Cat. No.: HY-116480

LY593093

LY593093 is an orally active, selective, partial, orthosteric M1AChR agonist. LY593093 stimulates hippocampal phosphoinositide hydrolysis. LY593093 is used in research on Alzheimer's disease and schizophrenia.

For research use only. We do not sell to patients.

Purity : 98.82%
CAS No.: 1108748-12-4
Formula: C₃₂H₃₀FN₃O₂
Molecular Weight:507.60

Storage:

Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month

LY593093 Chemical Structure

CAS No.: 1108748-12-4

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]

mAChR1

All mAChR Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	EC50	22.8 nM	Agonist-stimulated [35S]-GTPγS binding activity in CHO cells expressing muscarinic M1 receptor using anti-G protein antibody assay. Agonist-stimulated [35S]-GTPγS binding activity in CHO cells expressing muscarinic M1 receptor using anti-G protein antibody assay.	S0960894X15008355
CHO	EC50	693 nM	Agonist-stimulated [35S]-GTPγS binding activity in CHO cells expressing muscarinic M2 receptor using anti-G protein antibody assay. Agonist-stimulated [35S]-GTPγS binding activity in CHO cells expressing muscarinic M2 receptor using anti-G protein antibody assay.	S0960894X15008355
CHO	EC50	1060 nM	Agonist-stimulated [35S]-GTPγS binding activity in CHO cells expressing muscarinic M4 receptor using anti-G protein antibody assay. Agonist-stimulated [35S]-GTPγS binding activity in CHO cells expressing muscarinic M4 receptor using anti-G protein antibody assay.	S0960894X15008355
CHO	EC50	49.9 nM	Calcium mobilization in CHO cells stably overexpressing M1AChR assessed with Fluo-4 dye after 45-min loading and 6-min equilibration by FLIPR. Calcium mobilization in CHO cells stably overexpressing M1AChR assessed with Fluo-4 dye after 45-min loading and 6-min equilibration by FLIPR.	21558436
CHO	EC50	6053 nM	Calcium mobilization in CHO cells stably overexpressing M3AChR assessed with Fluo-4 dye after 45-min loading and 6-min equilibration by FLIPR. Calcium mobilization in CHO cells stably overexpressing M3AChR assessed with Fluo-4 dye after 45-min loading and 6-min equilibration by FLIPR.	21558436
CHO	EC50	100000 nM	Calcium mobilization in CHO cells stably overexpressing M5AChR assessed with Fluo-4 dye after 45-min loading and 6-min equilibration by FLIPR with EC50 ≥ 100000 nM. Calcium mobilization in CHO cells stably overexpressing M5AChR assessed with Fluo-4 dye after 45-min loading and 6-min equilibration by FLIPR with EC50 ≥ 100000 nM.	21558436
CHO-K1	EC50	1.95 μM	Partial agonist activity at M1AChR-mediated β-arrestin 3 recruitment in PathHunter CHO-K1 cells assessed by β-galactosidase complementation after 90-min ligand incubation and 60-min detection. Partial agonist activity at M1AChR-mediated β-arrestin 3 recruitment in PathHunter CHO-K1 cells assessed by β-galactosidase complementation after 90-min ligand incubation and 60-min detection.	21558436

In Vitro

Glutamate Release or ReceptorsOthers

Glutamate Release or Receptors

LY593093 (10 µM) shows minimal off-target affinity across 64 proteins, inhibiting more than 50% of radioligand binding only at the dopamine transporter, 5-HT2A receptor, and glutamate chloride-dependent site^[2].

Others

LY593093 is a potent M1 agonist (EC₅₀ = 22.8 nM, efficacy 110%) that exhibits weaker M2/M4 activity and no detectable M3/M5 activity in CHO cells expressing muscarinic receptors^[1].
LY593093 (1-10 µM; 2 h) competes with [³H]NMS at M1AChR and M2AChR with K_i values of 622 nM and 890 nM, respectively, and shows no significant affinity for M3-M5AChR in membrane binding assays^[2].
LY593093 (30 min) exhibits functional selective partial agonist activity at M1AChR in CHO membranes, with an EC₅₀ of 219 nM and an E_max of 94.3%, and shows only modest M2/M4 activity or no M3/M5 activity^[2].
LY593093 preferentially stimulates M1AChR-mediated Ca²⁺ mobilization in CHO cells, with an EC₅₀ of 49.9 nM and an E_max of 85.3%, and shows 100-fold and 2000-fold selectivity for M3AChR and M5AChR, respectively^[2].
LY593093 (90 min) exhibits partial agonist activity for M1AChR-mediated β-arrestin 3 recruitment in CHO-K1 cells with an EC₅₀ of 1.95 µM, and also antagonizes ACh-stimulated recruitment^[2].
LY593093 displaces [³H]NMS from the M1 muscarinic receptor with a pK_i of 6.21 and shows no [³H]NMS binding effect at M3-M5 AChRs^[3].
LY593093 stimulates β-arrestin recruitment in cells expressing muscarinic receptors^[3].
LY593093 does not enhance the functional activity of ACh, and its potency for M1 is 5-fold and 120-fold that for the other muscarinic receptor subtypes, respectively, with an E_max at least 2-fold higher^[3].
LY593093 binds the orthosteric site of muscarinic receptors with a pK_i of 6.21 and is not potentiated by BQCA^[4].
LY593093 is a potent recombinant M1 agonist with an EC₅₀ of ~50 nM and an E_max of ~85% ACh in calcium mobilization assays, showing >100-fold selectivity over hM3 and hM5^[4].
LY593093 activates recombinant hM1 GTPγ[³⁵S]-Gq binding with an EC₅₀ of 219 nM (E_max 95%), and shows weaker activity at hM2 (1.07 mM; <25%) and hM4 (>10 μM; <25%)^[4].
LY593093 exhibits >350-fold selectivity for native M1 over rat M2 and M3, and no agonist activity is detected at >30,000 nM in rat atria and ileum^[4].
LY593093 activates GTPγ[³⁵S]-Gq signaling in mouse hippocampus with an EC₅₀ of 4 nM (E_max 93%), and this response is mediated by M1, as it is abolished in M1 knockout hippocampus^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Parmacokinetics

