Step 4: Hit Validation

  1. Lokesh, G. L., Muralidhara, B. K., Negi, S., Natarajan, A.* “Thermodynamics of phosphopeptide tethering to BRCT: The structural minima for inhibitor design” J. Am. Chem. Soc. 2007, 129(35), 10658-10659. PMID: 17685618.

  2. Joseph, P. B. J., Yuan, Z., Kumar, E. A., Lokesh, G. L., Kizhake, S., Rajarathnam, K., Natarajan, A.* “Structural characterization of BRCT-tetrapeptide interaction” Biochem. Biophys. Res. Commun. 2010, 393(2), 207-210. PMCID: PMC2834807.

  3. Radhakrishnan, P., Bryant, V. C., Blowers, E. B., Rajule, R. N., Gautam, N., Anwar, M. M., Mohr, A. M., Grandgenett, P. A., Bunt, S. K., Arnst, J. L., Lele, S. M., Alnouti, Y., Hollingsworth, M. A., Natarajan, A.* “Targeting the NF-κB and mTOR pathways with a quinoxaline urea analog that inhibits IKKβ for pancreas cancer therapy” Clin. Cancer Res. 2013, 19, 2025-2035. PMCID: PMC3630250

  4. Kumar, E. A., Chen, Q., Kizhake, S., Kolar, C., Kang, M., Chang, C., Borgstahl, G. E. O., Natarajan, A.* “The paradox of conformational constrain in the design of Cbl(TKB)-binding peptides” Sci. Rep. 2013, 3, 1639, DOI: 10.1038/srep01639. PMCID: PMC3965358

  5. Arnst, J. L., Hein, A. L., Taylor, M. A., Palermo, N. Y., Contreras, J. I., Sonawane, Y. A., Wahl, A. O., Ouellette, M. M., Natarajan, A.,* Yan, Y. “Discovery and characterization of small molecule Rac1 inhibitors" Oncotarget, 2017, 8, 34586-600. PMCID: PMC5470993.

  6. Robb, C. M., Kour, S., Contreras, J. I., Agarwal, E., Carter, B., Rana, S., Sonawane, Y. A., Neilsen, B., Taylor, M. A., Kizhake, S., Thakare, R., Chowdhury, S., Wang, J., Black, J., Hollingsworth, M. A., Brattain, M., Natarajan, A.* “Characterization of CDK(5) inhibitor, 20-223 (aka CP668863) for colorectal cancer therapy" Oncotarget, 2018, 9, 5216-5232. PMCID: PMC5797045.

  7. Kour, S., Rana, S., Contreras, J. I., King, H. M., Robb, C. M., Sonawane, Y. A., Bendjennat, M., Crawford, A. J., Carter, B., Kizhake, S., Luo, X., Hollingsworth, M. A., Natarajan, A.* “CDK5 inhibitor downregulates Mcl-1 and sensitizes pancreatic cancer cell lines to Navitoclax” Mol. Pharm. 2019, 19, 419-429. PMCID: PMC6726458.

  8. Napoleon, J. V., Singh, S., Rana, S., Bendjennat, M., Kumar, V., Kizhake, S., Palermo, N. Y., Ouellette, M. M., Huxford, T., Natarajan, A.* “Small molecule binding to inhibitor of nuclear factor kappa-B kinase subunit beta in an ATP non-competitive manner" Chem. Commun., 2021, 57(38), 4678-81. PMCID: PMC8162871.

  9. Kour, S., Rana, S., Kubica, S. P., Kizhake, S., Ahmad, M., Muñoz-Trujillo, C., Klinkebiel, D., Singh, S., Mallareddy, J. R., Chandra, S., Woods, N. T., Karpf, A. R., Natarajan, A.* “Spirocyclic dimer SpiD7 activates the unfolded protein response to selectively inhibit growth and induce apoptosis of cancer cells” J. Biol. Chem. 2022, 298(5):101890. PMCID: PMC9062249.

  10. Wallin, S., Singh, S., Borgstahl, GEO., Natarajan, A.* “Design, synthesis and evaluation of a mitoxantrone probe (MXP) for biological studies” Bioorg. Med. Chem. Lett. 2023, 94: 1294645. PMCID: PMC10528225.

  11. Eiken, A. P., Smith, A. L., Skupa, S. A., Schmitz, E., Rana, S., Singh, S., Kumar, S., Mallareddy, J. R., de Cubas, A. A., Krishna, A., Kalluchi, A., Rowley, M. J., D’Angelo, C. R., Lunning, M. A., Bociek, R. G., Vose, J. M., Natarajan, A., El-Gamal, D. “Novel spirocyclic dimer, SpiD3, targets chronic lymphocytic leukemia survival pathways with potent preclinical effects” Cancer Res. Commun. 2024, 4(5), 1328-1343. PMCID: PMC11110724.

  12. Boghean, L., Singh, S., Mangalparthi, K. K., Kizhake, S., Umeta, L., Wishka, D., Grothaus, P., Pandey, A., Natarajan, A.*“A selective MAP3K1 inhibitor facilitates discovery of NPM1 as a member of the network” Molecules 2025, 30(9), 2001. PMCID: PMC12073402.

5. Hit to Lead Optimization