| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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Purity: ≥98%
Lanraplenib (also known as GS-9876; GS-SYK) is a highly selective and orally bioavailable Spleen Tyrosine Kinase (SYK) inhibitor with IC50 of 9.5 nM). It is currently under development by Gilead for the treatment of inflammatory diseases such as RA. Spleen Tyrosine Kinase (SYK) mediates signaling in a range of hematopoietic cells involved in the initiation and progression of RA including B cells, monocytes, macrophages, dendritic cells, and osteoclasts. There is strong preclinical validation for SYK as a therapeutic target for RA based on cellular data and animal models of disease. Lanraplenib (GS-9876) inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans. GS-9876 potently inhibits multiple cellular events implicated in RA pathogenesis and displays excellent in vivo efficacy in rat CIA models after once-daily dosing. GS-9876 has markedly improved selectivity over competitor SYK programs. These data support the development of GS-9876 in inflammatory diseases, with potential for an improved safety profile.
| ln Vitro |
With EC50 values of 24-51 nM, lambranplenib (GS-9876) suppresses anti-IgM-stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in B cells. Lanraplenib (GS-9876) suppresses B cell proliferation when combined with anti-IgM/anti-CD40 (EC50=108 nM), and it also inhibits anti-IgM-mediated CD69 and CD86 expression in B cells (EC50=112 nM and 164 nM). Lanraplenib (GS-9876) prevents IC stimulation in human macrophages. Lanraplenib (GS-9876) suppresses the release of human TNFα, IL-1β, and phospholipase Cγ2, as well as the phosphorylation of T cells caused by glycoprotein VI (GPVI) (EC50=121 nM and 9 nM)[1]. In whole blood, venous activation and aggregation are paired with subarterial collagen flow [2].
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| 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). |
| Molecular Formula |
C23H25N9O
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|---|---|
| Molecular Weight |
443.504302740097
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| CAS # |
1800046-95-0
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| Related CAS # |
Lanraplenib succinate;1800047-00-0;Lanraplenib monosuccinate;1800046-97-2
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| SMILES |
NC1=CN=CC(C2=CN3C(C(NC4=CC=C(N5CCN(C6COC6)CC5)C=C4)=N2)=NC=C3)=N1
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| InChi Key |
XCIGZBVOUQVIPI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H25N9O/c24-21-12-25-11-19(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/h1-6,11-13,18H,7-10,14-15H2,(H2,24,28)(H,27,29)
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| Chemical Name |
6-(6-aminopyrazin-2-yl)-N-{4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl}imidazo[1,2-a]pyrazin-8-amine
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| Synonyms |
GS-9876; GS 9876; GS9876; Lanraplenib; GS-SYK
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~20 mg/mL (~45.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2548 mL | 11.2740 mL | 22.5479 mL | |
| 5 mM | 0.4510 mL | 2.2548 mL | 4.5096 mL | |
| 10 mM | 0.2255 mL | 1.1274 mL | 2.2548 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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