Patents and Publications

Patents & patent applications related to Sareum programmes

TYK2/JAK1:

• Crystalline Forms of a TYK2 Inhibitor WO2021204762

• TYK2 Kinase Inhibitors. WO2020074661, US2021387981, EP3864009, CN113056456

• Pharmaceutical Compounds. WO2018073438, EP3528806, US 11,154,539 (Granted Oct 2021) 

• TYK2 Kinase Inhibitors. WO2015032423, EP2634185 (Granted Jan 2016), EP3040336,
  US 10,882,829 (Granted Jan 2021), JP6239118 (Granted Nov 2017),
  CN 105793245B (Granted Mar 2018)

Chk1:

• TFM compounds and therapeutic uses thereof. WO2013171470, US 9,663,503 (Granted May 2017), EP2855448 (Granted Feb 2017), JP6027230 (Granted Sept 2016), CN 104302635 (Granted July 2016)

• Pyridyl-amino-pyrazine carbonitrile compounds and thier therapeutic use. WO2013068755, US 9,040,540 (Granted May 2015), US 9,403,797 (Granted Aug 2016), EP2776417 (Granted Oct 2018), JP6073910 (Granted Dec 2016)

• Bicyclylaryl-aryl-amine Compounds and Their Use. WO2009103966 , US 8,530,468 (Granted Sept 2013), EP2288601 (Granted Sept 2014)

• Therapeutic Biarylamine Compounds and Their Use. WO2009044162, US 8,058,045 (Granted Dec 2011), US 8,367,658 (Granted Feb 2013), JP5511668 (Granted Feb 2014)

• Therapeutic Tricyclic Compounds and Their Use. WO2009004329, US 8,618,121 (Granted Dec 2013

FLT3+Aurora:

• Aurora and FLT3 Kinases Modulators. WO2013117522, US 9,133,180 (Granted Sept 2015), EP2812328 (Granted Nov 2015), JP 6034880 (Granted Oct 2016), CN 104169277 (Granted Oct 2016)

SKIL:

• Oxazole Tyrosine Kinase Inhibitors. WO2008139161, US 8,378,095 (Granted Feb 2013), JP 5555620 (Granted Jun 2014), CN101796038 (Granted Dec 2014), US 8,921,544 (Granted Jan 2015)
  
  

Publications related to Sareum programmes

TYK2/JAK1:

• Immunotherapeutic effects of the TYK2 inhibitor SAR-20351 in syngeneic tumour models. J Reader, T Mitchell et al, AACR-EORTC-NCI 2019 Abstract C086  Poster PDF
   

•  Inhibition of TYK2 and JAK1 Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis by Inhibiting IL-22 and the IL-23/IL-17 Axis. Works MG, Yin F, Yin CC, Yiu Y, Shew K, Tran TT, Dunlap N, Lam J, Mitchell T, Reader J, Stein PL, D'Andrea A. J Immunol. 2014, 193(7), 3278-3287 Abstract, Download PDF

• A New Regulatory Switch in a JAK Protein Kinase. Tsui, V., Gibbons, P., Ultsch, M., Motara, K., Chang, C., Blair, W., Pulk, R., Stanley, M., Starovasnik, M., Willimas, D., Lamers, M., Leonard, P., Magnuson, S., Liang, J. & Eigenbrot, C, Proteins: Structure, Function & Bioinformatics (2011) 79(2), 393-401. Abstract

Chk1

• A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer. R Jones R Plummer, V Moreno, L Carter, D Roda, E Garralda, R Kristeleit, D Sarker, T Arkenau, P Roxburgh, HS Walter, S Blagden, A Anthoney, BJ Klencke, MM Kowalski & U Banerji, Clin Cancer Res, 15 November 2022. Article
  
  
• A study of combinatorial growth inhibition, cell death and DNA damage repair caused by CHK1 inhibitor SRA737 and WEE1 inhibitor adavosertib in TP53 mutated cell line. A Stewart, L Pickard, A Hallsworth, S Sauvaigo, G Muggiolu, F Raynaud, U BANERJI, AACR Annual Meeting 2021 Abstract 1010 , Download Poster PDF
  
  

• CHK1 Inhibition Is Synthetically Lethal with Loss of B-Family DNA Polymerase Function in Human Lung and Colorectal Cancer Cells. R Rogers, M Walton, D Cherry, I Collins, P Clarke, M & P Workman, Cancer Research (2020) 80(8), 1735-1747 Article, Download PDF

