Initial testing of JNJ‐26854165 (Serdemetan) by the pediatric preclinical testing program
Open accessAbstract
JNJ‐26854165 was originally developed as an activator of p53 capable of inducing apoptosis in cancer cell lines. In vitro, JNJ‐26854165 demonstrated cytotoxic activity. The ALL cell line panel had a significantly lower median IC 50 (0.85 µM) than the remaining cell lines. In vivo JNJ‐26854165 induced significant differences in EFS distribution compared to control in 18 of 37 solid tumors and in 5 of 7 of the evaluable ALL xenografts. Objective responses were observed in 4 of 37 solid tumor xenografts, and 2 of 7 ALL xenografts achieved PR or CR. Responses were noted in xenografts with both mutant and wild‐type p53. Pediatr Blood Cancer 2012;59:329–332. © 2011 Wiley Periodicals, Inc.
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More preclinical studies reported that JNJ-26854165 increased p53 levels in U87 glioblastoma grafts, accompanied by apoptotic stimulation.
“More preclinical studies reported that JNJ-26854165 increased p53 levels in U87 glioblastoma grafts, accompanied by apoptotic stimulation.373–376”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [374]
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Cites
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy
Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B. T., Qing, W., Packman, K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507493103 · Cited by 708 · see citing works
The pediatric preclinical testing program: Description of models and early testing results
Houghton, P. J., Morton, C. L., Tucker, C., Payne, D., Favours, E., Cole, C., Gorlick, R., Kolb, E. A., Zhang, W., Lock, R., et al. (2007) · Pediatric Blood & Cancer · doi:10.1002/pbc.21078 · Cited by 480 · cited 2× · see citing works
“Cells were incubated in the presence of JNJ-26854165 for 96 hours at concentrations from 1 nM to 10 mM and analyzed as previously described [15].”
Self-citationSmall-Molecule Antagonists of p53-MDM2 Binding: Research Tools and Potential Therapeutics
Vassilev, L. T. (2004) · Cell Cycle · doi:10.4161/cc.3.4.801 · Cited by 271 · see citing works
Liem, N., Papa, R., Milross, C., Schmid, M. A., Tajbakhsh, M., Choi, S., Ramirez, C., Rice, A., Haber, M., Norris, M., et al. (2004) · Blood · doi:10.1182/blood-2003-08-2911 · Cited by 245 · cited 1× · see citing works
“Human leukemia cells were propagated by intravenous inoculation in female non-obese diabetic (NOD)/scid / mice as described previously [17].”
Self-citationSmall-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma
Maerken, T. V., Speleman, F., Vermeulen, J., Lambertz, I., Clercq, S. D., Smet, E. D., Yigit, N., Coppens, V., Philippé, J., Paepe, A. D., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0792 · Cited by 154 · cited 1× · see citing works
“For example, Nutlin-3 inhibited growth of neuroblastoma cell lines, with a greater effect on lines with wild-type p53 compared to those with p53 mutations [4], and it potentiated chemotherapy-induced apoptosis in neuroblastoma cell lines [5].”
MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell death
Barbieri, E., Mehta, P. S., Chen, Z., Zhang, L., Slack, A., Berg, S. L., & Shohet, J. M. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0305 · Cited by 142 · cited 1× · see citing works
“For example, Nutlin-3 inhibited growth of neuroblastoma cell lines, with a greater effect on lines with wild-type p53 compared to those with p53 mutations [4], and it potentiated chemotherapy-induced apoptosis in neuroblastoma cell lines [5].”
Friedman, H. S., Colvin, O. M., Skapek, S. X., LUDEMAN, S. M., Elion, G. B., Schold, S. C., Jacobsen, P. F., Muhlbaier, L. H., & Bigner, D. D. (1988) · PubMed · Cited by 132 · see citing works
Gu, L., Zhu, N., Findley, H. W., & Zhou, M. L. (2008) · Leukemia · doi:10.1038/leu.2008.11 · Cited by 112 · cited 1× · see citing works
“observed that Nutlin-3 was selectively active against ALL cell lines and primary ALL samples with wild-type p53 [6].”
Miyachi, M., Kakazu, N., Yagyu, S., Katsumi, Y., Tsubai-Shimizu, S., Kikuchi, K., Tsuchiya, K., Iehara, T., & Hosoi, H. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2955 · Cited by 101 · see citing works
Frgala, T., Kalous, O., Proffitt, R. T., & Reynolds, C. P. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-04-0331 · Cited by 97 · cited 1× · see citing works
“In vitro testing was performed using DIMSCAN, as previously described [14].”
