Ixazomib (MLN-2238)
featured

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

MedKoo CAT#: 205857

CAS#: 1072833-77-2 (free)

Description: Ixazomib, also known as MLN-2238, is a potent proteasome inhibitor (PI) with potential antineoplastic activity. MNL-2238 is also .the biologically active form of MLN9708. MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMyc(Cα)/Bcl-X(L) GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model.


Chemical Structure

img
Ixazomib (MLN-2238)
CAS# 1072833-77-2 (free)

Theoretical Analysis

MedKoo Cat#: 205857
Name: Ixazomib (MLN-2238)
CAS#: 1072833-77-2 (free)
Chemical Formula: C14H19BCl2N2O4
Exact Mass: 360.08149
Molecular Weight: 361.02866
Elemental Analysis: C, 46.58; H, 5.30; B, 2.99; Cl, 19.64; N, 7.76; O, 17.73

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 2650.0 Ready to ship
1.0g USD 3750.0 Ready to ship
2.0g USD 6250.0 Ready to ship
Click to view more sizes and prices
Bulk inquiry

Related CAS #: 1072833-77-2 (free)   1239908-20-3 (citrate)   1201902-80-8    

Synonym: MLN2238; MLN-2238; MLN 2238; Ixazomib. Trade name: Ninlaro.

IUPAC/Chemical Name: (R)-(1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)boronic acid

InChi Key: MXAYKZJJDUDWDS-LBPRGKRZSA-N

InChi Code: InChI=1S/C14H19BCl2N2O4/c1-8(2)5-12(15(22)23)19-13(20)7-18-14(21)10-6-9(16)3-4-11(10)17/h3-4,6,8,12,22-23H,5,7H2,1-2H3,(H,18,21)(H,19,20)/t12-/m0/s1

SMILES Code: CC(C)C[C@@H](B(O)O)NC(CNC(C1=CC(Cl)=CC=C1Cl)=O)=O

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 soluble in water.

Shelf Life: >5 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: Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 of 3.4 nM (Ki of 0.93 nM).
In vitro activity: To further examine the molecular mechanism through which ixazomib blocks cell proliferation, the effects of the drug on mitosis- and apoptosis-related genes was investigated. As shown in Fig. 4, ixazomib decreased the protein levels of cyclin E1, cyclin D1, and Bcl-2 in RPMI-8226 and U-266 cells. The reduction of cyclin E1, cyclin D1 and Bcl-2 protein levels by ixazomib was relieved by UBE2K transfection. Alternatively, ixazomib increased the protein levels of cyclin B1, McL-1, and PARP1 in cells, while UBE2K transfection blocked ixazomib’s effects. These findings demonstrate that ixazomib regulates mitosis- and apoptosis-related genes by lowering UBE2K expression, which leads to reduce proliferation of myeloma cells. Reference: Biochem Biophys Res Commun. 2021 Apr 16;549:1-7. https://www.sciencedirect.com/science/article/pii/S0006291X21002321?via%3Dihub
In vivo activity: Unlike the KRIB metastatic model, only ixazomib reduced the growth of 143B lung tumors whereas bortezomib was ineffective (Figure 5A). Ixazomib, not bortezomib, also delayed the formation of abdominal metastases (liver and/or kidneys) compared to saline (Figure 5B). Ixazomib-treated mice survived longer and some were asymptomatic at the endpoint of the experiment, whereas most saline- and bortezomib-treated mice required euthanasia due to intolerable tumor-related symptoms (Figure 5C–E). The most striking difference between ixazomib, compared to saline and bortezomib, was the reduced overall tumor burden in the lungs, liver and kidneys ex vivo (Figure 5E). The ex vivo bioluminescence of the lungs in ixazomib-treated mice was at least 100-fold lower than the mice treated with saline or bortezomib, despite being culled up to 21 days later. Reference: Cancers (Basel). 2020 May; 12(5): 1207. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281181/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 67.25 186.27
Ethanol 72.0 199.43

