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한국응용약물학회> Biomolecules & Therapeutics(구 응용약물학회지)

Biomolecules & Therapeutics(구 응용약물학회지) update

  • : 한국응용약물학회
  • : 의약학분야  >  약화학
  • : KCI등재
  • : SCOPUS
  • : 연속간행물
  • : 격월
  • : 1976-9148
  • : 2005-4483
  • : 응용약물학회지(~2007)→Biomolecules & Therapeutics(2008~)

수록정보
수록범위 : 1권1호(1993)~30권1호(2022) |수록논문 수 : 1,768
Biomolecules & Therapeutics(구 응용약물학회지)
30권1호(2022년 01월) 수록논문
최근 권호 논문
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KCI등재 SCOPUS

1Inhibition of Cytochrome P450 Enzymes by Drugs―Molecular Basis and Practical Applications

저자 : F. Peter Guengerich

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 1-18 (18 pages)

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Drug-drug interactions are a major cause of hospitalization and deaths related to drug use. A large fraction of these is due to inhibition of enzymes involved in drug metabolism and transport, particularly cytochrome P450 (P450) enzymes. Understanding basic mechanisms of enzyme inhibition is important, particularly in terms of reversibility and the use of the appropriate parameters. In addition to drug-drug interactions, issues have involved interactions of drugs with foods and natural products related to P450 enzymes. Predicting drug-drug interactions is a major effort in drug development in the pharmaceutical industry and regulatory agencies. With appropriate in vitro experiments, it is possible to stratify clinical drug-drug interaction studies. A better understanding of drug interactions and training of physicians and pharmacists has developed. Finally, some P450s have been the targets of drugs in some cancers and other disease states.

KCI등재 SCOPUS

2Chronicles of EGFR Tyrosine Kinase Inhibitors: Targeting EGFR C797S Containing Triple Mutations

저자 : Krishna Babu Duggirala , Yujin Lee , Kwangho Lee

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 19-27 (9 pages)

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Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wildtype EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and thirdgeneration EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/ T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

KCI등재 SCOPUS

3Melatonin Protects Chronic Kidney Disease Mesenchymal Stem/Stromal Cells against Accumulation of Methylglyoxal via Modulation of Hexokinase-2 Expression

저자 : Gyeongyun Go , Yeo Min Yoon , Sungtae Yoon , Gaeun Lee , Ji Ho Lim , Su-yeon Han , Sang Hun Lee

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 28-37 (10 pages)

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Treatment options for patients with chronic kidney disease (CKD) are currently limited; therefore, there has been significant interest in applying mesenchymal stem/stromal cell (MSC)-based therapy to treat CKD. However, MSCs harvested from CKD patients tend to show diminished viability and proliferation due to sustained exposure to uremic toxins in the CKD environment, which limits their utility for cell therapy. The application of melatonin has been demonstrated to improve the therapeutic efficacy of MSCs derived from and engrafted to tissues in patients suffering from CKD, although the underlying biological mechanism has not been elucidated. In this study, we observed overexpression of hexokinase-2 (HK2) in serum samples of CKD patients and MSCs harvested from an adenine-fed CKD mouse model (CKD-mMSCs). HK2 upregulation led to increased production levels of methylglyoxal (MG), a toxic metabolic intermediate of abnormal glycolytic processes. The overabundance of HK2 and MG was associated with impaired mitochondrial function and low cell proliferation in CKD-mMSCs. Melatonin treatment inhibited the increases in HK2 and MG levels, and further improved mitochondrial function, glycolytic metabolism, and cell proliferation. Our findings suggest that identifying and characterizing metabolic regulators such as HK2 in CKD may improve the efficacy of MSCs for treating CKD and other kidney disorders.

KCI등재 SCOPUS

4Lithocholic Acid Activates Mas-Related G Protein-Coupled Receptors, Contributing to Itch in Mice

저자 : Myung-hyun Song , Won-sik Shim

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 38-47 (10 pages)

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The present study focused on lithocholic acid (LCA), a secondary bile acid that contributes to cholestatic pruritus. Although recent studies have found that LCA acts on MAS-related G protein-coupled receptor family member X4 (MRGPRX4) in humans, it is unclear which subtypes of MRGPRs are activated by LCA in mice since there is no precise ortholog of human MRGPRX4 in the mouse genome. Using calcium imaging, we found that LCA could activate mouse Mrgpra1 when transiently expressed in HEK293T cells. Moreover, LCA similarly activates mouse Mrgprb2. Importantly, LCA-induced responses showed dose-dependent effects through Mrgpra1 and Mrgprb2. Moreover, treatment with QWF (an antagonist of Mrgpra1 and Mrgprb2), YM254890 (Gαq inhibitor), and U73122 (an inhibitor of phospholipase C) significantly suppressed the LCA-induced responses, implying that the LCA-induced responses are indeed mediated by Mrgpra1 and Mrgprb2. Furthermore, LCA activated primary cultures of mouse sensory neurons and peritoneal mast cells, suggesting that Mrgpra1 and Mrgprb2 contribute to LCA-induced pruritus. However, acute injection of LCA did not induce noticeable differences in scratching behavior, implying that the pruritogenic role of LCA may be marginal in non-cholestatic conditions. In summary, the present study identified for the first time that LCA can activate Mrgpra1 and Mrgprb2. The current findings provide further insight into the similarities and differences between human and mouse MRGPR families, paving a way to understand the complex roles of these pruriceptors.

