| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C22H24N4O3S |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
PK68 is a potent, orally active, specific type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC50 of approximately 90 nM, and it inhibits RIPK1-dependent necroptosis. It markedly ameliorates TNF-induced systemic inflammatory response syndrome and can be used in research on inflammatory disorders and cancer metastasis[1]. It is supplied as an off-white to light yellow solid (C22H24N4O3S, MW 424.52) at 99.92% purity.
Physical & Chemical Properties
| CAS Number | 2173556-69-7 |
|---|---|
| Molecular Formula | C22H24N4O3S |
| Molecular Weight | 424.52 g/mol |
| Purity | 99.92% |
| Appearance | Solid |
| Color | Off-white to light yellow |
| SMILES | O=C(OC1CCCCC1)NC2=CC(C3=CC=C4N=C(NC(C)=O)SC4=C3)=CN=C2C |
| Target | RIPK1 |
| Signaling Pathway | Apoptosis |
| Solubility | In Vitro: DMSO: 30 mg/mL (70.67 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 6 months; -20°C, 1 month. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target
|
RIPK1 90 nM (IC50) |
RIPK1 23 nM (EC50) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 30 mg/mL (70.67 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 90% (20% SBE-β-CD in saline) |
|---|---|
| Result | ≥ 3 mg/mL (7.07 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 3 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (30.0 mg/mL) to 900 μL 20% SBE-β-CD in saline. 20% SBE-β-CD in saline: dissolve 2 g SBE-β-CD powder in 10 mL saline until clear (4°C, store up to one week). |
Protocol 2
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 2.08 mg/mL (4.90 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.08 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (20.8 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 3
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 2.08 mg/mL (4.90 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.08 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (20.8 mg/mL) to 900 μL corn oil. |
Data provided by the manufacturer.
In Vitro
PK68 potently inhibits TNF-induced necroptosis, with EC50 values of 23 nM in human cells and 13 nM in mouse cells[1]. PK68 is a highly selective inhibitor of RIPK1 kinase activity (IC50 of 90 nM)[1]. At 100 nM for 1 h, PK68 blocks necroptosis by suppressing RIPK3 function or signaling upstream of RIPK3 activation[1].
Cell Viability Assay[1]
| Cell Line | Bone marrow-derived macrophages, NIH3T3-RIPK3 cells |
|---|---|
| Concentration | 100 nM |
| Incubation Time | 1 h |
| Result | PK68 block cellular activation of RIPK1, RIPK3, and MLKL upon necroptotic stimuli. PK68 inhibit TNF-induced necroptosis but not RIPK3 dimerization-induced cell death in NIH3T3-RIPK3 cells. |
Western Blot Analysis[1]
| Cell Line | HT-29 cells |
|---|---|
| Concentration | 100 nM |
| Incubation Time | 1 h |
| Result | Completely abolished phosphorylation of RIPK1, RIPK3, and MLKL. |
Immunofluorescence[1]
| Cell Line | HT-29 cells |
|---|---|
| Concentration | 100 nM |
| Incubation Time | 1 h |
| Result | Prevented generation of RIPK3 puncta. |
In Vivo
In mice, PK68 given at 5 mg/kg or 25 mg/kg by oral gavage once daily for 7 days, or at 2 mg/kg i.v. and 10 mg/kg p.o. for 14 days, shows a favorable pharmacokinetic profile and no obvious toxicity[1]. At 1 mg/kg i.p., PK68 ameliorates systemic inflammatory response syndrome induced by TNF[1]. PK68 (5 mg/kg, i.v.) inhibits RIPK1, which attenuates the transmigration of tumor cells through the endothelial barrier and suppresses tumor metastasis preventively[1].
| Animal Model | C57BL/6 mice[1] |
|---|---|
| Dosage | 5 mg/kg, 25 mg/kg |
| Administration | 5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days |
| Result | Exhibited favorable pharmacokinetic profiles and no obvious toxicity in mice treated with a 14-day course at a dose of 25 mg/kg. |
| Animal Model | C57BL/6 mice[1] |
|---|---|
| Dosage | 2 mg/kg, 10 mg/kg |
| Administration | 2 mg/kg, i.v.; 10 mg/kg, p.o; for 14 days |
| Result | PO (Gavage) IV (Bolus) Tmax (hr) 0.5 Cmax (ng/mL) 2423 AUC0-24 (ng/mL•hr) 4821 1588 AUCINF (ng/mL•hr) 4897 1590 t1/2 (hr) 1.3 1.0 MRT (hr) 1.8 0.8 CL (mL/hr/kg) 1258 CL (mL/min/kg) 21 Vss (mL/kg) 1009 Vss (L/kg) 1.0 F(%) 61 |
| Animal Model | C57BL/6 mice[1] |
|---|---|
| Dosage | 1 mg/kg |
| Administration | 1 mg/kg, i.p. |
| Result | Provided effective protection against TNFα-induced lethal shock. |
| Animal Model | C57BL/6 mice[1] |
|---|---|
| Dosage | 5 mg/kg |
| Administration | 5 mg/kg, i.v. |
| Result | Significantly reduced the number of pulmonary metastasis nodules, decreased lung metastasis, decreased number of RFP-LL/2 cells, attenuated transmigration of RFP-LL/2 cells through the endothelial cell monolayer and had no obvious influence on the proliferation rate and invasion ability of B16-F10 or RFP-LL/2 cells without the endothelial cell monolayer in vitro. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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bioRxiv. 2026 Jun 29.
