| Romidepsin, sold under the brand name Istodax, is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T-cell lymphomas (PTCLs). Romidepsin is a natural product obtained from the bacterium Chromobacterium violaceum, and works by blocking enzymes known as histone deacetylases, thus inducing apoptosis. It is sometimes referred to as depsipeptide, after the class of molecules to which it belongs. Romidepsin is branded and owned by Gloucester Pharmaceuticals, a part of Celgene.
|
|
Read full article at Wikipedia
|
InChI=1S/C24H36N4O6S2/c1- 6-16-21(30)28-20(14(4)5)24(33)34-15-9-7-8-10-35-36-12-17(22(31)25-16)26-23(32)19(13(2)3)27-18(29)11-15/h6-7,9,13-15,17,19-20H,8,10-12H2,1-5H3,(H,25,31)(H,26,32)(H,27,29)(H,28,30)/b9-7+,16-6-/t15-,17-,19-,20+/m1/s1 |
| OHRURASPPZQGQM-GCCNXGTGSA-N |
| C\C=C1/NC(=O)[C@H]2CSSCC\C=C\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C |
|
|
Chromobacterium violaceum
(NCBI:txid536)
|
of strain
968
See:
PubMed
|
|
Chromobacterium violaceum
(NCBI:txid536)
|
See:
PubMed
|
|
Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
|
|
|
EC 3.5.1.98 (histone deacetylase) inhibitor
An EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitor that interferes with the function of histone deacetylase (EC 3.5.1.98).
antimicrobial agent
A substance that kills or slows the growth of microorganisms, including bacteria, viruses, fungi and protozoans.
(via heterocyclic antibiotic )
|
|
|
antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
|
|
View more via ChEBI Ontology
|
(1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone
|
|
romidepsin
|
ChemIDplus
|
romidepsina
|
WHO MedNet
|
romidepsine
|
WHO MedNet
|
romidepsinum
|
WHO MedNet
|
|
Antibiotic FR 901228
|
ChemIDplus
|
|
FK228
|
SUBMITTER
|
|
FR901228
|
SUBMITTER
|
|
NSC-630176
|
ChEBI
|
|
Chromadax
|
KEGG DRUG
|
|
Istodax
|
SUBMITTER
|
|
128517-07-7
|
CAS Registry Number
|
KEGG DRUG
|
|
128517-07-7
|
CAS Registry Number
|
ChemIDplus
|
|
128517-07-7
|
CAS Registry Number
|
SUBMITTER
|
|
6854221
|
Reaxys Registry Number
|
Reaxys
|
Carafa V, Nebbioso A, Altucci L (2011)
Histone deacetylase inhibitors: recent insights from basic to clinical knowledge & patenting of anti-cancer actions.
Recent patents on anti-cancer drug discovery 6, 131-145 [PubMed:21110829]
[show Abstract]
Epigenetic modifications have been causally linked to cancer development and progression, and are potentially reversible by drug treatments. The N-terminal tails of histones contain amino acid residues modifiable by post-translational modifications such as acetylation. Given that HDAC inhibitors induce cancer cell differentiation and death, an increasing number of these compounds has been synthesized in the last ten years. Many HDAC inhibitors are in clinical trials for the treatment of cancer. Two of them, the hydroxamic acid (SAHA) and Romidepsin (FK 228), are approved in the second line treatment of refractory, persistent or relapsed Cutaneous T Cell Lymphoma (CTCL). The growing evidence of the potential benefits of an anti-cancer treatment based on the use of HDAC inhibitors have led to a large number of patent applications all over the world. The aim of this review is to give an overview of the basic current knowledge and molecular mechanisms of HDAC inhibitors and their clinical trials as well as to focus on the recent patent applications existing in the field of HDAC inhibitors and cancer treatment between 2008 and 2010 in USA. | Grant C, Rahman F, Piekarz R, Peer C, Frye R, Robey RW, Gardner ER, Figg WD, Bates SE (2010)
Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors.
Expert review of anticancer therapy 10, 997-1008 [PubMed:20645688]
[show Abstract]
Romidepsin is a histone deacetylase inhibitor (HDI), approved by the US FDA for the treatment of cutaneous T-cell lymphoma (CTCL). Although various mechanisms have been proposed for the activity of HDIs, including induction of genes controlling cell cycle, acetylation of cytoplasmic proteins and direct induction of apoptosis, the mechanism underlying activity of romidepsin and other HDIs in CTCL is not known. Romidepsin induces long-lasting responses. The side-effect profile is similar to that of other HDIs, causing fatigue, nausea and thrombocytopenia. Management of the CTCL population requires vigilence to prevent infection with skin contaminants, and monitoring of potassium and magnesium, electrolytes found to be low in a large proportion of patients. Electrocardiographic (ECG) changes are common but are not associated with myocardial damage. When molecular end points were evaluated in 61 patients enrolled on a Phase II trial with romidepsin, response was associated with persistence of acetylated histone H3, suggesting that drug exposure is important in effective therapy with romidepsin. Future studies will endeavor to identify combination strategies to increase the efficacy both in resistant CTCL and in solid tumors and to identify biomarkers of response that will allow selection of patients most likely to benefit from the therapy. | Greshock TJ, Johns DM, Noguchi Y, Williams RM (2008)
Improved total synthesis of the potent HDAC inhibitor FK228 (FR-901228).
Organic letters 10, 613-616 [PubMed:18205373]
[show Abstract]
A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key beta-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone. | Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M (1994)
FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity.
The Journal of antibiotics 47, 301-310 [PubMed:7513682]
[show Abstract]
A novel antitumor bicyclic depsipeptide, FR901228, was isolated from a broth culture of Chromobacterium violaceum No. 968 as colorless prisms and the molecular formula was determined as C24H36N4O6S2. This antibiotic reverted the transformed morphology of a Ha-ras transformant to normal, and exhibited prominent antitumor activities against murine and human tumor cell lines both in vitro and in vivo. | Shigematsu N, Ueda H, Takase S, Tanaka H, Yamamoto K, Tada T (1994)
FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination.
The Journal of antibiotics 47, 311-314 [PubMed:8175483] |
|
