Mitochondrial and cytosolic one-carbon metabolism is a targetable metabolic vulnerability in cisplatin-resistant ovarian cancer.
Mol Cancer Ther.
2024 Feb 20;. doi: 10.1158/1535-7163.MCT-23-0550. [Epub ahead of print] PubMed PMID:
38377173; NIHMSID:NIHMS1970022.
Structural Characterization of 5-Substituted Pyrrolo[3,2-d]pyrimidine Antifolate Inhibitors in Complex with Human Serine Hydroxymethyl Transferase 2.
Biochemistry.
2024 Feb 7;. doi: 10.1021/acs.biochem.3c00613. [Epub ahead of print] PubMed PMID:
38324671; NIHMSID:NIHMS1977339.
Part II: After you accept that faculty position ….
CNS Neurosci Ther.
2023 Nov;29(11):3118-3120. doi: 10.1111/cns.14390. Epub 2023 Aug 7. PubMed PMID:
37545431; PubMed Central PMCID:
PMC10580361.
The variance in phosphorylated, insoluble ⍺-synuclein in humans, rats, and mice is not mainly driven by biological sex.
Acta Neuropathol.
2023 Oct;146(4):651-654. doi: 10.1007/s00401-023-02621-w. Epub 2023 Aug 11. PubMed PMID:
37568067; PubMed Central PMCID:
PMC10576607.
Part I: Before you apply for that faculty position ….
CNS Neurosci Ther.
2023 Sep;29(9):2393-2396. doi: 10.1111/cns.14359. Epub 2023 Jul 14. PubMed PMID:
37452473; PubMed Central PMCID:
PMC10401177.
Structure-Based Design of Transport-Specific Multitargeted One-Carbon Metabolism Inhibitors in Cytosol and Mitochondria.
J Med Chem.
2023 Aug 24;66(16):11294-11323. doi: 10.1021/acs.jmedchem.3c00763. Epub 2023 Aug 15. PubMed PMID:
37582241; PubMed Central PMCID:
PMC10461232.
A 14-day pulse of PLX5622 modifies α-synucleinopathy in preformed fibril-infused aged mice of both sexes.
Neurobiol Dis.
2023 Aug;184:106196. doi: 10.1016/j.nbd.2023.106196. Epub 2023 Jun 12. PubMed PMID:
37315905; PubMed Central PMCID:
PMC10528721.
Multitargeted 6-Substituted Thieno[2,3-d]pyrimidines as Folate Receptor-Selective Anticancer Agents that Inhibit Cytosolic and Mitochondrial One-Carbon Metabolism.
ACS Pharmacol Transl Sci.
2023 May 12;6(5):748-770. doi: 10.1021/acsptsci.3c00020. eCollection 2023 May 12. PubMed PMID:
37200803; PubMed Central PMCID:
PMC10186366.
Simple monocyclic pyrimidine analogs as microtubule targeting agents binding to the colchicine site.
Bioorg Med Chem.
2023 Mar 15;82:117217. doi: 10.1016/j.bmc.2023.117217. Epub 2023 Feb 24. PubMed PMID:
36889150; PubMed Central PMCID:
PMC10084637.
Correction: Novel Pyrrolo[3,2-d]Pyrimidine Compounds Target Mitochondrial and Cytosolic One-Carbon Metabolism with Broad-spectrum Antitumor Efficacy.
Mol Cancer Ther.
2023 Feb 1;22(2):287. doi: 10.1158/1535-7163.MCT-22-0766. PubMed PMID:
36602953.
Folate transporter offers clues for anticancer drugs.
Nature.
2022 Dec;612(7938):39-41. doi: 10.1038/d41586-022-03767-5. PubMed PMID:
36418878; PubMed Central PMCID:
PMC9940820.
Biology and therapeutic applications of the proton-coupled folate transporter.
Expert Opin Drug Metab Toxicol.
2022 Oct;18(10):695-706. doi: 10.1080/17425255.2022.2136071. Epub 2022 Oct 20. PubMed PMID:
36239195; PubMed Central PMCID:
PMC9637735.
Targeted therapy of pyrrolo[2,3-d]pyrimidine antifolates in a syngeneic mouse model of high grade serous ovarian cancer and the impact on the tumor microenvironment.
Sci Rep.
2022 Jul 5;12(1):11346. doi: 10.1038/s41598-022-14788-5. PubMed PMID:
35790779; PubMed Central PMCID:
PMC9256750.
