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443 results on '"Lüscher, B."'

2. [1,2,4]Triazolo[3,4-b]benzothiazole scaffold as versatile nicotinamide mimic allowing nanomolar inhibition of different PARP enzymes

Author

Murthy, S. (Sudarshan), Nizi, M. G. (Maria Giulia), Maksimainen, M. M. (Mirko M.), Massari, S. (Serena), Alaviuhkola, J. (Juho), Lippok, B. E. (Barbara E.), Vagaggini, C. (Chiara), Sowa, S. T. (Sven T.), Galera-Prat, A. (Albert), Ashok, Y. (Yashwanth), Venkannagari, H. (Harikanth), Prunskaite-Hyyryläinen, R. (Renata), Dreassi, E. (Elena), Lüscher, B. (Bernhard), Korn, P. (Patricia), Tabarrini, O. (Oriana), Lehtiö, L. (Lari), Murthy, S. (Sudarshan), Nizi, M. G. (Maria Giulia), Maksimainen, M. M. (Mirko M.), Massari, S. (Serena), Alaviuhkola, J. (Juho), Lippok, B. E. (Barbara E.), Vagaggini, C. (Chiara), Sowa, S. T. (Sven T.), Galera-Prat, A. (Albert), Ashok, Y. (Yashwanth), Venkannagari, H. (Harikanth), Prunskaite-Hyyryläinen, R. (Renata), Dreassi, E. (Elena), Lüscher, B. (Bernhard), Korn, P. (Patricia), Tabarrini, O. (Oriana), and Lehtiö, L. (Lari)

Abstract

We report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogues and cocrystal structures with TNKS2, PARP2, PARP14, and PARP15. Based on the substitution pattern, we were able to identify 3-amino derivatives 21 (OUL243) and 27 (OUL232) as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15 at nM potencies, with 27 being the most potent PARP10 inhibitor described to date (IC50 of 7.8 nM) and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity toward PARP2. The scaffold does not possess inherent cell toxicity, and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of TBT scaffold for future drug development efforts toward selective inhibitors against specific enzymes.

Published
2023

5. Tumorsuppressorgene

Author

Nordheim, A., Lüscher, B., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor

Published
2006
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8. Einführung

Author

Nordheim, A., Lüscher, B., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor

Published
2006
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11. Cytokine-induced Inhibition of Myc Activity in Monocytic Cells

Author

Larsson, L.-G., Bahram, F., Wu, S., Öberg, F., Nilsson, K., Lüscher, B., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Koprowski, H., editor, Ito, Y., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1997
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12. Regulation of Cell Growth by the Myc-Max-Mad Network: Role of Mad Proteins and YY1

Author

Austen, M., Cerni, C., Henriksson, M., Hilfenhaus, S., Lüscher-Firzlaff, J. M., Menkel, A., Seelos, C., Sommer, A., Lüscher, B., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Koprowski, H., editor, Ito, Y., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1997
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16. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Author

