg USD 250.0 Ready to ship
500.0mg USD 550.0 Ready to ship
1.0g USD 950.0 Ready to ship
2.0g USD 1650.0 Ready to ship
5.0g USD 3650.0 Ready to ship
10.0g USD 6550.0 Ready to ship
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Synonym: MEK162; MEK-162; MEK 162; ARRY162; ARRY-162; ARRY 162; ARRY438162, Binimetinib; Brand name: Mektovi.

IUPAC/Chemical Name: 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide.

InChi Key: ACWZRVQXLIRSDF-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H15BrF2N4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)

SMILES Code: O=C(C1=C(NC2=CC=C(Br)C=C2F)C(F)=C3N=CN(C)C3=C1)NOCCO

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

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

Biological target: Binimetinib (MEK162) is an oral and selective MEK1/2 inhibitor. Binimetinib (MEK162) inhibits MEK with an IC50 of 12 nM.
In vitro activity: Cell lines with a KRAS (V12) mutation and KRAS gains or loss (n=7) are ∼10 times more resistant than those having neither a KRAS (V12) mutation nor KRAS CNV (n=14). Significant differences in baseline and MEK162-induced gene expression exist between the sensitive and resistant lines, especially in genes involved in RAS, EGF receptor and PI3K pathways. This was further supported by difference in signal transduction. MEK 162 blocked ERK1/2, as well as inhibited PI3K and S6 and increased p27KIP1 levels in the sensitive lines. Reference: Br J Cancer. 2014 Oct 28;111(9):1788-801. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25167228/
In vivo activity: Treatment with Binimetinib (ARRY-438162) reduces disease severity in a dose-related manner in both animal models. ARRY-438162 in the CIA model inhibits increases in ankle diameter by 27% and 50% at 1 and 3 mg/kg. Microscopic examination of the ankle joints show Binimetinib (ARRY-438162) significantly inhibits lesions (inflammation, cartilage damage, pannus formation and bone resorption) by 32% and 60% at 1 and 3 mg/kg. In AIA, 3 and 10 mg/kg of Binimetinib (ARRY-438162) inhibit AIA ankle diameter 11% and 34. Reference: J Pheneger, et al. 2006, ACR Annual Scientific Meeting. Abst 794. https://acr.confex.com/acr/2006/webprogram/Paper5558.html

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 113.32

Preparing Stock Solutions

The following data is based on the product molecular weight 441.22681 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. Hamidi H, Lu M, Chau K, Anderson L, Fejzo M, Ginther C, Linnartz R, Zubel A, Slamon DJ, Finn RS. KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition. Br J Cancer. 2014 Oct 28;111(9):1788-801. doi: 10.1038/bjc.2014.475. Epub 2014 Aug 28. PMID: 25167228; PMCID: PMC4453732. 2. Serra V, Eichhorn PJ, García-García C, Ibrahim YH, Prudkin L, Sánchez G, Rodríguez O, Antón P, Parra JL, Marlow S, Scaltriti M, Pérez-Garcia J, Prat A, Arribas J, Hahn WC, Kim SY, Baselga J. RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J Clin Invest. 2013 Jun;123(6):2551-63. doi: 10.1172/JCI66343. Epub 2013 May 1. Erratum in: J Clin Invest. 2014 Mar 3;124(3):1418. PMID: 23635776; PMCID: PMC3668839.
In vitro protocol: 1. Hamidi H, Lu M, Chau K, Anderson L, Fejzo M, Ginther C, Linnartz R, Zubel A, Slamon DJ, Finn RS. KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition. Br J Cancer. 2014 Oct 28;111(9):1788-801. doi: 10.1038/bjc.2014.475. Epub 2014 Aug 28. PMID: 25167228; PMCID: PMC4453732.
In vivo protocol: 1. Serra V, Eichhorn PJ, García-García C, Ibrahim YH, Prudkin L, Sánchez G, Rodríguez O, Antón P, Parra JL, Marlow S, Scaltriti M, Pérez-Garcia J, Prat A, Arribas J, Hahn WC, Kim SY, Baselga J. RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J Clin Invest. 2013 Jun;123(6):2551-63. doi: 10.1172/JCI66343. Epub 2013 May 1. Erratum in: J Clin Invest. 2014 Mar 3;124(3):1418. PMID: 23635776; PMCID: PMC3668839.

