ICCB-19 HCl is a TRADD (TNFRSF1A associated via death domain) inhibitor. ICCB-19 HCl binds to the N-terminal domain of TRADD (TRADD-N), disrupting its binding to TRADD-C and TRAF2. ICCB-19 HCl is an indirect inhibitor of RIPK1 kinase activity. ICCB-19 HCl effectively induces autophagy and degradation of long-lived proteins.

Physicochemical Properties

Molecular Formula	C12H22CLN3OS
Molecular Weight	291.84
Exact Mass	291.117
CAS #	1803605-68-6
PubChem CID	91654402
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	18
Complexity	286
Defined Atom Stereocenter Count	0
InChi Key	TZICOTBZKPHMMK-UHFFFAOYSA-N
InChi Code	InChI=1S/C12H21N3OS.ClH/c16-11(9-17-12-13-7-8-14-12)15-10-5-3-1-2-4-6-10;/h10H,1-9H2,(H,13,14)(H,15,16);1H
Chemical Name	N-cycloheptyl-2-(4,5-dihydro-1H-imidazol-2-ylsulfanyl)acetamide;hydrochloride
Synonyms	ICCB19 HClICCB 19 HClICCB-19 HClICCB-19hydrochlorideICCB 19hydrochlorideICCB19hydrochloride
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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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	ICCB-19 hydrochloride has an IC50 of roughly 1 μM and inhibits both RIPK1-dependent cellular fluorescence (RDA) and cellular fluorescence caused by benezomib [1]. mTOR is not affected by ICCB-19 hydrochloride. Using ICCB-19 hydrochloride (10 μM) as a therapy, autophagy is stimulated via the following mechanisms. The number of DsRed-FYVE spots, levels, and inhibitory inhibitory activity of VPS34 can be increased by cells via the E3 ubiquitin that links cIAP1 and cIAP2 and the adaptor TRAF2[1]. The fast activation of RIPK1 in complex I caused by TNF is lessened by ICCB-19 hydrochloride (10 μM). TRADD, HOIP, and A20 recruitment are increased upon treatment with ICCB-19 hydrochloride, however beclin 1 K63 ubiquitination is not affected [1]. RIPK1 recruitment to complex I is increased[1].
ln Vivo	Tradd is decreased by ICCB-19 hydrochloride?*? The TNF-induced factor target gene products NOS and COXII27, as well as the factor cytokine expression in cells stimulated by related molecular patterns, can all be downregulated by ICCB-19 hydrochloride [1].
References	[1]. Modulating TRADD to restore cellular homeostasis and inhibit apoptosis. Nature. 2020 Nov;587(7832):133-138.

Solubility Data

Solubility (In Vitro)

H2O : ≥ 100 mg/mL (~342.65 mM) DMSO : ~83.33 mg/mL (~285.53 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.13 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 20.8 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: ≥ 2.08 mg/mL (7.13 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 20.8 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: ≥ 2.08 mg/mL (7.13 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 20.8 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	3.4265 mL	17.1327 mL	34.2654 mL
	5 mM	0.6853 mL	3.4265 mL	6.8531 mL
	10 mM	0.3427 mL	1.7133 mL	3.4265 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.