Klionsky, DJ, Abdel-Aziz, AK, Abdelfatah, S, Abdellatif, M, Abdoli, A, Abel, S, Abeliovich, H, Abildgaard, MH, Abudu, YP, Acevedo-Arozena, A, Adamopoulos, IE, Adeli, K, Adolph, TE, Adornetto, A, Aflaki, E, Agam, G, Agarwal, A, Aggarwal, BB, Agnello, M, Agostinis, P, Agrewala, JN, Agrotis, A, Aguilar, PV, Ahmad, ST, Ahmed, ZM, Ahumada-Castro, U, Aits, S, Aizawa, S, Akkoc, Y, Akoumianaki, T, Akpinar, HA, Al-Abd, AM, Al-Akra, L, Al-Gharaibeh, A, Alaoui-Jamali, MA, Alberti, S, Alcocer-Gómez, E, Alessandri, C, Ali, M, Alim Al-Bari, MA, Aliwaini, S, Alizadeh, J, Almacellas, E, Almasan, A, Alonso, A, Alonso, GD, Altan-Bonnet, N, Altieri, DC, Álvarez, ÉMC, Alves, S, Alves da Costa, C, Alzaharna, MM, Amadio, M, Amantini, C, Amaral, C, Ambrosio, S, Amer, AO, Ammanathan, V, An, Z, Andersen, SU, Andrabi, SA, Andrade-Silva, M, Andres, AM, Angelini, S, Ann, D, Anozie, UC, Ansari, MY, Antas, P, Antebi, A, Antón, Z, Anwar, T, Apetoh, L, Apostolova, N, Araki, T, Araki, Y, Arasaki, K, Araújo, WL, Araya, J, Arden, C, Arévalo, M-A, Arguelles, S, Arias, E, Arikkath, J, Arimoto, H, Ariosa, AR, Armstrong-James, D, Arnauné-Pelloquin, L, Aroca, A, Arroyo, DS, Arsov, I, Artero, R, Asaro, DML, Aschner, M, Ashrafizadeh, M, Ashur-Fabian, O, Atanasov, AG, Au, AK, Auberger, P, Auner, HW, Aurelian, L, Autelli, R, Avagliano, L, Ávalos, Y, Aveic, S, Aveleira, CA, Avin-Wittenberg, T, Aydin, Y, Ayton, S, Ayyadevara, S, Azzopardi, M, Baba, M, Backer, JM, Backues, SK, Bae, D-H, Bae, O-N, Bae, SH, Baehrecke, EH, Baek, A, Baek, S-H, Baek, SH, Bagetta, G, Bagniewska-Zadworna, A, Bai, H, Bai, J, Bai, X, Bai, Y, Bairagi, N, Baksi, S, Balbi, T, Baldari, CT, Balduini, W, Ballabio, A, Ballester, M, Balazadeh, S, Balzan, R, Bandopadhyay, R, Banerjee, S, Bánréti, Á, Bao, Y, Baptista, MS, Baracca, A, Barbati, C, Bargiela, A, Barilà, D, Barlow, PG, Barmada, SJ, Barreiro, E, Barreto, GE, Bartek, J, Bartel, B, Bartolome, A, Barve, GR, Basagoudanavar, SH, Bassham, DC, Bast, RC, Basu, A, Batoko, H, Batten, I, Baulieu, EE, Baumgarner, BL, Bayry, J, Beale, R, Beau, I, Beaumatin, F, Bechara, LRG, Beck, GR, Beers, MF, Begun, J, Behrends, C, Behrens, GMN, Bei, R, Bejarano, E, Bel, S, Behl, C, Belaid, A, Belgareh-Touzé, N, Bellarosa, C, Belleudi, F, Belló Pérez, M, Bello-Morales, R, Beltran, JSDO, Beltran, S, Benbrook, DM, Bendorius, M, Benitez, BA, Benito-Cuesta, I, Bensalem, J, Berchtold, MW, Berezowska, S, Bergamaschi, D, Bergami, M, Bergmann, A, Berliocchi, L, Berlioz-Torrent, C, Bernard, A, Berthoux, L, Besirli, CG, Besteiro, S, Betin, VM, Beyaert, R, Bezbradica, JS, Bhaskar, K, Bhatia-Kissova, I, Bhattacharya, R, Bhattacharya, S, Bhattacharyya, S, Bhuiyan, MS, Bhutia, SK, Bi, L, Bi, X, Biden, TJ, Bijian, K, Billes, VA, Binart, N, Bincoletto, C, Birgisdottir, AB, Bjorkoy, G, Blanco, G, Blas-Garcia, A, Blasiak, J, Blomgran, R, Blomgren, K, Blum, JS, Boada-Romero, E, Boban, M, Boesze-Battaglia, K, Boeuf, P, Boland, B, Bomont, P, Bonaldo, P, Bonam, SR, Bonfili, L, Bonifacino, JS, Boone, BA, Bootman, MD, Bordi, M, Borner, C, Bornhauser, BC, Borthakur, G, Bosch, J, Bose, S, Botana, LM, Botas, J, Boulanger, CM, Boulton, ME, Bourdenx, M, Bourgeois, B, Bourke, NM, Bousquet, G, Boya, P, Bozhkov, PV, Bozi, LHM, Bozkurt, TO, Brackney, DE, Brandts, CH, Braun, RJ, Braus, GH, Bravo-Sagua, R, Bravo-San Pedro, JM, Brest, P, Bringer, M-A, Briones-Herrera, A, Broaddus, VC, Brodersen, P, Brodsky, JL, Brody, SL, Bronson, PG, Bronstein, JM, Brown, CN, Brown, RE, Brum, PC, Brumell, JH, Brunetti-Pierri, N, Bruno, D, Bryson-Richardson, RJ, Bucci, C, Buchrieser, C, Bueno, M, Buitrago-Molina, LE, Buraschi, S, Buch, S, Buchan, JR, Buckingham, EM, Budak, H, Budini, M, Bultynck, G, Burada, F, Burgoyne, JR, Burón, MI, Bustos, V, Büttner, S, Butturini, E, Byrd, A, Cabas, I, Cabrera-Benitez, S, Cadwell, K, Cai, J, Cai, L, Cai, Q, Cairó, M, Calbet, JA, Caldwell, GA, Caldwell, KA, Call, JA, Calvani, R, Calvo, AC, Calvo-Rubio Barrera, M, Camara, NO, Camonis, JH, Camougrand, N, Campanella, M, Campbell, EM, Campbell-Valois, F-X, Campello, S, Campesi, I, Campos, JC, Camuzard, O, Cancino, J, Candido de