Sotrastaurin is a potent and specific inhibitor of protein kinase C (PKC) with Ki at subnanomolar to low nanomolar range for a variety of PKC isotypes while selective for >200 other kinases. Sotrastaurin is an immunosuppressant that blocks early T-lymphocyte (T-cell) activation via protein kinase C inhibition. Sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy. Sotrastaurin inhibits nuclear factor (NF)-κB, which directly promotes the transcription of forkhead box protein 3 (FoxP3), the key regulator for the development and function of regulatory T cells (Tregs). Sotrastaurin is a potent inhibitor of alloreactivity in vitro, while it did not affect Treg function in patients after kidney transplantation. Sotrastaurin prevented TCR/CD28-induced T-cell activation and pro-inflammatory cytokine production, but preserved a stable Treg phenotype as evidenced by maintenance of suppressive capacity, high Foxp3 and CD25 expression, and lack of IL-17A and IFNγ production.
| Cell Experiment | |
|---|---|
| Cell lines | |
| Preparation method | |
| Concentrations | |
| Incubation time | |
| Animal Experiment | |
|---|---|
| Animal models | male Wistar/F rats |
| Formulation | Saline |
| Dosages | 10 mg/kg and 30 mg/kg |
| Administration | Orally administrated |
| Molecular Weight | 438.48 |
| Formula | C25H22N6O2 |
| CAS Number | 425637-18-9 |
| Solubility (25°C) | DMSO 50 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[5] Kovarik JM, et al. Ther Drug Monit. Overview of sotrastaurin clinical pharmacokinetics.
| Related PKC Products |
|---|
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PKC β pseudosubstrate is a selective cell-permeable inhibitor of PKC. |
| Protein Kinase C (19-31)
Protein Kinase C (19-31), a peptide inhibitor of protein kinase C (PKC), is used as protein kinase C substrate peptide for testing the protein kinase C activity. |
| Protein Kinase C (19-36)
Protein Kinase C (19-36) is a pseudosubstrate peptide inhibitor of protein kinase C (PKC), with an IC50 of 0.18 μM. |
| [Ala113]MBP(104-118)
[Ala113]MBP(104-118) is an noncompetitive peptide inhibitors of protein kinase C (PKC), with IC50s ranging from 28-62 μM. |
| [Ala107]MBP(104-118)
[Ala107]MBP(104-118) is an noncompetitive peptide inhibitors of protein kinase C (PKC), with IC50s ranging from 46-145 μM. |
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