Step 5: Hit to Lead Optimization

  1. Natarajan, A., Fan, Y.–H., Chen, H., Guo, Y., Iyasere, J., Harbinski, F., Christ, W. J., Aktas, H., Halperin, J. A. “3,3-Diaryl-1,3-dihydro-indol-2-ones as antiproliferatives mediated by translation initiation inhibition.” J. Med. Chem. 2004, 47(8), 1882-1885. PMID: 15055987.

  2. Natarajan, A., Guo, Y., Harbinski, F., Fan, Y.–H., Chen, H., Luus, L., Diercks, J., Aktas, H., Chorev, M., Halperin, J. A. “Novel arylsulfonamide-oxindole hybrid as an anticancer agent that Inhibits translation initiation" J. Med. Chem. 2004, 47(21), 4979-4982. PMCID: PMID: 15456240.

  3. Gautam, N., Bathena, S. R., Chen, Q., Natarajan, A., Alnouti, Y. “Pharmacokinetics, protein binding and metabolism of a quinoxaline urea analog as NF-κB inhibitor in mice and rats by LC-MS/MS” Biomed. Chromatogr. 2013, 7, 900-909. PMCID: PMC3760428

  4. 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

  5. Gautam, N., Thakare, R., Rana, S., Natarajan, A., Alnouti, Y. “Irreversible binding of an anticancer compound (BI-94) to plasma proteins” Xenobiotica 2015, 45, 858-73. PMCID: PMC4553108

  6. Sagar, S., Singh, S., Mallareddy, J. R., Sonawane, Y. A., Napoleon, J. V., Rana, S., Contreras, J. I., Rajesh, C., Ezell, E. L., Kizhake, S., Garrison, J. C., Radhakrishnan, P., Natarajan, A.* “Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy” Eur. J. Med. Chem. 2021, 222(113579) 1-15. PMCID: PMC8373685.

  7. Napoleon, J. V., Sagar, S., Kubica, S. P., Boghean, L., Kour, S., King, H. M., Sonawane, Y. A., Crawford, A. J., Gautam, N., Kizhake, S., Bialk, P. A., Kmiec, E., Mallareddy, J. R., Patil, P., Rana, S., Singh, S., Prahlad, J., Grandgenett, P.M., Borgstahl, G. E. O., Ghosal, G., Alnouti, Y., Hollingsworth, M.A., Radhakrishnan, P., Natarajan, A.* “Small molecule IKKβ activation modulator (IKAM) targets MAP3K1 and inhibits pancreatic tumor growth” Proc. Natl. Acad. Sci. USA 2022, 119(18):e2115071119 PMCID: PMC9170026.

6. In-Vivo Studies