Almeida, D, Canesi, L, Caniggia, I, Canonico, B, Cantí, C, Cao, B, Caraglia, M, Caramés, B, Carchman, EH, Cardenal-Muñoz, E, Cardenas, C, Cardenas, L, Cardoso, SM, Carew, JS, Carle, GF, Carleton, G, Carloni, S, Carmona-Gutierrez, D, Carneiro, LA, Carnevali, O, Carosi, JM, Carra, S, Carrier, A, Carrier, L, Carroll, B, Carter, AB, Carvalho, AN, Casanova, M, Casas, C, Casas, J, Cassioli, C, Castillo, EF, Castillo, K, Castillo-Lluva, S, Castoldi, F, Castori, M, Castro, AF, Castro-Caldas, M, Castro-Hernandez, J, Castro-Obregon, S, Catz, SD, Cavadas, C, Cavaliere, F, Cavallini, G, Cavinato, M, Cayuela, ML, Cebollada Rica, P, Cecarini, V, Cecconi, F, Cechowska-Pasko, M, Cenci, S, Ceperuelo-Mallafré, V, Cerqueira, JJ, Cerutti, JM, Cervia, D, Cetintas, VB, Cetrullo, S, Chae, H-J, Chagin, AS, Chai, C-Y, Chakrabarti, G, Chakrabarti, O, Chakraborty, T, Chami, M, Chamilos, G, Chan, DW, Chan, EYW, Chan, ED, Chan, HYE, Chan, HH, Chan, H, Chan, MTV, Chan, YS, Chandra, PK, Chang, C-P, Chang, C, Chang, H-C, Chang, K, Chao, J, Chapman, T, Charlet-Berguerand, N, Chatterjee, S, Chaube, SK, Chaudhary, A, Chauhan, S, Chaum, E, Checler, F, Cheetham, ME, Chen, C-S, Chen, G-C, Chen, J-F, Chen, LL, Chen, L, Chen, M, Chen, M-K, Chen, N, Chen, Q, Chen, R-H, Chen, S, Chen, W, Chen, X-M, Chen, X-W, Chen, X, Chen, Y, Chen, Y-G, Chen, Y-J, Chen, Y-Q, Chen, ZS, Chen, Z, Chen, Z-H, Chen, ZJ, Cheng, H, Cheng, J, Cheng, S-Y, Cheng, W, Cheng, X, Cheng, X-T, Cheng, Y, Cheng, Z, Cheong, H, Cheong, JK, Chernyak, BV, Cherry, S, Cheung, CFR, Cheung, CHA, Cheung, K-H, Chevet, E, Chi, RJ, Chiang, AKS, Chiaradonna, F, Chiarelli, R, Chiariello, M, Chica, N, Chiocca, S, Chiong, M, Chiou, S-H, Chiramel, AI, Chiurchiù, V, Cho, D-H, Choe, S-K, Choi, AMK, Choi, ME, Choudhury, KR, Chow, NS, Chu, CT, Chua, JP, Chua, JJE, Chung, H, Chung, KP, Chung, S, Chung, S-H, Chung, Y-L, Cianfanelli, V, Ciechomska, IA, Cifuentes, M, Cinque, L, Cirak, S, Cirone, M, Clague, MJ, Clarke, R, Clementi, E, Coccia, EM, Codogno, P, Cohen, E, Cohen, MM, Colasanti, T, Colasuonno, F, Colbert, RA, Colell, A, Čolić, M, Coll, NS, Collins, MO, Colombo, MI, Colón-Ramos, DA, Combaret, L, Comincini, S, Cominetti, MR, Consiglio, A, Conte, A, Conti, F, Contu, VR, Cookson, MR, Coombs, KM, Coppens, I, Corasaniti, MT, Corkery, DP, Cordes, N, Cortese, K, Costa, MDC, Costantino, S, Costelli, P, Coto-Montes, A, Crack, PJ, Crespo, JL, Criollo, A, Crippa, V, Cristofani, R, Csizmadia, T, Cuadrado, A, Cui, B, Cui, J, Cui, Y, Culetto, E, Cumino, AC, Cybulsky, AV, Czaja, MJ, Czuczwar, SJ, D'Adamo, S, D'Amelio, M, D'Arcangelo, D, D'Lugos, AC, D'Orazi, G, da Silva, JA, Dafsari, HS, Dagda, RK, Dagdas, Y, Daglia, M, Dai, X, Dai, Y, Dal Col, J, Dalhaimer, P, Dalla Valle, L, Dallenga, T, Dalmasso, G, Damme, M, Dando, I, Dantuma, NP, Darling, AL, Das, H, Dasarathy, S, Dasari, SK, Dash, S, Daumke, O, Dauphinee, AN, Davies, JS, Dávila, VA, Davis, RJ, Davis, T, Dayalan Naidu, S, De Amicis, F, De Bosscher, K, De Felice, F, De Franceschi, L, De Leonibus, C, de Mattos Barbosa, MG, De Meyer, GRY, De Milito, A, De Nunzio, C, De Palma, C, De Santi, M, De Virgilio, C, De Zio, D, Debnath, J, DeBosch, BJ, Decuypere, J-P, Deehan, MA, Deflorian, G, DeGregori, J, Dehay, B, Del Rio, G, Delaney, JR, Delbridge, LMD, Delorme-Axford, E, Delpino, MV, Demarchi, F, Dembitz, V, Demers, ND, Deng, H, Deng, Z, Dengjel, J, Dent, P, Denton, D, DePamphilis, ML, Der, CJ, Deretic, V, Descoteaux, A, Devis, L, Devkota, S, Devuyst, O, Dewson, G, Dharmasivam, M, Dhiman, R, di Bernardo, D, Di Cristina, M, Di Domenico, F, Di Fazio, P, Di Fonzo, A, Di Guardo, G, Di Guglielmo, GM, Di Leo, L, Di Malta, C, Di Nardo, A, Di Rienzo, M, Di Sano, F, Diallinas, G, Diao, J, Diaz-Araya, G, Díaz-Laviada, I, Dickinson, JM, Diederich, M, Dieudé, M, Dikic, I, Ding, S, Ding, W-X, Dini, L, Dinić, J, Dinic, M, Dinkova-Kostova, AT, Dionne, MS, Distler, JHW, Diwan, A, Dixon, IMC, Djavaheri-Mergny, M, Dobrinski, I, Dobrovinskaya, O, Dobrowolski, R, Dobson, RCJ, Đokić, J, Dokmeci Emre, S, Donadelli, M, Dong, B, Dong, X, Dong, Z, Dorn Ii, GW, Dotsch, V, Dou, H, Dou, J, Dowaidar, M, Dridi, S, Drucker, L, Du, A, Du, C, Du, G, Du, H-N, Du, L-L, du Toit, A, Duan, S-B, Duan, X, Duarte, SP, Dubrovska, A, Dunlop, EA, Dupont, N, Durán, RV, Dwarakanath, BS, Dyshlovoy, SA, Ebrahimi-Fakhari, D, Eckhart, L, Edelstein, CL, Efferth, T, Eftekharpour, E, Eichinger, L, Eid, N, Eisenberg, T, Eissa, NT, Eissa, S, Ejarque, M, El