CarloBallatore 185x245Associate Professor, UCSD

Skaggs School of Pharmacy and Pharmaceutical Sciences

Drug Discovery, MedicinalChemistry 

Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

Follow me: https://pharmacy.ucsd.edu/faculty/bios/ballatore.shtml

Dr. Ballatore’s laboratory specializes in the design and synthesis of small molecules as research tools or candidate therapeutics for a variety of human diseases. These activities, which typically involve Structure Activity and Structure Property Relationship (SAR/SPR) studies, are often directed towards the identification and development of probes suitable for mode of action studies, as well as candidate compounds optimized for pharmacokinetic and pharmacodynamic properties that could enable in vivo proof-of-concept studies or preclinical evaluation of efficacy and safety.

In collaboration with the CDIPD members, Dr. Ballatore’s laboratory is exploring the utility of brain-penetrant microtubule-stabilizing small molecules as potential therapeutics against parasites that affect the central nervous system (CNS).

PUBLICATIONS

Non-Naturally Occurring Small Molecule Microtubule-Stabilizing Agents: A Potential Tactic for CNS-Directed Therapies. ACS Chem Neurosci. 2017 Jan 18;8(1):5-7. doi: 10.1021/acschemneuro.6b00384. Review. Ballatore C, Brunden KR, Trojanowski JQ, Lee VM, Smith AB 3rd.

Altered microtubule dynamics in neurodegenerative disease: Therapeutic potential of microtubule-stabilizing drugs. Neurobiol Dis. 2016 Dec 22. pii: S0969-9961(16)30302-3. doi: 10.1016/j.nbd.2016.12.021. [Epub ahead of print] Brunden KR, Lee VM, Smith AB 3rd, Trojanowski JQ, Ballatore C.

Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in the PS19 tau transgenic mouse model of tauopathy. Acta Neuropathol Commun. 2016 Sep 29;4(1):106. Makani V, Zhang B, Han H, Yao Y, Lassalas P, Lou K, Paterson I, Lee VM, Trojanowski JQ, Ballatore C, Smith AB 3rd, Brunden KR.

Characterization of Brain-Penetrant Pyrimidine-Containing Molecules with Differential Microtubule-Stabilizing Activities Developed as Potential Therapeutic Agents for Alzheimer's Disease and Related Tauopathies. J Pharmacol Exp Ther. 2016 May;357(2):432-50. doi: 10.1124/jpet.115.231175. Kovalevich J, Cornec AS, Yao Y, James M, Crowe A, Lee VM, Trojanowski JQ, Smith AB 3rd, Ballatore C, Brunden KR.

Structure Property Relationships of Carboxylic Acid Isosteres. J Med Chem. 2016 Apr 14;59(7):3183-203. doi: 10.1021/acs.jmedchem.5b01963. Lassalas P, Gay B, Lasfargeas C, James MJ, Tran V, Vijayendran KG, Brunden KR, Kozlowski MC, Thomas CJ, Smith AB 3rd, Huryn DM, Ballatore C.

Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D. Neuropharmacology. 2016 Jun;105:84-95. doi: 10.1016/j.neuropharm.2016.01.002. Penazzi L, Tackenberg C, Ghori A, Golovyashkina N, Niewidok B, Selle K, Ballatore C, Smith AB 3rd, Bakota L, Brandt R.

Altered microtubule dynamics and vesicular transport in mouse and human MeCP2-deficient astrocytes. Hum Mol Genet. 2016 Jan 1;25(1):146-57. doi: 10.1093/hmg/ddv464. Delépine C, Meziane H, Nectoux J, Opitz M, Smith AB, Ballatore C, Saillour Y, Bennaceur-Griscelli A, Chang Q, Williams EC, Dahan M, Duboin A, Billuart P, Herault Y, Bienvenu T.

Region-specific dendritic simplification induced by Aβ, mediated by tau via dysregulation of microtubule dynamics: a mechanistic distinct event from other neurodegenerative processes. Mol Neurodegener. 2015 Nov 5;10:60. doi: 10.1186/s13024-015-0049-0. Golovyashkina N, Penazzi L, Ballatore C, Smith AB 3rd, Bakota L, Brandt R.

