[CAS NO. 2173556-69-7] PK68
PRODUCTS SPECIFICATIONS [2173556-69-7]
DESCRIPTION [2173556-69-7]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 424.52 |
| Molecular Formula | C22H24N4O3S |
| SMILES | O=C(OC1CCCCC1)NC2=CC(C3=CC=C4N=C(NC(C)=O)SC4=C3)=CN=C2C |
Summary
PK68 is a potent orally active and specifical type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC 50 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 (IC 50 ) |
RIPK1 23 nM (EC 50 ) |
In Vitro
PK68 has highly potent inhibition of TNF-induced necroptosis with EC
50
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 IC
50
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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]
.
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: |
|
| 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. |
Appearance
Solid
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
DMSO : 30 mg/mL ( 70.67 mM ; Need ultrasonic)
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 |
| 10 mM | 0.2356 mL | 1.1778 mL | 2.3556 mL |