The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism.
FASEB J.
2022 Feb;36(2):e22164. doi: 10.1096/fj.202101704R. Review. PubMed PMID:
35061292; PubMed Central PMCID:
PMC8978580.
Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents.
Molecules.
2022 Jan 5;27(1). doi: 10.3390/molecules27010321. PubMed PMID:
35011550; PubMed Central PMCID:
PMC8747035.
Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer.
Cancers (Basel).
2021 Dec 31;14(1). doi: 10.3390/cancers14010191. Review. PubMed PMID:
35008360; PubMed Central PMCID:
PMC8750473.
Novel pyrazolo[4,3-d]pyrimidine microtubule targeting agents (MTAs): Synthesis, structure-activity relationship, in vitro and in vivo evaluation as antitumor agents.
Bioorg Med Chem Lett.
2021 Jun 1;41:127923. doi: 10.1016/j.bmcl.2021.127923. Epub 2021 Mar 9. PubMed PMID:
33705908; PubMed Central PMCID:
PMC8113149.
Discovery of 6-substituted thieno[2,3-d]pyrimidine analogs as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis in folate receptor expressing human tumors.
Bioorg Med Chem.
2021 May 1;37:116093. doi: 10.1016/j.bmc.2021.116093. Epub 2021 Feb 26. PubMed PMID:
33773393; PubMed Central PMCID:
PMC8058616.
Potential of substituted quinazolines to interact with multiple targets in the treatment of cancer.
Bioorg Med Chem.
2021 Apr 1;35:116061. doi: 10.1016/j.bmc.2021.116061. Epub 2021 Feb 12. PubMed PMID:
33647840; PubMed Central PMCID:
PMC7995636.
Folate transporter dynamics and therapy with classic and tumor-targeted antifolates.
Sci Rep.
2021 Mar 18;11(1):6389. doi: 10.1038/s41598-021-85818-x. PubMed PMID:
33737637; PubMed Central PMCID:
PMC7973545.
The 3-D conformational shape of N-naphthyl-cyclopenta[d]pyrimidines affects their potency as microtubule targeting agents and their antitumor activity.
Bioorg Med Chem.
2021 Jan 1;29:115887. doi: 10.1016/j.bmc.2020.115887. Epub 2020 Nov 24. PubMed PMID:
33310545; PubMed Central PMCID:
PMC7875120.
Therapeutic Targeting of Mitochondrial One-Carbon Metabolism in Cancer.
Mol Cancer Ther.
2020 Nov;19(11):2245-2255. doi: 10.1158/1535-7163.MCT-20-0423. Epub 2020 Sep 2. Review. PubMed PMID:
32879053; PubMed Central PMCID:
PMC7921203.
Design, synthesis and biological evaluation of novel pyrrolo[2,3-d]pyrimidine as tumor-targeting agents with selectivity for tumor uptake by high affinity folate receptors over the reduced folate carrier.
Bioorg Med Chem.
2020 Jun 15;28(12):115544. doi: 10.1016/j.bmc.2020.115544. Epub 2020 May 6. PubMed PMID:
32503687; PubMed Central PMCID:
PMC7327796.
Cellular Pharmacodynamics of a Novel Pyrrolo[3,2-d]pyrimidine Inhibitor Targeting Mitochondrial and Cytosolic One-Carbon Metabolism.
Mol Pharmacol.
2020 Jan;97(1):9-22. doi: 10.1124/mol.119.117937. Epub 2019 Nov 9. PubMed PMID:
31707355; PubMed Central PMCID:
PMC6877291.
Discovery of amide-bridged pyrrolo[2,3-d]pyrimidines as tumor targeted classical antifolates with selective uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis.
Bioorg Med Chem.
2019 Dec 1;27(23):115125. doi: 10.1016/j.bmc.2019.115125. Epub 2019 Oct 17. PubMed PMID:
31679978; PubMed Central PMCID:
PMC6857795.
Novel Pyrrolo[3,2-d]pyrimidine Compounds Target Mitochondrial and Cytosolic One-carbon Metabolism with Broad-spectrum Antitumor Efficacy.
Mol Cancer Ther.
2019 Oct;18(10):1787-1799. doi: 10.1158/1535-7163.MCT-19-0037. Epub 2019 Jul 9. PubMed PMID:
31289137; PubMed Central PMCID:
PMC6774887.
