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MedKoo Cat#: 407345 | Name: MI-2 MALT1 inhibitor
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Description:

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

MI-2 MALT1 inhibitor, also known as MI-2, is a MALT1 inhibitor (IC50 = 5.84 μM). MI-2 binds directly to MALT1 and irreversibly suppresses protease function. Decreases NF-κB activity induced by MALT1. Mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), a paracaspase and essential regulator for nuclear factor kB (NF-κB) activation, plays an important role in innate and adaptive immunity. Suppression of MALT1 protease activity with small molecule inhibitors showed promising efficacies in subtypes of B cell lymphoma and improvement in experimental autoimmune encephalomyelitis model.

Chemical Structure

MI-2 MALT1 inhibitor
MI-2 MALT1 inhibitor
CAS#1047953-91-2

Theoretical Analysis

MedKoo Cat#: 407345

Name: MI-2 MALT1 inhibitor

CAS#: 1047953-91-2

Chemical Formula: C19H17Cl3N4O3

Exact Mass: 454.0366

Molecular Weight: 455.72

Elemental Analysis: C, 50.08; H, 3.76; Cl, 23.34; N, 12.29; O, 10.53

Price and Availability

Size Price Availability Quantity
5mg USD 75.00 Ready to ship
10mg USD 120.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,450.00 Ready to ship
1g USD 3,450.00 Ready to ship
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Related CAS #
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Synonym
MI-2; MI 2; MI2; MALT1 inhibitor
IUPAC/Chemical Name
2-chloro-N-(4-(5-(3,4-dichlorophenyl)-3-(2-methoxyethoxy)-1H-1,2,4-triazol-1-yl)phenyl)acetamide
InChi Key
TWJGQZBSEMDPQP-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H17Cl3N4O3/c1-28-8-9-29-19-24-18(12-2-7-15(21)16(22)10-12)26(25-19)14-5-3-13(4-6-14)23-17(27)11-20/h2-7,10H,8-9,11H2,1H3,(H,23,27)
SMILES Code
O=C(NC1=CC=C(N2N=C(OCCOC)N=C2C3=CC=C(Cl)C(Cl)=C3)C=C1)CCl
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
Biological target:
MALT1 inhibitor MI-2 is a MALT1 inhibitor with an IC50 of 5.84 μM.
In vitro activity:
MI-2 suppressed cleavage of the MALT-1-target protein, CYLD, and inhibited proliferation via G1 phase arrest in adult T-cell leukemia cell lines. MI-2 induced apoptosis through caspase-3/8/9 activation and inhibited the phosphorylation of IKKα/β and IκBα, resulting in the accumulation of IκBα and suppression of NF-κB-DNA binding. Additionally, MI-2 inhibited the expression of apoptosis- and cell cycle-related proteins regulated by NF-κB. Reference: Eur J Haematol. 2020 Oct;105(4):460-467. https://onlinelibrary.wiley.com/doi/10.1111/ejh.13467
In vivo activity:
In order to determine whether MI-2 could suppress DLBCLs in vivo, HBL-1 and TMD8 (MALT1-dependent) and OCI-Ly1 (MALT1-independent) DLBCL cells were engrafted into the right flank region of nonobese diabetic/severe combined immunodeficiency (NOD-SCID) mice. MI-2 profoundly suppressed the growth of both the TMD8 and HBL-1 ABC-DLBCL xenografts versus vehicle, whereas it had no effect on the growth of OCI-Ly1 tumors (Figure 7A). The fact that OCI-Ly1 tumors were unaffected suggests that MI-2 activity is due to its effects on lymphoma cells rather than the host microenvironment. Histological examination using the TUNEL assay to detect apoptotic cells showed a significant increase in apoptotic cells in MI-2-treated HBL-1 and TMD8 xenografts relative to vehicle but not in OCI-Ly1 xenografts (Figures 7B and S6A). A significant decrease in proliferation as measured by Ki-67 staining in HBL-1 and TMD8 xenografts compared to vehicle was also observed, but no difference in OCI-Ly1 xenografts was observed (Figures 7C and S6B). Reference: Cancer Cell. 2012 Dec 11;22(6):812-24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984478/
