Makoto Hirasawa
Daiichi Sankyo
Binding siteFusion geneLigand (biochemistry)BiophysicsInternal medicinePhenotypeCellHistone methyltransferaseCytotoxic T cellVirologyAntibodyChromatin remodelingReceptorChemistryPhage displayHuman leukocyte antigenHematologyIn vitroIn vivoATPaseIn silicoMechanism of actionPiperazineLung cancerLiver injuryHistone H3IsoquinolineNeurodegenerationLapatinibRUVBL2Synthetic lethalityDiffuse large B-cell lymphomaHemagglutinin (influenza)Myeloid leukemiaNevirapinePeptideAbacavirXimelagatranHaptenNon small cellPeptide bindingImmune infiltrationAtpase activityProtein structureGroove (joinery)EZH2Cancer researchBiochemistryPotencyRadioresistanceCell growthPhenotypic screeningMedicineDNA replicationCell cultureMultiprotein complexBiologyMethyltransferaseCancer cellPharmacology
9Publications
5H-index
74Citations
Publications 9
Newest
#1Tomohiro Shirayanagi (Chiba University)H-Index: 1
#2Shigeki Aoki (Chiba University)H-Index: 7
Last. Kousei Ito (Chiba University)H-Index: 29
view all 9 authors...
The interaction of human leukocyte antigen (HLA) with specific drugs is associated with delayed-type hypersensitivity reactions, which cause severe cutaneous toxicity. Such interactions induce structural alterations in HLA complexes via several different mechanisms such as the hapten theory, p-i concept, and altered peptide repertoire model, leading to the activation of cytotoxic T cells. To date, comprehensive detection of such structural alterations in preclinical studies has been difficult. H...
2 CitationsSource
#1Paul Yenerall (UTSW: University of Texas Southwestern Medical Center)H-Index: 6
#2Amit K. Das (UTSW: University of Texas Southwestern Medical Center)H-Index: 11
Last. Ralf Kittler (UTSW: University of Texas Southwestern Medical Center)H-Index: 32
view all 23 authors...
Source
#1Jean-Marc M. Grandjean (UCSF: University of California, San Francisco)H-Index: 2
#2Alexander Y. Jiu (UCSF: University of California, San Francisco)H-Index: 2
Last. Nick A. Paras (UCSF: University of California, San Francisco)H-Index: 9
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Tau prions feature in the brains of patients suffering from Alzheimer’s disease and other tauopathies. For the development of therapeutics that target the replication of tau prions, a high-content, fluorescence-based cell assay was developed. Using this high-content phenotypic screen for nascent tau prion formation, a 4-piperazine isoquinoline compound (1) was identified as a hit with an EC50 value of 390 nM and 0.04 Kp,uu. Analogs were synthesized using a hypothesis-based approach to improve po...
3 CitationsSource
#1Paul Yenerall (UTSW: University of Texas Southwestern Medical Center)H-Index: 6
#2Amit K. Das (UTSW: University of Texas Southwestern Medical Center)H-Index: 11
Last. Ralf Kittler (UTSW: University of Texas Southwestern Medical Center)H-Index: 32
view all 26 authors...
Summary RUVBL1 and RUVBL2 (collectively RUVBL1/2) are essential AAA+ ATPases that function as co-chaperones and have been implicated in cancer. Here we investigated the molecular and phenotypic role of RUVBL1/2 ATPase activity in non-small cell lung cancer (NSCLC). We find that RUVBL1/2 are overexpressed in NSCLC patient tumors, with high expression associated with poor survival. Utilizing a specific inhibitor of RUVBL1/2 ATPase activity, we show that RUVBL1/2 ATPase activity is necessary for th...
11 CitationsSource
#1Makoto HirasawaH-Index: 5
#2Katsunobu HagiharaH-Index: 10
Last. Noriaki Hirayama (Tokai University)H-Index: 21
view all 5 authors...
Human leukocyte antigen (HLA)-DRB1*01:01 has been shown to be involved in nevirapine-induced hepatic hypersensitivity reactions. In the present study, in silico docking simulations and molecular dynamics simulations were performed to predict the interaction mode of nevirapine with the peptide binding groove of HLA-DRB1*01:01 and its possible effect on the position and orientation of the ligand peptide derived from hemagglutinin (HA). In silico analyses suggested that nevirapine interacts with HL...
5 CitationsSource
#1Daisuke Honma (Daiichi Sankyo)H-Index: 5
#2Nobuaki Adachi (Daiichi Sankyo)H-Index: 4
Last. Kosaku Fujiwara (Daiichi Sankyo)H-Index: 6
view all 18 authors...
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27) and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 function as catalytic subunits of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Many reports suggest that inhibiting PRC2 activity through EZH2 knockdown gives rise to anti-cancer effect against hematological and solid cancers. To date, some EZH2 selective...
1 CitationsSource
#1Daisuke Honma (Daiichi Sankyo)H-Index: 5
#2Osamu KannoH-Index: 7
Last. Nobuaki Adachi (Daiichi Sankyo)H-Index: 4
view all 18 authors...
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, l...
44 CitationsSource
#1Makoto HirasawaH-Index: 5
#2Katsunobu HagiharaH-Index: 10
Last. Noriaki Hirayama (Tokai University)H-Index: 21
view all 5 authors...
Idiosyncratic ximelagatran-induced hepatotoxicity has been reported to be associated with human leukocyte antigen (HLA)-DRB1*07:01 and ximelagatran has been reported to inhibit the binding of the ligand peptide to HLA-DRB1*07:01 in vitro. In order to predict the possible interaction modes of ximelagatran with HLA-DR molecules, in silico docking simulations were performed. Molecular dynamics (MD) simulations were also performed to predict the effect of ximelagatran on the binding mode of the liga...
9 CitationsSource
#1Makoto Hirasawa (Daiichi Sankyo)H-Index: 5
#2Katsunobu Hagihara (Daiichi Sankyo)H-Index: 10
Last. Takashi Izumi (Daiichi Sankyo)H-Index: 17
view all 4 authors...
Idiosyncratic lapatinib-induced liver injury has been reported to be associated with human leukocyte antigen (HLA)-DRB1*07:01. In order to investigate its mechanism, interaction of lapatinib with HLA-DRB1*07:01 and its ligand peptide derived from tetanus toxoid, has been evaluated in vitro. Here we show that lapatinib enhances binding of the ligand peptide to HLA-DRB1*07:01. Furthermore in silico molecular dynamics analysis revealed that lapatinib could change the β chain helix in the HLA-DRB1*0...
9 CitationsSource