Carfilzomib

• CAT Number: A000280
• CAS Number: 868540-17-4
• Molecular Formula: C₄₀H₅₇N₅O₇
• Molecular Weight: 719.91
• Purity: ≥95%
• Synonyms: Carfilzomib; 868540-17-4; Kyprolis; Carfilzomib (PR-171); PR-171
• Target: Proteasome
• Solubility: >36mg/mL in DMSO
• Storage: 3 years -20C powder
• IUPAC Name: (2S)-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide
• 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
• InChIKey: BLMPQMFVWMYDKT-NZTKNTHTSA-N
• SMILES: CC(C)C[C@@H](C(=O)[C@]1(CO1)C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC3=CC=CC=C3)NC(=O)CN4CCOCC4

Carfilzomib（Cat No.:A000280）is a potent and selective proteasome inhibitor, primarily used to treat relapsed or refractory multiple myeloma. By irreversibly binding to the 20S core of the proteasome, carfilzomib disrupts protein degradation, leading to an accumulation of misfolded proteins, which induces apoptosis in rapidly dividing cancer cells. Its specificity and strong pro-apoptotic effects make it highly effective in targeting myeloma cells. Carfilzomib is also being researched for its potential in other hematologic malignancies and solid tumors, marking it as a significant agent in targeted cancer therapy.

Reference

1. J Pharm Pharmacol. 2013 Aug;65(8):1095-106. doi: 10.1111/jphp.12072. Epub 2013
Apr 24.

Carfilzomib: a novel agent for multiple myeloma.

Redic K(1).

Author information:
(1)University of Michigan College of Pharmacy, Ann Arbor, MI, USA; University of
Michigan Health System, Ann Arbor, MI 48109, USA.

OBJECTIVES: Carfilzomib is a new agent for the treatment of relapsed and
refractory multiple myeloma (MM). This article presents a comprehensive overview
of the pharmacokinetics, pharmacodynamics, dosing schedule, safety, efficacy,
preparation and administration of carfilzomib, and its role in treating MM
patients.
KEY FINDINGS: Carfilzomib is a selective proteasome inhibitor that differs
structurally and mechanistically from bortezomib. In patients’ whole-blood and
peripheral-blood mononuclear cells, carfilzomib inhibited proteasomal and
immunoproteasomal activity by 70-80%. Approved carfilzomib dosing is based on
body surface area, and is given on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle
(20 mg/m(2) in cycle 1; 27 mg/m(2) in cycle 2+). Premedication with dexamethasone
and adequate hydration are recommended to reduce the risk of adverse events. The
median t1/2 of carfilzomib is short (0.29-0.48 h), with no accumulation detected
between doses. In clinical studies in relapsed and refractory MM. and in
combinations in newly diagnosed MM, single-agent carfilzomib demonstrated
significant durable activity, good tolerability and a favourable safety profile,
supporting its extended use.
CONCLUSIONS: Carfilzomib represents an important addition to the treatment
armamentarium for patients with relapsed and/or refractory MM, and studies are
underway evaluating the role of single-agent carfilzomib in additional clinical
settings as well as in different combinations.

2. Ann Pharmacother. 2013 Jan;47(1):56-62. doi: 10.1345/aph.1R561. Epub 2013 Jan 8.

Carfilzomib: a second-generation proteasome inhibitor for the treatment of
relapsed and refractory multiple myeloma.

Thompson JL(1).

Author information:
(1)Pharmaceutical Management Branch, Cancer Therapy Evaluation Program, Division
of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes
of Health, Rockville, MD, USA.

OBJECTIVE: To review and summarize data on carfilzomib, which was approved by the
Food and Drug Administration (FDA) in July 2012 for the treatment of patients
with relapsed and refractory multiple myeloma (MM) who received prior bortezomib
and thalidomide or lenalidomide.
DATA SOURCES: A literature search through PubMed was conducted through October
2012 using the terms carfilzomib, PR-171, proteasome inhibitor (PI), and MM. Data
were also obtained through the American Society of Clinical Oncology and American
Society of Hematology abstracts and FDA briefing documents.
STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to human
studies published in English. Priority was placed on trials of carfilzomib in
relapsed and refractory MM.
DATA SYNTHESIS: Carfilzomib is a new PI that differs in pharmacology and
pharmacokinetics from bortezomib, the first-in-class PI. The FDA approval was
based on efficacy data from a Phase 2 study of carfilzomib in patients with
relapsed and refractory MM (n = 266). All patients had received prior bortezomib
and 80% were refractory or intolerant to both bortezomib and lenalidomide.
Patients were treated with intravenous carfilzomib 20 mg/m(2) (cycle 1) followed
by 27 mg/m(2) (cycles ≥2) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle.
The overall response rate was 23.7% (18.7-29.4), with a median duration of
response of 7.8 (5.6-9.2) months. Safety data from an integrated analysis
reported thrombocytopenia, anemia, fatigue, nausea, and diarrhea as the most
common adverse events, with minimal dose-limiting neutropenia or peripheral
neuropathy (PN) (n = 526). The incidence of grade 3 or higher thrombocytopenia
was 24.9%, while that of neutropenia was 11.9%, and the incidence of all grades
of treatment-emergent PN was 13%.
CONCLUSIONS: Carfilzomib is a safe and effective new treatment option for
patients with relapsed MM refractory to bortezomib and thalidomide or
lenalidomide. Randomized head-to-head trials with bortezomib will assist in
formulary and treatment decisions in the context of PIs as a drug class.