Effects of Immunomodulatory Derivatives of Thalidomide (IMiDs) and Their Analogs on Cell-Differentiation, Cyclooxygenase Activity and Angiogenesis

Fujimoto, Haruka; Noguchi, Takao; Kobayashi, Haruo; Miyachi, Hiroyuki; Hashimoto, Yuichi

doi:10.1248/cpb.54.855

Cited by 15 publications

(9 citation statements)

References 26 publications

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“…In 1998, TDM was approved as a treatment for Hansen's disease by the United States Food and Drug Administration (FDA), which was followed by investigations into other pharmacological applications of TDM and its derivatives. 5 The pharmacological effects of TDM include anti-tumor-promoting activities such as suppression of cell differentiation 6 and angiogenesis, 7 and many studies have been started to examine these new bioactivities.…”

Section: Figure 1 Hydantoin and Its Derivativesmentioning

confidence: 99%

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Synthesis of New Hydantoins Bearing Glutarimide or Succinimide Moiety and Their Evaluation for Cell Differentiation-inducing and Anti-angiogenic Activities

Yamaguchi¹,

Noguchi‐Yachide²,

Sakaguchi³

et al. 2015

HETEROCYCLES

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Several derivatives of hydantoin containing glutarimide or succinimide at the 3-position were synthesized. The new hydantoin derivatives had a structure similar to that of thalidomide, and so may possess activity similar to that of thalidomide and/or its analogs, such as effects on cell differentiation and angiogenesis. Some hydantoins showed enhancing effects on all-trans retinoic acid (ATRA)-induced cell differentiation of human leukemia cell line HL-60 and anti-angiogenic activity on human umbilical vein endothelial cells (HUVEC).These new hydantoin derivatives were more effective than thalidomide in cell differentiation-inducing activity on HL-60 and anti-angiogenic activity on HUVEC. INTRODUCTIONImidazolidine-2,4-dione (1), called hydantoin, and its derivatives have been investigated extensively and possess a wide range of biological activities. 1 Phenytoin (5,5-diphenylhydantoin, 2) and ethotoin (3-ethyl-5-phenylhydantoin, 3) are first-line medicines for the treatment of certain types of epileptic seizures. 2

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Section: Figure 1 Hydantoin and Its Derivativesmentioning

confidence: 99%

“…Compounds containing a glutarimide (piperidine-2,6-dione) moiety and a succinimide (pyrrolidine-2,5-dione) moiety are known to possess bioactivity, 8 so succinimide derivatives (6) also were synthesized.…”

Section: Figure 1 Hydantoin and Its Derivativesmentioning

confidence: 99%

Synthesis of New Hydantoins Bearing Glutarimide or Succinimide Moiety and Their Evaluation for Cell Differentiation-inducing and Anti-angiogenic Activities

Yamaguchi¹,

Noguchi‐Yachide²,

Sakaguchi³

et al. 2015

HETEROCYCLES

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“…In fact, IMiDs also inhibit the production of other pro-inflammatory cytokines, such as IL-1, IL-6, and IL-12, and increase the secretion of anti-inflammatory cytokines, such as IL-10 [28,37,114]. Furthermore, IMiDs are able to inhibit the expression of cyclooxygenase 2 (COX-2) [115], but not COX-1, in lipopolysaccharide-TNFa and IL-1b stimulated peripheral blood mononuclear cell (PBMC) [114]. COX-2 is an enzyme that catalyzes arachidonic acids into various pro-inflammatory prostaglandins (PGs).…”

Section: Effects Of Imids On the Interaction Between MM Cells And Bmscsmentioning

confidence: 99%

Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma

Chang¹,

Zhu²,

Shi³

et al. 2014

ABBS

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Although immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, are widely used in the treatment of multiple myeloma (MM), the molecular mechanism of IMiDs' action is largely unknown. In this review, we will summarize recent advances in the application of IMiDs in MM cancer treatment as well as their effects on immunomodulatory activities, anti-angiogenic activities, intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells, anti-inflammatory activities, anti-proliferation, pro-apoptotic effects, cell cycle arrest, and inhibition of cell migration and metastasis. In addition, the potential IMiDs' target protein, IMiDs' target protein's functional role, and the potential molecular mechanisms of IMiDs resistance will be discussed. We wish, by presentation of our naive discussion, that this review article will facilitate further investigation in these fields.

