![Dyfyr Jones](https://profiles-cardiff.imgix.net/attachments/1494?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Dyfyr Jones
Lecturer in Chemistry
- JonesD80@cardiff.ac.uk
- +44 29208 74082
- Main Building, Park Place, Cardiff, CF10 3AT
- Welsh speaking
- Available for postgraduate supervision
Overview
I am a medicinal chemist working at the Medicines Discovery Institute (MDI) and a Coleg Cymraeg Cenedlaethol-sponsored Lecturer at the chemistry department. Following training as a synthetic chemist, I have become interested in a number of areas that lie at the boundary of chemistry and biology that have the potential to be used to develop novel treatments for unmet clinical needs. I am currently part of a multi-disciplinary team working on a potential treatment option for a Lysosomal Storage Disorder.
I am interested in using synthetic chemistry in conjunction with the principles of medicinal chemistry to improve the properties of small molecules from the initial ‘hits’ to more suitable molecules that could be used to either validate biological targets/pathways or taken further onwards in the drug discovery process. Whilst improving the properties of these small molecules, I try to be observant of unusual reaction pathways that may be useful in their own right. I am fascinated by the relatively new technology of using bifunctional molecules, such as PROTACs and have a growing interest in diseases that are caused by the misfolding of proteins.
Cemegwr meddyginiaethol ydw i sydd yn gweithio yn y Sefydliad Darganfod Meddyginiaethau (SDM); rwyf hefyd yn ddarlithydd yn y adran gemeg dan nawdd y Coleg Cymraeg Cenedlaethol. Yn dilyn hyfforddiant fel cemegwr synthetig, rwyf wedi magu diddordeb mewn nifer o feysydd sydd yn bodoli ar y ffin rhwng cemeg a bioleg sydd â’r potensial i gael eu defnyddio i ddatblygu triniaethau newydd ar gyfer anghenion clinigol heb eu cwrdd. Ar hyn o bryd, rwyf yn rhan o dîm amlddisgyblaethol sy’n gweithio ar ddatblygu opsiwn o driniaeth bosib ar gyfer clefyd storio leisosomal.
Mae diddordeb gennyf mewn defnyddio cemeg synthetig mewn cyfuniad ag egwyddorion cemeg feddyginiaethol i wella priodweddau molecylau bychain dechreuol prosiect ymchwil i folecylau sydd yn fwy addas at gael eu defnyddio i wirio targedau/llwybrau biolegol neu a fydd yn cael eu dewis i fynd ymhellach ar hyd y broses darganfod meddyginiaethau. Wrth wella priodweddau’r molecylau bychain hyn, rwyf yn ceisio cadw golwg fanwl am adweithiau cemegol anarferol a allai fod yn ddefnyddiol. Rwyf yn gweld molecylau deuswyddogaethol, megis PROTACs, sydd yn dechnoleg eitha newydd, yn hynod o ddiddorol ac mae gennyf ddiddordeb cynyddol mewn afiechydon sy’n cael eu hachosi gan broteinau sydd wedi’u camblygu.
