WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H530398
CAS#: 1216665-49-4
Description: APY29, also known as ASC-29, is a IRE1α inhibitor. The accumulation of unfolded proteins under endoplasmic reticulum (ER) stress leads to the activation of the multidomain protein sensor IRE1α as part of the unfolded protein response (UPR). ATP-competitive inhibitors of IRE1α promote dimerization and activation of RNase activity despite blocking kinase autophosphorylation.
Hodoodo Cat#: H530398
Name: APY29
CAS#: 1216665-49-4
Chemical Formula: C17H16N8
Exact Mass: 332.15
Molecular Weight: 332.371
Elemental Analysis: C, 61.43; H, 4.85; N, 33.71
Synonym: APY29; APY-29; APY 29; ASC-29; ASC 29; ASC29;
IUPAC/Chemical Name: (E)-N-(6-((5-cyclopropyl-1H-pyrazol-3-yl)imino)-1,6-dihydropyrimidin-2-yl)-1H-benzo[d]imidazol-6-amine
InChi Key: WJNBSTLIALIIEW-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H16N8/c1-2-10(1)13-8-16(25-24-13)22-15-5-6-18-17(23-15)21-11-3-4-12-14(7-11)20-9-19-12/h3-10H,1-2H2,(H,19,20)(H3,18,21,22,23,24,25)
SMILES Code: C12=CC(NC3=NC=C/C(N3)=N\C4=NNC(C5CC5)=C4)=CC=C1N=CN2
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: >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: | APY29 inhibits IRE1α autophosphorylation by binding to the ATP-binding pocket with an IC50 of 280 nM. |
In vitro activity: | To test the hypothesis that IRE1 self-regulates its expression under ER stress through the activity of its kinase domain and subsequent activation of JNK and JNK-dependent transcription, SH-SY5Y cells were pretreated with APY29 before inducing ER stress, and whether IRE1 levels were affected was analyzed (Fig. 6, A and B). In cells treated with APY29 and Tg, IRE1 protein levels were lower compared with cells treated with Tg, demonstrating that ER stress-dependent induction of IRE1 expression was impaired in these cells. There was no IRE1 phosphorylation detectable in APY29-treated cells, indicating effective inhibition of IRE1 kinase. Deficient IRE1 activation was further illustrated by low levels of spliced XBP1 in the APY29-treated cells. c-JUN phosphorylation was reduced in APY29-treated cells compared with Tg only–treated cells, indicating inhibition of JNK and suggesting that IRE1 kinase-dependent phosphorylation was an upstream event. Reference: J Biol Chem. 2018 Nov 23;293(47):18270-18284. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254332/ |
In vivo activity: | TBD |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
Ethanol:PBS (pH 7.2) (1:3) | 0.3 | 0.75 | |
Ethanol | 15.0 | 45.13 |
The following data is based on the product molecular weight 332.37 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.
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. Walter F, O'Brien A, Concannon CG, Düssmann H, Prehn JHM. ER stress signaling has an activating transcription factor 6α (ATF6)-dependent "off-switch". J Biol Chem. 2018 Nov 23;293(47):18270-18284. doi: 10.1074/jbc.RA118.002121. Epub 2018 Oct 4. PMID: 30287689; PMCID: PMC6254332. |
In vitro protocol: | 1. Walter F, O'Brien A, Concannon CG, Düssmann H, Prehn JHM. ER stress signaling has an activating transcription factor 6α (ATF6)-dependent "off-switch". J Biol Chem. 2018 Nov 23;293(47):18270-18284. doi: 10.1074/jbc.RA118.002121. Epub 2018 Oct 4. PMID: 30287689; PMCID: PMC6254332. |
In vivo protocol: | TBD |