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Lanraplenib (GS-SYK) Syk inhibitor

Name: Lanraplenib (GS-SYK)
Brand: Selleck Chemicals
SKU: S9715
Availability: InStock
Rating: 5 (3 reviews)

Cat.No.S9715

Lanraplenib (GS-SYK) is a potent, highly selective and orally active inhibitor of Spleen Tyrosine Kinase (SYK) with IC50 of 9.5 nM. It inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans.

Chemical Structure

Molecular Weight: 443.50

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Quality Control

Batch: S971501 DMSO]89 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 98.64%

Cited in Nature Medicine for its top-tier quality
COA
NMR
HPLC
SDS
Datasheet

98.64

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src HIF FLT FLT3 HER2
Other Syk Products	R406 R406 (free base) PRT062607 (P505-15) HCl Entospletinib (GS-9973) Piceatannol BAY 61-3606 dihydrochloride PRT-060318 2HCl TAK-659 Hydrochloride RO9021 R112

Solubility

In vitro
Batch:

DMSO : 89 mg/mL (200.67 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.25mg/ml (0.56mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.25mg/ml (0.56mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

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: g

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

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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 μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, 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.

Chemical Information, Storage & Stability

Molecular Weight	443.50	Formula	C₂₃H₂₅N₉O	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1800046-95-0	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	GS-9876			Smiles	NC1=CN=CC(=N1)C2=C[N]3C=CN=C3C(=N2)NC4=CC=C(C=C4)N5CCN(CC5)C6COC6

Mechanism of Action

Targets/IC₅₀/Ki	GPVI receptor Syk (Cell-free assay) 9.5 nM
In vitro	Lanraplenib (GS-SYK) inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells with EC50 values of 24–51 nM. Functionally, it inhibits anti-IgM mediated CD69 and CD86 expression on B-cells (EC50=112±10 nM and 164±15 nM, respectively) and anti-IgM /anti-CD40 co-stimulated B cell proliferation (EC50=108±55 nM). In human macrophages, this compound inhibits IC-stimulated TNFα and IL-1β release (EC50=121±77 nM and 9±17 nM, respectively). Anti-CD3/anti-CD28 stimulated T cell proliferation is weakly inhibited (EC50=1291±398 nM), with selectivity >10-fold versus the inhibition of B cell proliferation. In human blood, it blocks SYK phosphorylation, CD69 expression on B cells, and CD63 expression in basophils. Additionally, it inhibits glycoprotein VI (GPVI)-induced phosphorylation of linker for activation of T cells and phospholipase Cγ2, platelet activation and aggregation in human whole blood, and platelet binding to collagen under arterial flow.
In vivo	Lanraplenib (GS-SYK) demonstrates a dose-dependent improvement in clinical score and histopathology parameters with once-daily dosing in short and long term rat models of collagen-induced arthritis (CIA). Significant efficacy can be achieved with this compound at doses that produce trough pSYK inhibition of <50%. Ex vivo, GPVI-stimulated platelet aggregation is inhibited in it-treated monkeys without a concomitant increase in bleeding time (BT). Similarly, orally administered GS-9876 does not increase BT in humans.
References	[1] https://ard.bmj.com/content/75/Suppl_2/443.3 [2] https://pubmed.ncbi.nlm.nih.gov/30172129/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05028751	Terminated	Acute Myeloid Leukemia\|Relapsed Acute Myeloid Leukemia\|Refractory Acute Myeloid Leukemia	Kronos Bio	August 5 2022	Phase 1\|Phase 2
NCT02959138	Completed	Inflammatory Disease	Gilead Sciences	November 21 2016	Phase 1

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