Preparing Stock Solutions

The following data is based on the product molecular weight 361.02866 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. Roeten MSF, van Meerloo J, Kwidama ZJ, Ter Huizen G, Segerink WH, Zweegman S, Kaspers GJL, Jansen G, Cloos J. Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells. Cells. 2021 Mar 17;10(3):665. doi: 10.3390/cells10030665. PMID: 33802801; PMCID: PMC8002577. 2. Wang Q, Dong Z, Su J, Huang J, Xiao P, Tian L, Chen Y, Ma L, Chen X. Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. Biochem Biophys Res Commun. 2021 Apr 16;549:1-7. doi: 10.1016/j.bbrc.2021.02.048. Epub 2021 Feb 26. PMID: 33647537. 3. Sánchez G, Chalmers S, Ahumada X, Montecinos L, Olmedo I, Eisner V, Riveros A, Kogan MJ, Lavandero S, Pedrozo Z, Donoso P. Inhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemia. PLoS One. 2020 May 26;15(5):e0233591. doi: 10.1371/journal.pone.0233591. PMID: 32453773; PMCID: PMC7250417. 4. Harris MA, Miles MA, Shekhar TM, Cerra C, Georgy SR, Ryan SD, Cannon CM, Hawkins CJ. The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice. Cancers (Basel). 2020 May 11;12(5):1207. doi: 10.3390/cancers12051207. PMID: 32403415; PMCID: PMC7281181.
In vitro protocol: 1. Roeten MSF, van Meerloo J, Kwidama ZJ, Ter Huizen G, Segerink WH, Zweegman S, Kaspers GJL, Jansen G, Cloos J. Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells. Cells. 2021 Mar 17;10(3):665. doi: 10.3390/cells10030665. PMID: 33802801; PMCID: PMC8002577. 2. Wang Q, Dong Z, Su J, Huang J, Xiao P, Tian L, Chen Y, Ma L, Chen X. Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. Biochem Biophys Res Commun. 2021 Apr 16;549:1-7. doi: 10.1016/j.bbrc.2021.02.048. Epub 2021 Feb 26. PMID: 33647537.
In vivo protocol: 1. Sánchez G, Chalmers S, Ahumada X, Montecinos L, Olmedo I, Eisner V, Riveros A, Kogan MJ, Lavandero S, Pedrozo Z, Donoso P. Inhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemia. PLoS One. 2020 May 26;15(5):e0233591. doi: 10.1371/journal.pone.0233591. PMID: 32453773; PMCID: PMC7250417. 2. Harris MA, Miles MA, Shekhar TM, Cerra C, Georgy SR, Ryan SD, Cannon CM, Hawkins CJ. The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice. Cancers (Basel). 2020 May 11;12(5):1207. doi: 10.3390/cancers12051207. PMID: 32403415; PMCID: PMC7281181.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548002/ PubMed PMID: 31643334.

2: Tzogani K, Florez B, Markey G, Caleno M, Olimpieri OM, Melchiorri D, Hovgaard DJ, Sarac SB, Penttilä K, Lapveteläinen T, Salmonson T, Bergh J, Gisselbrecht C, Pignatti F. European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. ESMO Open. 2019 Sep 8;4(5):e000570. doi: 10.1136/esmoopen-2019-000570. eCollection 2019. Review. PubMed PMID: 31555488; PubMed Central PMCID: PMC6735670.

3: Armoiry X, Spath HM, Clarke A, Connock M, Sutcliffe P, Dussart C. Comparison of health technology assessment for new medicines in France and England: an example based on ixazomib for patients with relapsed or refractory multiple myeloma. J Mark Access Health Policy. 2019 Jul 30;7(1):1648971. doi: 10.1080/20016689.2019.1648971. eCollection 2019. Review. PubMed PMID: 31489149; PubMed Central PMCID: PMC6711145.

4: Smolewski P, Rydygier D. Ixazomib: an investigational drug for the treatment of lymphoproliferative disorders. Expert Opin Investig Drugs. 2019 May;28(5):421-433. doi: 10.1080/13543784.2019.1596258. Epub 2019 Apr 13. Review. PubMed PMID: 30907163.

5: Richardson PG, Zweegman S, O'Donnell EK, Laubach JP, Raje N, Voorhees P, Ferrari RH, Skacel T, Kumar SK, Lonial S. Ixazomib for the treatment of multiple myeloma. Expert Opin Pharmacother. 2018 Dec;19(17):1949-1968. doi: 10.1080/14656566.2018.1528229. Epub 2018 Nov 13. Review. PubMed PMID: 30422008.

6: Zanwar S, Abeykoon JP, Kapoor P. Ixazomib: a novel drug for multiple myeloma. Expert Rev Hematol. 2018 Oct;11(10):761-771. doi: 10.1080/17474086.2018.1518129. Review. PubMed PMID: 30173621.

