Home Angiogenesis Syk inhibitor Lanraplenib (GS-SYK) For research use only.

Lanraplenib (GS-SYK)

Synonyms: GS-9876

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

Lanraplenib (GS-SYK) Chemical Structure

Lanraplenib (GS-SYK) Chemical Structure

CAS No. 1800046-95-0

Purity & Quality Control

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

Lanraplenib (GS-SYK) Related Products

Signaling Pathway

Syk Signaling Pathways

Syk Signaling Pathway

Biological Activity

Description Lanraplenib (GS-SYK)is a potent, highly selective and orally active inhibitor of Spleen Tyrosine Kinase (SYK) with IC50 of 9.5 nM. Lanraplenib inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans.
Targets
GPVI receptor [2] Syk [1]
(Cell-free assay)
9.5 nM
In vitro
In vitro

GS-9876 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, GS-9876 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, GS-9876 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, GS-9876 blocks SYK phosphorylation, CD69 expression on B cells, and CD63 expression in basophils.[1] GS-9876 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.[2]
Cell Research Cell lines Human blood platelets
Concentrations 0.01 μM to 100 μM
Incubation Time 15 min
Method

Blood is preincubated for 15 min with Lanraplenib (GS-9876) and activated with ADP (0.2 μM) or convulxin (30 ng/mL) for 2 min at room temperature. Samples are stained for CD61 and CD62P, fixed, and analyzed on a FACSCanto II flow cytometer. The percentages of CD62P+ platelets are quantified and the values are subjected to nonlinear regression analysis using Prism 6 to generate EC50 values.
In Vivo
In vivo

GS-9876 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 GS-9876 doses that produces trough pSYK inhibition of <50%.[1] Ex vivo, GPVI-stimulated platelet aggregation is inhibited in GS-9876-treated monkeys without a concomitant increase in bleeding time (BT). Similarly, orally administered GS-9876 does not increase BT in humans.[2]
Animal Research Animal Models female cynomolgus monkeys
Dosages 5 mg/kg, 15 mg/kg, 45 mg/kg
Administration Oral gavage
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

Chemical Information & Solubility

Molecular Weight 443.50 Formula

C23H25N9O
CAS No. 1800046-95-0 SDF --
Smiles NC1=CN=CC(=N1)C2=C[N]3C=CN=C3C(=N2)NC4=CC=C(C=C4)N5CCN(CC5)C6COC6
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 89 mg/mL ( (200.67 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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