Publication
2023
- Thomas, B., Lewis, L., Jones, D. and Ward, S. 2023. Central nervous system targeted protein degraders. Biomolecules 13(8), article number: 1164. (10.3390/biom13081164)
- Davies, M., Riseley, R., Jones, D. H. and Waller-Evans, H. 2023. Acid ceramidase inhibition as a mechanism to treat lysosomal disorders. Molecular Genetics and Metabolism 138(2), article number: 107069. (10.1016/j.ymgme.2022.107069)
2022
- Collins, R. et al. 2022. Comparative analysis of small-molecule limk1/2 inhibitors: chemical synthesis, biochemistry, and cellular activity. Journal of Medicinal Chemistry (10.1021/acs.jmedchem.2c00751)
- Romartinez-Alonso, B. et al. 2022. Structure-guided approach to relieving transcriptional repression inResistance to Thyroid Hormone α. Molecular and Cellular Biology 42(2), article number: e00363-21. (10.1128/MCB.00363-21)
2020
- Fromont, C. et al. 2020. Discovery of highly selective inhibitors of calmodulin-dependent kinases that restore insulin sensitivity in the diet-induced obese in vivo mouse model. Journal of Medicinal Chemistry 63(13), pp. 6784-6801. (10.1021/acs.jmedchem.9b01803)
2019
- Radhi, O. A. et al. 2019. Inhibition of the ULK1 protein complex suppresses Staphylococcus-induced autophagy and cell death. Journal of Biological Chemistry 294(39), pp. 14289-14307. (10.1074/jbc.RA119.008923)
2018
- Pariollaud, M. et al. 2018. Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation. Journal of Clinical Investigation 128(6), pp. 2281-2296. (10.1172/JCI93910)
- Frei, P., Jones, D. H., Kay, S. T., McLellan, J. A., Johnston, B. F., Kennedy, A. R. and Tomkinson, N. C. O. 2018. Regioselective reaction of heterocyclic N-oxides, an acyl chloride, and cyclic thioethers. Journal of Organic Chemistry 83(3), pp. 1510-1517. (10.1021/acs.joc.7b02457)
2017
- Jones, D. H., Kay, S. T., McLellan, J. A., Kennedy, A. R. and Tomkinson, N. C. O. 2017. Regioselective three-component reaction of pyridine N-oxides, acyl chlorides, and cyclic ethers. Organic Letters 19(13), pp. 3512-3515. (10.1021/acs.orglett.7b01481)
2016
- Jones, D. H., Tellam, J., Bresciani, S., Wojno-Picon, J., Cooper, A. and Tomkinson, N. 2016. Preparation of symmetrical and nonsymmetrical fluorene sulfonamide scaffolds. SYNLETT 28(5), pp. 577-582. (10.1055/s-0036-1588916)
- Saleh, B. A., Smith, K., Elliott, M. C., Jones, D. H., Kariuki, B. M. and El Hiti, G. A. 2016. Reactions of organoboranes with carbanions bearing three potential leaving groups: unusual processes, products and mechanisms. Tetrahedron 72(44), pp. 6914-6928. (10.1016/j.tet.2016.09.005)
- Dragan, A., Jones, D. H., Kennedy, A. R. and Tomkinson, N. C. O. 2016. Stereoselective synthesis of alkylidene phthalides. Organic Letters 18(13), pp. 3086-3089. (10.1021/acs.orglett.6b01203)
- Jones, D. H., Bresciani, S., Tellam, J. P., Wojno, J., Cooper, A. W. J., Kennedy, A. R. and Tomkinson, N. C. O. 2016. Synthesis of dibenzylamino-1-methylcyclohexanol and dibenzylamino-1-trifluoromethylcyclohexanol isomers. Organic and Biomolecular Chemistry 14(1), pp. 172-182. (10.1039/C5OB01924A)
2015
- Jones, D. H., Smith, K., Elliott, M. C. and El-Hiti, G. A. 2015. Factors affecting reactions of trialkylcyanoborates with imidoyl chlorides/trifluoroacetic anhydride. Tetrahedron 71(36), pp. 6285-6289. (10.1016/j.tet.2015.06.038)
2014
- El-Hiti, G. A., Smith, K., Hegazy, A. S., Jones, D. H. and Kariuki, B. 2014. 2-Ethyl-3-[(R)-2-phenylbutanamido]quinazolin-4(3H)-one monohydrate. Acta Crystallographica Section E - Structure Reports Online 70(4), article number: o467. (10.1107/S1600536814005996)
- Elliott, M. C. and Jones, D. H. 2014. [4 + 2] Cycloaddition as the key step. In: Muller, T. J. J. ed. Multicomponent Reactions 2. Reactions Involving an a,b-Unsaturated Carbonyl Compound as Electrophilic Component, Cycloadditions, and Boron-, Silicon-, Free-Radical-, and Metal-Mediated Reactions. Düsseldorf: Thieme, pp. 243-286.
