APY29 is an ATP competitive inhibitor, a specific allosteric modulator of IRE1α, which inhibits the autonomous phosphorylation of IRE1α by binding to the ATP binding pocket, with IC50 of 280 nM. APY29 can also allosterically activate the adjacent RNase domain of IRE1α.

Physicochemical Properties

Molecular Formula	C17H16N8
Molecular Weight	332.371
Exact Mass	332.149
CAS #	1216665-49-4
PubChem CID	42627755
Appearance	White to yellow solid powder
Density	1.6±0.1 g/cm3
Boiling Point	782.3±70.0 °C at 760 mmHg
Flash Point	426.9±35.7 °C
Vapour Pressure	0.0±2.7 mmHg at 25°C
Index of Refraction	1.861
LogP	1.66
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	25
Complexity	458
Defined Atom Stereocenter Count	0
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)
Chemical Name	2-N-(3H-benzimidazol-5-yl)-4-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
Synonyms	APY29 APY 29 APY-29
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	APY29 modifies IRE1α's oligomeric state and RNase activity in distinct ways. Using the same binding site, APY29 affects RNase activity in opposing ways. To varied degrees, APY29 influences the oligomerization of IRE1α. The dose-dependent action of APY29 on the activation of endogenous IRE1α RNase caused by ER stress is opposite [1].
References	[1]. Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors. Nat Chem Biol. 2012 Dec;8(12):982-9.

Solubility Data

Solubility (In Vitro)

DMSO : ~53.33 mg/mL (~160.46 mM) H2O : ~5 mg/mL (~15.04 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (15.04 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 5 mg/mL (15.04 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 5 mg/mL (15.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0087 mL	15.0435 mL	30.0870 mL
	5 mM	0.6017 mL	3.0087 mL	6.0174 mL
	10 mM	0.3009 mL	1.5043 mL	3.0087 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.