LS 102 is a selective inhibitor of the E3 ligase synoviolin (Syvn1). LS-102 inhibits Syvn1 autoubiquitination with IC50 of about 35 μM and may be used for studying rheumatoid arthritis.

Physicochemical Properties

Molecular Formula	C24H36N8O
Molecular Weight	452.595643997192
Exact Mass	452.301
CAS #	1456891-34-1
PubChem CID	118518043
Appearance	White to light yellow solid powder
LogP	5.6
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	11
Heavy Atom Count	33
Complexity	563
Defined Atom Stereocenter Count	1
SMILES	O1C=NC2=CC=C(C=C12)NC1N=C(N(CC)CCNCC)N=C(N=1)N[C@@H](C)C1CCCCC1
InChi Key	DEDHMXBDEJSZFE-KRWDZBQOSA-N
InChi Code	InChI=1S/C24H36N8O/c1-4-25-13-14-32(5-2)24-30-22(27-17(3)18-9-7-6-8-10-18)29-23(31-24)28-19-11-12-20-21(15-19)33-16-26-20/h11-12,15-18,25H,4-10,13-14H2,1-3H3,(H2,27,28,29,30,31)/t17-/m0/s1
Chemical Name	6-N-(1,3-benzoxazol-6-yl)-4-N-[(1S)-1-cyclohexylethyl]-2-N-ethyl-2-N-[2-(ethylamino)ethyl]-1,3,5-triazine-2,4,6-triamine
Synonyms	LS102; LS 102
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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	RSC proliferation is inhibited by LS-102, with an IC50 of 5.4 μM[1]. Rheumatoid synoviocyte (RSC) proliferation is inhibited by LS-102 in a way that is reliant on Syvn1. Syvn1 target proteins such as PGC-1β, V247M alpha-muscle mutant, and nuclear factor erythroid 2-related factor 2 (NRF2) are polyubiquitinated and inhibited by LS-102. Synoviolin (Syvn1)'s E3 ligase activity is inhibited by LS-102 [2].
ln Vivo	In the CIA model, LS-102 (1.3–4 mg/kg; intraperitoneally; once daily for 4 weeks) lowers clinical severity scores [1].
Cell Assay	Cell viability assay [1] Cell Types: Rheumatoid synoviocytes (RSC) Tested Concentrations: 20, 40, 60 μM Incubation Duration: 12 hrs (hours) Experimental Results: Inhibits RSC proliferation, IC50 is 5.4 μM.
Animal Protocol	Animal/Disease Models: 7weeks old DBA/1 male mice (CIA model) [1] Doses: 1.3, 4.0 mg/kg Route of Administration: IP; one time/day for 4 weeks Experimental Results: diminished clinical severity score.
References	[1]. RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoidarthritis. Int J Mol Med. 2012 Dec;30(6):1281-6. [2]. Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1. Mol Med Rep. 2018 Dec;18(6):5701-5708.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~220.95 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.52 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 25.0 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: ≥ 2.5 mg/mL (5.52 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 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	2.2095 mL	11.0473 mL	22.0946 mL
	5 mM	0.4419 mL	2.2095 mL	4.4189 mL
	10 mM	0.2209 mL	1.1047 mL	2.2095 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.