Andaloussi, A, El-Hage, N, El-Naggar, S, Eleuteri, AM, El-Shafey, ES, Elgendy, M, Eliopoulos, AG, Elizalde, MM, Elks, PM, Elsasser, H-P, Elsherbiny, ES, Emerling, BM, Emre, NCT, Eng, CH, Engedal, N, Engelbrecht, A-M, Engelsen, AST, Enserink, JM, Escalante, R, Esclatine, A, Escobar-Henriques, M, Eskelinen, E-L, Espert, L, Eusebio, M-O, Fabrias, G, Fabrizi, C, Facchiano, A, Facchiano, F, Fadeel, B, Fader, C, Faesen, AC, Fairlie, WD, Falcó, A, Falkenburger, BH, Fan, D, Fan, J, Fan, Y, Fang, EF, Fang, Y, Fanto, M, Farfel-Becker, T, Faure, M, Fazeli, G, Fedele, AO, Feldman, AM, Feng, D, Feng, J, Feng, L, Feng, Y, Feng, W, Fenz Araujo, T, Ferguson, TA, Fernández, ÁF, Fernandez-Checa, JC, Fernández-Veledo, S, Fernie, AR, Ferrante, AW, Ferraresi, A, Ferrari, MF, Ferreira, JCB, Ferro-Novick, S, Figueras, A, Filadi, R, Filigheddu, N, Filippi-Chiela, E, Filomeni, G, Fimia, GM, Fineschi, V, Finetti, F, Finkbeiner, S, Fisher, EA, Fisher, PB, Flamigni, F, Fliesler, SJ, Flo, TH, Florance, I, Florey, O, Florio, T, Fodor, E, Follo, C, Fon, EA, Forlino, A, Fornai, F, Fortini, P, Fracassi, A, Fraldi, A, Franco, B, Franco, R, Franconi, F, Frankel, LB, Friedman, SL, Fröhlich, LF, Frühbeck, G, Fuentes, JM, Fujiki, Y, Fujita, N, Fujiwara, Y, Fukuda, M, Fulda, S, Furic, L, Furuya, N, Fusco, C, Gack, MU, Gaffke, L, Galadari, S, Galasso, A, Galindo, MF, Gallolu Kankanamalage, S, Galluzzi, L, Galy, V, Gammoh, N, Gan, B, Ganley, IG, Gao, F, Gao, H, Gao, M, Gao, P, Gao, S-J, Gao, W, Gao, X, Garcera, A, Garcia, MN, Garcia, VE, García-Del Portillo, F, Garcia-Escudero, V, Garcia-Garcia, A, Garcia-Macia, M, García-Moreno, D, Garcia-Ruiz, C, García-Sanz, P, Garg, AD, Gargini, R, Garofalo, T, Garry, RF, Gassen, NC, Gatica, D, Ge, L, Ge, W, Geiss-Friedlander, R, Gelfi, C, Genschik, P, Gentle, IE, Gerbino, V, Gerhardt, C, Germain, K, Germain, M, Gewirtz, DA, Ghasemipour Afshar, E, Ghavami, S, Ghigo, A, Ghosh, M, Giamas, G, Giampietri, C, Giatromanolaki, A, Gibson, GE, Gibson, SB, Ginet, V, Giniger, E, Giorgi, C, Girao, H, Girardin, SE, Giridharan, M, Giuliano, S, Giulivi, C, Giuriato, S, Giustiniani, J, Gluschko, A, Goder, V, Goginashvili, A, Golab, J, Goldstone, DC, Golebiewska, A, Gomes, LR, Gomez, R, Gómez-Sánchez, R, Gomez-Puerto, MC, Gomez-Sintes, R, Gong, Q, Goni, FM, González-Gallego, J, Gonzalez-Hernandez, T, Gonzalez-Polo, RA, Gonzalez-Reyes, JA, González-Rodríguez, P, Goping, IS, Gorbatyuk, MS, Gorbunov, NV, Görgülü, K, Gorojod, RM, Gorski, SM, Goruppi, S, Gotor, C, Gottlieb, RA, Gozes, I, Gozuacik, D, Graef, M, Gräler, MH, Granatiero, V, Grasso, D, Gray, JP, Green, DR, Greenhough, A, Gregory, SL, Griffin, EF, Grinstaff, MW, Gros, F, Grose, C, Gross, AS, Gruber, F, Grumati, P, Grune, T, Gu, X, Guan, J-L, Guardia, CM, Guda, K, Guerra, F, Guerri, C, Guha, P, Guillén, C, Gujar, S, Gukovskaya, A, Gukovsky, I, Gunst, J, Günther, A, Guntur, AR, Guo, C, Guo, H, Guo, L-W, Guo, M, Gupta, P, Gupta, SK, Gupta, S, Gupta, VB, Gupta, V, Gustafsson, AB, Gutterman, DD, H B, R, Haapasalo, A, Haber, JE, Hać, A, Hadano, S, Hafrén, AJ, Haidar, M, Hall, BS, Halldén, G, Hamacher-Brady, A, Hamann, A, Hamasaki, M, Han, W, Hansen, M, Hanson, PI, Hao, Z, Harada, M, Harhaji-Trajkovic, L, Hariharan, N, Haroon, N, Harris, J, Hasegawa, T, Hasima Nagoor, N, Haspel, JA, Haucke, V, Hawkins, WD, Hay, BA, Haynes, CM, Hayrabedyan, SB, Hays, TS, He, C, He, Q, He, R-R, He, Y-W, He, Y-Y, Heakal, Y, Heberle, AM, Hejtmancik, JF, Helgason, GV, Henkel, V, Herb, M, 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C, Viret, C, Viscomi, MT, Visnjic, D, Vitale, I, Vocadlo, DJ, Voitsekhovskaja, OV, Volonté, C, Volta, M, Vomero, M, Von Haefen, C, Vooijs, MA, Voos, W, Vucicevic, L, Wade-Martins, R, Waguri, S, Waite, KA, Wakatsuki, S, Walker, DW, Walker, MJ, Walker, SA, Walter, J, Wandosell, FG, Wang, B, Wang, C-Y, Wang, C, Wang, D, Wang, F, Wang, G, Wang, H, Wang, H-G, Wang, J, Wang, K, Wang, L, Wang, MH, Wang, M, Wang, N, Wang, P, Wang, QJ, Wang, Q, Wang, QK, Wang, QA, Wang, W-T, Wang, W, Wang, X, Wang, Y, Wang, Y-Y, Wang, Z, Warnes, G, Warnsmann, V, Watada, H, Watanabe, E, Watchon, M, Wawrzyńska, A, Weaver, TE, Wegrzyn, G, Wehman, AM, Wei, H, Wei, L, Wei, T, Wei, Y, Weiergräber, OH, Weihl, CC, Weindl, G, Weiskirchen, R, Wells, A, Wen, RH, Wen, X, Werner, A, Weykopf, B, Wheatley, SP, Whitton, JL, Whitworth, AJ, Wiktorska, K, Wildenberg, ME, Wileman, T, Wilkinson, S, Willbold, D, Williams, B, Williams, RSB, Williams, RL, Williamson, PR, Wilson, RA, Winner, B, Winsor, NJ, Witkin, SS, Wodrich, H, 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Y, Oshima, S, Rong, Y, Sluimer, JC, Stallings, CL, and Tong, C-K