2013
- El-Hiti, G. A., Smith, K., Elliott, M. C., Jones, D. H. and Kariuki, B. 2013. (E)-2-(1,1-Dicyclohexyl-3-phenylallyl)-5,5-dimethyl-1,3,2-dioxaborinane. Acta Crystallographica Section E - Structure Reports Online 69(9), article number: o1403. (10.1107/S1600536813021739)
- El-Hiti, G. A., Smith, K., Jones, D. H., Masmali, A. and Kariuki, B. M. 2013. (Z)-N-(2,6-Diisopropylphenyl)-4-nitrobenzimidoyl chloride. Acta Crystallographica Section E 69(9), article number: o1384. (10.1107/S1600536813020862)
- Jones, D. H. 2013. Approaches to quaternary carbon centres using organoboron chemistry. PhD Thesis, Cardiff University.
- Elliott, M. C., Smith, K., Jones, D. H., Hussain, A. and Saleh, B. A. 2013. Factors affecting migration of tertiary alkyl groups in reactions of alkylboronic esters with bromomethyllithium. The Journal of Organic Chemistry 78(7), pp. 3057-3064. (10.1021/jo4000459)
- Smith, K., Elliott, M. C. and Jones, D. H. 2013. 3-Chloro-1-lithiopropene - a functional organolithium reagent - and its reactions with alkylboronates to give 3-Alkylprop-1-en-3-ols. Journal of Organic Chemistry 78(18), pp. 9526-9531. (10.1021/jo4018028)
Articles
- Thomas, B., Lewis, L., Jones, D. and Ward, S. 2023. Central nervous system targeted protein degraders. Biomolecules 13(8), article number: 1164. (10.3390/biom13081164)
- Davies, M., Riseley, R., Jones, D. H. and Waller-Evans, H. 2023. Acid ceramidase inhibition as a mechanism to treat lysosomal disorders. Molecular Genetics and Metabolism 138(2), article number: 107069. (10.1016/j.ymgme.2022.107069)
- Collins, R. et al. 2022. Comparative analysis of small-molecule limk1/2 inhibitors: chemical synthesis, biochemistry, and cellular activity. Journal of Medicinal Chemistry (10.1021/acs.jmedchem.2c00751)
- Romartinez-Alonso, B. et al. 2022. Structure-guided approach to relieving transcriptional repression inResistance to Thyroid Hormone α. Molecular and Cellular Biology 42(2), article number: e00363-21. (10.1128/MCB.00363-21)
- Fromont, C. et al. 2020. Discovery of highly selective inhibitors of calmodulin-dependent kinases that restore insulin sensitivity in the diet-induced obese in vivo mouse model. Journal of Medicinal Chemistry 63(13), pp. 6784-6801. (10.1021/acs.jmedchem.9b01803)
- Radhi, O. A. et al. 2019. Inhibition of the ULK1 protein complex suppresses Staphylococcus-induced autophagy and cell death. Journal of Biological Chemistry 294(39), pp. 14289-14307. (10.1074/jbc.RA119.008923)
- Pariollaud, M. et al. 2018. Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation. Journal of Clinical Investigation 128(6), pp. 2281-2296. (10.1172/JCI93910)
- Frei, P., Jones, D. H., Kay, S. T., McLellan, J. A., Johnston, B. F., Kennedy, A. R. and Tomkinson, N. C. O. 2018. Regioselective reaction of heterocyclic N-oxides, an acyl chloride, and cyclic thioethers. Journal of Organic Chemistry 83(3), pp. 1510-1517. (10.1021/acs.joc.7b02457)
