AZD3839 free base

Name: AZD3839 free base
Brand: MedChemExpress
SKU: HY-13438
Rating: 4.5 (1 reviews)

Cat. No.: HY-13438 Purity: 99.91%: Data Sheet
SDS

COA
Handling Instructions Technical Support

Solubility

In Vivo Dissolution Calculator

AZD3839 is an orally available, selective, reversible inhibitor of the β-site amyloid precursor protein cleaving enzyme BACE1 that can cross the blood-brain barrier. AZD3839 inhibits recombinant human BACE1 with a K_i=26.1 nM. AZD3839 inhibits A40 production in SH-SY5Y cells with an IC₅₀ of 4.8 nM. AZD3839 binds to BACE1 and reduces the Aβ amyloid produced by the cleavage of amyloid precursor protein (APP) by BACE1 and γ-secretase. AZD3839 can be used in the field of Alzheimer's disease research.

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

AZD3839 free base Chemical Structure

CAS No. : 1227163-84-9

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 257	In-stock	Estimated Time of Arrival: April 24
Solution
10 mM * 1 mL in DMSO	USD 270	In-stock	Estimated Time of Arrival: April 24
Solid
5 mg	USD 245	In-stock	Estimated Time of Arrival: April 24
10 mg	USD 396	In-stock	Estimated Time of Arrival: April 24
50 mg		Get quote
100 mg		Get quote

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Customer Review

Based on 1 publication(s) in Google Scholar

Other Forms of AZD3839 free base:

(Rac)-AZD3839 Get quote

1 Publications Citing Use of MCE AZD3839 free base

•Neuron. 2023 Apr 4;S0896-6273(23)00220-9. [Abstract]

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BACE1 BACE2

Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

BACE1

Cellular Effect

Cell Line	Type	Value	Description	References
Cerebral cortex neuron	IC₅₀	51 nM Compound: (S)-32	Inhibition of BACE1-mediated amyloid beta 40 release in C57/BL6 mouse primary cortical neurons after overnight incubation by ELISA Inhibition of BACE1-mediated amyloid beta 40 release in C57/BL6 mouse primary cortical neurons after overnight incubation by ELISA	[PMID: 22924815]
CHO	IC₅₀	4.8 μM Compound: (S)-32	Inhibition of human ERG expressed in CHO cells by IonWorks assay Inhibition of human ERG expressed in CHO cells by IonWorks assay	[PMID: 22924815]
SH-SY5Y	IC₅₀	16.7 nM Compound: (S)-32	Inhibition of BACE1 in human SH-SY5Y cells assessed as inhibition of sAPPbeta release after 16 hrs by immunoassay Inhibition of BACE1 in human SH-SY5Y cells assessed as inhibition of sAPPbeta release after 16 hrs by immunoassay	[PMID: 22924815]

In Vitro

In the hBACE1 and hBACE2 time-resolved fluorescence resonance energy transfer (TR-FRET) experiment, AZD3839 free base can inhibit the cleavage of APP sequence by recombinant human BACE1 in a concentration-dependent manner and inhibit the activity of BACE2. The inhibitory effect on BACE1 is 14 times stronger than that on BACE2^[1].
AZD3839 free base can effectively reduce the levels of A40 or sAPP_β secreted by the corresponding cells or neurons in the SH-SY5Y sAPP_β release assay, SH-SY5Y A40 release assay, N2A A40 release assay, mouse primary neuron A40 release assay, and guinea pig primary neuron A40 release assay, and the IC₅₀ values ??in different cells are different. For example, the IC₅₀ for inhibiting A40 levels in SH-SY5Y cells is 4.8 nM, and that in mouse primary neurons is 50.9 nM^[1].

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

Western Blot Analysis^[1]

Cell Line:	SH-SY5Y
Concentration:	IC50
Incubation Time:	16 h
Result:	Significantly reduced the levels of A40 and sAPP_β secreted by SH-SY5Y cells with IC₅₀s of 4.8 nM, and 16.7 nM. There was no mention of effects on cell viability, cell apoptosis, cell cycle, WB, qPCR, cell migration, or IF experiments in the document, so no relevant conclusions can be drawn in this regard.

In Vivo

In the female C57BL/6 mouse model, the brain concentration of AZD3839 free base (80 μmol/kg, 160 μmol/kg; oral gavage; single dose) increases rapidly and reaches a peak at 0.5 h. The levels of Aβ40, Aβ42 and sAPP in the brain decreased in a dose- and time-dependent manner. The plasma Aβ40 level is also significantly reduced, and the high dose (160 μmol/kg) had a more significant effect and lasted longer^[1].
AZD3839 free base (100 μmol/kg; oral gavage; twice a day; 7 days) inhibits the level and accumulation of Aβ40 in the mouse brain and plasma in the female C57BL/6 mouse model^[1].
AZD3839 free base (100 μmol/kg, 200 μmol/kg; oral gavage; single dose) reduces the levels of Aβ40 and Aβ42 in plasma, brain and cerebrospinal fluid of guinea pigs in a concentration- and time-dependent manner in the male Dunkin-Hartley guinea pig model^[1].
AZD3839 free base (5.5 μmol/kg, 20 μmol/kg; intravenous injection; single dose) significantly reduces the levels of Aβ40, Aβ42 and sAPP in the cerebrospinal fluid of 3-5 year old female cynomolgus monkeys^[1].

