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.

Physicochemical Properties

Molecular Formula	C22H23N5O2
Molecular Weight	389.45
Exact Mass	389.185
CAS #	1206163-45-2
Related CAS #	1206163-45-2
PubChem CID	44603362
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.723
LogP	1.51
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	29
Complexity	648
Defined Atom Stereocenter Count	0
InChi Key	MPYACSQFXVMWNO-UHFFFAOYSA-N
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)
Chemical Name	N-[5-[4-(3,3-dimethylazetidine-1-carbonyl)phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide
Synonyms	GLPG-0778; GSK-2586184; GSK2586184A;GLPG 0778; GLPG0778; GSK 2586184; GSK-2586184A;G154578; GSK2586184; GSK 2586184A; Solcitinib
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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.
Animal Protocol	Oral; 100 mg, 200 mg and 400 mg GSK2586184 twice-daily groups Clinical trials
References	[1]. Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study. Br J Dermatol. 2016 May;174(5):985-95.

Solubility Data

Solubility (In Vitro)

DMSO:20 mg/mL Water:<1 mg/mL Ethanol:<1 mg/mL

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.