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MedKoo Cat#: 563997 | Name: MKC-8866
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Description:

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

MKC-8866, also known as IRE1-IN-8866, is an inhibitor of IRE1 RNase activity. MKC8866 strongly inhibits prostate cancer (PCa) tumor growth as monotherapy in multiple preclinical models in mice and shows synergistic antitumor effects with current PCa drugs. Interestingly, global transcriptomic analysis reveal that IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in PCa.

Chemical Structure

MKC-8866
MKC-8866
CAS#1338934-59-0

Theoretical Analysis

MedKoo Cat#: 563997

Name: MKC-8866

CAS#: 1338934-59-0

Chemical Formula: C18H19NO7

Exact Mass: 361.1162

Molecular Weight: 361.35

Elemental Analysis: C, 59.83; H, 5.30; N, 3.88; O, 30.99

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,350.00 Ready to ship
200mg USD 2,250.00 Ready to ship
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Related CAS #
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Synonym
MKC-8866; MKC 8866; MKC8866; IRE1-IN-8866; IRE1IN8866; IRE1 IN 8866; IRE1-IN8866; IRE1-IN 8866; IRE1IN-8866; IRE1IN 8866
IUPAC/Chemical Name
7-Hydroxy-6-methoxy-4-methyl-3-(2-morpholino-2-oxoethyl)-2-oxo-2H-chromene-8-carbaldehyde
InChi Key
IFDGMRMUJYGWQQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H19NO7/c1-10-11-7-14(24-2)16(22)13(9-20)17(11)26-18(23)12(10)8-15(21)19-3-5-25-6-4-19/h7,9,22H,3-6,8H2,1-2H3
SMILES Code
O=CC1=C(O)C(OC)=CC2=C1OC(C(CC(N3CCOCC3)=O)=C2C)=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
Shelf Life
>3 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:
MKC8866, a salicylaldehyde analog, is a potent, selective IRE1 RNase inhibitor with an IC50 of 0.29 μM in human vitro as well as strongly inhibits Dithiothreitol-induced X-box-binding protein 1-spliced (XBP1s) expression with an EC50 of 0.52 μM and unstresses RPMI 8226 cells with an IC50 of 0.14 μM.
In vitro activity:
First, to document the effects of MKC8866 on GL261 cells in vitro, it was evaluated whether MKC8866 blocked ER stress induced by tunicamycin (TUN, an inhibitor of protein N-glycosylation and inducer of ER stress). As expected MKC8866 treatment impaired IRE1 signals as assessed by the inhibition of XBP1 mRNA splicing upon treatment with the N-glycosylation inhibitor tunicamycin. To further document these results, the expression of a genuine XBP1s target gene, ERdj4, was evaluated. ERdj4 expression increased dramatically upon TUN treatment with kinetics compatible with the activation of XBP1s and attenuated upon MKC8866 treatment. No major change was observed upon TMZ treatment. MKC8866 did not affect TUN-induced ATF4 expression, indicating that MKC8866 did not impact on PERK signaling, another ER stress sensor. Finally, since treatment of GL261 cells with MKC8866 appeared to impact on the response of these cells to different stressors, the impact IRE1 RNase inhibition on cell sensitivity to TMZ was evaluated. GL261 cells’ sensitivity to TMZ was increased upon treatment with MKC8866, phenomenon further amplified with combined irradiation. These results suggest that TMZ-induced damages to the cells promote the activation of IRE1 dependent adaptive signals that if blocked by MKC8866, decrease the cell ability to cope with TMZ treatment. Reference: Cancer Lett. 2020 Dec 1;494:73-83. https://pubmed.ncbi.nlm.nih.gov/32882336/
In vivo activity:
To test whether the adjuvant use of MKC8866 could impact on mouse survival, the combination of this inhibitor with Stupp-like treatment using the fibrin-collagen gel plug as delivery tool was evaluated. In the first instance the impact of MKC8866, Stupp-like treatment and combined therapy on tumor morphology at sacrifice was evaluated. Tumors developing in the presence of the MKC8866 containing plug and upon Stupp-like treatment presented a totally different phenotype from those developing under Stupp-like treatment alone. This phenotype corresponded to much smaller tumors with tumor escape significantly delayed. Furthermore, when necrosis was measured in tumors collected at sacrific, it was observed that the combination of Stupp-like treatment and MKC8866 yielded much important necrosis, reflecting treatment efficacy. It was found that MKC8866 yielded a significant increase of mice survival (of about 20%) compared to Stupp alone, however with no significant impact of the drug concentration used in the gel. Reference: Cancer Lett. 2020 Dec 1;494:73-83. https://pubmed.ncbi.nlm.nih.gov/32882336/
Solvent mg/mL mM comments
Solubility
DMSO 16.7 46.13