Development of substituted pyrido[3,2-d]pyrimidines as potent and selective dihydrofolate reductase inhibitors for pneumocystis pneumonia infection.
Bioorg Med Chem Lett.
2019 Aug 1;29(15):1874-1880. doi: 10.1016/j.bmcl.2019.06.004. Epub 2019 Jun 4. PubMed PMID:
31176699; PubMed Central PMCID:
PMC6588427.
Regulation of differential proton-coupled folate transporter gene expression in human tumors: transactivation by KLF15 with NRF-1 and the role of Sp1.
Biochem J.
2019 Apr 26;476(8):1247-1266. doi: 10.1042/BCJ20180394. PubMed PMID:
30914440; PubMed Central PMCID:
PMC6794195.
Sterically induced conformational restriction: Discovery and preclinical evaluation of novel pyrrolo[3,2-d]pyrimidines as microtubule targeting agents.
Bioorg Med Chem.
2018 Nov 1;26(20):5470-5478. doi: 10.1016/j.bmc.2018.09.025. Epub 2018 Sep 21. PubMed PMID:
30297118; PubMed Central PMCID:
PMC6252143.
Design, synthesis and preclinical evaluation of 5-methyl-N(4)-aryl-furo[2,3-d]pyrimidines as single agents with combination chemotherapy potential.
Bioorg Med Chem Lett.
2018 Oct 1;28(18):3085-3093. doi: 10.1016/j.bmcl.2018.07.039. Epub 2018 Jul 27. PubMed PMID:
30098869.
Targeting species specific amino acid residues: Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors and potential anti-opportunistic infection agents.
Bioorg Med Chem.
2018 May 15;26(9):2640-2650. doi: 10.1016/j.bmc.2018.04.032. Epub 2018 Apr 17. PubMed PMID:
29691153; PubMed Central PMCID:
PMC5967623.
Structure based drug design and in vitro metabolism study: Discovery of N-(4-methylthiophenyl)-N,2-dimethyl-cyclopenta[d]pyrimidine as a potent microtubule targeting agent.
Bioorg Med Chem.
2018 May 15;26(9):2437-2451. doi: 10.1016/j.bmc.2018.04.010. Epub 2018 Apr 4. PubMed PMID:
29655610; PubMed Central PMCID:
PMC5967629.
Fluorine-Substituted Pyrrolo[2,3- d]Pyrimidine Analogues with Tumor Targeting via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.
J Med Chem.
2018 May 10;61(9):4228-4248. doi: 10.1021/acs.jmedchem.8b00408. Epub 2018 Apr 27. PubMed PMID:
29701475; PubMed Central PMCID:
PMC6097718.
Development and validation of chemical features-based proton-coupled folate transporter/activity and reduced folate carrier/activity models (pharmacophores).
J Mol Graph Model.
2018 May;81:125-133. doi: 10.1016/j.jmgm.2018.02.007. Epub 2018 Feb 20. PubMed PMID:
29550744; PubMed Central PMCID:
PMC5959037.
Tumor Targeting with Novel Pyridyl 6-Substituted Pyrrolo[2,3- d]Pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of De Novo Purine Nucleotide Biosynthesis.
J Med Chem.
2018 Mar 8;61(5):2027-2040. doi: 10.1021/acs.jmedchem.7b01708. Epub 2018 Feb 21. PubMed PMID:
29425443; PubMed Central PMCID:
PMC6382392.
The promise and challenges of exploiting the proton-coupled folate transporter for selective therapeutic targeting of cancer.
Cancer Chemother Pharmacol.
2018 Jan;81(1):1-15. doi: 10.1007/s00280-017-3473-8. Epub 2017 Nov 10. Review. PubMed PMID:
29127457; PubMed Central PMCID:
PMC5756103.
AG488 as a therapy against gliomas.
Oncotarget.
2017 Sep 22;8(42):71833-71844. doi: 10.18632/oncotarget.18284. eCollection 2017 Sep 22. PubMed PMID:
29069750; PubMed Central PMCID:
PMC5641093.
Design, synthesis, and structure-activity relationships of pyrimido[4,5-b]indole-4-amines as microtubule depolymerizing agents that are effective against multidrug resistant cells.
Bioorg Med Chem Lett.
2017 Aug 1;27(15):3423-3430. doi: 10.1016/j.bmcl.2017.05.085. Epub 2017 May 27. PubMed PMID:
28610978; PubMed Central PMCID:
PMC5603926.
