タイトル | Structure-Based Design of Inhibitors Selective for Human Proteasome beta 2c or beta 2i Subunits. |
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ジャーナル・号・ページ | J. Med. Chem., Vol. 62, Page 1626-1642, Year 2019 |
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掲載日 | 2018年10月3日 (構造データの登録日) |
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著者 | Xin, B.T. / Huber, E.M. / de Bruin, G. / Heinemeyer, W. / Maurits, E. / Espinal, C. / Du, Y. / Janssens, M. / Weyburne, E.S. / Kisselev, A.F. ...Xin, B.T. / Huber, E.M. / de Bruin, G. / Heinemeyer, W. / Maurits, E. / Espinal, C. / Du, Y. / Janssens, M. / Weyburne, E.S. / Kisselev, A.F. / Florea, B.I. / Driessen, C. / van der Marel, G.A. / Groll, M. / Overkleeft, H.S. |
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リンク | J. Med. Chem. / PubMed:30657666 |
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手法 | X線回折 |
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解像度 | 2.3 - 3.4 Å |
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構造データ | PDB-6htb: Yeast 20S proteasome with human beta2c (S171G) 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å PDB-6htc: Yeast 20S proteasome with human beta2c (S171G) in complex with ONX 0914 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6htd: Yeast 20S proteasome with human beta2c (S171G) in complex with 4 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-6htp: Yeast 20S proteasome with human beta2c (S171G) in complex with 7 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-6htr: Yeast 20S proteasome with human beta2c (S171G) in complex with 13 手法: X-RAY DIFFRACTION / 解像度: 2.6 Å PDB-6hub: Yeast 20S proteasome with human beta2c (S171G) in complex with 16 手法: X-RAY DIFFRACTION / 解像度: 2.9 Å PDB-6huc: Yeast 20S proteasome with human beta2c (S171G) in complex with 18 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-6huq: Yeast 20S proteasome with human beta2c (S171G) in complex with 20 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-6huu: Yeast 20S proteasome with human beta2c (S171G) in complex with 29 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6huv: Yeast 20S proteasome with human beta2c (S171G) in complex with 39 手法: X-RAY DIFFRACTION / 解像度: 3.1 Å PDB-6hv3: Yeast 20S proteasome with human beta2i (1-53) 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å PDB-6hv4: Yeast 20S proteasome with human beta2i (1-53) in complex with ONX 0914 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-6hv5: Yeast 20S proteasome with human beta2i (1-53) in complex with 4 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-6hv7: Yeast 20S proteasome with human beta2i (1-53) in complex with 7 手法: X-RAY DIFFRACTION / 解像度: 3.4 Å PDB-6hva: Yeast 20S proteasome with human beta2i (1-53) in complex with 13 手法: X-RAY DIFFRACTION / 解像度: 2.9 Å PDB-6hvr: Yeast 20S proteasome with human beta2i (1-53) in complex with 16 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å PDB-6hvs: Yeast 20S proteasome with human beta2i (1-53) in complex with 18 手法: X-RAY DIFFRACTION / 解像度: 3.1 Å PDB-6hvt: Yeast 20S proteasome with human beta2i (1-53) in complex with 20 手法: X-RAY DIFFRACTION / 解像度: 2.9 Å PDB-6hvu: Yeast 20S proteasome with human beta2i (1-53) in complex with 29 手法: X-RAY DIFFRACTION / 解像度: 2.9 Å PDB-6hvv: Yeast 20S proteasome with human beta2i (1-53) in complex with 39 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å PDB-6hvw: Yeast 20S proteasome with human beta2i (1-53) in complex with 43 手法: X-RAY DIFFRACTION / 解像度: 3 Å PDB-6hvx: Yeast 20S proteasome in complex with 4 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6hvy: Yeast 20S proteasome in complex with 5 (7- and 6-membered ring) 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å PDB-6hw0: Yeast 20S proteasome in complex with 7 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6hw3: Yeast 20S proteasome in complex with 13 手法: X-RAY DIFFRACTION / 解像度: 2.6 Å PDB-6hw4: Yeast 20S proteasome in complex with 16 手法: X-RAY DIFFRACTION / 解像度: 2.9 Å PDB-6hw5: Yeast 20S proteasome in complex with 18 手法: X-RAY DIFFRACTION / 解像度: 2.9 Å PDB-6hw6: Yeast 20S proteasome in complex with 20 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å PDB-6hw7: Yeast 20S proteasome in complex with 29 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å PDB-6hw8: Yeast 20S proteasome in complex with 39 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6hw9: Yeast 20S