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Items: 1 to 50 of 97

1.

Potentiation of PBD dimers by lipophilicity manipulation.

Cailleau T, Adams LR, Arora N, Kang GD, Masterson L, Patel N, Hartley JA, Mao S, Harper J, Howard PW.

Curr Top Med Chem. 2019 Mar 31. doi: 10.2174/1568026619666190401112517. [Epub ahead of print]

PMID:
30931859
2.

An Alternative Focus for Route Design for the Synthesis of Antibody-Drug Conjugate Payloads.

Tiberghien AC, Howard PW, Goundry WRF, McCormick M, Parker JS.

J Org Chem. 2019 Apr 19;84(8):4830-4836. doi: 10.1021/acs.joc.8b02876. Epub 2019 Jan 11.

PMID:
30602115
3.

Preclinical assessment of an antibody-PBD conjugate that targets BCMA on multiple myeloma and myeloma progenitor cells.

Kinneer K, Flynn M, Thomas SB, Meekin J, Varkey R, Xiao X, Zhong H, Breen S, Hynes PG, Fleming R, Bezabeh B, Chen CT, Wetzel L, Chen R, Dimasi N, Tai YT, Anderson KC, Herbst R, Howard PW, Hurt EM, Tice DA.

Leukemia. 2019 Mar;33(3):766-771. doi: 10.1038/s41375-018-0278-7. Epub 2018 Oct 12. No abstract available.

PMID:
30315237
4.

Using long term mortality to determine which perioperative risk factors of mortality following hip and knee replacement may be causal.

Hunt LP, Whitehouse MR, Howard PW, Ben-Shlomo Y, Blom AW.

Sci Rep. 2018 Oct 9;8(1):15026. doi: 10.1038/s41598-018-33314-0.

5.

SLC46A3 as a Potential Predictive Biomarker for Antibody-Drug Conjugates Bearing Noncleavable Linked Maytansinoid and Pyrrolobenzodiazepine Warheads.

Kinneer K, Meekin J, Tiberghien AC, Tai YT, Phipps S, Kiefer CM, Rebelatto MC, Dimasi N, Moriarty A, Papadopoulos KP, Sridhar S, Gregson SJ, Wick MJ, Masterson L, Anderson KC, Herbst R, Howard PW, Tice DA.

Clin Cancer Res. 2018 Dec 15;24(24):6570-6582. doi: 10.1158/1078-0432.CCR-18-1300. Epub 2018 Aug 21.

PMID:
30131388
6.

Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer.

Cho S, Zammarchi F, Williams DG, Havenith CEG, Monks NR, Tyrer P, D'Hooge F, Fleming R, Vashisht K, Dimasi N, Bertelli F, Corbett S, Adams L, Reinert HW, Dissanayake S, Britten CE, King W, Dacosta K, Tammali R, Schifferli K, Strout P, Korade M 3rd, Masson Hinrichs MJ, Chivers S, Corey E, Liu H, Kim S, Bander NH, Howard PW, Hartley JA, Coats S, Tice DA, Herbst R, van Berkel PH.

Mol Cancer Ther. 2018 Oct;17(10):2176-2186. doi: 10.1158/1535-7163.MCT-17-0982. Epub 2018 Jul 31.

PMID:
30065100
7.

Pre-clinical pharmacology and mechanism of action of SG3199, the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine.

Hartley JA, Flynn MJ, Bingham JP, Corbett S, Reinert H, Tiberghien A, Masterson LA, Antonow D, Adams L, Chowdhury S, Williams DG, Mao S, Harper J, Havenith CEG, Zammarchi F, Chivers S, van Berkel PH, Howard PW.

Sci Rep. 2018 Jul 11;8(1):10479. doi: 10.1038/s41598-018-28533-4.

8.

ADCT-402, a PBD dimer-containing antibody drug conjugate targeting CD19-expressing malignancies.

Zammarchi F, Corbett S, Adams L, Tyrer PC, Kiakos K, Janghra N, Marafioti T, Britten CE, Havenith CEG, Chivers S, D'Hooge F, Williams DG, Tiberghien A, Howard PW, Hartley JA, van Berkel PH.

Blood. 2018 Mar 8;131(10):1094-1105. doi: 10.1182/blood-2017-10-813493. Epub 2018 Jan 3.

9.

Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity.

Wei B, Gunzner-Toste J, Yao H, Wang T, Wang J, Xu Z, Chen J, Wai J, Nonomiya J, Tsai SP, Chuh J, Kozak KR, Liu Y, Yu SF, Lau J, Li G, Phillips GD, Leipold D, Kamath A, Su D, Xu K, Eigenbrot C, Steinbacher S, Ohri R, Raab H, Staben LR, Zhao G, Flygare JA, Pillow TH, Verma V, Masterson LA, Howard PW, Safina B.