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 361.35 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. McCarthy N, Dolgikh N, Logue S, Patterson JB, Zeng Q, Gorman AM, Samali A, Fulda S. The IRE1 and PERK arms of the unfolded protein response promote survival of rhabdomyosarcoma cells. Cancer Lett. 2020 Oct 10;490:76-88. doi: 10.1016/j.canlet.2020.07.009. Epub 2020 Jul 15. PMID: 32679165. 2. Dastghaib S, Shojaei S, Mostafavi-Pour Z, Sharma P, Patterson JB, Samali A, Mokarram P, Ghavami S. Simvastatin Induces Unfolded Protein Response and Enhances Temozolomide-Induced Cell Death in Glioblastoma Cells. Cells. 2020 Oct 22;9(11):2339. doi: 10.3390/cells9112339. PMID: 33105603; PMCID: PMC7690447. 3. Sheng X, Nenseth HZ, Qu S, Kuzu OF, Frahnow T, Simon L, Greene S, Zeng Q, Fazli L, Rennie PS, Mills IG, Danielsen H, Theis F, Patterson JB, Jin Y, Saatcioglu F. IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling. Nat Commun. 2019 Jan 24;10(1):323. doi: 10.1038/s41467-018-08152-3. PMID: 30679434; PMCID: PMC6345973. 4. Le Reste PJ, Pineau R, Voutetakis K, Samal J, Jégou G, Lhomond S, Gorman AM, Samali A, Patterson JB, Zeng Q, Pandit A, Aubry M, Soriano N, Etcheverry A, Chatziioannou A, Mosser J, Avril T, Chevet E. Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo. Cancer Lett. 2020 Dec 1;494:73-83. doi: 10.1016/j.canlet.2020.08.028. Epub 2020 Sep 1. PMID: 32882336.
In vitro protocol:
1. McCarthy N, Dolgikh N, Logue S, Patterson JB, Zeng Q, Gorman AM, Samali A, Fulda S. The IRE1 and PERK arms of the unfolded protein response promote survival of rhabdomyosarcoma cells. Cancer Lett. 2020 Oct 10;490:76-88. doi: 10.1016/j.canlet.2020.07.009. Epub 2020 Jul 15. PMID: 32679165. 2. Dastghaib S, Shojaei S, Mostafavi-Pour Z, Sharma P, Patterson JB, Samali A, Mokarram P, Ghavami S. Simvastatin Induces Unfolded Protein Response and Enhances Temozolomide-Induced Cell Death in Glioblastoma Cells. Cells. 2020 Oct 22;9(11):2339. doi: 10.3390/cells9112339. PMID: 33105603; PMCID: PMC7690447.
In vivo protocol:
1. Sheng X, Nenseth HZ, Qu S, Kuzu OF, Frahnow T, Simon L, Greene S, Zeng Q, Fazli L, Rennie PS, Mills IG, Danielsen H, Theis F, Patterson JB, Jin Y, Saatcioglu F. IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling. Nat Commun. 2019 Jan 24;10(1):323. doi: 10.1038/s41467-018-08152-3. PMID: 30679434; PMCID: PMC6345973. 2. Le Reste PJ, Pineau R, Voutetakis K, Samal J, Jégou G, Lhomond S, Gorman AM, Samali A, Patterson JB, Zeng Q, Pandit A, Aubry M, Soriano N, Etcheverry A, Chatziioannou A, Mosser J, Avril T, Chevet E. Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo. Cancer Lett. 2020 Dec 1;494:73-83. doi: 10.1016/j.canlet.2020.08.028. Epub 2020 Sep 1. PMID: 32882336.
1: Dastghaib S, Shojaei S, Mostafavi-Pour Z, Sharma P, Patterson JB, Samali A, Mokarram P, Ghavami S. Simvastatin Induces Unfolded Protein Response and Enhances Temozolomide-Induced Cell Death in Glioblastoma Cells. Cells. 2020 Oct 22;9(11):2339. doi: 10.3390/cells9112339. PMID: 33105603; PMCID: PMC7690447. 2: Vieri M, Preisinger C, Schemionek M, Salimi A, Patterson JB, Samali A, Brümmendorf TH, Appelmann I, Kharabi Masouleh B. Targeting of BCR-ABL1 and IRE1α induces synthetic lethality in Philadelphia-positive acute lymphoblastic leukemia. Carcinogenesis. 2021 Feb 25;42(2):272-284. doi: 10.1093/carcin/bgaa095. PMID: 32915195. 3: Le Reste PJ, Pineau R, Voutetakis K, Samal J, Jégou G, Lhomond S, Gorman AM, Samali A, Patterson JB, Zeng Q, Pandit A, Aubry M, Soriano N, Etcheverry A, Chatziioannou A, Mosser J, Avril T, Chevet E. Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo. Cancer Lett. 2020 Dec 1;494:73-83. doi: 10.1016/j.canlet.2020.08.028. Epub 2020 Sep 1. PMID: 32882336. 4: McCarthy N, Dolgikh N, Logue S, Patterson JB, Zeng Q, Gorman AM, Samali A, Fulda S. The IRE1 and PERK arms of the unfolded protein response promote survival of rhabdomyosarcoma cells. Cancer Lett. 2020 Oct 10;490:76-88. doi: 10.1016/j.canlet.2020.07.009. Epub 2020 Jul 15. PMID: 32679165. 5: Sheng X, Nenseth HZ, Qu S, Kuzu OF, Frahnow T, Simon L, Greene S, Zeng Q, Fazli L, Rennie PS, Mills IG, Danielsen H, Theis F, Patterson JB, Jin Y, Saatcioglu F. IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling. Nat Commun. 2019 Jan 24;10(1):323. doi: 10.1038/s41467-018-08152-3. PMID: 30679434; PMCID: PMC6345973. 6: Wilhelm T, Bick F, Peters K, Mohta V, Tirosh B, Patterson JB, Kharabi- Masouleh B, Huber M. Infliction of proteotoxic stresses by impairment of the unfolded protein response or proteasomal inhibition as a therapeutic strategy for mast cell leukemia. Oncotarget. 2017 Dec 17;9(3):2984-3000. doi: 10.18632/oncotarget.23354. PMID: 29423023; PMCID: PMC5790440.