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

Animal Model:	Female C57BL/6 mice (11-14 weeks old)^[1]
Dosage:	80 μmol/kg (35 mg/kg), 160 μmol/kg (69 mg/kg), 100 μmol/kg (43 mg/kg)
Administration:	80 μmol/kg (35 mg/kg), 160 μmol/kg (69 mg/kg) as a single dose; 100 μmol/kg (43 mg/kg) as repeated doses twice daily for 7 days (dissolved in 5% dimethylacetamide and 20% hydroxypropyl-β-cyclodextrin in 0.3 M gluconic acid, pH 3, or 0.3 M gluconic acid, pH 3 alone)
Result:	Treated with a single dose of 80 μmol/kg or 160 μmol/kg, the brain concentration of AZD3839 peaked at 0.5 h after dosing. Brain Aβ40 levels decreased by 30% (80 μmol/kg dose) or 50% (160 μmol/kg dose) versus vehicle at 1.5 h after dose, and returned to baseline after 4.5 h (80 μmol/kg) or 8 h (160 μmol/kg). The levels of brain Aβ42 and sAPP followed the same pattern as Aβ40. Both doses reduced plasma levels of Aβ40 by 60% versus vehicle over a prolonged period. At 8 h after administration, the inhibitory effect started to decline within the low dose group, while maximal efficacy was maintained within the high dose group. When treated with 100 μmol/kg twice daily for 7 days, the effect on brain and plasma Aβ40 was comparable to a single administration, and no drug accumulation was observed.

Animal Model:	Male Dunkin-Hartley guinea pigs (4-9 weeks old)
Dosage:	100 μmol/kg (43 mg/kg), 200 μmol/kg (86 mg/kg)
Administration:	Oral gavage; 100 μmol/kg (43 mg/kg), 200 μmol/kg (86 mg/kg) as a single dose (dissolved in 20% hydroxypropyl-β-cyclodextrin in 0.3 M gluconic acid, pH 3)
Result:	After a single dose of 100 μmol/kg or 200 μmol/kg, brain Aβ40 was reduced up to 8 h after the dose in animals receiving the higher dose (20-60% versus vehicle), while guinea pigs receiving the lower dose demonstrated a reduction at 1.5-4.5 h after dose (20-30% versus vehicle). Reduced CSF Aβ40 levels by 50% at 3 h after 200 μmol/kg dose, and still reduced the levels were by 40% at 8 h after dose, although the reduction failed to reach statistical significance at this later time point.

Animal Model:	Female cynomolgus monkeys (3-5 years old)^[1]
Dosage:	5.5 μmol/kg (2.4 mg/kg), 20 μmol/kg (8.6 mg/kg)
Administration:	Intravenous injection via an implanted cannula in the vena cava at a constant infusion rate of 10 ml/kg/h for 15 min; single dose; dissolved in 0.3 M gluconic acid, pH 3.89
Result:	Despite a large variation in the basal CSF levels of Aβ40, Aβ42, and sAPP, an intravenous infusion of 20 μmol/kg AZD3839 significantly reduced the levels of Aβ40, Aβ42, and sAPP in CSF between 3 and 12 h after dose. The inhibitory effect on sAPP was more pronounced than the effect

Clinical Trial

Molecular Weight

431.41

Formula

C₂₄H₁₆F₃N₅

CAS No.

1227163-84-9

Appearance

Solid

Color

White to off-white

SMILES

FC1=C2C([C@](C3=CC=CC(C4=CN=CN=C4)=C3)(C5=CC(C(F)F)=NC=C5)N=C2N)=CC=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 125 mg/mL (289.75 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3180 mL	11.5899 mL	23.1798 mL
5 mM	0.4636 mL	2.3180 mL	4.6360 mL
10 mM	0.2318 mL	1.1590 mL	2.3180 mL

View the Complete Stock Solution Preparation Table

* 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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

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: ≥ 2.08 mg/mL (4.82 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (4.82 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (4.82 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 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 (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, PEG300/PEG400, Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Purity & Documentation

Purity: 99.91%

Select Batch:

Data Sheet (290 KB) SDS (392 KB)

COA (256 KB) HNMR (135 KB) LCMS (94 KB)

Handling Instructions (2659 KB)

References

[1]. Sparve E et al. Prediction and modeling of effects on the QTc interval for clinical safety margin assessment, based on single-ascending-dose study data with AZD3839. J Pharmacol Exp Ther. 2014 Aug;350(2):469-78. [Content Brief]

[2]. Jeppsson F et al. Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease. J Biol Chem. 2012 Nov 30;287(49):41245-57. [Content Brief]

[3]. Eketjäll S, et al. AZD3293: A Novel, Orally Active BACE1 Inhibitor with High Potency and Permeability and Markedly Slow Off-Rate Kinetics. J Alzheimers Dis. 2016;50(4):1109-23. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.3180 mL	11.5899 mL	23.1798 mL	57.9495 mL
	5 mM	0.4636 mL	2.3180 mL	4.6360 mL	11.5899 mL
	10 mM	0.2318 mL	1.1590 mL	2.3180 mL	5.7950 mL
	15 mM	0.1545 mL	0.7727 mL	1.5453 mL	3.8633 mL
	20 mM	0.1159 mL	0.5795 mL	1.1590 mL	2.8975 mL
	25 mM	0.0927 mL	0.4636 mL	0.9272 mL	2.3180 mL
	30 mM	0.0773 mL	0.3863 mL	0.7727 mL	1.9317 mL
	40 mM	0.0579 mL	0.2897 mL	0.5795 mL	1.4487 mL
	50 mM	0.0464 mL	0.2318 mL	0.4636 mL	1.1590 mL
	60 mM	0.0386 mL	0.1932 mL	0.3863 mL	0.9658 mL
	80 mM	0.0290 mL	0.1449 mL	0.2897 mL	0.7244 mL
	100 mM	0.0232 mL	0.1159 mL	0.2318 mL	0.5795 mL