• Combination treatment of the oral CHK1 inhibitor, SRA737 and low dose gemcitabine, enhances the effect of PD-L1 blockade by modulating the immune microenvironment in small cell lung cancer. T Sen et. al, J Thoracic Oncology 27 Aug 2019 Abstract

• The CHK1 inhibitor SRA737 synergizes with PARP1 inhibitors to kill carcinoma cells, L Booth, J Roberts, A Poklepovic & P Dent. Cancer Biology & Therapy 2018 (19:9) 786-796 Article

• An orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation. R Patel, HE Barker, J Kyula, M McLaughlin, MT Dillon, U Schick, H Hafsi, A Thompson, V Khoo, K Harrington & S Zaidi, Radiother Oncol (2017) Article,  Download PDF

• DNA replication stress mediates APOBEC3 family mutagenesis in breast cancer. N Kanu, MA Cerone, G Goh, L-P Zalmas, J Bartkova, M Dietzen, N McGranahan, R Rogers, EK Law, I Gromova, M Kschischo, MI Walton, OW Rossanese, J Bartek, RS Harris, S Venkatesan and C Swanton, Genome Biology (2016) 17:185 Article,  Download PDF
  

• CHK1 inhibition radiosensitises head and neck cancers to paclitaxel-based chemoradiotherapy. HE Barker, R Patel, M McLaughlin, U Schick, S Zaidi, CM Nutting, KL Newbold, S Bhide, KJ Harrington, Mol Cancer Therapeutics (2016) July vol 15 Article
  

• Multi-parameter lead optimization to give an oral checkpoint kinase 1 (CHK1) inhibitor clinical candidate: (R)-5-((4-((morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). JD Osborne, TP Matthews, T McHardy, N Proisy, K-M J Cheung, M Lainchbury, N Brown, MI Walton, PD Eve, KJ Boxall, A Hayes, AT Henley, MR Valenti, AK De Haven Brandon, G Box, Y Jamin, SP Robinson, IM Westwood, RLM van Montfort, PM Leonard, MBAC Lamers, JC Reader, GW Aherne, FI Raynaud, SA Eccles, MD Garrett and I Collins, J. Med. Chem. 2016, 59(11), 5221-5237 Abstract

• The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. MI Walton, PD Eve, A Hayes, AT Henley, MR Valenti, AK De Haven Brandon, G Box, KJ Boxall, M Tall, K Swales, TP Matthews, T McHardy, M Lainchbury, J Osborne, JE Hunter, ND Perkins, GW Aherne, JC Reader, FI Raynaud, SA Eccles, I Collins and MD Garrett, Oncotarget 2015, 7(3) 2329-2342 Abstract , Download PDF

• Targeted radiosensitization by the Chk1 inhibitor SAR-020106. GR Borst, M McLaughlin, JN Kyula, S Neijenhuis, A Khan, J Good … & KJ Harrington, International Journal of Radiation Oncology Biology Physics, 2013 85(4), 1110-1118. Abstract

• Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies. Matthews TP, Jones AM, Collins I. Expert Opin Drug Discov. 2013 Jun;8(6):621-40. Abstract

•  CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs. Walton MI, Eve PD, Hayes A, Valenti MR, Alexis K, Box G, … & Garrett MD, Clinical Cancer Research 2012, 18(20), 5650-5661. Download PDF

• Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino) pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors. Lainchbury M, Matthews TP, McHardy T, Boxall KJ, Walton MI, Eve PD, … & Collins, I, Journal of Medicinal Chemistry 2012, 55(22), 10229-10240. Download PDF

• Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing. JC Reader, TP Matthews, S Klair, K-MJ Cheung, J Scanlon, N Proisy, G Addison, J Ellard, N Piton, S Taylor, M Cherry, M Fisher, K Boxall, S Burns, MI Walton, IM Westwood, A Hayes, P Eve, M Valenti, A de Haven Brandon, G Box, RLM van Montfort, DH Williams, GW Aherne, FI Raynaud, SA Eccles, MD Garrett and Ian Collins, J. Med. Chem., 2011, 54 (24), 8328–8342. Abstract