proteasome in complex with 41b 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6hwa: Yeast 20S proteasome in complex with 43 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6hwb: Yeast 20S proteasome in complex with 44b 手法: X-RAY DIFFRACTION / 解像度: 2.6 Å PDB-6hwc: Yeast 20S proteasome beta2-G45A mutant 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6hwd: Yeast 20S proteasome beta2-G45A mutant in complex with bortezomib 手法: X-RAY DIFFRACTION / 解像度: 2.8 Å PDB-6hwe: Yeast 20S proteasome beta2-G45A mutant in complex with carfilzomib 手法: X-RAY DIFFRACTION / 解像度: 2.3 Å PDB-6hwf: Yeast 20S proteasome beta2-G45A mutant in complex with ONX 0914 手法: X-RAY DIFFRACTION / 解像度: 2.5 Å |
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化合物 | ChemComp-GQK: (2~{S})-3-(4-methoxyphenyl)-~{N}-[(2~{S},3~{R})-4-methyl-3,4-bis(oxidanyl)-1-phenyl-pentan-2-yl]-2-[[(2~{S})-2-(2-morpholin-4-ylethanoylamino)propanoyl]amino]propanamide
ChemComp-GQH: (2~{S})-~{N}-[(2~{S})-1-[[(2~{S})-1-[4-(aminomethyl)phenyl]-4-methylsulfonyl-butan-2-yl]amino]-1-oxidanylidene-propan-2-yl]-2-[[(2~{S})-2-azido-3-phenyl-propanoyl]amino]-4-methyl-pentanamide
ChemComp-GQQ: ~{N}-[(2~{S})-1-[[(2~{S})-1-[[(2~{S})-1-[4-(aminomethyl)phenyl]-4-methylsulfonyl-butan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]pyrazine-2-carboxamide
ChemComp-GQT: (2~{S})-~{N}-[(2~{S})-1-[[(2~{S})-1-[4-(aminomethyl)phenyl]-4-methylsulfonyl-butan-2-yl]amino]-3-oxidanyl-1-oxidanylidene-propan-2-yl]-2-[[(2~{S})-2-azido-3-phenyl-propanoyl]amino]-4-methyl-pentanamide
ChemComp-GRW: (2~{S})-~{N}-[(2~{S},3~{R})-1-[[(2~{S})-1-[4-(aminomethyl)phenyl]-4-methylsulfonyl-butan-2-yl]amino]-3-oxidanyl-1-oxidanylidene-butan-2-yl]-2-[[(2~{R})-2-azido-3-phenyl-propanoyl]amino]-4-methyl-pentanamide
ChemComp-GRT: (2~{S})-~{N}-[2-[[(2~{S})-1-[4-(aminomethyl)phenyl]-4-methylsulfonyl-butan-2-yl]amino]-2-oxidanylidene-ethyl]-2-[[(2~{S})-2-azido-3-phenyl-propanoyl]amino]-4-methyl-pentanamide
ChemComp-GT5: ~{N}-[(2~{S})-1-[[(2~{S})-1-[[(2~{S})-1-[4-(aminomethyl)phenyl]-4-methylsulfonyl-butan-2-yl]amino]-3-methoxy-1-oxidanylidene-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide
ChemComp-GTW: ~{N}-[(2~{S})-1-[[(2~{S})-1-[[(2~{S})-1-[4-(aminomethyl)phenyl]-4-methylsulfonyl-butan-2-yl]amino]-3-cyclohexyl-1-oxidanylidene-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide
ChemComp-GT8: (2~{S})-~{N}-[(3~{S},4~{R})-1-cyclohexyl-5-methyl-4,5-bis(oxidanyl)hexan-3-yl]-3-(4-methoxyphenyl)-2-[[(2~{S})-2-(2-morpholin-4-ylethanoylamino)propanoyl]amino]propanamide
ChemComp-GVW: (2~{S})-~{N}-[(2~{S},3~{R})-1-[(4~{a}~{S},8~{a}~{S})-1,2,3,4,4~{a},5,6,7,8,8~{a}-decahydronaphthalen-2-yl]-4-methyl-3,4-bis(oxidanyl)pentan-2-yl]-3-(4-methoxyphenyl)-2-[[(2~{S})-2-(2-morpholin-4-ylethanoylamino)propanoyl]amino]propanamide
ChemComp-GVZ: (2~{S})-~{N}-[(2~{S},3~{R})-1-[(1~{S},4~{a}~{S},8~{a}~{R})-1,2,3,4,4~{a},5,6,7,8,8~{a}-decahydronaphthalen-1-yl]-4-methyl-3,4-bis(oxidanyl)pentan-2-yl]-3-(4-methoxyphenyl)-2-[[(2~{S})-2-(2-morpholin-4-ylethanoylamino)propanoyl]amino]propanamide
ChemComp-GW2: (2~{S})-~{N}-[(2~{S},3~{S},4~{R})-1-[(1~{S},4~{a}~{S},8~{a}~{R})-1,2,3,4,4~{a},5,6,7,8,8~{a}-decahydronaphthalen-1-yl]-4-methyl-3,5-bis(oxidanyl)pentan-2-yl]-3-(4-methoxyphenyl)-2-[[(2~{S})-2-(2-morpholin-4-ylethanoylamino)propanoyl]amino]propanamide
ChemComp-GWK: (2~{S})-3-(4-methoxyphenyl)-~{N}-[(2~{S},3~{R})-4-methyl-1-(4-methylcyclohexyl)-3,4-bis(oxidanyl)pentan-2-yl]-2-[[(2~{S})-2-(2-morpholin-4-ylethanoylamino)propanoyl]amino]propanamide
ChemComp-GWT: (2~{S})-~{N}-[(2~{S},3~{R})-1-(4-cyclohexylcyclohexyl)-4-methyl-3,4-bis(oxidanyl)pentan-2-yl]-3-(4-methoxyphenyl)-2-[[(2~{S})-2-(2-morpholin-4-ium-4-ylethanoylamino)propanoyl]amino]propanamide
ChemComp-BO2: N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE / ボルテゾミブ / 薬剤, 抗がん剤*YM
ChemComp-GWZ: (2~{S})-~{N}-[(2~{S})-1-[[(3~{R},4~{S})-2,6-dimethyl-2,3-bis(oxidanyl)heptan-4-yl]amino]-1-oxidanylidene-3-phenyl-propan-2-yl]-4-methyl-2-[[(2~{S})-2-(2-morpholin-4-ylethanoylamino)-4-phenyl-butanoyl]amino]pentanamide
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由来 | homo sapiens (ヒト)![](img/tx_yeast.gif) saccharomyces cerevisiae (strain atcc 204508 / s288c) (パン酵母)![](img/tx_yeast.gif) saccharomyces cerevisiae s288c (パン酵母)
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キーワード | HYDROLASE / Proteasome / Mutant / Inhibitor / Binding Analysis |
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