Abstract

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Published
2021

18. Evaluation of 3- and 4-phenoxybenzamides as selective inhibitors of the Mono-ADP ribosyltransferase PARP10

Author

Korn, P. (Patricia), Classen, A. (Arno), Murthy, S. (Sudarshan), Guareschi, R. (Riccardo), Maksimainen, M. M. (Mirko M.), Lippok, B. E. (Barbara E.), Galera-Prat, A. (Albert), Sowa, S. T. (Sven T.), Voigt, C. (Catharina), Rossetti, G. (Giulia), Lehtiö, L. (Lari), Bolm, C. (Carsten), and Lüscher, B. (Bernhard)

Subjects
cell proliferation, molecular modeling, DNA repair, compound screening, ADP-ribosylation
Abstract

Intracellular ADP-ribosyltransferases catalyze mono- and poly-ADP-ribosylation and affect a broad range of biological processes. The mono-ADP-ribosyltransferase PARP10 is involved in signaling and DNA repair. Previous studies identified OUL35 as a selective, cell permeable inhibitor of PARP10. We have further explored the chemical space of OUL35 by synthesizing and investigating structurally related analogs. Key synthetic steps were metal-catalyzed cross-couplings and functional group modifications. We identified 4-(4-cyanophenoxy)benzamide and 3-(4-carbamoylphenoxy)benzamide as PARP10 inhibitors with distinct selectivities. Both compounds were cell permeable and interfered with PARP10 toxicity. Moreover, both revealed some inhibition of PARP2 but not PARP1, unlike clinically used PARP inhibitors, which typically inhibit both enzymes. Using crystallography and molecular modeling the binding of the compounds to different ADP-ribosyltransferases was explored regarding selectivity. Together, these studies define additional compounds that interfere with PARP10 function and thus expand our repertoire of inhibitors to further optimize selectivity and potency.

Published
2021

20. ADP-ribosyltransferases, an update on function and nomenclature

Author

Lüscher, B. (Bernhard), Ahel, I. (Ivan), Altmeyer, M. (Matthias), Ashworth, A. (Alan), Bai, P. (Peter), Chang, P. (Paul), Cohen, M. (Michael), Corda, D. (Daniela), Dantzer, F. (Françoise), Daugherty, M. D. (Matthew D.), Dawson, T. M. (Ted M.), Dawson, V. L. (Valina L.), Deindl, S. (Sebastian), Fehr, A. R. (Anthony R.), Feijs, K. L. (Karla L. H.), Filippov, D. V. (Dmitri V.), Gagné, J.-P. (Jean-Philippe), Grimaldi, G. (Giovanna), Guettler, S. (Sebastian), Hoch, N. C. (Nicolas C.), Hottiger, M. O. (Michael O.), Korn, P. (Patricia), Kraus, W. L. (W. Lee), Ladurner, A. (Andreas), Lehtiö, L. (Lari), Leung, A. K. (Anthony K. L.), Lord, C. J. (Christopher J.), Mangerich, A. (Aswin), Matic, I. (Ivan), Matthews, J. (Jason), Moldovan, G.-L. (George-Lucian), Moss, J. (Joel), Natoli, G. (Gioacchino), Nielsen, M. L. (Michael L.), Niepel, M. (Mario), Nolte, F. (Friedrich), Pascal, J. (John), Paschal, B. M. (Bryce M.), Pawłowski, K. (Krzysztof), Poirier, G. G. (Guy G.), Smith, S. (Susan), Timinszky, G. (Gyula), Wang, Z.-Q. (Zhao-Qi), Yélamos, J. (José), Yu, X. (Xiaochun), Zaja, R. (Roko), Ziegler, M. (Mathias), Lüscher, B. (Bernhard), Ahel, I. (Ivan), Altmeyer, M. (Matthias), Ashworth, A. (Alan), Bai, P. (Peter), Chang, P. (Paul), Cohen, M. (Michael), Corda, D. (Daniela), Dantzer, F. (Françoise), Daugherty, M. D. (Matthew D.), Dawson, T. M. (Ted M.), Dawson, V. L. (Valina L.), Deindl, S. (Sebastian), Fehr, A. R. (Anthony R.), Feijs, K. L. (Karla L. H.), Filippov, D. V. (Dmitri V.), Gagné, J.-P. (Jean-Philippe), Grimaldi, G. (Giovanna), Guettler, S. (Sebastian), Hoch, N. C. (Nicolas C.), Hottiger, M. O. (Michael O.), Korn, P. (Patricia), Kraus, W. L. (W. Lee), Ladurner, A. (Andreas), Lehtiö, L. (Lari), Leung, A. K. (Anthony K. L.), Lord, C. J. (Christopher J.), Mangerich, A. (Aswin), Matic, I. (Ivan), Matthews, J. (Jason), Moldovan, G.-L. (George-Lucian), Moss, J. (Joel), Natoli, G. (Gioacchino), Nielsen, M. L. (Michael L.), Niepel, M. (Mario), Nolte, F. (Friedrich), Pascal, J. (John), Paschal, B. M. (Bryce M.), Pawłowski, K. (Krzysztof), Poirier, G. G. (Guy G.), Smith, S. (Susan), Timinszky, G. (Gyula), Wang, Z.-Q. (Zhao-Qi), Yélamos, J. (José), Yu, X. (Xiaochun), Zaja, R. (Roko), and Ziegler, M. (Mathias)