KCI등재 SCOPUS

5Novel GPR43 Agonists Exert an Anti-Inflammatory Effect in a Colitis Model

저자 : Bi-oh Park , Jong Soon Kang , Suresh Paudel , Sung Goo Park , Byoung Chul Park , Sang-bae Han , Young-shin Kwak , Jeong-hoon Kim , Sunhong Kim

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 48-54 (7 pages)

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GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gαi/o and Gαq/11 heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca2+ flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-κB. However, GPR43 shares the same ligands as GPR41, including acetate, propionate, and butyrate, and determination of its precise functions in association with endogenous ligands, such as SCFAs alone, therefore remains a considerable challenge. In this study, we generated novel synthetic agonists that display allosteric modulatory effects on GPR43 and downregulate NF-κB activity. In particular, the potency of compound 187 was significantly superior to that of preexisting compounds in vitro. However, in the colitis model in vivo, compound 110 induced more potent attenuation of inflammation. These novel allosteric agonists of GPR43 clearly display anti-inflammatory potential, supporting their clinical utility as therapeutic drugs.

KCI등재 SCOPUS

6Oleanolic Acid Provides Neuroprotection against Ischemic Stroke through the Inhibition of Microglial Activation and NLRP3 Inflammasome Activation

저자 : Arjun Sapkota , Ji Woong Choi

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 55-63 (9 pages)

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Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

KCI등재 SCOPUS

7Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1

저자 : Ahrim Lee , Jieun Sung , Dipesh S. Harmalkar , Hyeseul Kang , Hwayoung Lee , Kyeong Lee , Choongho Lee

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 64-71 (8 pages)

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Norovirus (NV) is the most common cause of viral gastroenteritis, with the potential to develop into a fatal disease in those who are immuno-compromised, and effective vaccines and treatments are still non-existent. In this study, we aimed to elucidate the molecular mechanism of the previously identified NV replication inhibitor utilizing a vinyl-stilbene backbone, AC-1858. First, we confirmed the inhibition of the NV RNA replication by a structural analog of AC-1858, AC-2288 with its exclusive cytoplasmic subcellular localization. We further validated the induction of one specific host factor, the phosphorylated form of heat shock factor (HSF)-1, and its increased nuclear localization by AC-1858 treatment. Finally, we verified the positive and negative impact of the siRNA-mediated downregulation and lentivirus-mediated overexpression of HSF-1 on NV RNA replication. In conclusion, these data suggest the restrictive role of the host factor HSF-1 in overall viral RNA genome replication during the NV life cycle.

KCI등재 SCOPUS

8Licochalcone H Induces Cell Cycle Arrest and Apoptosis in Human Skin Cancer Cells by Modulating JAK2/STAT3 Signaling

저자 : Kyung-ho Park , Sang Hoon Joo , Ji-hye Seo , Jumi Kim , Goo Yoon , Young-joo Jeon , Mee-hyun Lee , Jung-il Chae , Woo-keun Kim , Jung-hyun Shim

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 72-79 (8 pages)

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Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.

KCI등재 SCOPUS

9Enhancement of Radiosensitivity by DNA Hypomethylating Drugs through Apoptosis and Autophagy in Human Sarcoma Cells

저자 : Moon-taek Park , Sung-dae Kim , Yu Kyeong Han , Jin Won Hyun , Hae-june Lee , Joo Mi Yi

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 80-89 (10 pages)

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The targeting of DNA methylation in cancer using DNA hypomethylating drugs has been well known to sensitize cancer cells to chemotherapy and immunotherapy by affecting multiple pathways. Herein, we investigated the combinational effects of DNA hypomethylating drugs and ionizing radiation (IR) in human sarcoma cell lines both in vitro and in vivo. Clonogenic assays were performed to determine the radiosensitizing properties of two DNA hypomethylating drugs on sarcoma cell lines we tested in this study with multiple doses of IR. We analyzed the effects of 5-aza-dC or SGI-110, as DNA hypomethylating drugs, in combination with IR in vitro on the proliferation, apoptosis, caspase-3/7 activity, migration/invasion, and Western blotting using apoptosis- or autophagy-related factors. To confirm the combined effect of DNA hypomethylating drugs and IR in our in vitro experiment, we generated the sarcoma cells in nude mouse xenograft models. Here, we found that the combination of DNA hypomethylating drugs and IR improved anticancer effects by inhibiting cell proliferation and by promoting synergistic cell death that is associated with both apoptosis and autophagy in vitro and in vivo. Our data demonstrated that the combination effects of DNA hypomethylating drugs with radiation exhibited greater cellular effects than the use of a single agent treatment, thus suggesting that the combination of DNA hypomethylating drugs and radiation may become a new radiotherapy to improve therapeutic efficacy for cancer treatment.

KCI등재 SCOPUS

10Botulinum Toxin A Ameliorates Neuroinflammation in the MPTP and 6-OHDA-Induced Parkinson's Disease Models

저자 : Hyeon Joo Ham , In Jun Yeo , Seong Hee Jeon , Jun Hyung Lim , Sung Sik Yoo , Dong Ju Son , Sung-su Jang , Haksup Lee , Seung-jin Shin , Sang Bae Han , Jae Suk Yun , Jin Tae Hong

발행기관 : 한국응용약물학회 간행물 : Biomolecules & Therapeutics(구 응용약물학회지) 30권 1호 발행 연도 : 2022 페이지 : pp. 90-97 (8 pages)

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Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson's disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

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