Carfilzomib, Proteasome Inhibitor

Carfilzomib is a selective, irreversible proteasome inhibitor (over 80% inhibition at doses of 10 nM and above). In models of multiple myeloma, Carfilzomib potently bound and specifically inhibited the chymotrypsin-like proteasome and immunoproteasome activities, resulting in accumulation of ubiquitinated substrates. It induced a dose- and time-dependent inhibition of proliferation, ultimately leading to apoptosis. It also inhibited proliferation and activated apoptosis in patient-derived MM cells and neoplastic cells from patients with other hematologic malignancies. Carfilzomib showed increased efficacy compared with bortezomib and was active against bortezomib-resistant MM cell lines and samples from patients with clinical bortezomib resistance. Currently it is approved by US FDA for relapsed and refractory multiple myeloma in 2012.

Product information

CAS Number: 868540-17-4

Molecular Weight: 719.91

Formula: C40H57N5O7

Synonym:

PR-171

Kyprolis

PR 171

PR171

Chemical Name: (S)-4-methyl-N-((S)-1-(((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide

Smiles: C[C@@]1(CO1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1C=CC=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC1C=CC=CC=1)NC(=O)CN1CCOCC1

InChiKey: BLMPQMFVWMYDKT-NZTKNTHTSA-N

InChi: InChI=1S/C40H57N5O7/c1-27(2)22-32(36(47)40(5)26-52-40)42-39(50)34(24-30-14-10-7-11-15-30)44-38(49)33(23-28(3)4)43-37(48)31(17-16-29-12-8-6-9-13-29)41-35(46)25-45-18-20-51-21-19-45/h6-15,27-28,31-34H,16-26H2,1-5H3,(H,41,46)(H,42,50)(H,43,48)(H,44,49)/t31-,32-,33-,34-,40+/m0/s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Carfilzomib was used at 0.1 µM in vitro and in cellular assays.

In Vivo:

Carfilzomib was dosed to mice/rats by intravenous administration at 0.5-4 mg/kg once per day.

References:

1. Kuhn DJ, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. (2007) Blood. 110(9):3281-90.
2. Parlati F,et al. Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. (2009) Blood.114(16):3439-47.
3. Dasmahapatra G, et al. Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. (2011) Mol Cancer Ther. 10(9):1686-97.
4. Sacco A, et al. Carfilzomib-dependent selective inhibition of the chymotrypsin-like activity of the proteasome leads to antitumor activity in Waldenstrom's Macroglobulinemia. (2011) Clin Cancer Res. 17(7):1753-64.

Products are for research use only. Not for human use.