- Jones, D. H., Kay, S. T., McLellan, J. A., Kennedy, A. R. and Tomkinson, N. C. O. 2017. Regioselective three-component reaction of pyridine N-oxides, acyl chlorides, and cyclic ethers. Organic Letters 19(13), pp. 3512-3515. (10.1021/acs.orglett.7b01481)
- Jones, D. H., Tellam, J., Bresciani, S., Wojno-Picon, J., Cooper, A. and Tomkinson, N. 2016. Preparation of symmetrical and nonsymmetrical fluorene sulfonamide scaffolds. SYNLETT 28(5), pp. 577-582. (10.1055/s-0036-1588916)
- Saleh, B. A., Smith, K., Elliott, M. C., Jones, D. H., Kariuki, B. M. and El Hiti, G. A. 2016. Reactions of organoboranes with carbanions bearing three potential leaving groups: unusual processes, products and mechanisms. Tetrahedron 72(44), pp. 6914-6928. (10.1016/j.tet.2016.09.005)
- Dragan, A., Jones, D. H., Kennedy, A. R. and Tomkinson, N. C. O. 2016. Stereoselective synthesis of alkylidene phthalides. Organic Letters 18(13), pp. 3086-3089. (10.1021/acs.orglett.6b01203)
- Jones, D. H., Bresciani, S., Tellam, J. P., Wojno, J., Cooper, A. W. J., Kennedy, A. R. and Tomkinson, N. C. O. 2016. Synthesis of dibenzylamino-1-methylcyclohexanol and dibenzylamino-1-trifluoromethylcyclohexanol isomers. Organic and Biomolecular Chemistry 14(1), pp. 172-182. (10.1039/C5OB01924A)
- Jones, D. H., Smith, K., Elliott, M. C. and El-Hiti, G. A. 2015. Factors affecting reactions of trialkylcyanoborates with imidoyl chlorides/trifluoroacetic anhydride. Tetrahedron 71(36), pp. 6285-6289. (10.1016/j.tet.2015.06.038)
- El-Hiti, G. A., Smith, K., Hegazy, A. S., Jones, D. H. and Kariuki, B. 2014. 2-Ethyl-3-[(R)-2-phenylbutanamido]quinazolin-4(3H)-one monohydrate. Acta Crystallographica Section E - Structure Reports Online 70(4), article number: o467. (10.1107/S1600536814005996)
- El-Hiti, G. A., Smith, K., Elliott, M. C., Jones, D. H. and Kariuki, B. 2013. (E)-2-(1,1-Dicyclohexyl-3-phenylallyl)-5,5-dimethyl-1,3,2-dioxaborinane. Acta Crystallographica Section E - Structure Reports Online 69(9), article number: o1403. (10.1107/S1600536813021739)
- El-Hiti, G. A., Smith, K., Jones, D. H., Masmali, A. and Kariuki, B. M. 2013. (Z)-N-(2,6-Diisopropylphenyl)-4-nitrobenzimidoyl chloride. Acta Crystallographica Section E 69(9), article number: o1384. (10.1107/S1600536813020862)
- Elliott, M. C., Smith, K., Jones, D. H., Hussain, A. and Saleh, B. A. 2013. Factors affecting migration of tertiary alkyl groups in reactions of alkylboronic esters with bromomethyllithium. The Journal of Organic Chemistry 78(7), pp. 3057-3064. (10.1021/jo4000459)
- Smith, K., Elliott, M. C. and Jones, D. H. 2013. 3-Chloro-1-lithiopropene - a functional organolithium reagent - and its reactions with alkylboronates to give 3-Alkylprop-1-en-3-ols. Journal of Organic Chemistry 78(18), pp. 9526-9531. (10.1021/jo4018028)
Book sections
- Elliott, M. C. and Jones, D. H. 2014. [4 + 2] Cycloaddition as the key step. In: Muller, T. J. J. ed. Multicomponent Reactions 2. Reactions Involving an a,b-Unsaturated Carbonyl Compound as Electrophilic Component, Cycloadditions, and Boron-, Silicon-, Free-Radical-, and Metal-Mediated Reactions. Düsseldorf: Thieme, pp. 243-286.