J Med Chem. 2018 Feb 8;61(3):989-1000. doi: 10.1021/acs.jmedchem.7b01430. Epub 2017 Dec 21.

PMID:
29227683
10.

Pyrrolobenzodiazepine Dimer Antibody-Drug Conjugates: Synthesis and Evaluation of Noncleavable Drug-Linkers.

Gregson SJ, Masterson LA, Wei B, Pillow TH, Spencer SD, Kang GD, Yu SF, Raab H, Lau J, Li G, Lewis Phillips GD, Gunzner-Toste J, Safina BS, Ohri R, Darwish M, Kozak KR, Dela Cruz-Chuh J, Polson A, Flygare JA, Howard PW.

J Med Chem. 2017 Dec 14;60(23):9490-9507. doi: 10.1021/acs.jmedchem.7b00736. Epub 2017 Nov 16.

PMID:
29112410
11.

Ceramic-on-ceramic bearing fractures in total hip arthroplasty: an analysis of data from the National Joint Registry.

Howard DP, Wall PDH, Fernandez MA, Parsons H, Howard PW.

Bone Joint J. 2017 Aug;99-B(8):1012-1019. doi: 10.1302/0301-620X.99B8.BJJ-2017-0019.R1.

PMID:
28768777
12.

Fractionated Dosing Improves Preclinical Therapeutic Index of Pyrrolobenzodiazepine-Containing Antibody Drug Conjugates.

Hinrichs MJM, Ryan PM, Zheng B, Afif-Rider S, Yu XQ, Gunsior M, Zhong H, Harper J, Bezabeh B, Vashisht K, Rebelatto M, Reed M, Ryan PC, Breen S, Patel N, Chen C, Masterson L, Tiberghien A, Howard PW, Dimasi N, Dixit R.

Clin Cancer Res. 2017 Oct 1;23(19):5858-5868. doi: 10.1158/1078-0432.CCR-17-0219. Epub 2017 Jun 19.

13.

Preclinical Evaluation of MEDI0641, a Pyrrolobenzodiazepine-Conjugated Antibody-Drug Conjugate Targeting 5T4.

Harper J, Lloyd C, Dimasi N, Toader D, Marwood R, Lewis L, Bannister D, Jovanovic J, Fleming R, D'Hooge F, Mao S, Marrero AM, Korade M 3rd, Strout P, Xu L, Chen C, Wetzel L, Breen S, van Vlerken-Ysla L, Jalla S, Rebelatto M, Zhong H, Hurt EM, Hinrichs MJ, Huang K, Howard PW, Tice DA, Hollingsworth RE, Herbst R, Kamal A.

Mol Cancer Ther. 2017 Aug;16(8):1576-1587. doi: 10.1158/1535-7163.MCT-16-0825. Epub 2017 May 18.

14.

Modulating Therapeutic Activity and Toxicity of Pyrrolobenzodiazepine Antibody-Drug Conjugates with Self-Immolative Disulfide Linkers.

Pillow TH, Schutten M, Yu SF, Ohri R, Sadowsky J, Poon KA, Solis W, Zhong F, Del Rosario G, Go MAT, Lau J, Yee S, He J, Liu L, Ng C, Xu K, Leipold DD, Kamath AV, Zhang D, Masterson L, Gregson SJ, Howard PW, Fang F, Chen J, Gunzner-Toste J, Kozak KK, Spencer S, Polakis P, Polson AG, Flygare JA, Junutula JR.

Mol Cancer Ther. 2017 May;16(5):871-878. doi: 10.1158/1535-7163.MCT-16-0641. Epub 2017 Feb 21.

15.

Synthesis and in vitro evaluation of SG3227, a pyrrolobenzodiazepine dimer antibody-drug conjugate payload based on sibiromycin.

Kemp GC, Tiberghien AC, Patel NV, D'Hooge F, Nilapwar SM, Adams LR, Corbett S, Williams DG, Hartley JA, Howard PW.

Bioorg Med Chem Lett. 2017 Mar 1;27(5):1154-1158. doi: 10.1016/j.bmcl.2017.01.074. Epub 2017 Jan 30.

PMID:
28188066
16.

Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload.

Tiberghien AC, Levy JN, Masterson LA, Patel NV, Adams LR, Corbett S, Williams DG, Hartley JA, Howard PW.

ACS Med Chem Lett. 2016 May 24;7(11):983-987. eCollection 2016 Nov 10.

