| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Solcitinib (formerly GSK2586184; GSK-2586184A; GLPG-0778; GLPG0778) is a potent, selective, and orally bioavailable Janus kinase (JAK)1 inhibitor being evaluated as a treatment for moderate-to-severe plaque-type psoriasis. It may also be used for systemic lupus erythematosus, ulcerative colitis. Solcitinib has an IC50 of 9.8 nM for JAK1 and is 11-, 55- and 23-fold more selective over JAK2, JAK3 and TYK2, respectively. 12 weeks of treatment with GSK2586184 resulted in clinical improvement and was generally well tolerated in patients with moderate-to-severe plaque-type psoriasis. Overall, the incidence of adverse events (AEs) was similar across treatment groups, and no relationship between frequency of AE and GSK2586184 dose was identified. Differential gene expression was observed in involved and uninvolved skin at baseline and in involved skin after 2 weeks of treatment with GSK2586184.
| Targets |
Solcitinib (GSK2586184) targets Janus kinase 1 (JAK1); [1]
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| ln Vitro |
Solcitinib is a JAK1 inhibitor that can be taken orally. It has an IC50 of 9.8 nM and exhibits 11-, 55-, and 23-fold selectivity over JAK2, JAK3, and TYK2, respectively. Research on moderate-to-severe plaque-type psoriasis uses solucitinib[1].
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| ln Vivo |
12 weeks of treatment with GSK2586184 resulted in clinical improvement and was generally well tolerated in patients with moderate-to-severe plaque-type psoriasis. Overall, the incidence of adverse events (AEs) was similar across treatment groups, and no relationship between frequency of AE and GSK2586184 dose was identified. Differential gene expression was observed in involved and uninvolved skin at baseline and in involved skin after 2 weeks of treatment with GSK2586184.
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| Animal Protocol |
Oral; 100 mg, 200 mg and 400 mg GSK2586184 twice-daily groups
Clinical trials |
| Toxicity/Toxicokinetics |
1. In the Phase IIa clinical trial, the incidence of adverse events (AEs) was similar in all dose groups of soxitinib (GSK2586184) (100 mg, 200 mg, 400 mg twice daily) and the placebo group; no correlation was found between the frequency of adverse events and the dose of soxitinib (GSK2586184) [1]
2. Common treatment-related adverse events (TEAEs) in the soxitinib (GSK2586184) group included nasopharyngitis (17%), headache (13%), upper respiratory tract infection (10%), and diarrhea (8%); all TEAEs were mild to moderate in severity [1] |
| References | |
| Additional Infomation |
1. Solcitinib (GSK2586184) is a selective oral Janus kinase 1 (JAK1) inhibitor designed to block JAK1-mediated signaling pathways involved in the pathogenesis of psoriasis [1]
2. A randomized, double-blind, placebo-controlled phase IIa clinical trial was conducted to evaluate the efficacy and safety of Solcitinib (GSK2586184) in patients with moderate to severe plaque psoriasis; 60 patients were randomized in a 1:1:1:1:1 ratio to receive placebo (n=12), 100 mg socitinib (GSK2586184) twice daily (n=12), 200 mg socitinib (GSK2586184) twice daily (n=12), 400 mg socitinib (GSK2586184) twice daily (n=12), or an open-label 400 mg socitinib twice daily. Soxitinib (GSK2586184) (n=12), treatment duration 12 weeks [1] 3. The primary efficacy endpoint was the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 75); in the intention-to-treat (ITT) population, the PASI 75 response rates were: 0% in placebo, 13% in 100 mg BID, 25% in 200 mg BID, and 57% in 400 mg BID [1] 4. Secondary efficacy endpoints included PASI 50/90 response, Physician Overall Assessment (PGA) score of 0/1 (clearance/minor disease), and pruritus severity (measured by the Visual Analogue Scale [VAS]) and quality of life (measured by the Dermatology Quality of Life Index [DLQI]). Improvement in the measurement of efficacy; all secondary endpoints showed a dose-dependent improvement in efficacy in the soxitinib (GSK2586184) group compared with the placebo group [1] 5. In the open-label cohort (400 mg, twice daily), gene expression analysis of skin biopsies from lesions at baseline and week 2 showed that soxitinib (GSK2586184) downregulated genes associated with the JAK-STAT signaling pathway, Th1/Th2/Th17 immune response and excessive proliferation of keratinocytes [1] 6. This study suggests that soxitinib (GSK2586184) has a good benefit-risk ratio in moderate to severe plaque psoriasis, and its clinical efficacy is associated with the inhibition of the JAK1-mediated inflammatory pathway [1] |
| Molecular Formula |
C22H23N5O2
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|---|---|---|
| Molecular Weight |
389.45
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| Exact Mass |
389.185
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| CAS # |
1206163-45-2
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| Related CAS # |
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| PubChem CID |
44603362
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.723
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| LogP |
1.51
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
648
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MPYACSQFXVMWNO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N5O2/c1-22(2)12-26(13-22)20(29)16-10-6-14(7-11-16)17-4-3-5-18-23-21(25-27(17)18)24-19(28)15-8-9-15/h3-7,10-11,15H,8-9,12-13H2,1-2H3,(H,24,25,28)
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| Chemical Name |
N-[5-[4-(3,3-dimethylazetidine-1-carbonyl)phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.67 mg/mL (4.29 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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: 1.67 mg/mL (4.29 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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. View More
Solubility in Formulation 3: 1.67 mg/mL (4.29 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5677 mL | 12.8386 mL | 25.6772 mL | |
| 5 mM | 0.5135 mL | 2.5677 mL | 5.1354 mL | |
| 10 mM | 0.2568 mL | 1.2839 mL | 2.5677 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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