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HomeProduct name listMKC9989

MKC9989

  • CAS NO.:1338934-20-5
  • Empirical Formula: C17H20O7
  • Molecular Weight: 336.34
  • Update Date: 2024-11-19 23:02:33
MKC9989 Structural

What is MKC9989?

Description

MKC9989 is a Hydroxy aryl aldehydes (HAA) inhibitor and also inhibits IRE1α with an IC50 of 0.23 to 44 μM.

At 10 μM concentration, MKC9989 completely inhibits both basal and thapsigargin induced splicing of XBP1 mRNA. These effects are observed even in cells pre-treated with thapsigargin, indicating that MKC9989 can fully reverse the onset of XPB1 splicing after the UPR is initiated. In parallel analysis, MKC9989, significantly stabilizes the RIDD target CD59 mRNA when co-administered with thapsigargin relative to thapsigargin treatment alone and modestly increases levels of CD59 mRNA in non-stressed cells, the latter likely reflects the inhibition of baseline RIDD activity. In contrast to effects on XBP1 splicing, MKC9989 moderately stabilizes CD59 levels when administered 2 hour post treatment with thapsigargin. Finally, the potency of MKC9989 against the splicing of XBP1 mRNA (EC50=0.33 μM) is comparable to its potency against RNA cleavage in vitro[1].

Reactions

From a functional point of the view, the MKC9989 inhibitor belongs to a series of IRE1 RNase inhibitors termed hydroxy aryl aldehydes (HAA) where the aldehyde moiety reacts chemically with the amine side chain of K907 through a Schiff base reaction[2].

References

[1]. Sanches M, et al. Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat Commun. 2014 Aug 28;5:4202.
[2] Mahdizadeh S, et al. Deciphering the selectivity of inhibitor MKC9989 towards residue K907 in IRE1α; a multiscale in silico approach. RSC Advances, 2020; 10: 19720-19729.

Properties of MKC9989

storage temp.  Store at -20°C
solubility  DMSO : ≥ 50 mg/mL (148.66 mM);Water : < 0.1 mg/mL (insoluble)
form  Solid
color  Light yellow to yellow

Safety information for MKC9989

Computed Descriptors for MKC9989

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