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1: McLoughlin EM, Fadul CE, Patel SH, Hall RD, Gentzler RD. Clinical and Radiographic Response of Leptomeningeal and Brain Metastases to Encorafenib and Binimetinib in a Patient With BRAF V600E-Mutated Lung Adenocarcinoma. J Thorac Oncol. 2019 Dec;14(12):e269-e271. doi: 10.1016/j.jtho.2019.07.019. PubMed PMID: 31757377.

2: Gravbrot N, Sundararajan S. Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib. Case Rep Oncol Med. 2019 Oct 7;2019:3051945. doi: 10.1155/2019/3051945. eCollection 2019. PubMed PMID: 31687241; PubMed Central PMCID: PMC6800898.

3: Holbrook K, Lutzky J, Davies MA, Davis JM, Glitza IC, Amaria RN, Diab A, Patel SP, Amin A, Tawbi H. Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series. Cancer. 2019 Oct 28. doi: 10.1002/cncr.32547. [Epub ahead of print] PubMed PMID: 31658370.

4: Binimetinib plus encorafenib for metastatic melanoma. Aust Prescr. 2019 Oct;42(5):168. doi: 10.18773/austprescr.2019.057. Epub 2019 Sep 13. Review. PubMed PMID: 31631932; PubMed Central PMCID: PMC6787304.

5: Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. doi: 10.1056/NEJMoa1908075. Epub 2019 Sep 30. PubMed PMID: 31566309.

6: Ngo P, Bycroft R. Encorafenib and binimetinib for the treatment of BRAF-mutated metastatic melanoma in the setting of combined hepatic and renal impairment. BMJ Case Rep. 2019 Sep 16;12(9). pii: e230974. doi: 10.1136/bcr-2019-230974. PubMed PMID: 31527213.

7: Gogas HJ, Flaherty KT, Dummer R, Ascierto PA, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Sileni VC, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Gollerkeri A, Pickard MD, Robert C. Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management. Eur J Cancer. 2019 Sep;119:97-106. doi: 10.1016/j.ejca.2019.07.016. Epub 2019 Aug 19. PubMed PMID: 31437754.

8: Goldinger SM, Valeska Matter A, Urner-Bloch U, Narainsing J, Micaletto S, Blume I, Mangana J, Dummer R. Binimetinib in heavily pretreated patients with NRAS-mutant melanoma with brain metastases. Br J Dermatol. 2019 Aug 22. doi: 10.1111/bjd.18449. [Epub ahead of print] PubMed PMID: 31436845.

9: Bardia A, Gounder M, Rodon J, Janku F, Lolkema MP, Stephenson JJ, Bedard PL, Schuler M, Sessa C, LoRusso P, Thomas M, Maacke H, Evans H, Sun Y, Tan DSW. Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. Oncologist. 2019 Aug 8. pii: theoncologist.2019-0297. doi: 10.1634/theoncologist.2019-0297. [Epub ahead of print] PubMed PMID: 31395751.

10: Kim JW, Lee KH, Kim JW, Suh KJ, Nam AR, Bang JH, Bang YJ, Oh DY. Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS/RAF/MEK/ERK pathway: phase Ib study. Br J Cancer. 2019 Aug;121(4):332-339. doi: 10.1038/s41416-019-0523-5. Epub 2019 Jul 17. PubMed PMID: 31312030; PubMed Central PMCID: PMC6738070.

11: Rosenbaum E, Kelly C, D'Angelo SP, Dickson MA, Gounder M, Keohan ML, Movva S, Condy M, Adamson T, Mcfadyen CR, Antonescu CR, Hwang S, Singer S, Qin LX, Tap WD, Chi P. A Phase I Study of Binimetinib (MEK162) Combined with Pexidartinib (PLX3397) in Patients with Advanced Gastrointestinal Stromal Tumor. Oncologist. 2019 Oct;24(10):1309-e983. doi: 10.1634/theoncologist.2019-0418. Epub 2019 Jun 18. PubMed PMID: 31213500; PubMed Central PMCID: PMC6795162.