Abstract

ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs), which transfer ADP-ribose from NAD⁺ onto substrates. The modification, which occurs as mono- or poly-ADP-ribosylation, is reversible due to the action of different ADP-ribosylhydrolases. Importantly, inhibitors of ARTs are approved or are being developed for clinical use. Moreover, ADP-ribosylhydrolases are being assessed as therapeutic targets, foremost as antiviral drugs and for oncological indications. Due to the development of novel reagents and major technological advances that allow the study of ADP-ribosylation in unprecedented detail, an increasing number of cellular processes and pathways are being identified that are regulated by ADP-ribosylation. In addition, characterization of biochemical and structural aspects of the ARTs and their catalytic activities have expanded our understanding of this protein family. This increased knowledge requires that a common nomenclature be used to describe the relevant enzymes. Therefore, in this viewpoint, we propose an updated and broadly supported nomenclature for mammalian ARTs that will facilitate future discussions when addressing the biochemistry and biology of ADP-ribosylation. This is combined with a brief description of the main functions of mammalian ARTs to illustrate the increasing diversity of mono- and poly-ADP-ribose mediated cellular processes.

Published
2021

21. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Author

Klionsky, D, Abdel-Aziz, A, Abdelfatah, S, Abdellatif, M, Abdoli, A, Abel, S, Abeliovich, H, Abildgaard, M, Abudu, Y, Acevedo-Arozena, A, Adamopoulos, I, Adeli, K, Adolph, T, Adornetto, A, Aflaki, E, Agam, G, Agarwal, A, Aggarwal, B, Agnello, M, Agostinis, P, Agrewala, J, Agrotis, A, Aguilar, P, Ahmad, S, Ahmed, Z, Ahumada-Castro, U, Aits, S, Aizawa, S, Akkoc, Y, Akoumianaki, T, Akpinar, H, Al-Abd, A, Al-Akra, L, Al-Gharaibeh, A, Alaoui-Jamali, M, Alberti, S, Alcocer-Gómez, E, Alessandri, C, Ali, M, Alim Al-Bari, M, Aliwaini, S, Alizadeh, J, Almacellas, E, Almasan, A, Alonso, A, Alonso, G, Altan-Bonnet, N, Altieri, D, Álvarez, É, Alves, S, Alves da Costa, C, Alzaharna, M, Amadio, M, Amantini, C, Amaral, C, Ambrosio, S, Amer, A, Ammanathan, V, An, Z, Andersen, S, Andrabi, S, Andrade-Silva, M, Andres, A, Angelini, S, Ann, D, Anozie, U, Ansari, M, Antas, P, Antebi, A, Antón, Z, Anwar, T, Apetoh, L, Apostolova, N, Araki, T, Araki, Y, Arasaki, K, Araújo, W, Araya, J, Arden, C, Arévalo, M, Arguelles, S, Arias, E, Arikkath, J, Arimoto, H, Ariosa, A, Armstrong-James, D, Arnauné-Pelloquin, L, Aroca, A, Arroyo, D, Arsov, I, Artero, R, Asaro, D, Aschner, M, Ashrafizadeh, M, Ashur-Fabian, O, Atanasov, A, Au, A, Auberger, P, Auner, H, Aurelian, L, Autelli, R, Avagliano, L, Ávalos, Y, Aveic, S, Aveleira, C, Avin-Wittenberg, T, Aydin, Y, Ayton, S, Ayyadevara, S, Azzopardi, M, Baba, M, Backer, J, Backues, S, Bae, D, Bae, O, Bae, S, Baehrecke, E, Baek, A, Baek, S, Bagetta, G, Bagniewska-Zadworna, A, Bai, H, Bai, J, Bai, X, Bai, Y, Bairagi, N, Baksi, S, Balbi, T, Baldari, C, Balduini, W, Ballabio, A, Ballester, M, Balazadeh, S, Balzan, R, Bandopadhyay, R, Banerjee, S, Bánréti, Á, Bao, Y, Baptista, M, Baracca, A, Barbati, C, Bargiela, A, Barilà, D, Barlow, P, Barmada, S, Barreiro, E, Barreto, G, Bartek, J, Bartel, B, Bartolome, A, Barve, G, Basagoudanavar, S, Bassham, D, Bast, R, Basu, A, Batoko, H, Batten, I, Baulieu, E, Baumgarner, B, Bayry, J, Beale, R, Beau, I, Beaumatin, F, Bechara, L, Beck, G, Beers, M, Begun, J, Behrends, C, Behrens, G, Bei, R, Bejarano, E, Bel, S, Behl, C, Belaid, A, Belgareh-Touzé, N, Bellarosa, C, Belleudi, F, Belló Pérez, M, Bello-Morales, R, Beltran, J, Beltran, S, Benbrook, D, Bendorius, M, Benitez, B, Benito-Cuesta, I, Bensalem, J, Berchtold, M, Berezowska, S, Bergamaschi, D, Bergami, M, Bergmann, A, Berliocchi, L, Berlioz-Torrent, C, Bernard, A, Berthoux, L, Besirli, C, Besteiro, S, Betin, V, Beyaert, R, Bezbradica, J, Bhaskar, K, Bhatia-Kissova, I, Bhattacharya, R, Bhattacharya, S, Bhattacharyya, S, Bhuiyan, M, Bhutia, S, Bi, L, Bi, X, Biden, T, Bijian, K, Billes, V, Binart, N, Bincoletto, C, Birgisdottir, A, Bjorkoy, G, Blanco, G, Blas-Garcia, A, Blasiak, J, Blomgran, R, Blomgren, K, Blum, J, Boada-Romero, E, Boban, M, Boesze-Battaglia, K, Boeuf, P, Boland, B, Bomont, P, Bonaldo, P, Bonam, S, Bonfili, L, Bonifacino, J, Boone, B, Bootman, M, Bordi, M, Borner, C, Bornhauser, B, Borthakur, G, Bosch, J, Bose, S, Botana, L, Botas, 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A, Walter, Jochen, Wandosell, Francisco G, Wang, Bo, Wang, Chao-Yung, Wang, Chen, Wang, Chenran, Wang, Chenwei, Wang, Cun-Yu, Wang, Dong, Wang, Fangyang, Wang, Feng, Wang, Fengming, Wang, Guansong, Wang, Han, Wang, Hao, Wang, Hexiang, Wang, Hong-Gang, Wang, Jianrong, Wang, Jigang, Wang, Jiou, Wang, Jundong, Wang, Kui, Wang, Lianrong, Wang, Liming, Wang, Maggie Haitian, Wang, Meiqing, Wang, Nanbu, Wang, Pengwei, Wang, Peipei, Wang, Ping, Wang, Qing Jun, Wang, Qing, Wang, Qing Kenneth, Wang, Qiong A, Wang, Wen-Tao, Wang, Wuyang, Wang, Xinnan, Wang, Xuejun, Wang, Yan, Wang, Yanchang, Wang, Yanzhuang, Wang, Yen-Yun, Wang, Yihua, Wang, Yipeng, Wang, Yu, Wang, Yuqi, Wang, Zhe, Wang, Zhenyu, Wang, Zhouguang, Warnes, Gary, Warnsmann, Verena, Watada, Hirotaka, Watanabe, Eizo, Watchon, Maxinne, Wawrzyńska, Anna, Weaver, Timothy E, Wegrzyn, Grzegorz, Wehman, Ann M, Wei, Huafeng, Wei, Lei, Wei, Taotao, Wei, Yongjie, Weiergräber, Oliver H, Weihl, Conrad C, Weindl, Günther, Weiskirchen, Ralf, Wells, Alan, Wen, Runxia H, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally P, Whitton, J Lindsay, Whitworth, Alexander J, Wiktorska, Katarzyna, Wildenberg, Manon E, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin S B, Williams, Roger L, Williamson, Peter R, Wilson, Richard A, Winner, Beate, Winsor, Nathaniel J, Witkin, Steven S, Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard W, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth K, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William K K, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik J, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-Tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, JinRong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna M S, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul M, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin K, Yiu, Stephanie Pei Tung, Yoo, Young H, Yoshida, Kiyotsugu, Yoshii, Saori R, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor C, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou F, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond L, Zacks, David N, Zaffagnini, Gabriele, Zambelli, Vanessa O, Zanella, Isabella, Zang, Qun S, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos S, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott O, Zeng, Jialiu, Zeng, Ju-Deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna D, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin Y B, Zhang, Leshuai W, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, Zhou, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-Jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine M, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry B, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith C, Stallings, Christina L, and Tong, Chun-Kit

