Abstract:
BACKGROUND:Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. METHODS:Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. RESULT:The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion:Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.
journal_name
Anticancer Agents Med Chemjournal_title
Anti-cancer agents in medicinal chemistryauthors
Dogra R,Bhatia R,Shankar R,Bansal P,Rawal RKdoi
10.2174/1871520618666181025091128subject
Has Abstractpub_date
2018-01-01 00:00:00pages
1936-1951issue
14eissn
1871-5206issn
1875-5992pii
ACAMC-EPUB-93959journal_volume
18pub_type
杂志文章,评审abstract:BACKGROUND:Colorectal Cancer (CRC) is one of the most common fatal diseases with high morbidity. Alteration of glucose metabolism is one of the hallmarks in the development of CRC. Glucose Transporter 1 (GLUT1) is a key rate-limiting protein in hyperactive glucose metabolism and up-regulated in CRC, however, the underl...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666200318094618
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:The cause of cervical cancer can be traced to Human Papilloma Virus (HPV) along with other, nonviral factors. The uterine cervix is reactive to hormones, and female hormones have been implicated in cervical cancer pathogenesis. Previous studies have indicated that malignant cervical cells tend to lose Estrog...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520618666180830162517
更新日期:2018-01-01 00:00:00
abstract::The androgen receptor (AR) plays a crucial role in the physiological and pathological functions of androgen. As a transcription factor, the AR modulates androgen activity by regulating the transcription of target genes that are involved in numerous physiological functions and pathological disorders, such as acne vulga...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152009789124655
更新日期:2009-10-01 00:00:00
abstract::This article aims to give an overview on etiology, diagnosis and treatment options of osteonecrosis of the jaw bone among cancer patients receiving anti-resorptive drugs (ARDs). The physiologic bone function of continuous resorption and buildup is modified by the use of ARDs. Although ARDs proved to reduce pain and to...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520615666150325232857
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:A monoterpene, perillyl alcohol, has attracted attention in medicinal chemistry since it exhibited chemo-preventive and therapeutic properties against a variety of cancers. OBJECTIVE:In the present work, it was aimed to obtain derivatives of perillyl alcohol through microbial biotransformation and investiga...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520617666170103093923
更新日期:2017-01-01 00:00:00
abstract:INTRODUCTION:Esophageal cancer remains an aggressive disease with poor survival rates. FAK and IGF-1R are two important tyrosine kinases important for cell survival signaling and found to be upregulated in esophageal cancer. Our hypothesis is that a novel small molecule compound that disrupts FAK and IGF-1R protein-pro...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/187152011796817718
更新日期:2011-09-01 00:00:00
abstract::Colorectal cancer is a major global health problem with more than a million new cases diagnosed worldwide in 2005. In the United States, this malignancy is the third most common with 145,000 new cases and the second most lethal with 56,000 deaths in 2005. Unfortunately, preclinical diagnostic screening in the U.S. pop...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152007781668742
更新日期:2007-09-01 00:00:00
abstract::As early as the 1920s, the eminent physician and chemist, Otto Warburg, nominated for a second Nobel Prize for his work on fermentation, observed that the core metabolic signature of cancer cells is a high glycolytic flux. Warburg averred that the prime mover of cancer is defective mitochondrial respiration, which dri...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520614666140804224637
更新日期:2014-01-01 00:00:00
abstract::Protein kinase B (PKB or Akt) is a central component of the PI3K - PKB - mTOR signalling cascade and is firmly established as an attractive target for pharmacological intervention in cancer. A number of small molecule inhibitors with well-defined, direct molecular interactions with PKB are now known, covering a range ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152009787047734
更新日期:2009-01-01 00:00:00
abstract::Glioblastoma Multiforme (GMB) is the most aggressive primary brain tumor with poor survival rates and universal recurrence despite aggressive treatments. Recent research suggested that GBM has multiple glioma cell populations, some of which are organized in a stem cell hierarchical order with different stages of diffe...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520614666140825105145
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Multi-kinase inhibitor sorafenib showed dramatic effects in acute myeloid leukemia (AML) cells harboring fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation. However, FLT3-ITD mutation only occurs in 25% of AML cases. The therapeutic effects of sorafenib in AML patients without FLT3...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520618666180307125544
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or t...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520621666201207090702
更新日期:2020-12-06 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Glucosamine is a widely prescribed dietary supplement used in the treatment of osteoarthritis. In the present study, the chemoprotectant ability of glucosamine was evaluated against cisplatin-induced genotoxicity and cytotoxicity in rat bone marrow cells. METHODS:Glucosamine was orally adminis...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666190704164126
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Peniciketal A (Pe-A), a spiroketal compound, shows potent anticancer activities in human acute monocytic leukemia. However, the detailed mechanisms and potent targets of Pe-A remain largely unexplored. Here, we investigated the differentially expressed proteins between the Pe-A-treated group and the control ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666190212124339
