SID 26681509 quarterhydrate is a potent, reversible, competitive, and selective inhibitor of human cathepsin L with IC50 of 56 nM. SID 26681509 quarterhydrate inhibits the in vitro propagation of Plasmodium falciparum and inhibits Leishmania major with IC50 of 15.4 μM and 12.5 μM respectively. SID 26681509 quarterhydrate has no inhibitory effect against cathepsin G.

Physicochemical Properties

Molecular Formula	C27H33N5O5S.1/4H2O
Molecular Weight	544.16
Related CAS #	SID 26681509;958772-66-2
Appearance	White to off-white solid powder
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

Targets	Plasmodium
ln Vitro	SID 26681509 gains potency and exhibits an IC50 of 1.0 nM following a 4-hour preincubation with cathepsin L. The findings indicate that SID 26681509 functions as a slowly reversible and slowly binding competitive inhibitor. For single-step reversibility, inhibition rate constants were determined using a transient kinetic analysis to be kon = 24,000 M-1s-1 and koff = 2.2 × 10-5 s-1 (Ki = 0.89 nM). Utilizing the experimentally-derived X-ray crystal structure of papin/CLIK-148, molecular docking investigations are conducted [1]. After an hour, the IC50 values of SID 26681509 were found to range from 618 nM to 8.442 μM, indicating its inhibition of papin and cathepsins B, K, S, and V. When it comes to the serine protease cathepsin G, SID 26681509 has no inhibitory activity[1]. With an IC50 value of 0.5 μM, 26681509 inhibits the activity of cathepsin V. SID 26681509 (1-30 μM) dose-dependently inhibits TNF-α production generated by high-mobility group box 1 (HMGB1) without compromising cell viability[2].
ln Vivo	Treatment with SID 26681509 dramatically increases survival in mice sepsis models and decreases liver damage during warm hepatic ischemia/reperfusion (I/R) models[2].
References	[1]. Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L. Mol Pharmacol. 2008 Jul;74(1):34-41. [2]. The HIV Protease Inhibitor Saquinavir Inhibits HMGB1-Driven Inflammation by Targeting the Interaction of Cathepsin V with TLR4/MyD88. Mol Med. 2015 Dec;21(1):749-757.

Solubility Data

Solubility (In Vitro)

DMSO :~50 mg/mL (~91.88 mM) Ethanol :~5 mg/mL (~9.19 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (3.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8377 mL	9.1885 mL	18.3769 mL
	5 mM	0.3675 mL	1.8377 mL	3.6754 mL
	10 mM	0.1838 mL	0.9188 mL	1.8377 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.