Kongensin A is a naturally occurring compound extracted from Croton kongensis. Kongensin A is a potent, covalent HSP90 inhibitor that blocks RIP3-dependent necrosis. Kongensin A is a potent inhibitor of necrosis and inducer of apoptosis and has potential anti-necrotic and anti~inflammatory applications.

Physicochemical Properties

Molecular Formula	C22H30O5
Molecular Weight	374.47
Exact Mass	374.209
CAS #	885315-96-8
PubChem CID	91895304
Appearance	White to light yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	525.7±50.0 °C at 760 mmHg
Flash Point	178.4±23.6 °C
Vapour Pressure	0.0±3.1 mmHg at 25°C
Index of Refraction	1.542
LogP	2.77
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	27
Complexity	731
Defined Atom Stereocenter Count	5
SMILES	CC(=O)O[C@@H]1CCC([C@@H]2[C@@]1(C(=O)CC[C@@H]3C=C([C@@H](C2)O)C(=O)C3=C)C)(C)C
InChi Key	NUUWPMNNBHROPI-ASAQZKIWSA-N
InChi Code	InChI=1S/C22H30O5/c1-12-14-6-7-18(25)22(5)17(11-16(24)15(10-14)20(12)26)21(3,4)9-8-19(22)27-13(2)23/h10,14,16-17,19,24H,1,6-9,11H2,2-5H3/t14-,16-,17-,19-,22-/m1/s1
Chemical Name	[(2R,4R,8R,9S,13R)-2-hydroxy-5,5,9-trimethyl-14-methylidene-10,15-dioxo-8-tricyclo[11.2.1.04,9]hexadec-1(16)-enyl] acetate
Synonyms	KA; Kongensin-A; Kongensin A
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: This product requires protection from light (avoid light exposure) during transportation and storage.
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	In some cancer cell lines, kongensin A (0–15 μM; 6 hours; HT29 cells) treatment causes dose-dependent caspase activation and apoptosis [1]. When HT29 cells are treated with kongensin A (0–15 μM) for 24 hours, oncogenic kinases like ERBB2, AKT, EGFR, and B-raf are degraded, and HSP90A and HSP90B are upregulated [1]. By binding covalently to cysteine 420 in the middle domain of HSP90, kongensin A separates HSP90 from its cochaperone, CDC37. The HSP90-CDC37 complex is necessary for RIP3 activation, and KA inhibits RIP3 aggregation and LPS/Smac mimic/Z-VAD-induced cell death, wherein RIP3 is required for cell death but not its upstream kinase, RIP1 [1].
Cell Assay	Apoptosis analysis[1] Cell Types: HT29 Cell Tested Concentrations: 0 μM, 2.5 μM, 5 μM, 15 μM Incubation Duration: 6 hrs (hours) Experimental Results: Induces caspase activation and apoptosis in a dose-dependent manner. Western Blot Analysis[1] Cell Types: HT29 Cell Tested Concentrations: 0 μM, 2.5 μM, 5 μM, 15 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induces RIPK1 and oncogenic kinases (such as ERBB2, AKT, EGFR and B-) to degrade raf, and induces upregulation of HSP90A and HSP90B.
References	[1]. Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis. Cell Chem Biol. 2016 Feb 18;23(2):257-266.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6704 mL	13.3522 mL	26.7044 mL
	5 mM	0.5341 mL	2.6704 mL	5.3409 mL
	10 mM	0.2670 mL	1.3352 mL	2.6704 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.