Abstract

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Published
2021

29. The GABAA Receptors

Author

Mohler, H., primary, Fritschy, J. M., additional, Lüscher, B., additional, Rudolph, U., additional, Benson, J., additional, and Benke, D., additional

Published
1996
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32. Hör mal! – eTraining Auskultation

Author

Camenisch, A, Ledergerber, C, and Lüscher, B

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Im cardio-pulmonalen Unterricht lernen BSc-Studierende Physiotherapie der ZHAW das Auskultieren der Lungen. Als Novizinnen und Novizen fällt es den Studierenden schwer, Atemgeräusche korrekt zu interpretieren und diese mit anderen Befunden sowie klinischen Bildern in Verbindung[zum vollständigen Text gelangen Sie über die oben angegebene URL], Gemeinsame Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA) und des Arbeitskreises zur Weiterentwicklung der Lehre in der Zahnmedizin (AKWLZ)

Published
2017
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37. 4-(phenoxy) and 4-(benzyloxy)benzamides as potent and selective inhibitors of mono-ADP-ribosyltransferase PARP10/ARTD10

Author

Murthy, S. (Sudarshan), Desantis, J. (Jenny), Verheugd, P. (Patricia), Maksimainen, M. M. (Mirko M.), Venkannagari, H. (Harikanth), Massari, S. (Serena), Ashok, Y. (Yashwanth), Obaji, E. (Ezeogo), Nkizinkinko, Y. (Yves), Lüscher, B. (Bernhard), Tabarrini, O. (Oriana), Lehtiiö, L. (Lari), Murthy, S. (Sudarshan), Desantis, J. (Jenny), Verheugd, P. (Patricia), Maksimainen, M. M. (Mirko M.), Venkannagari, H. (Harikanth), Massari, S. (Serena), Ashok, Y. (Yashwanth), Obaji, E. (Ezeogo), Nkizinkinko, Y. (Yves), Lüscher, B. (Bernhard), Tabarrini, O. (Oriana), and Lehtiiö, L. (Lari)

