Welcome to LookChem.com Sign In|Join Free


  • or


Post Buying Request

868540-17-4 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

868540-17-4 Usage


Carfilzomib, also known as PR-171, is a second-generation proteasome inhibitor that was approved by the US FDA in July 2012 for the treatment of patients with multiple myeloma (MM) who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression within 60 days of completion of the last therapy. It binds to and irreversibly inhibits the chymotrypsin-like protease activity of the constitutive proteosome (β5) and immunoproteosome (β5i) via its epoxyketone pharmacophore, leading to the accumulation of polyubiquitinated proteins and induction of apoptosis through activation of both the intrinsic and extrinsic caspase pathways.


Used in Oncology:
Carfilzomib is used as a treatment for relapsed and refractory multiple myeloma, a type of blood cancer. It is particularly effective in patients who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression within 60 days of completion of the last therapy. The proteosome inhibition induced by Carfilzomib results in cell cycle arrest and apoptosis in a variety of hematologic and solid tumor cell lines, such as MM, acute myeloid leukemia (AML), pancreatic cancer, and lung cancer.


Carfilzomib is a tetrapeptide-based epoxy-proteasome inhibitor that irreversibly binds to the 20S proteasome containing the threonine N-terminal active site and the in vivo proteolysis core particle of 26S proteasome. In animal, carfilzomib has antiproliferative and apoptosis activity in vitro in solid and hematological granulocytes. In animals, carfilzomib inhibits proteasome activity in blood and tissue and delays tumor growth in multiple myeloma, hematological and solid tumor models.

Side effects

The most common adverse events observed in clinical trials (incidence ≥30%) were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea and fever; the most common serious adverse events (overall incidence 45%) include pneumonia, acute renal failure, fever and congestive heart failure.

Efficacy and Safety

To assess the safety and efficacy of the drug, one study included 266 patients who had received at least two prior therapies, including bortezomib and thalidomide. It was assessed of the complete or partial disappearance of the tumor in the treated patient (overall response rate). The overall response rate was 23% and the median response time was 7.8 months. Common adverse effects of carfilzomib were observed in more than 30% of the subjects include fatigue, low blood cell counts and platelet counts, dyspnea, diarrhea and fever. Severe adverse reactions include heart failure and dyspnea. Upon the occurrence of serious adverse reactions, the patient should be closely monitored and stop the drug treatment. Information regarding the pharmacological effects, indications, mechanism of action, indications and side effects of Carfilzomib, a drug for treating multiple myeloma (MM), were compiled and edited by Xiao Nan of lookchem.


Proteolix Inc. (United States)

Clinical Use

Carfilzomib is an irreversible inhibitor of the chymotrypsin-like protease in the proteasome and was approved in the U.S. for the treatment of multiple myeloma. Carfilzomib was discovered by Proteolix which was later acquired by Onyx Therapeutics who completed the development of this drug. Carfilzomib is also undergoing clinical evaluation for additional oncology indications such as relapsed solid tumors, lymphoma, prolymphocytic leukemia, acute myeloid leukemia and acute lymphocytic leukemia.


Carfilzomib is an analog of the natural product epoxomicin which was first synthesized in the laboratories of Professor Crews at Yale University. Subsequent development of the SAR led to the discovery of YU-101 in which 3 of the amino acids of this pentapeptide were modified to improve the potency of the molecule. After licensing the molecule to Proteolix, the introduction of the morpholino group was found to improve the solubility of the drug while maintaining efficient interaction with the target. The most scalable route to carfilzomib closely resembles the original route developed toward epoximicin and is described herein.The synthesis was initiated with the amide coupling of phenyl alanine methyl ester (53) and N-Boc leucine (54) using standard coupling reagents to afford dipeptide 55 in high yield the Scheme below. Acidic removal of the amine protecting group followed by a second amide coupling reaction with N-Boc homophenyl alanine provided tripeptide 56 in 85% yield for the two steps. Acidic removal of the amine protecting group followed by acylation with chloroacetyl chloride provided β-chloro amide 57 in 67% yield. Reaction of 57 with morpholine in the presence of catalytic amounts of potassium iodide followed by saponification of the methyl ester with lithium hydroxide provided acid 58 in 87% yield for the two steps. Amide coupling between acid 58 and keto-epoxyamine 59 (whose preparation is described in the scheme below) using HOBT as the coupling reagent followed by recrystallization of the resulting product ultimately gave carfilzomib (IX) in 75% yield. Keto-epoxyamine 59 was prepared from N-Boc leucine (54) as described in the Scheme below. Reaction of 54 with isobutyl chloroformate followed by N,O-dimethylhydroxylamine provided Weinreb amide 60 in 94% yield. Grignard addition of isopropenylmagnesium bromide 60 provided enone 62 in 81% yield. Epoxidation of 62 with calcium hypochlorite provided a mixture of epoxides giving 41% yield of the desired isomer (presumably isolated by chromatography), and subsequent treatment with TFA liberated the amine, providing the TFA salt of ketoepoxy amine 59 in 92% yield.

Drug interactions

Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine - increased risk of agranulocytosis.


Carfilzomib was rapidly and extensively metabolised by mainly peptidase cleavage and epoxide hydrolysis. Cytochrome P450 mediated mechanisms played a minor role in overall carfilzomib metabolism. The metabolites have no known biologic activity.


1) Bennett and Kirk (2008)?Development of proteasome inhibitors in oncology and autoimmune diseases; Curr. Opin. Drug Disc. Dev.?11?616 2) Hanada?et al.?(1992),?Epoxomicin, a new antitumor agent of microbial origin; J. Antibiot. (Tokyo),?45?174 3) Demo?et al. (2007)?Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome; Cancer Res.?67?6383 4) Kuhn?et al. (2007),?Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma; Blood,?110?328

Check Digit Verification of cas no

The CAS Registry Mumber 868540-17-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,6,8,5,4 and 0 respectively; the second part has 2 digits, 1 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 868540-17:
204 % 10 = 4
So 868540-17-4 is a valid CAS Registry Number.



According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 16, 2017

Revision Date: Aug 16, 2017


1.1 GHS Product identifier

Product name Carfilzomib

1.2 Other means of identification

Product number -
Other names Carfilzomib (PR-171)

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:868540-17-4 SDS

868540-17-4Downstream Products

868540-17-4Relevant articles and documents

Water-removable ynamide coupling reagent for racemization-free syntheses of peptides, amides, and esters

Liu, Tao,Zhang, Xue,Peng, Zejun,Zhao, Junfeng

, p. 9916 - 9921 (2021/12/24)

A novel ynamide coupling reagent, the by-product of which can be removed by water, was reported. It promotes the direct coupling between carboxylic acids and amines, alcohols or thiols to provide amides, peptides, esters and thioesters, respectively. No detectable racemization was observed for all the coupling reactions of carboxylic acids containing an α-chiral center. Importantly, a simple acidic aqueous work-up removed the by-product readily to afford pure coupling products in good to excellent yields without the use of column chromatography, thus making this method more environmentally benign, user friendly and cost-effective. The robustness of the water-removable ynamide coupling reagent was further exemplified by the racemization/epimerization-free synthesis of carfilzomib, in which no column chromatography purification was involved for the entire 12-step synthesis.



Page/Page column 12-15, (2021/01/22)

The present invention relates to a process for purification of carfilzomib free from its impurities using preparative high performance liquid chromatography (prep-HPLC).



Page/Page column 17-18, (2018/03/28)

The present invention relates to a process for preparation of Carfilzomib of formula (I).

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)


What can I do for you?
Get Best Price

Get Best Price for 868540-17-4