7: Gupta N, Hanley MJ, Xia C, Labotka R, Harvey RD, Venkatakrishnan K. Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor. Clin Pharmacokinet. 2019 Apr;58(4):431-449. doi: 10.1007/s40262-018-0702-1. Review. PubMed PMID: 30117017; PubMed Central PMCID: PMC6397141.

8: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500850/ PubMed PMID: 29999909.

9: Machida M, Fukunaga S, Hara T. [Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO(®) capsules; 2.3 mg, 3 mg, and 4 mg)]. Nihon Yakurigaku Zasshi. 2018;151(4):166-178. doi: 10.1254/fpj.151.166. Review. Japanese. PubMed PMID: 29628465.

10: Armoiry X, Connock M, Tsertsvadze A, Cummins E, Melendez-Torres GJ, Royle P, Clarke A. Ixazomib for Relapsed or Refractory Multiple Myeloma: Review from an Evidence Review Group on a NICE Single Technology Appraisal. Pharmacoeconomics. 2018 Sep;36(9):1073-1081. doi: 10.1007/s40273-018-0644-3. Review. PubMed PMID: 29582405.

11: Touzeau C, Moreau P. Ixazomib in the management of relapsed multiple myeloma. Future Oncol. 2018 Aug;14(20):2013-2020. doi: 10.2217/fon-2017-0710. Epub 2018 Feb 22. Review. PubMed PMID: 29469592.

12: Gupta N, Hanley MJ, Diderichsen PM, Yang H, Ke A, Teng Z, Labotka R, Berg D, Patel C, Liu G, van de Velde H, Venkatakrishnan K. Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor. Clin Pharmacol Ther. 2019 Feb;105(2):376-387. doi: 10.1002/cpt.1047. Epub 2018 Mar 23. Review. PubMed PMID: 29446068; PubMed Central PMCID: PMC6585617.

13: Salvini M, Troia R, Giudice D, Pautasso C, Boccadoro M, Larocca A. Pharmacokinetic drug evaluation of ixazomib citrate for the treatment of multiple myeloma. Expert Opin Drug Metab Toxicol. 2018 Jan;14(1):91-99. doi: 10.1080/17425255.2018.1417388. Epub 2017 Dec 19. Review. PubMed PMID: 29235380.

14: Richardson PG, Kumar S, Laubach JP, Paba-Prada C, Gupta N, Berg D, van de Velde H, Moreau P. New developments in the management of relapsed/refractory multiple myeloma - the role of ixazomib. J Blood Med. 2017 Aug 22;8:107-121. doi: 10.2147/JBM.S102328. eCollection 2017. Review. PubMed PMID: 28860887; PubMed Central PMCID: PMC5573039.

15: Brayer J, Baz R. The potential of ixazomib, a second-generation proteasome inhibitor, in the treatment of multiple myeloma. Ther Adv Hematol. 2017 Jul;8(7):209-220. doi: 10.1177/2040620717710171. Epub 2017 Jun 28. Review. PubMed PMID: 28694935; PubMed Central PMCID: PMC5495505.

16: Bonnet A, Moreau P. Safety of ixazomib for the treatment of multiple myeloma. Expert Opin Drug Saf. 2017 Aug;16(8):973-980. doi: 10.1080/14740338.2017.1344212. Epub 2017 Jul 12. Review. PubMed PMID: 28661711.

17: Al-Salama ZT, Garnock-Jones KP, Scott LJ. Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. Target Oncol. 2017 Aug;12(4):535-542. doi: 10.1007/s11523-017-0504-7. Review. PubMed PMID: 28660423.

18: Ramirez KG. Ixazomib: An Oral Proteasome Inhibitor for the Treatment of Multiple Myeloma. J Adv Pract Oncol. 2017 May-Jun;8(4):401-405. Epub 2017 May 1. Review. PubMed PMID: 30018846; PubMed Central PMCID: PMC6040877.

19: Shirley M. Ixazomib: First Global Approval. Drugs. 2016 Mar;76(3):405-11. doi: 10.1007/s40265-016-0548-5. Review. PubMed PMID: 26846321.

20: Muz B, Ghazarian RN, Ou M, Luderer MJ, Kusdono HD, Azab AK. Spotlight on ixazomib: potential in the treatment of multiple myeloma. Drug Des Devel Ther. 2016 Jan 11;10:217-26. doi: 10.2147/DDDT.S93602. eCollection 2016. Review. PubMed PMID: 26811670; PubMed Central PMCID: PMC4714737.



Additional Information