Carfilzomib (PR-171) is a tetrapeptide epoxyketone and a selective proteasome inhibitor. Carfilzomib irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme that degrades unwanted cellular proteins. Carfilzomib (PR-171) induced a dose- and time-dependent inhibition of proliferation, ultimately leading to apoptosis. Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. In clinical trials, carfilzomib (PR-171) has exhibited potent anti-myeloma efficacy and decreased side effects compared with bortezomib. At clinically relevant concentrations, carfilzomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Carfilzomib is currently in a phase III confirmatory clinical trial, known as the ASPIRE trial, comparing carfilzomib, lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed multiple myeloma.Carfilzomib showed stronger inhibitory activity and longer inhibition time against bortezomib resistant cells, and showed higher selectivity against proteasome. Its IC50 against 20S proteasome β5 was 3.4nmol/L.
*The compound is unstable in solutions, freshly prepared is recommended.
| Molecular Weight | 719.91 |
| Formula | C40H57N5O7 |
| CAS Number | 868540-17-4 |
| Solubility (25°C) | DMSO 45 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.
| Related Proteasome Products |
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| NIC-0102
NIC-0102 is an orally potent proteasome inhibitor (pIC50=7.55) that specifically inhibits NLRP3 inflammasome activation.NIC-0102 showed potent anti-inflammatory effects in vivo in a DSS-induced ulcerative colitis model. In addition, NIC-0102 inhibited the production of pro-IL-1β. |
| Ac-WLA-AMC
Ac-WLA-AMC is a specific 20S constitutive proteasome β5 fluorogenic substrate. |
| Ac-Nle-Pro-Nle-Asp-AMC
Ac-Nle-Pro-Nle-Asp-AMC is a specific substrate for 26S proteasome. |
| PR-39
PR-39, a natural proline- and arginine-rich antibacterial peptide, is a noncompetitive, reversible and allosteric proteasome inhibitor. |
| PSI
PSI (Proteasome Inhibitor 1) is a potent proteasome inhibitor. |
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