Thesis
- Jones, D. H. 2013. Approaches to quaternary carbon centres using organoboron chemistry. PhD Thesis, Cardiff University.
Research
Current and past projects that I am/have been involved in within the MDI:
- Investigation of GABA receptor subtype-selective small molecules as a potential treatment for the cognitive impairment that accompanies Huntington’s disease (funded by the Wellcome Trust).
- Research into a small molecule target that may deliver a treatment option for Fragile X Syndrome (funded by the MRC).
- A Coleg Cymraeg Cenedlaethol (CCC)-funded project to look at an innovative method of treatment for prion diseases.
- A Cardiff University seedcorn-funded proof of concept project to research whether activation of a lysosomal target could be used as an alternative treatment for prion diseases.
- Lead chemist on a project aiming to develop a treatment for a Lysosomal Storage Disorder.
- Lead applicant on Wellcome Trust iTPA award 'Commercialising novel prodrugs of miglustat for treating lysosomal storage and neurodegenerative diseases'.
Prosiectau rwyf yn/wedi bod yn ymwneud â hwy o fewn y SDM:
- Ymchwil i mewn i folecylau bychain sydd â detholusrwydd ar draws is-fathau o dderbynyddion GABA ar gyfer triniaeth bosib i ddirywiad deallusol sydd yn gysylltuedig â chlefyd Huntington (ariannwyd gan y Wellcome Trust).
- Ymchwil i mewn i darged molecylau bychain a allai olygu opsiwn am driniaeth i Syndrom Fragile X (ariannwyd gan yr MRC).
- Prosiect wedi’i ariannu gan y Coleg Cymraeg Cenedlaethol (CCC) i edrych ar ddull arloesol o drin afiechydon prion.
- Prosiect wedi’i ariannu gan Brifysgol Caerdydd i ymchwilio a allai actifeiddio targed leisosomal arwain at driniaeth amgen ar gyfer afiechydon prion.
- Prif gemegydd ar brosiect i geisio datblygu triniaeth ar gyfer Clefyd Storio Leisosomal.
- Prif ymchwilydd ar wobr Wellcome Trust iTPA award 'Commercialising novel prodrugs of miglustat for treating lysosomal storage and neurodegenerative diseases'.
Patents
(1) 'Compounds’, Application number 2201949.1, filed 15/02/2022 (GABA alpha 5 negative allosteric modulators).
(2) ‘Compounds’, Application number 2106385.4, filed 5/05/2021 (GABA alpha 5 negative allosteric modulators).
(3) CaMK1D Kinase Inhibitors with reversed tail structure, P. Fischer, C. Fromont, B. Stevenson, S. Butterworth, G. Iacobini, G. Greco, M. Garzon-Sanz, H. Jones, D. Kaur, PCT/GB2020/052423, 2020.
(4) Kinase Inhibitors, P. Fischer, C. Fromont, B. Stevenson, S. Butterworth, G. Iacobini, G. Greco, M. Garzon-Sanz, H. Jones, D. Kaur, WO2019220101, 2019.