17.

ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer-Containing Antibody-Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies.

Flynn MJ, Zammarchi F, Tyrer PC, Akarca AU, Janghra N, Britten CE, Havenith CE, Levy JN, Tiberghien A, Masterson LA, Barry C, D'Hooge F, Marafioti T, Parren PW, Williams DG, Howard PW, van Berkel PH, Hartley JA.

Mol Cancer Ther. 2016 Nov;15(11):2709-2721. Epub 2016 Aug 17.

18.

Fatal pulmonary embolism following elective total hip arthroplasty: a 12-year study.

Bayley E, Brown S, Bhamber NS, Howard PW.

Bone Joint J. 2016 May;98-B(5):585-8. doi: 10.1302/0301-620X.98B5.34996.

PMID:
27143726
19.

Human Cytomegalovirus gH/gL Forms a Stable Complex with the Fusion Protein gB in Virions.

Vanarsdall AL, Howard PW, Wisner TW, Johnson DC.

PLoS Pathog. 2016 Apr 15;12(4):e1005564. doi: 10.1371/journal.ppat.1005564. eCollection 2016 Apr.

20.

Genetically Encoded Azide Containing Amino Acid in Mammalian Cells Enables Site-Specific Antibody-Drug Conjugates Using Click Cycloaddition Chemistry.

VanBrunt MP, Shanebeck K, Caldwell Z, Johnson J, Thompson P, Martin T, Dong H, Li G, Xu H, D'Hooge F, Masterson L, Bariola P, Tiberghien A, Ezeadi E, Williams DG, Hartley JA, Howard PW, Grabstein KH, Bowen MA, Marelli M.

Bioconjug Chem. 2015 Nov 18;26(11):2249-60. doi: 10.1021/acs.bioconjchem.5b00359. Epub 2015 Sep 11.

PMID:
26332743
21.

Herpes simplex virus gE/gI extracellular domains promote axonal transport and spread from neurons to epithelial cells.

Howard PW, Wright CC, Howard T, Johnson DC.

J Virol. 2014 Oct;88(19):11178-86. doi: 10.1128/JVI.01627-14. Epub 2014 Jul 16.

22.

An extended pyrrolobenzodiazepine-polyamide conjugate with selectivity for a DNA sequence containing the ICB2 transcription factor binding site.

Brucoli F, Hawkins RM, James CH, Jackson PJ, Wells G, Jenkins TC, Ellis T, Kotecha M, Hochhauser D, Hartley JA, Howard PW, Thurston DE.

J Med Chem. 2013 Aug 22;56(16):6339-51. doi: 10.1021/jm4001852. Epub 2013 Jul 26.

PMID:
23889553
23.

Interaction of mouse TTC30/DYF-1 with multiple intraflagellar transport complex B proteins and KIF17.

Howard PW, Jue SF, Maurer RA.

Exp Cell Res. 2013 Aug 15;319(14):2275-81. doi: 10.1016/j.yexcr.2013.06.010. Epub 2013 Jun 25.

24.

A potent anti-CD70 antibody-drug conjugate combining a dimeric pyrrolobenzodiazepine drug with site-specific conjugation technology.

Jeffrey SC, Burke PJ, Lyon RP, Meyer DW, Sussman D, Anderson M, Hunter JH, Leiske CI, Miyamoto JB, Nicholas ND, Okeley NM, Sanderson RJ, Stone IJ, Zeng W, Gregson SJ, Masterson L, Tiberghien AC, Howard PW, Thurston DE, Law CL, Senter PD.

Bioconjug Chem. 2013 Jul 17;24(7):1256-63. doi: 10.1021/bc400217g. Epub 2013 Jun 28.

PMID:
23808985
25.

GC-targeted C8-linked pyrrolobenzodiazepine-biaryl conjugates with femtomolar in vitro cytotoxicity and in vivo antitumor activity in mouse models.

Rahman KM, Jackson PJ, James CH, Basu BP, Hartley JA, de la Fuente M, Schatzlein A, Robson M, Pedley RB, Pepper C, Fox KR, Howard PW, Thurston DE.

J Med Chem. 2013 Apr 11;56(7):2911-35. doi: 10.1021/jm301882a. Epub 2013 Mar 21.

PMID:
23514599
26.
27.

Failure rates of metal-on-metal hip resurfacings: analysis of data from the National Joint Registry for England and Wales.

Smith AJ, Dieppe P, Howard PW, Blom AW; National Joint Registry for England and Wales.

Lancet. 2012 Nov 17;380(9855):1759-66. doi: 10.1016/S0140-6736(12)60989-1. Epub 2012 Oct 2.