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Colorectal cancer is among the leading causes of death worldwide. The incidence of deaths is expected to be 11.4 million in 2030. OBJECTIVE:We aimed to evaluate the in vitro and in vivo antioxidant and antitumor activities of a novel Bithiophene- Fluorobenzamidine (BFB) against DMH-induced colorectal cancer...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666191021162411
更新日期:2020-01-01 00:00:00
abstract::Polyphenol-protein interaction (PPI) is reversible in that polyphenol-protein complex can be dissociated and release the free polyphenols. The aim of this study is to evaluate the contribution of polyphenol-protein interaction on improving the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging capacity of polyphe...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/187152012802650101
更新日期:2012-10-01 00:00:00
abstract::Cancer is the main cause of death, so the search for active agents to be used in the therapy of this disease, is necessary. According to studies conducted, substances derived from natural products have shown to be promising in this endeavor. To these researches, one can associate with the aid of computational chemistr...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520618666181119110934
更新日期:2019-01-01 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. Currently it is known that mTOR functions as two complexes, mTOR...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152010793498663
更新日期:2010-09-01 00:00:00
abstract::Breast cancer is the most common cancer among women, and ranks second among cancer deaths in women. Approximately 60% of all breast cancer patients have hormone-dependent breast cancer, which contains estrogen receptors and requires estrogen for tumor growth. Estradiol is biosynthesized from androgens by the cytochrom...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152006776930873
更新日期:2006-05-01 00:00:00
abstract::Sphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramid...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152011795677571
更新日期:2011-05-01 00:00:00
abstract:AIM:This study aimed to characterize the cellular basis of the platinum cytotoxicity of two novel platinum complexes, 3Pt and 1Pt, in comparison with that of cisplatin. 3Pt comprises anionic phosphate moieties, while 1Pt comprises neutral aromatic ligands. METHODS:We compared the cytotoxic potency of 3Pt and 1Pt with ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520615666141216151547
更新日期:2015-01-01 00:00:00
abstract::The rapid approval of several novel agents has given prostate cancer patients and their treating physicians many new and effective therapeutic options. Four new medical therapies were recently approved on the basis of prolonged overall survival in castration-resistant prostate cancer (CRPC) patients: sipuleucel-T, cab...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/18715206113139990077
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of Brazilian green propolis, and possesses, among other things, anticancer properties. However, to the best of our knowledge, there are no studies of artepillin C in cervical cancer. METHOD:To explore a new therapeutic candid...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520618666180604092930
更新日期:2018-01-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is the most frequent type of hematological cancer in the Western World. An accumulation of leukemic cells in peripheral blood of patients is a result of apoptosis disturbances as well as an increase in germinal centers CLL cell proliferation. The differences between CLL patients in t...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152010794479799
更新日期:2010-11-01 00:00:00
abstract::A novel process for the preparation of two ketomethylenic antifolates, 2-(2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-amino]- phenyl}-2-oxo-ethyl) pentanedioic acid and 2-(2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-phenyl}-2-oxo-ethyl) pentanedioic acid is described herein. Both compounds were compared with met...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520611313020022
更新日期:2013-02-01 00:00:00
abstract::Recently, intensive laboratory and preclinical studies have identified and validated therapeutic molecular targets in cancer, particularly the receptor tyrosine kinases, the intracellular pathways, and the genetic and epigenetic alterations, resulting in an unprecedented surge of novel, targeted therapies and therapeu...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152008784533099
更新日期:2008-06-01 00:00:00
abstract::Adrenocortical carcinoma (ACC) is a rare but typically aggressive malignancy. Radical surgery remains the potentially curative option. However, about one third of patients initially present with distant metastases. Regarding to chemotherapy, mitotane alone or in combination with cytotoxic drugs should be the first sel...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520611313020010
更新日期:2013-02-01 00:00:00
abstract::Ras association domain family member 5 (RASSF5, also named NORE1) is an identified member of the RASSF gene family which could bind selectively to activate Ras and function as an antineoplastic effector in multiple cellular regulations. While highly expressed in majority of normal tissues, RASSF5 is epigenetically ina...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520617666170327120747
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:Multiparametric Magnetic Resonance Imaging (mpMRI) has become a very useful tool in the management of PCa. Particularly, there is a great interest in using mpMRI for men on Active Surveillance (AS) for low risk PCa. The aim of this systematic review was to critically review the latest literature concerning th...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520618666180105105413
更新日期:2018-01-01 00:00:00
abstract::Natural and synthetic carbazoles, either in a pure substituted or in an annellated substituted form, represent an important and heterogeneous class of anticancer agents, which has grown considerably over the last two decades. Many carbazole derivatives have been tested for cyctotoxic activity, some of them have entere...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152007780058678
更新日期:2007-03-01 00:00:00