Pharmacokinetic, pharmacodynamic and metabolic characterization of a brain retentive microtubule (MT)-stabilizing triazolopyrimidine. Bioorg Med Chem Lett. 2015 Nov 1;25(21):4980-2. doi: 10.1016/j.bmcl.2015.03.002. Cornec AS, James MJ, Kovalevich J, Trojanowski JQ, Lee VM, Smith AB 3rd, Ballatore C, Brunden KR.

Potent, long-acting cyclopentane-1,3-Dione thromboxane (A2)-receptor antagonists. ACS Med Chem Lett. 2014 Jul 24;5(9):1015-20. doi: 10.1021/ml5002085. Wang X, Liu L, Huang L, Herbst-Robinson K, Cornec AS, James MJ, Sugiyama S, Bassetto M, Brancale A, Trojanowski JQ, Lee VM, Smith AB 3rd, Brunden KR, Ballatore C.

Evaluation of the cyclopentane-1,2-dione as a potential bio-isostere of the carboxylic acid functional group. Bioorg Med Chem Lett. 2014 Sep 1;24(17):4171-5. doi: 10.1016/j.bmcl.2014.07.047. Ballatore C, Gay B, Huang L, Robinson KH, James MJ, Trojanowski JQ, Lee VM, Brunden KR, Smith AB 3rd.

Brain-penetrant, orally bioavailable microtubule-stabilizing small molecules are potential candidate therapeutics for Alzheimer's disease and related tauopathies. J Med Chem. 2014 Jul 24;57(14):6116-27. doi: 10.1021/jm5005623. Lou K, Yao Y, Hoye AT, James MJ, Cornec AS, Hyde E, Gay B, Lee VM, Trojanowski JQ, Smith AB 3rd, Brunden KR, Ballatore C.

MT-Stabilizer, Dictyostatin, Exhibits Prolonged Brain Retention and Activity: Potential Therapeutic Implications. ACS Med Chem Lett. 2013 Jul 23;4(9):886-9. doi: 10.1021/ml400233e. Brunden KR, Gardner NM, James MJ, Yao Y, Trojanowski JQ, Lee VM, Paterson I, Ballatore C, Smith AB 3rd.

Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease. Bioorg Med Chem. 2014 Sep 15;22(18):5040-9. doi: 10.1016/j.bmc.2013.12.046. Review. Brunden KR, Trojanowski JQ, Smith AB 3rd, Lee VM, Ballatore C.

Aminothienopyridazines as imaging probes of tau pathology: a patent evaluation of WO2013090497. Expert Opin Ther Pat. 2014 Mar;24(3):355-60. doi: 10.1517/13543776.2014.871526. Ballatore C, Smith AB 3rd, Lee VM, Trojanowski JQ, Brunden KR.

Design, synthesis, and biological evaluation of 1-phenylpyrazolo[3,4-e]pyrrolo[3,4-g]indolizine-4,6(1H,5H)-diones as new glycogen synthase kinase-3β inhibitors. J Med Chem. 2013 Dec 27;56(24):10066-78. doi: 10.1021/jm401466v. La Pietra V, La Regina G, Coluccia A, Famiglini V, Pelliccia S, Plotkin B, Eldar-Finkelman H, Brancale A, Ballatore C, Crowe A, Brunden KR, Marinelli L, Novellino E, Silvestri R.

Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation. J Biol Chem. 2013 Apr 19;288(16):11024-37. doi: 10.1074/jbc.M112.436006. Crowe A, James MJ, Lee VM, Smith AB 3rd, Trojanowski JQ, Ballatore C, Brunden KR.

Carboxylic acid (bio)isosteres in drug design. ChemMedChem. 2013 Mar;8(3):385-95. doi: 10.1002/cmdc.201200585. Review. Ballatore C, Huryn DM, Smith AB 3rd.

Brain-penetrant tetrahydronaphthalene thromboxane A2-prostanoid (TP) receptor antagonists as prototype therapeutics for Alzheimer's disease. ACS Chem Neurosci. 2012 Nov 21;3(11):928-40. doi: 10.1021/cn3000795. Soper JH, Sugiyama S, Herbst-Robinson K, James MJ, Wang X, Trojanowski JQ, Smith AB 3rd, Lee VM, Ballatore C, Brunden KR.

Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies. J Med Chem. 2012 Nov 8;55(21):8979-96. doi: 10.1021/jm301079z. Review. Ballatore C, Brunden KR, Huryn DM, Trojanowski JQ, Lee VM, Smith AB 3rd.

Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies. Biochem Soc Trans. 2012 Aug;40(4):661-6. doi: 10.1042/BST20120010. Review. Brunden KR, Ballatore C, Lee VM, Smith AB 3rd, Trojanowski JQ.

Aminothienopyridazine inhibitors of tau aggregation: evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties. Bioorg Med Chem. 2012 Jul 15;20(14):4451-61. doi: 10.1016/j.bmc.2012.05.027. Ballatore C, Crowe A, Piscitelli F, James M, Lou K, Rossidivito G, Yao Y, Trojanowski JQ, Lee VM, Brunden KR, Smith AB 3rd.

The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci. 2012 Mar 14;32(11):3601-11. doi: 10.1523/JNEUROSCI.4922-11.2012. Zhang B, Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak JS, Hogan AM, Xie SX, Ballatore C, Smith AB 3rd, Lee VM, Brunden KR.

Cyclopentane-1,3-dione: a novel isostere for the carboxylic acid functional group. Application to the design of potent thromboxane (A2) receptor antagonists. J Med Chem. 2011 Oct 13;54(19):6969-83. doi: 10.1021/jm200980u. Ballatore C, Soper JH, Piscitelli F, James M, Huang L, Atasoylu O, Huryn DM, Trojanowski JQ, Lee VM, Brunden KR, Smith AB.

High Throughput Screening for Small Molecule Inhibitors of Heparin-induced Tau Fibril Formation. 2009 May 18 [updated 2010 Sep 2]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Johnson RL, Huang W, Huang R, Crowe A, Ballatore C, Trojanowski JQ, Brunden KR, Lee VMY.

Modulation of protein-protein interactions as a therapeutic strategy for the treatment of neurodegenerative tauopathies. Curr Top Med Chem. 2011;11(3):317-30. Review. Ballatore C, Brunden KR, Trojanowski JQ, Lee VM, Smith AB 3rd, Huryn DM.

The characterization of microtubule-stabilizing drugs as possible therapeutic agents for Alzheimer's disease and related tauopathies. Pharmacol Res. 2011 Apr;63(4):341-51. doi: 10.1016/j.phrs.2010.12.002. Brunden KR, Yao Y, Potuzak JS, Ferrer NI, Ballatore C, James MJ, Hogan AM, Trojanowski JQ, Smith AB 3rd, Lee VM.

Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci. 2010 Oct 13;30(41):13861-6. doi: 10.1523/JNEUROSCI.3059-10.2010. Brunden KR, Zhang B, Carroll J, Yao Y, Potuzak JS, Hogan AM, Iba M, James MJ, Xie SX, Ballatore C, Smith AB 3rd, Lee VM, Trojanowski JQ.

Discovery of brain-penetrant, orally bioavailable aminothienopyridazine inhibitors of tau aggregation. J Med Chem. 2010 May 13;53(9):3739-47. doi: 10.1021/jm100138f. Ballatore C, Brunden KR, Piscitelli F, James MJ, Crowe A, Yao Y, Hyde E, Trojanowski JQ, Lee VM, Smith AB 3rd.

Solid phase synthesis of 2-aminobenzothiazoles. Bioorg Med Chem Lett. 2010 Jan 15;20(2):644-8. doi: 10.1016/j.bmcl.2009.11.055. Piscitelli F, Ballatore C, Smith AB 3rd.

Tau-directed drug discovery for Alzheimer's disease and related tauopathies: a focus on tau assembly inhibitors. Exp Neurol. 2010 Jun;223(2):304-10. doi: 10.1016/j.expneurol.2009.08.031. Review. Brunden KR, Ballatore C, Crowe A, Smith AB 3rd, Lee VM, Trojanowski JQ.

Identification of aminothienopyridazine inhibitors of tau assembly by quantitative high-throughput screening. Biochemistry. 2009 Aug 18;48(32):7732-45. doi: 10.1021/bi9006435. Crowe A, Huang W, Ballatore C, Johnson RL, Hogan AM, Huang R, Wichterman J, McCoy J, Huryn D, Auld DS, Smith AB 3rd, Inglese J, Trojanowski JQ, Austin CP, Brunden KR, Lee VM.

In situ blood-brain barrier permeability of a C-10 paclitaxel carbamate. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6119-21. doi: 10.1016/j.bmcl.2008.10.024. Ballatore C, Zhang B, Trojanowski JQ, Lee VM, Smith AB 3rd.

Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci. 2007 Sep;8(9):663-72. Review. Ballatore C, Lee VM, Trojanowski JQ.

Paclitaxel C-10 carbamates: potential candidates for the treatment of neurodegenerative tauopathies. Bioorg Med Chem Lett. 2007 Jul 1;17(13):3642-6. Ballatore C, Hyde E, Deiches RF, Lee VM, Trojanowski JQ, Huryn D, Smith AB 3rd.

High throughput screening for small molecule inhibitors of heparin-induced tau fibril formation. Biochem Biophys Res Commun. 2007 Jun 22;358(1):1-6. Crowe A, Ballatore C, Hyde E, Trojanowski JQ, Lee VM.

Targeting heat shock proteins on cancer cells: selection, characterization, and cell-penetrating properties of a peptidic GRP78 ligand. Biochemistry. 2006 Aug 8;45(31):9434-44. Kim Y, Lillo AM, Steiniger SC, Liu Y, Ballatore C, Anichini A, Mortarini R, Kaufmann GF, Zhou B, Felding-Habermann B, Janda KD.

Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5194-8. Aspland SE, Ballatore C, Castillo R, Desharnais J, Eustaquio T, Goelet P, Guo Z, Li Q, Nelson D, Sun C, Castellino AJ, Newman MJ.

The design, synthesis, and evaluation of two universal doxorubicin-linkers: preparation of conjugates that retain topoisomerase II activity. Bioorg Med Chem Lett. 2006 Jan 1;16(1):104-7. Sun C, Aspland SE, Ballatore C, Castillo R, Smith AB 3rd, Castellino AJ.

A facile route to paclitaxel C-10 carbamates. Bioorg Med Chem Lett. 2005 May 16;15(10):2477-80. Ballatore C, Aspland SE, Castillo R, Desharnais J, Eustaquio T, Sun C, Castellino AJ, Smith AB 3rd.

Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA. Bioorg Med Chem Lett. 2001 Apr 23;11(8):1053-6. Ballatore C, McGuigan C, De Clercq E, Balzarini J.

Phosphoramidate derivatives of stavudine as inhibitors of HIV: unnatural amino acids may substitute for alanine. Antivir Chem Chemother. 2000 Mar;11(2):111-6. McGuigan C, Bidois L, Hiouni A, Ballatore C, De Clercq E, Balzarini J.

Enhancing the aqueous solubility of d4T-based phosphoramidate prodrugs. Bioorg Med Chem Lett. 2000 Feb 21;10(4):381-4. Siddiqui A, McGuigan C, Ballatore C, Srinivasan S, De Clercq E, Balzarini J.

Design and synthesis of lipophilic phosphoramidate d4T-MP prodrugs expressing high potency against HIV in cell culture: structural determinants for in vitro activity and QSAR. J Med Chem. 1999 Oct 7;42(20):4122-8. Siddiqui AQ, McGuigan C, Ballatore C, Zuccotto F, Gilbert IH, De Clercq E, Balzarini J.

Simple mono-derivatisation of the aryl moiety of D4A and DDA-based phosphoramidate prodrugs significantly enhances their anti-HIV potency in cell culture. Bioorg Med Chem Lett. 1999 Sep 6;9(17):2555-60. Siddiqui AQ, McGuigan C, Ballatore C, Wedgwood O, De Clercq E, Balzarini J.

An in situ pig liver esterase assay as a useful predictive tool for the likely in vitro anti viral activity of phosphoramidate pro-drugs. Nucleosides Nucleotides. 1999 Apr-May;18(4-5):967-9. Ballatore C, McGuigan C, De Clercq E, Balzarini J.

The presence of substituents on the aryl moiety of the aryl phosphoramidate derivative of d4T enhances anti-HIV efficacy in cell culture: A structure-activity relationship. J Med Chem. 1999 Feb 11;42(3):393-9. Siddiqui AQ, Ballatore C, McGuigan C, De Clercq E, Balzarini J.

Lactate cannot substitute for alanine in d4T-based anti-HIV nucleotide prodrugs--despite efficient esterase-mediated hydrolysis. Bioorg Med Chem Lett. 1998 Nov 3;8(21):2949-54. McGuigan C, Cahard D, Ballatore C, Siddiqui A, De Clercq E, Balzarini J.