Lanraplenib succinate

Lanraplenib succinate (GS-9876 succinate) is a highly selective and orally active SYK inhibitor (IC50=9.5 nM) in development for the treatment of inflammatory diseases. Lanraplenib succinate (GS-9876 succinate) inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans.

Product information

CAS Number: 1800047-00-0

Molecular Weight: 620.64

Formula: C58H68N18O14

Chemical Name: bis(6-[8-({4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl}amino)imidazo[1,2-a]pyrazin-6-yl]pyrazin-2-amine); tris(butanedioic acid)

Smiles: NC1=CN=CC(=N1)C1=CN2C=CN=C2C(NC2C=CC(=CC=2)N2CCN(CC2)C2COC2)=N1.NC1=CN=CC(=N1)C1=CN2C=CN=C2C(NC2C=CC(=CC=2)N2CCN(CC2)C2COC2)=N1.OC(=O)CCC(O)=O.OC(=O)CCC(O)=O.OC(=O)CCC(O)=O

InChiKey: SUXNLHAGYIRFJQ-UHFFFAOYSA-N

InChi: InChI=1S/2C23H25N9O.3C4H6O4/c2*24-21-12-25-11-19(28-21)20-13-32-6-5-26-23(32)22(29-20)27-16-1-3-17(4-2-16)30-7-9-31(10-8-30)18-14-33-15-18;3*5-3(6)1-2-4(7)8/h2*1-6,11-13,18H,7-10,14-15H2,(H2,24,28)(H,27,29);3*1-2H2,(H,5,6)(H,7,8)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 83.33 mg/mL (134.26 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Lanraplenib succinate (GS-9876 succinate) inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells with EC50 values of 24-51 nM. Lanraplenib monosuccinate 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, Lanraplenib succinate inhibits IC-stimulated TNFα and IL-1β release (EC50=121±77 nM and 9±17 nM, respectively). Lanraplenib succinate (GS-9876 succinate) 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.

References:

1. Di Paolo J, et al. FRI0049 Preclinical Characterization of GS-9876, A Novel, Oral SYK Inhibitor That Shows Efficacy in Multiple Established Rat Models of Collagen-Induced Arthritis.Annals of the Rheumatic Diseases 2016;75:443-444.
2. Clarke AS, et al. Effects of GS-9876, a novel spleen tyrosine kinase inhibitor, on platelet function and systemic hemostasis. Thromb Res. 2018 Oct;170:109-118.
3. Kivitz AJ, et al. GS-9876, a Novel, Highly Selective, SYK Inhibitor in Patients with Active Rheumatoid Arthritis: Safety, Tolerability and Efficacy Results of a Phase 2 Study [abstract]. Arthritis Rheumatol.2018; 70 (suppl 10).

Products are for research use only. Not for human use.