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“…Additionally, different thalidomide analogs were vastly been used in experimental studies using in vitro and in vivo models while they showed different effect on several pathways involving development to inflammation. To have a birds eye view on thalidomide analogs and their physiological effect, We further tabulated the effect of known thalidomide analogues on different possible pathways ( Table 1) [79][80][81][82][83][84][85][86][87][88][89][90][91][92]. Therefore, development of new potential analogs of thalidomide with higher anti-TNF-activity and specificity and having lower toxicity is the need for present day therapeutics.…”

Section: Thalidomide and Its Analogs As Poten-tial Inhibitor Of Tnf-mentioning

confidence: 99%

TNF α Signaling Beholds Thalidomide Saga: A Review of Mechanistic Role of TNF-α Signaling Under Thalidomide

Majumder¹,

Sreedhara²,

Banerjee³

et al. 2012

CTMC

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Tumor necrosis factor alpha (TNF-α) is a pleiotropic inflammatory cytokine. The cytokine possesses both growth stimulating properties and growth inhibitory processes, and it appears to have self regulatory properties as well. Agents like etanercept and infliximab showed beneficial effects against rheumatoid arthritis by modulationg TNF-α proteins, however, these agents are largely unable to penetrate the blood-brain barrier, which severely limits their use in different conditions. Thalidomide, an inhibitor of TNF-α protein synthesis is readily capable of crossing the blood-brain barrier and thus thalidomide and its analogs are excellent candidates for use in determining the potential value of anti-TNF-α therapies in a variety of diseases. Thalidomide blocks TNF-α expression by different possible mechanisms. Down regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), an essential transcription factor for TNF and other cytokines under thalidomide treatment leads to reduction in the TNF-α expression. Additionally, myeloid differentiation factor 88 (MyD88), an adapter protein regulates the expression of TNF under thalidomide treatment. Thalidomide treatment also leads to destruction of TNF-α mRNA thus, reducing the total expression of TNF-α protein. Thalidomide also targets reactive oxygen species (ROS) and α(1)-acid glycoprotein (AGP) to regulate TNF-α. In the present review, we discuss different possible mechanism that regulates TNF-α under thalidomide treatment. Additionally, we suggest novel strategies for the future targeting combination therapies of thalidomide and its analogs with different other anti-inflammatory drug to curb TNF-α associated diseases.

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Effects of Immunomodulatory Derivatives of Thalidomide (IMiDs) and Their Analogs on Cell-Differentiation, Cyclooxygenase Activity and Angiogenesis

Cited by 15 publications

References 26 publications

Synthesis of New Hydantoins Bearing Glutarimide or Succinimide Moiety and Their Evaluation for Cell Differentiation-inducing and Anti-angiogenic Activities

Synthesis of New Hydantoins Bearing Glutarimide or Succinimide Moiety and Their Evaluation for Cell Differentiation-inducing and Anti-angiogenic Activities

Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma

TNF α Signaling Beholds Thalidomide Saga: A Review of Mechanistic Role of TNF-α Signaling Under Thalidomide

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Effects of Immunomodulatory Derivatives of Thalidomide (IMiDs) and Their Analogs on Cell-Differentiation, Cyclooxygenase Activity and Angiogenesis

Cited by 15 publications

References 26 publications

Synthesis of New Hydantoins Bearing Glutarimide or Succinimide Moiety and Their Evaluation for Cell Differentiation-inducing and Anti-angiogenic Activities

Synthesis of New Hydantoins Bearing Glutarimide or Succinimide Moiety and Their Evaluation for Cell Differentiation-inducing and Anti-angiogenic Activities

Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma

TNF &alpha; Signaling Beholds Thalidomide Saga: A Review of Mechanistic Role of TNF-&alpha; Signaling Under Thalidomide

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TNF α Signaling Beholds Thalidomide Saga: A Review of Mechanistic Role of TNF-α Signaling Under Thalidomide