Selumetinib (AZD6244)
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MedKoo CAT#: 200300

CAS#: 606143-52-6

Description: Selumetinib, also known as AZD6244, is an orally bioavailable small molecule with potential antineoplastic activity. Selumetinib inhibits mitogen-activated protein kinase kinases (MEK or MAPK/ERK kinases) 1 and 2, which may prevent the activation of MEK1/2-dependent effector proteins and transcription factors, and so may inhibit cellular proliferation in MEK-overexpressing tumor cells.


Chemical Structure

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Selumetinib (AZD6244)
CAS# 606143-52-6

Theoretical Analysis

MedKoo Cat#: 200300
Name: Selumetinib (AZD6244)
CAS#: 606143-52-6
Chemical Formula: C17H15BrClFN4O3
Exact Mass: 456.00001
Molecular Weight: 457.68
Elemental Analysis: C, 44.61; H, 3.30; Br, 17.46; Cl, 7.75; F, 4.15; N, 12.24; O, 10.49

Price and Availability

Size Price Availability Quantity
200.0mg USD 150.0 Ready to ship
500.0mg USD 250.0 Ready to ship
1.0g USD 450.0 Ready to ship
2.0g USD 650.0 Ready to ship
5.0g USD 1150.0 Ready to ship
10.0g USD 1950.0 Ready to ship
20.0g USD 2950.0 Ready to ship
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Synonym: AZD6244; AZD-6244; AZD 6244; ARRY142886; ARRY 142886; ARRY-142886; ARRY886; ARRY-886; ARRY 886 ; selumetinib.

IUPAC/Chemical Name: 6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide

InChi Key: CYOHGALHFOKKQC-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H15BrClFN4O3/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=C2Cl)C(F)=C3C(N(C)C=N3)=C1)NOCCO

Appearance: white 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

Biological target: Selumetinib (AZD6244) is a non-ATP-competitive MEK1/2 inhibitor, with an IC50 of 14 nM for MEK1.
In vitro activity: Differentiated C2C12 myotubes were incubated with Selumetinib or vehicle for 48 h, with a media change after the first 24 h. Western blotting showed that 1 and 10 nM Selumetinib reduced ERK1/2 phosphorylation in C2C12 myotubes by ~30% (Figure 1A). Myotube hypertrophy (diameter +15.42%, P < 0.05) was observed at a concentration of 10 nM but not 1 nM Selumetinib (Figure 1B), and higher concentrations were toxic (data not shown). Reference: Front Physiol. 2016; 7: 682. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241300/
In vivo activity: Importantly, this study observed a significant survival increase in the selumetinib-treated mice (Fig. 7B) with a median survival time of 55.5 days relative to 44 days for vehicle controls. Moreover, CD271 levels were downregulated in all selumetinib-treated tumors (Fig. 7C). These results support in vitro studies and demonstrate the potential clinical utility of selumetinib for targeting CD271+ cells in a biologically relevant in vivo medulloblastoma tumor model. Reference: Cancer Res. 2018 Aug 15;78(16):4745-4759. https://cancerres.aacrjournals.org/content/78/16/4745.long

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 13.05 28.51
DMSO:PBS (pH 7.2) (1:1) 0.5 1.09
DMF 15.0 32.77

Preparing Stock Solutions

The following data is based on the product molecular weight 457.68 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. Au ED, Desai AP, Koniaris LG, Zimmers TA. The MEK-Inhibitor Selumetinib Attenuates Tumor Growth and Reduces IL-6 Expression but Does Not Protect against Muscle Wasting in Lewis Lung Cancer Cachexia. Front Physiol. 2017 Jan 18;7:682. doi: 10.3389/fphys.2016.00682. PMID: 28149280; PMCID: PMC5241300. 2. Li C, Chen Z, Yang H, Luo F, Chen L, Cai H, Li Y, You G, Long D, Li S, Zhang Q, Rao L. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway. PLoS One. 2016 Jul 20;11(7):e0159079. doi: 10.1371/journal.pone.0159079. PMID: 27438013; PMCID: PMC4954659. 3. Liang L, Coudière-Morrison L, Tatari N, Stromecki M, Fresnoza A, Porter CJ, Del Bigio MR, Hawkins C, Chan JA, Ryken TC, Taylor MD, Ramaswamy V, Werbowetski-Ogilvie TE. CD271+ Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma. Cancer Res. 2018 Aug 15;78(16):4745-4759. doi: 10.1158/0008-5472.CAN-18-0027. Epub 2018 Jun 21. PMID: 29930101. 4. Ullrich M, Weber M, Post AM, Popp S, Grein J, Zechner M, Guerrero González H, Kreis A, Schmitt AG, Üçeyler N, Lesch KP, Schuh K. OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency. Mol Psychiatry. 2018 Feb;23(2):444-458. doi: 10.1038/mp.2016.232. Epub 2017 Jan 10. PMID: 28070119; PMCID: PMC5794898.
In vitro protocol: 1. Au ED, Desai AP, Koniaris LG, Zimmers TA. The MEK-Inhibitor Selumetinib Attenuates Tumor Growth and Reduces IL-6 Expression but Does Not Protect against Muscle Wasting in Lewis Lung Cancer Cachexia. Front Physiol. 2017 Jan 18;7:682. doi: 10.3389/fphys.2016.00682. PMID: 28149280; PMCID: PMC5241300. 2. Li C, Chen Z, Yang H, Luo F, Chen L, Cai H, Li Y, You G, Long D, Li S, Zhang Q, Rao L. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway. PLoS One. 2016 Jul 20;11(7):e0159079. doi: 10.1371/journal.pone.0159079. PMID: 27438013; PMCID: PMC4954659.
In vivo protocol: 1. Liang L, Coudière-Morrison L, Tatari N, Stromecki M, Fresnoza A, Porter CJ, Del Bigio MR, Hawkins C, Chan JA, Ryken TC, Taylor MD, Ramaswamy V, Werbowetski-Ogilvie TE. CD271+ Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma. Cancer Res. 2018 Aug 15;78(16):4745-4759. doi: 10.1158/0008-5472.CAN-18-0027. Epub 2018 Jun 21. PMID: 29930101. 2. Ullrich M, Weber M, Post AM, Popp S, Grein J, Zechner M, Guerrero González H, Kreis A, Schmitt AG, Üçeyler N, Lesch KP, Schuh K. OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency. Mol Psychiatry. 2018 Feb;23(2):444-458. doi: 10.1038/mp.2016.232. Epub 2017 Jan 10. PMID: 28070119; PMCID: PMC5794898.