Solvent mg/mL mM comments
Solubility
DMF 33.0 72.41
DMSO 54.1 188.71
DMSO:PBS (pH 7.2) (1:3) 0.3 0.55
Ethanol 38.7 84.92
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 455.72 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. Ishikawa C, Mori N. MALT-1 as a novel therapeutic target for adult T-cell leukemia. Eur J Haematol. 2020 Oct;105(4):460-467. doi: 10.1111/ejh.13467. Epub 2020 Jul 24. PMID: 32574386. 2. Dezorella N, Ashkenazi E, Shapiro M, Perry C, Kamdjou T, Katz BZ, Herishanu Y. Wide-range effects of the MALT-1 inhibitor Mi-2 in CLL cells results in apoptosis. Leuk Lymphoma. 2019 Mar;60(3):817-820. doi: 10.1080/10428194.2018.1498489. Epub 2018 Oct 4. PMID: 30284489. 3. Lee KW, Kim M, Lee CH. Treatment of Dextran Sulfate Sodium-Induced Colitis with Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor MI-2 Is Associated with Restoration of Gut Immune Function and the Microbiota. Infect Immun. 2018 Nov 20;86(12):e00091-18. doi: 10.1128/IAI.00091-18. PMID: 30249750; PMCID: PMC6246915. 4. Fontan L, Yang C, Kabaleeswaran V, Volpon L, Osborne MJ, Beltran E, Garcia M, Cerchietti L, Shaknovich R, Yang SN, Fang F, Gascoyne RD, Martinez-Climent JA, Glickman JF, Borden K, Wu H, Melnick A. MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo. Cancer Cell. 2012 Dec 11;22(6):812-24. doi: 10.1016/j.ccr.2012.11.003. PMID: 23238016; PMCID: PMC3984478.
In vitro protocol:
1. Ishikawa C, Mori N. MALT-1 as a novel therapeutic target for adult T-cell leukemia. Eur J Haematol. 2020 Oct;105(4):460-467. doi: 10.1111/ejh.13467. Epub 2020 Jul 24. PMID: 32574386. 2. Dezorella N, Ashkenazi E, Shapiro M, Perry C, Kamdjou T, Katz BZ, Herishanu Y. Wide-range effects of the MALT-1 inhibitor Mi-2 in CLL cells results in apoptosis. Leuk Lymphoma. 2019 Mar;60(3):817-820. doi: 10.1080/10428194.2018.1498489. Epub 2018 Oct 4. PMID: 30284489.
In vivo protocol:
1. Lee KW, Kim M, Lee CH. Treatment of Dextran Sulfate Sodium-Induced Colitis with Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor MI-2 Is Associated with Restoration of Gut Immune Function and the Microbiota. Infect Immun. 2018 Nov 20;86(12):e00091-18. doi: 10.1128/IAI.00091-18. PMID: 30249750; PMCID: PMC6246915. 2. Fontan L, Yang C, Kabaleeswaran V, Volpon L, Osborne MJ, Beltran E, Garcia M, Cerchietti L, Shaknovich R, Yang SN, Fang F, Gascoyne RD, Martinez-Climent JA, Glickman JF, Borden K, Wu H, Melnick A. MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo. Cancer Cell. 2012 Dec 11;22(6):812-24. doi: 10.1016/j.ccr.2012.11.003. PMID: 23238016; PMCID: PMC3984478.
1: Fusco R, Siracusa R, D'Amico R, Cordaro M, Genovese T, Gugliandolo E, Peritore AF, Crupi R, Di Paola R, Cuzzocrea S, Impellizzeri D. Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor as a Novel Therapeutic Tool for Lung Injury. Int J Mol Sci. 2020 Oct 20;21(20):7761. doi: 10.3390/ijms21207761. PMID: 33092214; PMCID: PMC7589767. 2: Wang R, Zhang H, Xu J, Zhang N, Pan T, Zhong X, Zhang H, Yin L, Yao Y, Wu Q, Li Z, Liu X, Xu K, Niu M. MALT1 Inhibition as a Therapeutic Strategy in T-Cell Acute Lymphoblastic Leukemia by Blocking Notch1-Induced NF-κB Activation. Front Oncol. 2020 Sep 23;10:558339. doi: 10.3389/fonc.2020.558339. PMID: 33072583; PMCID: PMC7538650. 