Teaching
Lecturer on the following courses:
CH5103 - Foundations of Organic Chemistry
CH5108 - Introduction to University Chemistry
CH5110 - Year 1 Chemistry Foundation Practical
I contribute to the following courses:
CH5203 - Further Organic and Biological Chemistry
CH5206 - Communicating Chemistry: Key skills for chemists
CH5207 - Introduction to the chemistry of life
CH3325 - Final year project
CH3401 - Final year project
Darlithydd ar gyfer:
CH5103 - Cemeg Organig Sylfaenol
CH5108 - Introduction to University Chemistry
CH5110 - Year 1 Chemistry Foundation Practical
Rwy'n cymryd rhan yn y modiwlau canlynol:
CH5203 - Cemeg organig a biolegol pellhach
CH5206 - Cyfathrebu Cemeg: Sgiliau hanfodol i cemegwyr
CH5207 - Cyflwyniad i cemeg bywyd
CH3325 - Prosiect blwyddyn olaf
CH3401 - Prosiect blwyddyn olaf
Biography
My undergraduate studies (MChem) were carried out at Cardiff University. Along with my final year project on the generation of quaternary carbon centres using novel organoboron chemistry (Prof. Keith Smith), I was given the opportunity by the Cardiff Undergraduate Research Opportunities Programme (CUROP) to work on the synthesis of dorsomorphin (Prof. Mark Bagley). I continued my research under the supervision of Prof. Keith Smith in collaboration with Dr Mark Elliot at Cardiff University, working on the cyanidation, DCME, 1-lithio-3-chloropropene and bromomethyl lithium organoboron reactions. Following completion of the PhD, I spent just over three years at the University of Strathclyde with Prof. Nick Tomkinson’s research group, working on two main projects: small molecule modulation of REV-ERBα/RORα nuclear receptors and small molecule promoted proliferation of liver progenitor cells (UK stem cell hub). I was also involved in a number of additional medicinal chemistry and organic chemistry projects. In 2016, I moved to the University of Manchester to work with Dr. Sam Butterworth on a multi-collaborative drug discovery project, to develop novel inhibitors of the calmodulin-dependent kinases. Following this, I started my current position at the newly-formed Medicines Discovery Institute (MDI) at Cardiff University in 2018, where I have been working on several CNS drug discovery targets.
Cyflewnais fy astudiaethau israddedig (MChem) ym Mhrifysgol Caerdydd. Yn ogystal â fy mhrosiect blwyddyn olaf ar greu atomau carbon cwaternaidd gan ddefnyddio cemeg organoboron (yr Athro Keith Smith), cefais y cyfle gan Raglen Cyfleoedd Ymchwil Israddedig Caerdydd (CUROP) i weithio ar syntheseiddio dorsomorphin (yr Athro Mark Bagley). Parheais fy ymchwil dan oruchwyliad yr Athro Keith Smith gan gydweithio â Dr Mark Elliot ym Mhrifysgol Caerdydd, drwy weithio ar yr adweithiau organoboron cyanideiddio, DCME, 1-lithio-3-cloropropin a bromomethyl lithiwm. Yn dilyn cwblhad y ddoethuriaeth, treuliais fymryn dros dair blynedd ym Mhrifysgol Ystrad Clud gyda grŵp ymchwil yr Athro Nick Tomkinson yn gweithio ar ddau brif brosiect: modiwleiddio derbynyddion niwclear REV-ERBα/RORα a hybu tyfiant celloedd bôn yr afu drwy ddefnyddio molecylau bychain (hwb celloedd bôn y DU). Yn ogystal, roeddwn yn rhan o sawl prosiect cemeg organig a chemeg feddyginiaethol ychwanegol. Yn 2016, symudais i Brifysgol Manceinion i weithio gyda Dr Sam Butterworth ar brosiect darganfod meddyginiaethau aml-gydweithredol i ddatblygu atalyddion nofel i’r cinasau sy’n ddibynnol ar galmodwlin. Yn dilyn hyn, dechreuais fy swydd gyfredol yn y Sefydliad Darganfod Meddyginiaethau (SDM) ym Mhrifysgol Caerdydd yn 2018, lle rwyf wedi bod yn gweithio ar sawl targed ymchwil darganfod feddyginiaethol o fewn y System Nerfol Ganolog (SNG).
Supervisions
Position currently available for summer internship on:
Removing toxic levels of Zn2+; a potential therapy for Lysosomal Storage Disorders
Safle ar gael dros yr hâf:
Gwaredu ar lefelau tocsig o Zn2+; therapi arloesol ar gyfer Clefydau Storio Lysosomal