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Targeting BER enzymes in cancer therapy.

Visnes T, Grube M, Hanna BMF, Benitez-Buelga C, Cázares-Körner A, Helleday T.

DNA Repair (Amst). 2018 Aug 25. pii: S1568-7864(18)30180-0. doi: 10.1016/j.dnarep.2018.08.015. [Epub ahead of print]


Structure-metabolism-relationships in the microsomal clearance of piperazin-1-ylpyridazines.

Llona-Minguez S, Ghassemian A, Baranczewski P, Desroses M, Koolmeister T, Artursson P, Scobie M, Helleday T.

Medchemcomm. 2017 Jul 4;8(7):1553-1560. doi: 10.1039/c7md00230k. eCollection 2017 Jul 1.


Mechanisms for stalled replication fork stabilization: new targets for synthetic lethality strategies in cancer treatments.

Liao H, Ji F, Helleday T, Ying S.

EMBO Rep. 2018 Sep;19(9). pii: e46263. doi: 10.15252/embr.201846263. Epub 2018 Aug 13. Review.


STAT3 differential scanning fluorimetry and differential scanning light scattering assays: Addressing a missing link in the characterization of STAT3 inhibitor interactions.

Desroses M, Busker S, Astorga-Wells J, Attarha S, Kolosenko I, Zubarev RA, Helleday T, Grandér D, Page BDG.

J Pharm Biomed Anal. 2018 Oct 25;160:80-88. doi: 10.1016/j.jpba.2018.07.018. Epub 2018 Jul 17.


A synthetic diphosphoinositol phosphate analogue of inositol trisphosphate.

Riley AM, Unterlass J, Konieczny V, Taylor CW, Helleday T, Potter BVL.

Medchemcomm. 2018 Jul 1;9(7):1105-1113. doi: 10.1039/C8MD00149A. Epub 2018 Jun 4.


A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma.

Einarsdottir BO, Karlsson J, Söderberg EMV, Lindberg MF, Funck-Brentano E, Jespersen H, Brynjolfsson SF, Bagge RO, Carstam L, Scobie M, Koolmeister T, Wallner O, Stierner U, Berglund UW, Ny L, Nilsson LM, Larsson E, Helleday T, Nilsson JA.

Cell Death Dis. 2018 Jul 24;9(8):810. doi: 10.1038/s41419-018-0865-6.


Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity.

Berglund E, Maaskola J, Schultz N, Friedrich S, Marklund M, Bergenstråhle J, Tarish F, Tanoglidi A, Vickovic S, Larsson L, Salmén F, Ogris C, Wallenborg K, Lagergren J, Ståhl P, Sonnhammer E, Helleday T, Lundeberg J.

Nat Commun. 2018 Jun 20;9(1):2419. doi: 10.1038/s41467-018-04724-5.


Germline variation in the oxidative DNA repair genes NUDT1 and OGG1 is not associated with hereditary colorectal cancer or polyposis.

Mur P, Jemth AS, Bevc L, Amaral N, Navarro M, Valdés-Mas R, Pons T, Aiza G, Urioste M, Valencia A, Lázaro C, Moreno V, Puente XS, Stenmark P, Warpman-Berglund U, Capellá G, Helleday T, Valle L.

Hum Mutat. 2018 Sep;39(9):1214-1225. doi: 10.1002/humu.23564. Epub 2018 Jul 4.


An orthotopic glioblastoma animal model suitable for high-throughput screenings.

Pudelko L, Edwards S, Balan M, Nyqvist D, Al-Saadi J, Dittmer J, Almlöf I, Helleday T, Bräutigam L.

Neuro Oncol. 2018 May 10. doi: 10.1093/neuonc/noy071. [Epub ahead of print]


Human NUDT22 Is a UDP-Glucose/Galactose Hydrolase Exhibiting a Unique Structural Fold.

Carter M, Jemth AS, Carreras-Puigvert J, Herr P, Martínez Carranza M, Vallin KSA, Throup A, Helleday T, Stenmark P.

Structure. 2018 Feb 6;26(2):295-303.e6. doi: 10.1016/j.str.2018.01.004.


Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.

Page BDG, Valerie NCK, Wright RHG, Wallner O, Isaksson R, Carter M, Rudd SG, Loseva O, Jemth AS, Almlöf I, Font-Mateu J, Llona-Minguez S, Baranczewski P, Jeppsson F, Homan E, Almqvist H, Axelsson H, Regmi S, Gustavsson AL, Lundbäck T, Scobie M, Strömberg K, Stenmark P, Beato M, Helleday T.