Abstract

Human Diphtheria toxin-like ADP-ribosyltranferases (ARTD) 10 is an enzyme carrying out mono-ADP-ribosylation of a range of cellular proteins and affecting their activities. It shuttles between cytoplasm and nucleus and influences signaling events in both compartments, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and S phase DNA repair. Furthermore, overexpression of ARTD10 induces cell death. We recently reported on the discovery of a hit compound, OUL35 (compound 1), with 330 nM potency and remarkable selectivity towards ARTD10 over other enzymes in the human protein family. Here we aimed at establishing a structure-activity relationship of the OUL35 scaffold, by evaluating an array of 4-phenoxybenzamide derivatives. By exploring modifications on the linker between the aromatic rings, we identified also a 4-(benzyloxy)benzamide derivative, compound 32, which is potent (IC50 = 230 nM) and selective, and like OUL35 was able to rescue HeLa cells from ARTD10-induced cell death. Evaluation of an enlarged series of derivatives produced detailed knowledge on the structural requirements for ARTD10 inhibition and allowed the discovery of further tool compounds with submicromolar cellular potency that will help in understanding the roles of ARTD10 in biological systems.

Published
2018

41. Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30IIaccessory protein and the induction of oncogenic cellular transformation by p30II/c-MYC

Author

Romeo, MM, Ko, B, Kim, J, Brady, R, Heatley, HC, He, J, Harrod, CK, Barnett, B, Ratner, L, Lairmore, MD, Martinez, E, Lüscher, B, Robson, CN, Henriksson, M, and Harrod, R

Abstract

© 2014 Elsevier Inc. The human T-cell leukemia retrovirus type-1 (HTLV-1) p30IIprotein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30IIinteracts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30IIand c-MYC remain to be completely understood. Herein we demonstrate that p30IIinduces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30IIin c-myc-/-HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30IIis present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30IIinhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30II/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis.

Published
2015
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44. Small-molecule chemical probe rescues cells from mono-ADP-ribosyltransferase ARTD10/PARP10-induced apoptosis and sensitizes cancer cells to DNA damage

Author

Venkannagari, H. (Harikanth), Verheugd, P. (Patricia), Koivunen, J. (Jarkko), Haikarainen, T. (Teemu), Obaji, E. (Ezeogo), Ashok, Y. (Yashwanth), Narwal, M. (Mohit), Pihlajaniemi, T. (Taina), Lüscher, B. (Bernhard), Lehtiö, L. (Lari), Venkannagari, H. (Harikanth), Verheugd, P. (Patricia), Koivunen, J. (Jarkko), Haikarainen, T. (Teemu), Obaji, E. (Ezeogo), Ashok, Y. (Yashwanth), Narwal, M. (Mohit), Pihlajaniemi, T. (Taina), Lüscher, B. (Bernhard), and Lehtiö, L. (Lari)

Abstract

Summary Members of the human diphtheria toxin-like ADP-ribosyltransferase (ARTD or PARP) family play important roles in regulating biological activities by mediating either a mono-ADP-ribosylation (MARylation) of a substrate or a poly-ADP-ribosylation (PARylation). ARTD10/PARP10 belongs to the MARylating ARTDs (mARTDs) subfamily, and plays important roles in biological processes that range from cellular signaling, DNA repair, and cell proliferation to immune response. Despite their biological and disease relevance, no selective inhibitors for mARTDs are available. Here we describe a small-molecule ARTD10 inhibitor, OUL35, a selective and potent inhibitor for this enzyme. We characterize its selectivity profile, model its binding, and demonstrate activity in HeLa cells where OUL35 rescued cells from ARTD10 induced cell death. Using OUL35 as a cell biology tool we show that ARTD10 inhibition sensitizes the cells to the hydroxyurea-induced genotoxic stress. Our study supports the proposed role of ARTD10 in DNA-damage repair and provides a tool compound for selective inhibition of ARTD10-mediated MARylation.

Published
2016

47. Activation of Eme1-mediated DNA repair by Cetuximab: A novel mechanism for therapy resistance

Author

Dreier, A, Piroth, MD, Eble, M, Clusmann, H, Lüscher, B, and Weis, J

Subjects
ddc: 610, therapy resistance, Cetuximab, DNA repair, 610 Medical sciences, Medicine
Abstract

Objective: Overexpression of the epidermal growth factor receptor (EGFR) is observed in a large number of neoplasms including high grade gliomas. Diverse strategies have been established to target and inhibit EGFR, including monoclonal antibodies and tyrosine kinase inhibitors. The recombinant antibody[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2014
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48. Symposium swissYPG 2011 'La Pharmacie en mutation'

Author

Widmer, N., Bezençon, J., Locca, J.F., and Lüscher, B.

Abstract

Comme en 2009, le groupe des jeunes pharma- ciens suisses (swissYPG) organise cette année un nouveau symposium de formation et de ré- flexion à destination des jeunes pharmaciennes et pharmaciens suisses. Ce dernier aura lieu à Interlaken le 30 novembre 2011, dans le cadre du 1er congrès suisse des pharmaciens.

Published
2011

49. Symposium swissYPG 2011 'Die Apotheke im Wandel'

Author

Widmer, N., Bezençon, J., Locca, J.F., and Lüscher, B.

Abstract

Wie im Jahre 2009 organisiert die swiss Young Pharmacists Group (swissYPG) in diesem Jahr erneut ein interessantes Symposium für junge Schweizer Apothekerinnen und Apotheker. Das Symposium wird im Rahmen des 1. Schweizerischen Apothekerkongresses, am 30. November 2011 in Interlaken stattfinden.

Published
2011

50. Progress in the function and regulation of ADP-Ribosylation

Author

Hottiger, M O, Boothby, M, Koch-Nolte, F, Lüscher, B, Martin, N M B, Plummer, R, Wang, Z Q, Ziegler, M, and University of Zurich

Subjects
1307 Cell Biology, 1303 Biochemistry, 1312 Molecular Biology, 570 Life sciences, biology, 10226 Department of Molecular Mechanisms of Disease
Published
2011

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