PMID:
23036895
28.

Antibody-drug conjugates - a perfect synergy.

Adair JR, Howard PW, Hartley JA, Williams DG, Chester KA.

Expert Opin Biol Ther. 2012 Sep;12(9):1191-206. doi: 10.1517/14712598.2012.693473. Epub 2012 Jun 1. Review.

PMID:
22650648
29.

Antistaphylococcal activity of DNA-interactive pyrrolobenzodiazepine (PBD) dimers and PBD-biaryl conjugates.

Rahman KM, Rosado H, Moreira JB, Feuerbaum EA, Fox KR, Stecher E, Howard PW, Gregson SJ, James CH, de la Fuente M, Waldron DE, Thurston DE, Taylor PW.

J Antimicrob Chemother. 2012 Jul;67(7):1683-96. doi: 10.1093/jac/dks127. Epub 2012 Apr 30.

30.

Novel C8-linked pyrrolobenzodiazepine (PBD)-heterocycle conjugates that recognize DNA sequences containing an inverted CCAAT box.

Brucoli F, Hawkins RM, James CH, Wells G, Jenkins TC, Ellis T, Hartley JA, Howard PW, Thurston DE.

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3780-3. doi: 10.1016/j.bmcl.2011.04.054. Epub 2011 Apr 20.

PMID:
21570842
31.

Anterograde transport of herpes simplex virus capsids in neurons by both separate and married mechanisms.

Wisner TW, Sugimoto K, Howard PW, Kawaguchi Y, Johnson DC.

J Virol. 2011 Jun;85(12):5919-28. doi: 10.1128/JVI.00116-11. Epub 2011 Mar 30.

32.

DNA interstrand cross-linking and in vivo antitumor activity of the extended pyrrolo[2,1-c][1,4]benzodiazepine dimer SG2057.

Hartley JA, Hamaguchi A, Suggitt M, Gregson SJ, Thurston DE, Howard PW.

Invest New Drugs. 2012 Jun;30(3):950-8. doi: 10.1007/s10637-011-9647-z. Epub 2011 Mar 8.

PMID:
21384134
33.

SG2285, a novel C2-aryl-substituted pyrrolobenzodiazepine dimer prodrug that cross-links DNA and exerts highly potent antitumor activity.

Hartley JA, Hamaguchi A, Coffils M, Martin CR, Suggitt M, Chen Z, Gregson SJ, Masterson LA, Tiberghien AC, Hartley JM, Pepper C, Lin TT, Fegan C, Thurston DE, Howard PW.

Cancer Res. 2010 Sep 1;70(17):6849-58. doi: 10.1158/0008-5472.CAN-10-0790. Epub 2010 Jul 26.

34.

Transcription intermediary factor 1gamma decreases protein expression of the transcriptional cofactor, LIM-domain-binding 1.

Howard PW, Ransom DG, Maurer RA.

Biochem Biophys Res Commun. 2010 Jun 4;396(3):674-8. doi: 10.1016/j.bbrc.2010.04.160. Epub 2010 May 4.

35.

Regulation of LIM-domain-binding 1 protein expression by ubiquitination of Lys134.

Howard PW, Jue SF, Ransom DG, Maurer RA.

Biochem J. 2010 Jul 1;429(1):127-36. doi: 10.1042/BJ20091461.

36.

Structure-activity relationships of monomeric C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine (PBD) antitumor agents.

Antonow D, Kaliszczak M, Kang GD, Coffils M, Tiberghien AC, Cooper N, Barata T, Heidelberger S, James CH, Zloh M, Jenkins TC, Reszka AP, Neidle S, Guichard SM, Jodrell DI, Hartley JA, Howard PW, Thurston DE.

J Med Chem. 2010 Apr 8;53(7):2927-41. doi: 10.1021/jm901722v.

PMID:
20218628
37.

Synthesis of a novel C2/C2'-aryl-substituted pyrrolo[2,1-c][1,4]benzodiazepine dimer prodrug with improved water solubility and reduced DNA reaction rate.

Howard PW, Chen Z, Gregson SJ, Masterson LA, Tiberghien AC, Cooper N, Fang M, Coffils MJ, Klee S, Hartley JA, Thurston DE.

Bioorg Med Chem Lett. 2009 Nov 15;19(22):6463-6. doi: 10.1016/j.bmcl.2009.09.012. Epub 2009 Sep 9.

PMID:
19811912
38.

Expression of the synaptotagmin I gene is enhanced by binding of the pituitary-specific transcription factor, POU1F1.

Howard PW, Jue SF, Maurer RA.