Nat Commun. 2018 Jan 17;9(1):250. doi: 10.1038/s41467-017-02293-7.


Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer.

Thålin C, Lundström S, Seignez C, Daleskog M, Lundström A, Henriksson P, Helleday T, Phillipson M, Wallén H, Demers M.

PLoS One. 2018 Jan 11;13(1):e0191231. doi: 10.1371/journal.pone.0191231. eCollection 2018.


Crystal Structures and Inhibitor Interactions of Mouse and Dog MTH1 Reveal Species-Specific Differences in Affinity.

Narwal M, Jemth AS, Gustafsson R, Almlöf I, Warpman Berglund U, Helleday T, Stenmark P.

Biochemistry. 2018 Feb 6;57(5):593-603. doi: 10.1021/acs.biochem.7b01163. Epub 2018 Jan 16.


Glioblastoma and glioblastoma stem cells are dependent on functional MTH1.

Pudelko L, Rouhi P, Sanjiv K, Gad H, Kalderén C, Höglund A, Squatrito M, Schuhmacher AJ, Edwards S, Hägerstrand D, Berglund UW, Helleday T, Bräutigam L.

Oncotarget. 2017 Jul 20;8(49):84671-84684. doi: 10.18632/oncotarget.19404. eCollection 2017 Oct 17.


A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family.

Carreras-Puigvert J, Zitnik M, Jemth AS, Carter M, Unterlass JE, Hallström B, Loseva O, Karem Z, Calderón-Montaño JM, Lindskog C, Edqvist PH, Matuszewski DJ, Ait Blal H, Berntsson RPA, Häggblad M, Martens U, Studham M, Lundgren B, Wählby C, Sonnhammer ELL, Lundberg E, Stenmark P, Zupan B, Helleday T.

Nat Commun. 2017 Nov 16;8(1):1541. doi: 10.1038/s41467-017-01642-w.


Distinct mechanistic responses to replication fork stalling induced by either nucleotide or protein deprivation.

Henriksson S, Groth P, Gustafsson N, Helleday T.

Cell Cycle. 2018;17(5):568-579. doi: 10.1080/15384101.2017.1387696. Epub 2018 Apr 2.


Fragment-Based Discovery and Optimization of Enzyme Inhibitors by Docking of Commercial Chemical Space.

Rudling A, Gustafsson R, Almlöf I, Homan E, Scobie M, Warpman Berglund U, Helleday T, Stenmark P, Carlsson J.

J Med Chem. 2017 Oct 12;60(19):8160-8169. doi: 10.1021/acs.jmedchem.7b01006. Epub 2017 Oct 3.


Chemotherapy-induced toxicity-a secondary effect caused by released DNA?

Helleday T.

Ann Oncol. 2017 Sep 1;28(9):2054-2055. doi: 10.1093/annonc/mdx349. No abstract available.


Novel spirocyclic systems via multicomponent aza-Diels-Alder reaction.

Llona-Minguez S, Throup A, Steiner E, Lightowler M, Van der Haegen S, Homan E, Eriksson L, Stenmark P, Jenmalm-Jensen A, Helleday T.

Org Biomol Chem. 2017 Sep 26;15(37):7758-7764. doi: 10.1039/c7ob02069d.


Correction to Piperazin-1-ylpyridazine Derivatives Are a Novel Class of Human dCTP Pyrophosphatase 1 Inhibitors.

Llona-Minguez S, Höglund A, Ghassemian A, Desroses M, Calderón-Montaño JM, Burgos Morón E, Valerie NCK, Wiita E, Almlöf I, Koolmeister T, Mateus A, Cazares-Körner C, Sanjiv K, Homan E, Loseva O, Baranczewski P, Darabi M, Mehdizadeh A, Fayezi S, Jemth AS, Warpman Berglund U, Sigmundsson K, Lundbäck T, Jenmalm Jensen A, Artursson P, Scobie M, Helleday T.

J Med Chem. 2017 Sep 14;60(17):7614. doi: 10.1021/acs.jmedchem.7b01137. Epub 2017 Sep 1. No abstract available.


Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.