Species	Dose	Route	Bioavailability
Rat^[1]	10 mg/kg	p.o.	32 %

In Vivo

LY593093 (1 mg/kg; p.o.) produces robust efficacy in the rat 8-arm radial maze with a minimum effective oral dose of 1 mg/kg^[1].
LY593093 (3-10 mg/kg; p.o.; single administration) increases hippocampal phosphoinositide hydrolysis in rats^[2].
LY593093 (3-30 mg/kg (Experiment 1); 0.3-3 mg/kg (Experiment 2); p.o.; once daily; 3 h before each of 4 daily maze sessions) improves spatial learning acquisition in rats, reducing day 4 radial arm maze errors at 3 and 10 mg/kg in Experiment 1 and at 3 mg/kg in Experiment 2^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Rat^[1]
Dosage:

1 mg/kg
Administration:

p.o.
Result:

Showed robust efficacy over a range of doses in the rat 8-arm radial maze, with a minimum effective dose of 1 mg/kg when orally dosed.

Animal Model:

Sprague-Dawley (male, 95-110 g)^[2]
Dosage:

3 mg/kg; 10 mg/kg
Administration:

p.o.; single administration 1 h after lithium chloride
Result:

Hippocampal conversion of 3H radioactivity to [3H]inositol monophosphates increased in a dose-related manner.
A 10 mg/kg dose produced a 165% increase compared with the lithium-alone group.

Animal Model:

Sprague-Dawley (male, approximately 200-225 g)^[2]
Dosage:

3, 10, and 30 mg/kg (Experiment 1); 0.3, 1, and 3 mg/kg (Experiment 2)
Administration:

p.o.; once daily; 3 h before each of 4 daily maze sessions
Result:

In Experiment 1, day 4 total errors were reduced relative to vehicle at 3 mg/kg and 10 mg/kg.
In Experiment 2, day 4 total errors were reduced relative to vehicle at 3 mg/kg.

Related Protocols :

Alzheimer’s Disease Modeling

Chemical Information

CAS No. 1108748-12-4
Appearance Solid
Molecular Weight 507.60
Formula C₃₂H₃₀FN₃O₂
Color White to off-white
SMILES

O=C(C1=CC=C(C2=CC=CC=C2)C=C1)N[C@@H]3C4=CC(/N=C(C)/N(C)CC5=CC=C(C=C5)F)=CC=C4C[C@H]3O
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (197.01 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.9701 mL

9.8503 mL

19.7006 mL

5 mM

0.3940 mL

1.9701 mL

3.9401 mL

10 mM

0.1970 mL

0.9850 mL

1.9701 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (4.93 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (4.93 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (294 KB)
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Liu B, et al. Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl] arylamides as selective and potent muscarinic M1 agonists[J]. Bioorganic & Medicinal Chemistry Letters, 2015, 25(19): 4158-4163.

[2]. Watt ML, et al. Pharmacological characterization of LY593093, an M1 muscarinic acetylcholine receptor-selective partial orthosteric agonist. J Pharmacol Exp Ther. 2011 Aug;338(2):622-32.

[3]. Volpato D, et al. Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer's Disease. Molecules. 2018 Dec 7;23(12):3230.

[4]. Felder CC, et al. Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases. Neuropharmacology. 2018 Jul 1;136(Pt C):449-458. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.9701 mL	9.8503 mL	19.7006 mL	49.2514 mL
	5 mM	0.3940 mL	1.9701 mL	3.9401 mL	9.8503 mL
	10 mM	0.1970 mL	0.9850 mL	1.9701 mL	4.9251 mL
	15 mM	0.1313 mL	0.6567 mL	1.3134 mL	3.2834 mL
	20 mM	0.0985 mL	0.4925 mL	0.9850 mL	2.4626 mL
	25 mM	0.0788 mL	0.3940 mL	0.7880 mL	1.9701 mL
	30 mM	0.0657 mL	0.3283 mL	0.6567 mL	1.6417 mL
	40 mM	0.0493 mL	0.2463 mL	0.4925 mL	1.2313 mL
	50 mM	0.0394 mL	0.1970 mL	0.3940 mL	0.9850 mL
	60 mM	0.0328 mL	0.1642 mL	0.3283 mL	0.8209 mL
	80 mM	0.0246 mL	0.1231 mL	0.2463 mL	0.6156 mL
	100 mM	0.0197 mL	0.0985 mL	0.1970 mL	0.4925 mL

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

LY593093

All mAChR Isoforms