Mol Endocrinol. 2009 Oct;23(10):1563-71. doi: 10.1210/me.2009-0111. Epub 2009 Jul 16.

39.

Biaryl polyamides as a new class of DNA quadruplex-binding ligands.

Rahman KM, Reszka AP, Gunaratnam M, Haider SM, Howard PW, Fox KR, Neidle S, Thurston DE.

Chem Commun (Camb). 2009 Jul 21;(27):4097-9. doi: 10.1039/b902359c. Epub 2009 Jun 5.

PMID:
19568645
40.

Efficient solid-phase synthesis of a library of distamycin analogs containing novel biaryl motifs on SynPhase Lanterns.

Brucoli F, Howard PW, Thurston DE.

J Comb Chem. 2009 Jul-Aug;11(4):576-86. doi: 10.1021/cc900009r.

PMID:
19530662
41.

Generation of mice with a conditional allele for Ift172.

Howard PW, Howard TL, Maurer RA.

Transgenic Res. 2010 Feb;19(1):121-6. doi: 10.1007/s11248-009-9292-x. Epub 2009 Jun 12.

42.

Observation of a dynamic equilibrium between DNA hairpin and duplex forms of covalent adducts of a minor groove binding agent.

Rahman KM, Mussa V, Narayanaswamy M, James CH, Howard PW, Thurston DE.

Chem Commun (Camb). 2009 Jan 8;(2):227-9. doi: 10.1039/b816163a. Epub 2008 Nov 17.

PMID:
19099077
43.

Solution structure of a 2:1 C2-(2-naphthyl) pyrrolo[2,1-c][1,4]benzodiazepine DNA adduct: molecular basis for unexpectedly high DNA helix stabilization.

Antonow D, Barata T, Jenkins TC, Parkinson GN, Howard PW, Thurston DE, Zloh M.

Biochemistry. 2008 Nov 11;47(45):11818-29. doi: 10.1021/bi801225q. Epub 2008 Oct 17.

PMID:
18925745
44.

Femoral impaction bone allografting with an Exeter cemented collarless, polished, tapered stem in revision hip replacement: a mean follow-up of 10.5 years.

Wraighte PJ, Howard PW.

J Bone Joint Surg Br. 2008 Aug;90(8):1000-4. doi: 10.1302/0301-620X.90B8.20390.

PMID:
18669953
45.

Inhibition of DNA binding of the NF-Y transcription factor by the pyrrolobenzodiazepine-polyamide conjugate GWL-78.

Kotecha M, Kluza J, Wells G, O'Hare CC, Forni C, Mantovani R, Howard PW, Morris P, Thurston DE, Hartley JA, Hochhauser D.

Mol Cancer Ther. 2008 May;7(5):1319-28. doi: 10.1158/1535-7163.MCT-07-0475.

46.

Fluorescent 7-diethylaminocoumarin pyrrolobenzodiazepine conjugates: synthesis, DNA interaction, cytotoxicity and differential cellular localization.

Wells G, Suggitt M, Coffils M, Baig MA, Howard PW, Loadman PM, Hartley JA, Jenkins TC, Thurston DE.

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2147-51. doi: 10.1016/j.bmcl.2008.01.083. Epub 2008 Jan 30.

PMID:
18280154
47.

An asymmetric C8/C8'-tripyrrole-linked sequence-selective pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer DNA interstrand cross-linking agent spanning 11 DNA base pairs.

Tiberghien AC, Evans DA, Kiakos K, Martin CR, Hartley JA, Thurston DE, Howard PW.

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2073-7. doi: 10.1016/j.bmcl.2008.01.096. Epub 2008 Jan 30.

PMID:
18272367
48.

An assay combining high-performance liquid chromatography and mass spectrometry to measure DNA interstrand cross-linking efficiency in oligonucleotides of varying sequences.

Narayanaswamy M, Griffiths WJ, Howard PW, Thurston DE.

Anal Biochem. 2008 Mar 1;374(1):173-81. Epub 2007 Nov 17.

PMID:
18082123
49.

Parallel synthesis of a novel C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine (PBD) library.

Antonow D, Cooper N, Howard PW, Thurston DE.

J Comb Chem. 2007 May-Jun;9(3):437-45. Epub 2007 Mar 31.

PMID:
17397227
50.

Synthesis of a novel C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione library: effect of C2-aryl substitution on cytotoxicity and non-covalent DNA binding.

Antonow D, Jenkins TC, Howard PW, Thurston DE.

Bioorg Med Chem. 2007 Apr 15;15(8):3041-53. Epub 2007 Feb 2.

PMID:
17317191

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