2. Apoptosis
  3. RIP kinase
  4. PK68

PK68 is a potent orally active and specifical type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC50 of ~90 nM, displays inhibition of RIPK1-dependent necroptosis. PK68 powerfully ameliorates TNF-induced systemic inflammatory response syndrome, and can be used for the research of inflammatory disorders and cancer metastasis.

For research use only. We do not sell to patients.

PK68 Chemical Structure

PK68 Chemical Structure

CAS No. : 2173556-69-7

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 242 In-stock
Solution
10 mM * 1 mL in DMSO USD 242 In-stock
Solid
1 mg USD 150 In-stock
5 mg USD 220 In-stock
10 mg USD 350 In-stock
25 mg USD 660 In-stock
50 mg USD 1120 In-stock
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Customer Review

Based on 1 publication(s) in Google Scholar

PK68 Related Antibodies

Top Publications Citing Use of Products

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

PK68 is a potent orally active and specifical type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC50 of ~90 nM, displays inhibition of RIPK1-dependent necroptosis. PK68 powerfully ameliorates TNF-induced systemic inflammatory response syndrome, and can be used for the research of inflammatory disorders and cancer metastasis[1].

IC50 & Target

RIPK1

90 nM (IC50)

RIPK1

23 nM (EC50)

In Vitro

PK68 has highly potent inhibition of TNF-induced necroptosis with EC50 values of 23 nM and 13 nM in human and mouse cells, respectively[1].
PK68 is a highly selective inhibitor of RIPK1 kinase activity with IC50 value of 90 nM[1].
PK68 (100 nM, 1 h) blocks necroptosis through the suppression of RIPK3 function or signaling upstream of RIPK3 activation[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PK68 Related Antibodies

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

PK68 (5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days) or (2 mg/kg, i.v.; 10 mg/kg, p.o.; for 14 days) exhibits a favorable pharmacokinetic profile and no obvious toxicity in mice[1].
PK68 (1 mg/kg, i.p.) ameliorates TNF-induced systemic inflammatory response syndrome[1].
PK68 (5 mg/kg, i.v.) inhibits RIPK1 that results in attenuated tumor cell transmigration across the endothelial barrier and preventive suppression of tumor metastasis[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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.
Molecular Weight

424.52

Formula

C22H24N4O3S
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 30 mg/mL (70.67 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.3556 mL 11.7780 mL 23.5560 mL
5 mM 0.4711 mL 2.3556 mL 4.7112 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 3 mg/mL (7.07 mM); Clear solution

    This protocol yields a clear solution of ≥ 3 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (30.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.08 mg/mL (4.90 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.92%

COA (245 KB) HNMR (228 KB) RP-HPLC (162 KB) LCMS (158 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.3556 mL 11.7780 mL 23.5560 mL 58.8900 mL
5 mM 0.4711 mL 2.3556 mL 4.7112 mL 11.7780 mL
10 mM 0.2356 mL 1.1778 mL 2.3556 mL 5.8890 mL
15 mM 0.1570 mL 0.7852 mL 1.5704 mL 3.9260 mL
20 mM 0.1178 mL 0.5889 mL 1.1778 mL 2.9445 mL
25 mM 0.0942 mL 0.4711 mL 0.9422 mL 2.3556 mL
30 mM 0.0785 mL 0.3926 mL 0.7852 mL 1.9630 mL
40 mM 0.0589 mL 0.2945 mL 0.5889 mL 1.4723 mL
50 mM 0.0471 mL 0.2356 mL 0.4711 mL 1.1778 mL
60 mM 0.0393 mL 0.1963 mL 0.3926 mL 0.9815 mL
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PK68 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PK682173556-69-7PK 68PK-68RIP kinaseReceptor-interacting protein kinasesRIPKoraltype II inhibitorreceptor-interacting kinase 1 (RIPK1)TNFinflammatorycancerInhibitorinhibitorinhibit

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