GSK256066

Name: GSK256066
Brand: Selleck Chemicals
SKU: S2620
Rating: 5 (1 reviews)

For research use only.

Catalog No.S2620

1 publication

Molecular Weight(MW): 518.58

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7.Phase 2.

Selleck's GSK256066 has been cited by 1 publication

J Aerosol Med Pulm Drug Deliv, 2019, 32(6):396-404

PubMed: 31573405

Purity & Quality Control

Choose Selective PDE Inhibitors

Biological Activity

Description

Targets

PDE4B ^[1]

3.2 pM

In vitro

GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 × 10⁵-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 10³-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity. ^[1]

In vivo

GSK256066 inhibits the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 μg/kg, achieving maximal inhibition of 72% at 30 μg/kg when given in the aqueous suspension. GSK256066 inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/kg, achieving maximal inhibition of 62% when given in the dry powder formulation. GSK256066 shows a moderate plasma clearance of 39 ml/min/kg, a moderate volume of distribution of 0.8 L/kg, and a relatively short half-life of 1.1 hour in the male CD rat. ^[1] GSK256066 sustains at a high lung concentration of 2.6 μg/g after intra-tracheal administration as an aqueous suspension at a dose of 30 μg/kg in rats. ^[2] GSK256066 (10 μg/kg) is administered intratracheally at different times (2, 6, 12, 18, 24, and 36 hours) before LPS administration, inhibiting LPS-Induced Pulmonary Neutrophilia in rat lipopolysaccharide (LPS)-induced models of acute pulmonary inflammation. GSK256066 (0.3–100 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. GSK256066 (10 μg/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 μg/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 μg/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 μg/kg without inducing emetic episodes. ^[3]

Protocol

Animal Research:^[1]	- Collapse Animal Models: Male CD rats Dosages: 0.1–100 μg/kg Administration: Administered intratracheally as an aqueous suspension or a dry powder 2 h before LPS challenge. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	5 mg/mL (9.64 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 30% propylene glycol, 5% Tween 80, 65% D5W For best results, use promptly after mixing.	30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download GSK256066 SDF

Molecular Weight	518.58
Formula	C₂₇H₂₆N₄O₅S
CAS No.	801312-28-7
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=CC(=CC2=C(C(=CN=C12)C(=O)N)NC3=CC(=CC=C3)OC)S(=O)(=O)C4=CC=CC(=C4)C(=O)N(C)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage

mg/kg

Average weight of animals

Dosing volume per animal

Number of animals

Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

Calculate Reset

Calculation results:

Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00612118	Completed	Drug: GSK256066\|Drug: azelastine hydrochloride	Allergic Rhinitis\|Rhinitis Allergic Seasonal	GlaxoSmithKline	February 2008	Phase 2
NCT00612820	Completed	Drug: GSK256066\|Drug: fluticasone propionate	Rhinitis Allergic Seasonal	GlaxoSmithKline	January 2008	Phase 2
NCT00549744	Completed	Drug: GSK256066	Asthma	GlaxoSmithKline	November 16 2007	Phase 2
NCT00549679	Completed	Drug: GSK256066\|Drug: Placebo	Pulmonary Disease Chronic Obstructive	GlaxoSmithKline	October 4 2007	Phase 2
NCT00515268	Completed	Drug: GSK256066\|Drug: Placebo	Pulmonary Disease Chronic Obstructive	GlaxoSmithKline	September 27 2007	Phase 1
NCT00464568	Completed	Drug: GSK256066	Rhinitis Allergic Seasonal	GlaxoSmithKline	March 28 2007	Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

PDE Signaling Pathway Map

Related PDE Products

U73122 ^New

U73122 is a potent phospholipase C (PLC) inhibitor, which reduces agonist-induced Ca²⁺ increases in platelets and PMN. U73122 potently inhibits human 5-lipoxygenase (5-LO).
Liproxstatin-1 ^New

Liproxstatin-1 is a potent ferroptosis inhibitor with an IC50 of 22 nM.
Epacadostat (INCB024360) ^New

Epacadostat (INCB024360) is a potent and selective indoleamine 2,3-dioxygenase (IDO1) inhibitor with IC50 of 10 nM and displays high selectivity over other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO).
Sildenafil Citrate

Sildenafil Citrate, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction.
Rolipram

The PDE4 selective inhibitor, Rolipram (ZK-62711, SB 95952), inhibited immunopurified PDE4B and PDE4D activities similarly, with IC50 values of approx. 130 nM and 240 nM respectively; an anti-inflammatory agent.
Tadalafil

Tadalafil (IC351) is a PDE-5 inhibitor with IC50 of 1.8 nM in a cell-free assay. Tadalafil is at least 9000 times more selective for PDE5 than most of the other families of PDEs, with the exception of PDE11. It can partial inhibits PDE11

Features:Much more potent to PDE-5 than PDE-1 or PDE-6.
Mardepodect (PF-2545920)

PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM, with >1000-fold selectivity over the PDE.
Apremilast (CC-10004)

Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.
Roflumilast

Roflumilast is a selective inhibitor of PDE4 with IC50 of 0.2-4.3 nM in a cell-free assay.
Luteolin

Luteolin is a flavonoid found in Terminalia chebula, which is a non-selective phisphodiesterase PDE inhibitor for PDE1-5 with Ki of 15.0 μM, 6.4 μM, 13.9 μM, 11.1 μM and 9.5 μM, respectively. Phase 2.

Choose Your Country or Region

By Signaling Pathways

By product type

GSK256066