• CCT244747 is a novel, potent and selective inhibitor of CHK1 with oral efficacy both alone in neuroblastoma and in combination with genotoxic chemotherapeutic agents. MI. Walton, PE. Eve, A Hayes, MR. Valenti, AK. de Haven Brandon, G Box, A Hallsworth, EL. Smith, KJ. Boxall, M Lainchbury, TP. Matthews, Y Jamin, SP Robinson, GW Aherne, JC. Reader, L Chesler, FI. Raynaud, SE Eccles, I Collins, MD Garrett, AACR NCI EORTC “Molecular Targets and Cancer Therapeutics”, San Francisco, CA, Nov 12-16, 2011 Abstract

• Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing. TP Matthews, S Klair, K-MJ Cheung, J Scanlon, M Lainchbury, N Piton, M Fisher, M Cherry, K Boxall, MI. Walton, IM Westwood, A Hayes, P Eve, M Valenti, A de Haven Brandon, G Box, RLM van Montfort, DH. Williams, W Aherne, FI Raynaud, SA Eccles, MD Garrett, JC. Reader, I Collins,.AACR NCI EORTC “Molecular Targets and Cancer Therapeutics”, San Francisco, CA, Nov 12-16, 2011 Abstract

• Design and Evaluation of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines as Inhibitors of Checkpoint and Other Kinases. Matthews, T.P., McHardy, T., Klair, S., Boxhall, K., Fisher, M., Cherry, M., Allen, C.E., Addison, G.J., Ellard, J., Aherne, G.W., Westwood, I.M, van Montfort, R., Garrett, M.D., Reader, J.C. & Collins, I., Bioorg & Med Chem Lett (2010), 20(14), 4045-4049. Abstract

• The Preclinical Pharmacology and Therapeutic Activity of the Novel CHK1 Inhibitor SAR-020106. Walton, M.I., Eve, P.D., Hayes, A., Valenti, M., De Haven Brandon, A., Box, G., Boxall, K.J., Aherne, G.W., Eccles, S.A., Raynauld, F.I., Williams, D.H., Reader, J.C., Collins, I., Garrett, M.D., Mol Cancer Ther (2010), 9(1), 89-100. Abstract

• Identification of Inhibitors of Checkpoint Kinase 1 through Template Screening. Matthews, T.P., Klair, S., Burns, S., Boxall, K., Cherry, M., Fisher, M., Westwood, I.M., Walton, M.I., McHardy, T., Kwai-Ming, J.C., Van Montfort, R., Williams, D., Aherne, G.W., Garrett, M.D., Reader, J and Collins, I, J Medicinal Chemistry (2009), 52(15), 4810-4819.  Abstract

• Identification and Structure-guided Optimisation of Novel Inhibitors of Checkpoint Kinase 1 (Chk1) through Combined Biochemical and Crystallographic Screening. Reader, J., Williams, D., Klair, S., Cherry, M., Fisher, M., Scanlon, J., Piton, N., Addison, G., Lamers, M., et al. AACR Annual Meeting, San Diego, CA, Apr 12-16, 2008. Download PDF

Publications related to Sareum expertise

·        Introduction to Fragment-based Drug Discovery, T Mitchell & M Cherry in “Fragment-Based Drug Discovery: Practical Aspects”, E.R. Zartler & M.J. Shapiro, Eds, John Wiley & Sons (2008). Buy at Amazon

·         Fragment-Based Drug Design, Tim Mitchell,MedChem News(Japan), (2007), 1, 8-15

·         Finding protein kinase hits using structural information. Cherry, M., Reader, J. and Williams, D.H. Prog. Med. Chem., (2006). 44, 1-63.

·         Fragment-Based Drug Design, Mitchell, T. and Cherry, M. Innovations in Pharmaceutical Technology, (2005). 16, 34-36. Download PDF

·         The design of a new potent and selective ligand for the BRS3 receptor. Boyle, R.G., Humphries, J., Mitchell, T., Showell, G.A., Iijima, H., Shimada, H., Arai, T., Ueno, H., Usui, H., Sakaki, T., Wada, E. and Wada, K.   J Peptide Research, (2005). 11(3), 136-141.

·         Automation in medicinal chemistry. Reader, John C.   Current Topics in Medicinal Chemistry, (2004), 4(7), 671-686.

·         Solid phase synthesis of tetrahydro-1,4-benzodiazepin-2-ones. Hone, Neal D.; Wilson, William; Reader, John C.   Tetrahedron Letters, (2003). 44(46), 8493-8495.

·         Solid-phase synthesis of dibenzoxazepinones. Hone, Neal D., Salter, James I., Reader, John C.   Tetrahedron Letters, (2003). 44(44), 8169-8172.