APY29 | CAS#1216665-49-4 | IRE1α inhibitor

MedKoo Cat#: 530398 | Name: APY29

Description:

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

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.

Chemical Structure

APY29

CAS#1216665-49-4

Theoretical Analysis

MedKoo Cat#: 530398

Name: APY29

CAS#: 1216665-49-4

Chemical Formula: C17H16N8

Exact Mass: 332.1498

Molecular Weight: 332.37

Elemental Analysis: C, 61.43; H, 4.85; N, 33.71

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 180.00	Ready to ship
50mg	USD 300.00	Ready to ship
100mg	USD 500.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,650.00	Ready to ship

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Related CAS #

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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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A21T01K28

QC Data

View QC data: current batch, Lot#A21T01K28

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	Ethanol:PBS (pH 7.2) (1:3)	0.3	0.75
	Ethanol	15.0	45.13

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 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:

In vivo protocol:

TBD

1: Mi B, Chen L, Xiong Y, Yang Y, Panayi AC, Xue H, Hu Y, Yan C, Hu L, Xie X, Lin Z, Zhou W, Cao F, Xiao X, Feng Q, Liu G. Osteoblast/Osteoclast and Immune Cocktail Therapy of an Exosome/Drug Delivery Multifunctional Hydrogel Accelerates Fracture Repair. ACS Nano. 2022 Jan 25;16(1):771-782. doi: 10.1021/acsnano.1c08284. Epub 2022 Jan 3. PMID: 34979087. 2: Qiao Y, Yu L, Yang P, Chen M, Sun H, Wang L, Wu B, Oh CD, Yang H, Bai J, Geng D. Spatiotemporal Immunomodulation and Biphasic Osteo-Vascular Aligned Electrospun Membrane for Diabetic Periosteum Regeneration. Adv Sci (Weinh). 2023 Dec;10(36):e2302874. doi: 10.1002/advs.202302874. Epub 2023 Nov 16. PMID: 37973554; PMCID: PMC10754081. 3: Li H, Li T, Hu Q, Yao Z, Li L, Huang Q, Zhou R. Inhibitors targeting the autophosphorylation of serine/threonine kinase of Streptococcus suis show potent antimicrobial activity. Front Microbiol. 2022 Sep 2;13:990091. doi: 10.3389/fmicb.2022.990091. PMID: 36118193; PMCID: PMC9478340. 4: Fan F, Liu F, Shen P, Tao L, Zhang H, Wu H. Salvianolic acid B, a new type I IRE1 kinase inhibitor, abrogates AngII-induced angiogenesis by interacting with IRE1 in its active conformation. Clin Exp Pharmacol Physiol. 2023 Jan;50(1):82-95. doi: 10.1111/1440-1681.13726. Epub 2022 Oct 11. PMID: 36153795. 5: Yuan J, Yao C, Tang J, Liu Y, Huang C, Yu S, Wei H, Han Y, Chen G. Enhanced GRP78 protein expression via the IRE1α/ASK1/p38 MAPK pathway during As₂O₃-induced endoplasmic reticulum stress in BEAS-2B cells. Toxicology. 2021 Oct;462:152962. doi: 10.1016/j.tox.2021.152962. Epub 2021 Sep 21. PMID: 34560123. 6: 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. 7: Zhu X, Xiong T, Liu P, Guo X, Xiao L, Zhou F, Tang Y, Yao P. Quercetin ameliorates HFD-induced NAFLD by promoting hepatic VLDL assembly and lipophagy via the IRE1a/XBP1s pathway. Food Chem Toxicol. 2018 Apr;114:52-60. doi: 10.1016/j.fct.2018.02.019. Epub 2018 Feb 10. PMID: 29438776.