MKC8866 (IRE-1α inhibitor 1) (Synonyms: Orin1001) |
| Katalog-Nr.GC32889 |
MKC8866 (IRE-1α Inhibitor 1), ein Salicylaldehyd-Analogon, ist ein potenter, selektiver IRE1-RNase-Inhibitor mit einem IC50 von 0,29μM in human vitro. MKC8866 (IRE-1α Inhibitor 1) hemmt stark die Expression von Dithiothreitol-induziertem X-box-bindendem Protein 1-gespleißt (XBP1s) mit einem EC50 von 0,52&7#956;M und entstresst RPMI 8226-Zellen mit einem IC50 von 0,14μM. MKC8866 (IRE-1α Inhibitor 1) hemmt die IRE1-RNase in Brustkrebszellen, was zu einer verringerten Produktion von protumorigenen Faktoren fÜhrt, und kann das Tumorwachstum von Prostatakrebs (PCa) hemmen.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1338934-59-0
Sample solution is provided at 25 µL, 10mM.
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MKC8866 is an inositol requiring enzyme 1 (IRE-1α) inhibitor with an IC50 of less than 0.1 μM.
Protein folding stress in the endoplasmic reticulum of a cell initiates a signal transduction cascade termed the unfolded protein response or UPR. A key enzyme, inositol requiring enzyme 1 (IRE-1α), relieves protein folding stress by enhancing molecular chaperone activity and therefore protects cells from stress induced apoptosis. MKC8866 is useful for treating at least B cell autoimmune diseases, certain cancers, and some viral infections. MKC8866 (Compound 167) inhibits IRE-1α in the in vitro assay with an IC50 of <0.1 μM. MKC8866 (Compound 167) IRE-1α in an in vivo XBP-1 splicing assay (e.g., in myeloma cells) with an EC50<10 μM[1].
MKC8866 is a selective IRE1 RNase inhibitor that exhibits acceptable pharmacokinetic and toxicity profiles. To determine the efficacy of MKC8866 treatment in vivo, MDA-MB-231 tumor xenografts are established in athymic nude mice. Once tumors have reached a palpable size (225-250 mm3), animals are randomized into treatment groups and treated with vehicle alone, 300 mg/kg MKC8866 alone, 10 mg/kg Paclitaxel alone or a combination of Paclitaxel and MKC8866. Treatments in all groups are administered until tumors reach maximal size (2000 mm3) or on day 60, whichever came first. MKC8866 is well tolerated after 60 consecutive oral doses and, based on pharmacokinetic allometric scaling, systemic exposures are well above anticipated clinical therapeutic levels. Following MDA-MB-231 tumor formation, mice are treated with Paclitaxel alone (7.5 mg/kg) for days 1-10, or a combination of Paclitaxel (days 1-10) and MKC8866 (300 mg/kg, days 1-28). After withdrawal of Paclitaxel treatment on day 10, an initial reduction in tumor volume is apparent in both treatment groups. Tumor re-growth, evident after day 18 in those animals receiving no further treatment, is repressed in the treatment group still receiving MKC8866. Tumor re-growth is only apparent in this group following cessation of MKC8866 on day 28[2].
[1]. Zeng, Qingping, et al. IRE-1α inhibitors. US9867803. [2]. Logue SE, et al. Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy. Nat Commun. 2018 Aug 15;9(1):3267.
| Cas No. | 1338934-59-0 | SDF | |
| Überlieferungen | Orin1001 | ||
| Canonical SMILES | O=CC1=C(O2)C(C(C)=C(CC(N3CCOCC3)=O)C2=O)=CC(OC)=C1O | ||
| Formula | C18H19NO7 | M.Wt | 361.35 |
| Löslichkeit | DMSO : 16.67 mg/mL (46.13 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7674 mL | 13.837 mL | 27.674 mL |
| 5 mM | 0.5535 mL | 2.7674 mL | 5.5348 mL |
| 10 mM | 0.2767 mL | 1.3837 mL | 2.7674 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)
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