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1: El-Hoss J, Kolind M, Jackson MT, Deo N, Mikulec K, McDonald MM, Little CB, Little DG, Schindeler A. Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib). Bone. 2013 Nov 20. doi:pii: S8756-3282(13)00474-2. 10.1016/j.bone.2013.11.013. [Epub ahead of print] PubMed PMID: 24269278.

2: Jain N, Curran E, Iyengar NM, Diaz-Flores E, Kunnavakkam R, Popplewell L, Kirschbaum MH, Karrison TG, Erba HP, Green M, Poire X, Koval G, Shannon K, Reddy PL, Joseph L, Atallah EL, Dy P, Thomas SP, Smith S, Doyle A, Stadler WM, Larson R, Stock W, Odenike OM. Phase II Study Of The Oral MEK Inhibitor Selumetinib In Advanced Acute Myeloid Leukemia (AML): A University Of Chicago Phase II Consortium Trial. Clin Cancer Res. 2013 Oct 31. [Epub ahead of print] PubMed PMID: 24178622.

3: Bid HK, Kibler A, Phelps DA, Manap S, Xiao L, Lin J, Capper D, Oswald D, Geier B, Dewire M, Smith PD, Kurmasheva RT, Mo X, Fernandez S, Houghton PJ. Development, Characterization, and Reversal of Acquired Resistance to the MEK1 Inhibitor Selumetinib (AZD6244) in an In Vivo Model of Childhood Astrocytoma. Clin Cancer Res. 2013 Nov 22. [Epub ahead of print] PubMed PMID: 24132923.

4: Paolo M, Assunta S, Antonio R, Claudia SP, Anna BM, Clorinda S, Francesca C, Fortunato C, Cesare G. Selumetinib in advanced non small cell lung cancer (NSCLC) harbouring KRAS mutation: endless clinical challenge to KRAS-mutant NSCLC. Rev Recent Clin Trials. 2013 Jun;8(2):93-100. PubMed PMID: 24063423.

5: Beloueche-Babari M, Jamin Y, Arunan V, Walker-Samuel S, Revill M, Smith PD, Halliday J, Waterton JC, Barjat H, Workman P, Leach MO, Robinson SP. Acute tumour response to the MEK1/2 inhibitor selumetinib (AZD6244, ARRY-142886) evaluated by non-invasive diffusion-weighted MRI. Br J Cancer. 2013 Sep 17;109(6):1562-9. doi: 10.1038/bjc.2013.456. Epub 2013 Aug 13. PubMed PMID: 23942066; PubMed Central PMCID: PMC3776979.

6: Selumetinib shows promise in metastatic uveal melanoma. Cancer Discov. 2013 Jul;3(7):OF8. doi: 10.1158/2159-8290.CD-NB2013-086. Epub 2013 Jun 6. PubMed PMID: 23847383.

7: Selumetinib increases the efficacy of first-line dacarbazine. Cancer Discov. 2013 Jul;3(7):OF16. doi: 10.1158/2159-8290.CD-RW2013-129. Epub 2013 Jun 13. PubMed PMID: 23847359.

8: Spreafico A, Tentler JJ, Pitts TM, Tan AC, Gregory MA, Arcaroli JJ, Klauck PJ, McManus MC, Hansen RJ, Kim J, Micel LN, Selby HM, Newton TP, McPhillips KL, Gustafson DL, Degregori JV, Messersmith WA, Winn RA, Eckhardt SG. Rational combination of a MEK inhibitor, selumetinib, and the Wnt/calcium pathway modulator, cyclosporin A, in preclinical models of colorectal cancer. Clin Cancer Res. 2013 Aug 1;19(15):4149-62. doi: 10.1158/1078-0432.CCR-12-3140. Epub 2013 Jun 11. PubMed PMID: 23757356.

9: Robert C, Dummer R, Gutzmer R, Lorigan P, Kim KB, Nyakas M, Arance A, Liszkay G, Schadendorf D, Cantarini M, Spencer S, Middleton MR. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. Lancet Oncol. 2013 Jul;14(8):733-40. doi: 10.1016/S1470-2045(13)70237-7. Epub 2013 Jun 2. PubMed PMID: 23735514.

10: Sabnis GJ, Kazi A, Golubeva O, Shah P, Brodie A. Effect of selumetinib on the growth of anastrozole-resistant tumors. Breast Cancer Res Treat. 2013 Apr;138(3):699-708. doi: 10.1007/s10549-013-2474-5. Epub 2013 Mar 19. PubMed PMID: 23508762.  



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