3: Ishikawa C, Mori N. MALT-1 as a novel therapeutic target for adult T-cell leukemia. Eur J Haematol. 2020 Oct;105(4):460-467. doi: 10.1111/ejh.13467. Epub 2020 Jul 24. PMID: 32574386. 4: Liu X, Yue C, Shi L, Liu G, Cao Q, Shan Q, Wang Y, Chen X, Li H, Wang J, Gao S, Niu M, Yu R. MALT1 is a potential therapeutic target in glioblastoma and plays a crucial role in EGFR-induced NF-κB activation. J Cell Mol Med. 2020 Jul;24(13):7550-7562. doi: 10.1111/jcmm.15383. Epub 2020 May 25. PMID: 32452133; PMCID: PMC7339184. 5: Izumi K, Nishikori M, Yuan H, Otsuka Y, Nakao K, Takaori-Kondo A. Establishment and characterization of a MALT lymphoma cell line carrying an API2-MALT1 translocation. Genes Chromosomes Cancer. 2020 Sep;59(9):517-524. doi: 10.1002/gcc.22855. Epub 2020 May 6. PMID: 32348592. 6: Dezorella N, Ashkenazi E, Shapiro M, Perry C, Kamdjou T, Katz BZ, Herishanu Y. Wide-range effects of the MALT-1 inhibitor Mi-2 in CLL cells results in apoptosis. Leuk Lymphoma. 2019 Mar;60(3):817-820. doi: 10.1080/10428194.2018.1498489. Epub 2018 Oct 4. PMID: 30284489. 7: Lee KW, Kim M, Lee CH. Treatment of Dextran Sulfate Sodium-Induced Colitis with Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor MI-2 Is Associated with Restoration of Gut Immune Function and the Microbiota. Infect Immun. 2018 Nov 20;86(12):e00091-18. doi: 10.1128/IAI.00091-18. PMID: 30249750; PMCID: PMC6246915. 8: Wu G, Wang H, Zhou W, Zeng B, Mo W, Zhu K, Liu R, Zhou J, Chen C, Chen H. Synthesis and structure-activity relationship studies of MI-2 analogues as MALT1 inhibitors. Bioorg Med Chem. 2018 Jul 23;26(12):3321-3344. doi: 10.1016/j.bmc.2018.04.059. Epub 2018 May 2. PMID: 29751989. 9: Saba NS, Wong DH, Tanios G, Iyer JR, Lobelle-Rich P, Dadashian EL, Liu D, Fontan L, Flemington EK, Nichols CM, Underbayev C, Safah H, Melnick A, Wiestner A, Herman SEM. MALT1 Inhibition Is Efficacious in Both Naïve and Ibrutinib- Resistant Chronic Lymphocytic Leukemia. Cancer Res. 2017 Dec 15;77(24):7038-7048. doi: 10.1158/0008-5472.CAN-17-2485. Epub 2017 Oct 9. PMID: 28993409; PMCID: PMC5732856. 10: Lee CH, Bae SJ, Kim M. Mucosa-associated lymphoid tissue lymphoma translocation 1 as a novel therapeutic target for rheumatoid arthritis. Sci Rep. 2017 Sep 19;7(1):11889. doi: 10.1038/s41598-017-12349-9. PMID: 28928392; PMCID: PMC5605699. 11: Liu W, Guo W, Hang N, Yang Y, Wu X, Shen Y, Cao J, Sun Y, Xu Q. MALT1 inhibitors prevent the development of DSS-induced experimental colitis in mice via inhibiting NF-κB and NLRP3 inflammasome activation. Oncotarget. 2016 May 24;7(21):30536-49. doi: 10.18632/oncotarget.8867. PMID: 27105502; PMCID: PMC5058699. 12: Xin BT, Schimmack G, Du Y, Florea BI, van der Marel GA, Driessen C, Krappmann D, Overkleeft HS. Development of new Malt1 inhibitors and probes. Bioorg Med Chem. 2016 Aug 1;24(15):3312-29. doi: 10.1016/j.bmc.2016.03.035. Epub 2016 Mar 28. PMID: 27085674. 13: Li H, He H, Gong L, Fu M, Wang TT. Short Communication: Preferential Killing of HIV Latently Infected CD4(+) T Cells by MALT1 Inhibitor. AIDS Res Hum Retroviruses. 2016 Feb;32(2):174-7. doi: 10.1089/AID.2015.0343. PMID: 26728103; PMCID: PMC4761853. 14: Fontan L, Yang C, Kabaleeswaran V, Volpon L, Osborne MJ, Beltran E, Garcia M, Cerchietti L, Shaknovich R, Yang SN, Fang F, Gascoyne RD, Martinez-Climent JA, Glickman JF, Borden K, Wu H, Melnick A. MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo. Cancer Cell. 2012 Dec 11;22(6):812-24. doi: 10.1016/j.ccr.2012.11.003. PMID: 23238016; PMCID: PMC3984478.