Asim M, Tarish F, Zecchini HI, Sanjiv K, Gelali E, Massie CE, Baridi A, Warren AY, Zhao W, Ogris C, McDuffus LA, Mascalchi P, Shaw G, Dev H, Wadhwa K, Wijnhoven P, Forment JV, Lyons SR, Lynch AG, O'Neill C, Zecchini VR, Rennie PS, Baniahmad A, Tavaré S, Mills IG, Galanty Y, Crosetto N, Schultz N, Neal D, Helleday T.

Nat Commun. 2017 Aug 29;8(1):374. doi: 10.1038/s41467-017-00393-y.


Tetrahydrobenzothiophene carboxamides: Beyond the kinase domain and into the fatty acid realm.

Llona-Minguez S, Fayezi S, Alihemmati A, Juárez-Jiménez J, Piedrafita FJ, Helleday T.

Bioorg Med Chem Lett. 2017 Sep 15;27(18):4462-4466. doi: 10.1016/j.bmcl.2017.08.006. Epub 2017 Aug 5.


Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by homologous recombination.

Orta ML, Pastor N, Burgos-Morón E, Domínguez I, Calderón-Montaño JM, Huertas Castaño C, López-Lázaro M, Helleday T, Mateos S.

DNA Repair (Amst). 2017 Sep;57:116-124. doi: 10.1016/j.dnarep.2017.07.002. Epub 2017 Jul 12.


Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 1: Triazoles, triazolopyrimidines, triazinoindoles, quinoline hydrazones and arylpiperazines.

Llona-Minguez S, Häggblad M, Martens U, Throup A, Loseva O, Jemth AS, Lundgren B, Scobie M, Helleday T.

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3897-3904. doi: 10.1016/j.bmcl.2017.06.038. Epub 2017 Jun 16.


Mutations in Cancer Cause Gain of Cysteine, Histidine, and Tryptophan at the Expense of a Net Loss of Arginine on the Proteome Level.

Tsuber V, Kadamov Y, Brautigam L, Berglund UW, Helleday T.

Biomolecules. 2017 Jul 3;7(3). pii: E49. doi: 10.3390/biom7030049.


Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 2: Pyridone- and pyrimidinone-derived systems.

Llona-Minguez S, Häggblad M, Martens U, Johansson L, Sigmundsson K, Lundbäck T, Loseva O, Jemth AS, Lundgren B, Jensen AJ, Scobie M, Helleday T.

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3219-3225. doi: 10.1016/j.bmcl.2017.06.039. Epub 2017 Jun 15.


Identification of novel small molecules that inhibit STAT3-dependent transcription and function.

Kolosenko I, Yu Y, Busker S, Dyczynski M, Liu J, Haraldsson M, Palm Apergi C, Helleday T, Tamm KP, Page BDG, Grander D.

PLoS One. 2017 Jun 21;12(6):e0178844. doi: 10.1371/journal.pone.0178844. eCollection 2017.


U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.

Glimelius B, Melin B, Enblad G, Alafuzoff I, Beskow A, Ahlström H, Bill-Axelson A, Birgisson H, Björ O, Edqvist PH, Hansson T, Helleday T, Hellman P, Henriksson K, Hesselager G, Hultdin M, Häggman M, Höglund M, Jonsson H, Larsson C, Lindman H, Ljuslinder I, Mindus S, Nygren P, Pontén F, Riklund K, Rosenquist R, Sandin F, Schwenk JM, Stenling R, Stålberg K, Stålberg P, Sundström C, Thellenberg Karlsson C, Westermark B, Bergh A, Claesson-Welsh L, Palmqvist R, Sjöblom T.

Acta Oncol. 2018 Feb;57(2):187-194. doi: 10.1080/0284186X.2017.1337926. Epub 2017 Jun 20.


ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration.

Jaiswal H, Benada J, Müllers E, Akopyan K, Burdova K, Koolmeister T, Helleday T, Medema RH, Macurek L, Lindqvist A.

EMBO J. 2017 Jul 14;36(14):2161-2176. doi: 10.15252/embj.201696082. Epub 2017 Jun 12.


Piperazin-1-ylpyridazine Derivatives Are a Novel Class of Human dCTP Pyrophosphatase 1 Inhibitors.

Llona-Minguez S, Höglund A, Ghassemian A, Desroses M, Calderón-Montaño JM, Burgos Morón E, Valerie NCK, Wiita E, Almlöf I, Koolmeister T, Mateus A, Cazares-Körner C, Sanjiv K, Homan E, Loseva O, Baranczewski P, Darabi M, Mehdizadeh A, Fayezi S, Jemth AS, Warpman Berglund U, Sigmundsson K, Lundbäck T, Jenmalm Jensen A, Artursson P, Scobie M, Helleday T.

