Azoramide 932986-18-0_Apoptosis_Apoptosis_Signaling Pathways_Products

Azoramide is a small-molecule modulator of the unfolded protein response (UPR) and an ER stress alleviator that is reported to have antidiabetic activity. It can improve ER protein-folding ability and activates ER chaperone capacity to protect cells against ER stress. Azoramide also displayed potent antidiabetic efficacy in two mouse models with obesity by improving by improving peripheral insulin sensitivity and pancreatic β-cell function. Therefore, azoramide has the potential to be developed as a drug for type 2 diabete. In addition, a recent study showed that azoramide may serve as an antagonist against GLP-1R in MSC (mesenchymal stem cells) lineage determination, and azoramide favors adipogenesis against osteogenesis through inhibiting the GLP-1 receptor-PKA-β-catenin pathway.

Physicochemical Properties

Molecular Formula

C15H17CLN2OS

Molecular Weight

308.83

Exact Mass

308.075

Elemental Analysis

C, 58.34; H, 5.55; Cl, 11.48; N, 9.07; O, 5.18; S, 10.38

CAS #

932986-18-0

Related CAS #

932986-18-0

PubChem CID

7518316

Appearance

White to off-white solid powder

Density

1.2±0.1 g/cm3

Index of Refraction

1.574

LogP

3.97

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

308

Defined Atom Stereocenter Count

SMILES

O=C(CCC)NCCC1=CSC(C2C=CC(Cl)=CC=2)=N1

InChi Key

VYBFWKKCWTXCQX-UHFFFAOYSA-N

InChi Code

InChI=1S/C15H17ClN2OS/c1-2-3-14(19)17-9-8-13-10-20-15(18-13)11-4-6-12(16)7-5-11/h4-7,10H,2-3,8-9H2,1H3,(H,17,19)

Chemical Name

N-[2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]ethyl]butanamide

Synonyms

Azoramide

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

Targets

UPR

ln Vitro

Azoramide may be protective because it increases chaperone expression while decreasing protein synthesis and does not cause cytotoxicity or apoptosis. To fully increase chaperone capacity, azoramide may need the IRE1 and PERK branches of the UPR to be present and functional. Azoramide has been discovered to be a particular type of compound with the dual ability to promote ER homeostasis by activating ER chaperone capacity both acutely and chronically. Its treatment effectively shields cells from ER stress conditions brought on by chemicals. During ER stress brought on by metabolic stress, azoramide maintains beta cell survival and function. Azoramide pretreatment's initial action does not compromise ER function. Treatment with azoramide increases SERCA expression, which improves Ca+2 retention in the ER. Azoramide interacts with UPR pathways to support ER stress resolution and enhance ER functionality[1].

ln Vivo

In mice with genetic obesity and diet-induced obesity, azoramide improves glucose homeostasis. Surprisingly, azoramide treatment significantly increases beta cell function, glucose tolerance, and insulin sensitivity in obese mice in several preclinical models[1].

Cell Assay

In either the absence or presence of 20 mM azoramide, INS1 cells are treated for 60 hours with 25 mM glucose and 500 mM palmitate (G/P). Using the CellTiter-Glo cell viability assay system, viability is evaluated after incubation.

Animal Protocol

i.p. injection; azoramide compound (20 mg/ml, 30 μl per injection) was administered via intraperitoneal injection once a day for 14 consecutive days.

C57BL/6 mice

References

[1]. Phenotypic assays identify azoramide as a small-molecule modulator of the unfolded protein response with antidiabetic activity. Sci Transl Med. 2015 Jun 17;7(292):292ra98.

[2]. Azoramide protects iPSC-derived dopaminergic neurons with PLA2G6 D331Y mutation through restoring ER function and CREB signaling. Cell Death Dis. 2020 Feb 18;11(2):130.

Solubility Data

Solubility (In Vitro)

DMSO: >61 mg/mL (~197.5 mM)

Water: < 1mg/mL

Ethanol: >61 mg/mL (~197.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.10 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 25.0 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: ≥ 2.5 mg/mL (8.10 mM) (saturation unknown) 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.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (8.10 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 25.0 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	3.2380 mL	16.1901 mL	32.3803 mL
	5 mM	0.6476 mL	3.2380 mL	6.4761 mL
	10 mM	0.3238 mL	1.6190 mL	3.2380 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.

PeptideDB

Azoramide 932986-18-0

CAS No.: 932986-18-0

Physicochemical Properties

Biological Activity

Solubility Data