12: Sakakibara K, Tsujioka T, Kida JI, Kurozumi N, Nakahara T, Suemori SI, Kitanaka A, Arao Y, Tohyama K. Binimetinib, a novel MEK1/2 inhibitor, exerts anti-leukemic effects under inactive status of PI3Kinase/Akt pathway. Int J Hematol. 2019 Aug;110(2):213-227. doi: 10.1007/s12185-019-02667-1. Epub 2019 May 25. PubMed PMID: 31129802.

13: Rose AAN. Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma. Drugs Today (Barc). 2019 Apr;55(4):247-264. doi: 10.1358/dot.2019.55.4.2958476. Review. PubMed PMID: 31050693.

14: van Herpen CML, Agarwala SS, Hauschild A, Berking C, Beck JT, Schadendorf D, Jansen R, Queirolo P, Ascierto PA, Blank CU, Heinrich MC, Pal RR, Derti A, Antona V, Nauwelaerts H, Zubel A, Dummer R. Biomarker results from a phase II study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced NRAS- or BRAF-mutated melanoma. Oncotarget. 2019 Mar 5;10(19):1850-1859. doi: 10.18632/oncotarget.26753. eCollection 2019 Mar 5. PubMed PMID: 30956763; PubMed Central PMCID: PMC6442999.

15: Van Cutsem E, Huijberts S, Grothey A, Yaeger R, Cuyle PJ, Elez E, Fakih M, Montagut C, Peeters M, Yoshino T, Wasan H, Desai J, Ciardiello F, Gollerkeri A, Christy-Bittel J, Maharry K, Sandor V, Schellens JHM, Kopetz S, Tabernero J. Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. J Clin Oncol. 2019 Jun 10;37(17):1460-1469. doi: 10.1200/JCO.18.02459. Epub 2019 Mar 20. PubMed PMID: 30892987.

16: Trojaniello C, Festino L, Vanella V, Ascierto PA. Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations. Expert Rev Clin Pharmacol. 2019 Mar;12(3):259-266. doi: 10.1080/17512433.2019.1570847. Epub 2019 Jan 24. Review. PubMed PMID: 30652516.

17: Shen Y, Crassini K, Sandhu S, Fatima N, Christopherson RI, Mulligan SP, Best OG. Dual inhibition of MEK1/2 and AKT by binimetinib and MK2206 induces apoptosis of chronic lymphocytic leukemia cells under conditions that mimic the tumor microenvironment. Leuk Lymphoma. 2019 Jul;60(7):1632-1643. doi: 10.1080/10428194.2018.1542148. Epub 2019 Jan 16. PubMed PMID: 30648436.

18: Maiti A, Naqvi K, Kadia TM, Borthakur G, Takahashi K, Bose P, Daver NG, Patel A, Alvarado Y, Ohanian M, DiNardo CD, Cortes JE, Jabbour EJ, Garcia-Manero G, Kantarjian HM, Ravandi F. Phase II Trial of MEK Inhibitor Binimetinib (MEK162) in RAS-mutant Acute Myeloid Leukemia. Clin Lymphoma Myeloma Leuk. 2019 Mar;19(3):142-148.e1. doi: 10.1016/j.clml.2018.12.009. Epub 2018 Dec 20. PubMed PMID: 30635233.

19: Sun J, Zager JS, Eroglu Z. Encorafenib/binimetinib for the treatment of BRAF-mutant advanced, unresectable, or metastatic melanoma: design, development, and potential place in therapy. Onco Targets Ther. 2018 Dec 14;11:9081-9089. doi: 10.2147/OTT.S171693. eCollection 2018. Review. PubMed PMID: 30588020; PubMed Central PMCID: PMC6299465.

20: Lowery MA, Bradley M, Chou JF, Capanu M, Gerst S, Harding JJ, Dika IE, Berger M, Zehir A, Ptashkin R, Wong P, Rasalan-Ho T, Yu KH, Cercek A, Morgono E, Salehi E, Valentino E, Hollywood E, O'Reilly EM, Abou-Alfa GK. Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers. Clin Cancer Res. 2019 Feb 1;25(3):937-945. doi: 10.1158/1078-0432.CCR-18-1927. Epub 2018 Dec 18. PubMed PMID: 30563938; PubMed Central PMCID: PMC6615467.



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