J Med Chem. 2017 May 25;60(10):4279-4292. doi: 10.1021/acs.jmedchem.7b00182. Epub 2017 May 16.


With me or against me: Tumor suppressor and drug resistance activities of SAMHD1.

Herold N, Rudd SG, Sanjiv K, Kutzner J, Myrberg IH, Paulin CBJ, Olsen TK, Helleday T, Henter JI, Schaller T.

Exp Hematol. 2017 Aug;52:32-39. doi: 10.1016/j.exphem.2017.05.001. Epub 2017 May 11.


Global survey of the immunomodulatory potential of common drugs.

Vladimer GI, Snijder B, Krall N, Bigenzahn JW, Huber KVM, Lardeau CH, Sanjiv K, Ringler A, Berglund UW, Sabler M, de la Fuente OL, Knöbl P, Kubicek S, Helleday T, Jäger U, Superti-Furga G.

Nat Chem Biol. 2017 Jun;13(6):681-690. doi: 10.1038/nchembio.2360. Epub 2017 Apr 24.


SAMHD1 protects cancer cells from various nucleoside-based antimetabolites.

Herold N, Rudd SG, Sanjiv K, Kutzner J, Bladh J, Paulin CBJ, Helleday T, Henter JI, Schaller T.

Cell Cycle. 2017 Jun 3;16(11):1029-1038. doi: 10.1080/15384101.2017.1314407. Epub 2017 Apr 24.


dUTPase inhibition augments replication defects of 5-Fluorouracil.

Hagenkort A, Paulin CBJ, Desroses M, Sarno A, Wiita E, Mortusewicz O, Koolmeister T, Loseva O, Jemth AS, Almlöf I, Homan E, Lundbäck T, Gustavsson AL, Scobie M, Helleday T.

Oncotarget. 2017 Apr 4;8(14):23713-23726. doi: 10.18632/oncotarget.15785.


CHD1: a new treatment biomarker for recombination deficiency in castration resistant prostate cancer?

Helleday T.

Ann Oncol. 2017 Jul 1;28(7):1407-1408. doi: 10.1093/annonc/mdx166. No abstract available.


Validation of an enzyme-linked immunosorbent assay for the quantification of citrullinated histone H3 as a marker for neutrophil extracellular traps in human plasma.

Thålin C, Daleskog M, Göransson SP, Schatzberg D, Lasselin J, Laska AC, Kallner A, Helleday T, Wallén H, Demers M.

Immunol Res. 2017 Jun;65(3):706-712. doi: 10.1007/s12026-017-8905-3.


Identification of Triazolothiadiazoles as Potent Inhibitors of the dCTP Pyrophosphatase 1.

Llona-Minguez S, Höglund A, Wiita E, Almlöf I, Mateus A, Calderón-Montaño JM, Cazares-Körner C, Homan E, Loseva O, Baranczewski P, Jemth AS, Häggblad M, Martens U, Lundgren B, Artursson P, Lundbäck T, Jenmalm Jensen A, Warpman Berglund U, Scobie M, Helleday T.

J Med Chem. 2017 Mar 9;60(5):2148-2154. doi: 10.1021/acs.jmedchem.6b01786. Epub 2017 Feb 15.


Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies.

Herold N, Rudd SG, Ljungblad L, Sanjiv K, Myrberg IH, Paulin CB, Heshmati Y, Hagenkort A, Kutzner J, Page BD, Calderón-Montaño JM, Loseva O, Jemth AS, Bulli L, Axelsson H, Tesi B, Valerie NC, Höglund A, Bladh J, Wiita E, Sundin M, Uhlin M, Rassidakis G, Heyman M, Tamm KP, Warpman-Berglund U, Walfridsson J, Lehmann S, Grandér D, Lundbäck T, Kogner P, Henter JI, Helleday T, Schaller T.

Nat Med. 2017 Feb;23(2):256-263. doi: 10.1038/nm.4265. Epub 2017 Jan 9.


Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities.

Sanjiv K, Hagenkort A, Calderón-Montaño JM, Koolmeister T, Reaper PM, Mortusewicz O, Jacques SA, Kuiper RV, Schultz N, Scobie M, Charlton PA, Pollard JR, Berglund UW, Altun M, Helleday T.

Cell Rep. 2016 Dec 20;17(12):3407-3416. doi: 10.1016/j.celrep.2016.12.031. No abstract available.