Dual Targeting of Epithelial Ovarian Cancer Via Folate Receptor α and the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]pyrimidine Antifolates.
Mol Cancer Ther.
2017 May;16(5):819-830. doi: 10.1158/1535-7163.MCT-16-0444. Epub 2017 Jan 30. PubMed PMID:
28138029; PubMed Central PMCID:
PMC5443351.
Synthesis and evaluation of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents.
Bioorg Med Chem Lett.
2017 Apr 1;27(7):1602-1607. doi: 10.1016/j.bmcl.2017.02.018. Epub 2017 Feb 11. PubMed PMID:
28258797; PubMed Central PMCID:
PMC5398096.
AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization.
Cancer Lett.
2017 Mar 1;388:149-157. doi: 10.1016/j.canlet.2016.11.040. Epub 2016 Dec 8. PubMed PMID:
27939695; PubMed Central PMCID:
PMC5318233.
Correction to Structural and Enzymatic Analysis of Tumor-Targeted Antifolates That Inhibit Glycinamide Ribonucleotide Formyltransferase.
Biochemistry.
2017 Feb 21;56(7):1025. doi: 10.1021/acs.biochem.7b00092. Epub 2017 Feb 10. PubMed PMID:
28186409.
Discovery and preclinical evaluation of 7-benzyl-N-(substituted)-pyrrolo[3,2-d]pyrimidin-4-amines as single agents with microtubule targeting effects along with triple-acting angiokinase inhibition as antitumor agents.
Bioorg Med Chem.
2017 Jan 15;25(2):545-556. doi: 10.1016/j.bmc.2016.11.026. Epub 2016 Nov 15. PubMed PMID:
27894589; PubMed Central PMCID:
PMC5191990.
Janus Compounds, 5-Chloro-N⁴-methyl-N⁴-aryl-9H-pyrimido[4,5-b]indole-2,4-diamines, Cause Both Microtubule Depolymerizing and Stabilizing Effects.
Molecules.
2016 Dec 2;21(12). doi: 10.3390/molecules21121661. PubMed PMID:
27918450; PubMed Central PMCID:
PMC5470396.
Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.
J Med Chem.
2016 Sep 8;59(17):7856-76. doi: 10.1021/acs.jmedchem.6b00594. Epub 2016 Aug 26. PubMed PMID:
27458733; PubMed Central PMCID:
PMC5018213.
Structural and Enzymatic Analysis of Tumor-Targeted Antifolates That Inhibit Glycinamide Ribonucleotide Formyltransferase.
Biochemistry.
2016 Aug 16;55(32):4574-82. doi: 10.1021/acs.biochem.6b00412. Epub 2016 Aug 3. PubMed PMID:
27439469; PubMed Central PMCID:
PMC5238714.
Design, Synthesis, and Preclinical Evaluation of 4-Substituted-5-methyl-furo[2,3-d]pyrimidines as Microtubule Targeting Agents That Are Effective against Multidrug Resistant Cancer Cells.
J Med Chem.
2016 Jun 23;59(12):5752-65. doi: 10.1021/acs.jmedchem.6b00237. Epub 2016 Jun 7. PubMed PMID:
27213719; PubMed Central PMCID:
PMC5590101.
Correction to Structure-Activity Profiles of Novel 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Antifolates with Modified Amino Acids for Cellular Uptake by Folate Receptors α and β and the Proton-Coupled Folate Transporter.
J Med Chem.
2016 Apr 28;59(8):4032. doi: 10.1021/acs.jmedchem.6b00502. Epub 2016 Apr 15. PubMed PMID:
27082426; PubMed Central PMCID:
PMC4852313.
Targeting Nonsquamous Nonsmall Cell Lung Cancer via the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]Pyrimidine Thienoyl Antifolates.
Mol Pharmacol.
2016 Apr;89(4):425-34. doi: 10.1124/mol.115.102798. Epub 2016 Feb 2. PubMed PMID:
26837243; PubMed Central PMCID:
PMC4809305.
6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor α and the Proton-Coupled Folate Transporter in Human Tumors.
J Med Chem.
2015 Sep 10;58(17):6938-59. doi: 10.1021/acs.jmedchem.5b00801. Epub 2015 Aug 28. PubMed PMID:
26317331; PubMed Central PMCID:
PMC4714714.
What would you like to do?