The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing.

Tanikawa M, Sanjiv K, Helleday T, Herr P, Mortusewicz O.

Oncogenesis. 2016 Dec 19;5(12):e280. doi: 10.1038/oncsis.2016.70.


Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.

Sokolova M, Turunen M, Mortusewicz O, Kivioja T, Herr P, Vähärautio A, Björklund M, Taipale M, Helleday T, Taipale J.

Cell Cycle. 2017 Jan 17;16(2):189-199. doi: 10.1080/15384101.2016.1261765. Epub 2016 Dec 8.


hMYH and hMTH1 cooperate for survival in mismatch repair defective T-cell acute lymphoblastic leukemia.

Eshtad S, Mavajian Z, Rudd SG, Visnes T, Boström J, Altun M, Helleday T.

Oncogenesis. 2016 Dec 5;5(12):e275. doi: 10.1038/oncsis.2016.72.


Crystal Structure of the Emerging Cancer Target MTHFD2 in Complex with a Substrate-Based Inhibitor.

Gustafsson R, Jemth AS, Gustafsson NM, Färnegårdh K, Loseva O, Wiita E, Bonagas N, Dahllund L, Llona-Minguez S, Häggblad M, Henriksson M, Andersson Y, Homan E, Helleday T, Stenmark P.

Cancer Res. 2017 Feb 15;77(4):937-948. doi: 10.1158/0008-5472.CAN-16-1476. Epub 2016 Nov 29.


Validation and development of MTH1 inhibitors for treatment of cancer.

Warpman Berglund U, Sanjiv K, Gad H, Kalderén C, Koolmeister T, Pham T, Gokturk C, Jafari R, Maddalo G, Seashore-Ludlow B, Chernobrovkin A, Manoilov A, Pateras IS, Rasti A, Jemth AS, Almlöf I, Loseva O, Visnes T, Einarsdottir BO, Gaugaz FZ, Saleh A, Platzack B, Wallner OA, Vallin KS, Henriksson M, Wakchaure P, Borhade S, Herr P, Kallberg Y, Baranczewski P, Homan EJ, Wiita E, Nagpal V, Meijer T, Schipper N, Rudd SG, Bräutigam L, Lindqvist A, Filppula A, Lee TC, Artursson P, Nilsson JA, Gorgoulis VG, Lehtiö J, Zubarev RA, Scobie M, Helleday T.

Ann Oncol. 2016 Dec;27(12):2275-2283. doi: 10.1093/annonc/mdw429. Epub 2016 Nov 8.


A novel method for crosstalk analysis of biological networks: improving accuracy of pathway annotation.

Ogris C, Guala D, Helleday T, Sonnhammer EL.

Nucleic Acids Res. 2017 Jan 25;45(2):e8. doi: 10.1093/nar/gkw849. Epub 2016 Sep 22.


NUDT15 Hydrolyzes 6-Thio-DeoxyGTP to Mediate the Anticancer Efficacy of 6-Thioguanine.

Valerie NC, Hagenkort A, Page BD, Masuyer G, Rehling D, Carter M, Bevc L, Herr P, Homan E, Sheppard NG, Stenmark P, Jemth AS, Helleday T.

Cancer Res. 2016 Sep 15;76(18):5501-11. doi: 10.1158/0008-5472.CAN-16-0584. Epub 2016 Aug 16.


Pathways controlling dNTP pools to maintain genome stability.

Rudd SG, Valerie NCK, Helleday T.

DNA Repair (Amst). 2016 Aug;44:193-204. doi: 10.1016/j.dnarep.2016.05.032. Epub 2016 May 28. Review.


Overexpression of the scaffold WD40 protein WRAP53β enhances the repair of and cell survival from DNA double-strand breaks.

Rassoolzadeh H, Böhm S, Hedström E, Gad H, Helleday T, Henriksson S, Farnebo M.

Cell Death Dis. 2016 Jun 16;7:e2267. doi: 10.1038/cddis.2016.172.


DNA REPAIR. Drugging DNA repair.

Jackson SP, Helleday T.

Science. 2016 Jun 3;352(6290):1178-9. doi: 10.1126/science.aab0958. No abstract available.


PathwAX: a web server for network crosstalk based pathway annotation.

Ogris C, Helleday T, Sonnhammer EL.

Nucleic Acids Res. 2016 Jul 8;44(W1):W105-9. doi: 10.1093/nar/gkw356. Epub 2016 May 5.

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