Self-citationKojima, K., Burks, J. K., Arts, J., & Andreeff, M. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0337 · Cited by 78 · cited 3× · see citing works
“Consistent with this proposed mechanism, JNJ-26854165 induced apoptosis in acute myeloid and lymphoid leukemia cell lines and in primary acute leukemia isolates [3].”
InfluentialSelf-citationNutlin-3a Is a Potential Therapeutic for Ewing Sarcoma
Pishas, K. I., Al-Ejeh, F., Zinonos, I., Kumar, R., Evdokiou, A., Brown, M. P., Callen, D. F., & Neilsen, P. M. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1587 · Cited by 71 · see citing works
Andreeff, M., Kojima, K., Padmanabhan, S., STRAIR, R. K., Kirschbaum, M. H., Maslak, P. G., Hillmen, P., O'Brien, S. M., Samaniego, F., Borthakur, G. M., et al. (2010) · Blood · doi:10.1182/blood.v116.21.657.657 · Cited by 29 · see citing works
Tabernero, J. M., Dirix, L. Y., Schöffski, P., Cervantes, A. M. R., Capdevila, J., Baselga, J. M., van Beijsterveldt, L., Winkler, H. J. S., Kraljevic, S., & Zhuang, S. H. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.3514 · Cited by 18 · cited 1× · see citing works
“A phase 1 trial of JNJ-26854165 has been completed, with the most common dose-limiting toxicity being Grade-3 QTc prolongation [18] (and manuscript in press).”
Ray-Coquard, I., Blay, J., Italiano, A., Cesne, A. L., Penel, N., Zhi, J., Beryozkina, A., Heil, F., Rueger, R., NICHOLS, G. L., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.10007b · Cited by 11 · see citing works
Beryozkina, A., NICHOLS, G. L., Reckner, M., Vassilev, L. T., Rueger, R., Jukofsky, L., Middleton, S., Andreeff, M., Padmanabhan, S., STRAIR, R. K., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.3039 · Cited by 9 · see citing works
Karger, G. A., & Lee, W. (2008) · PubMed · Cited by 1 · see citing works
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Research works printed but not linked: 2
- [1]Arts J Page M Valckx A JNJ-26854165 - a novel Hdm2 antagonist in clinical development showing broad-spectrum preclinical antitumor activity against solid malignancies Proceedings of the 99th Annual Meeting of the American Association for Cancer Research 2008 Abstr #1592.
- [2]Arts J Smans KA Andries L Preclinical and clinical pharmacodynamic activity of JNJ-26854165: A novel Hdm2 antagonist in clinical development Proceedings of the 100th Annual Meeting of the American Association for Cancer Research 2009 Abstr #1924.
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Marengo, B., Nitti, M., Furfaro, A. L., Colla, R., Ciucis, C. D., Marinari, U. M., Pronzato, M. A., Traverso, N., & Domenicotti, C. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/6235641 · Cited by 319 · see citing works
The Roles of MDM2 and MDMX in Cancer
Karni-Schmidt, O., Lokshin, M., & Prives, C. L. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040349 · Cited by 294 · see citing works
Targeting the p53 signaling pathway in cancer therapy – the promises, challenges and perils
Stegh, A. H. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.643299 · Cited by 192 · see citing works
“Candidates include reactivation of p53 and induction of tumor cell apoptosis (RITA), which showed antitumor effects in murine colon cancer models by inducing conformational changes in p53 thereby preventing interaction with Mdm proteins [184], and the tryptamine derivate JNJ-26854165, which blocked p53 proteasomal deg…”
BackgroundTargeting MDM2-p53 Interaction for Cancer Therapy: Are We There Yet?
Nag, S. A., Zhang, X., Srivenugopal, K. S., Wang, M.-H., Wang, W., & Zhang, R. (2014) · Current Medicinal Chemistry · doi:10.2174/09298673113206660325 · Cited by 151 · see citing works
Targeting p53-MDM2-MDMX Loop for Cancer Therapy
Zhang, Q., Zeng, S. X., & Lu, H. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-017-9211-0_16 · Cited by 83 · see citing works
Small molecule compounds targeting the p53 pathway: are we finally making progress?
Yu, X., Narayanan, S., Vázquez, A., & Carpizo, D. R. (2014) · APOPTOSIS · doi:10.1007/s10495-014-0990-3 · Cited by 65 · see citing works
“Other pre-clinical studies have also found activity in both wild-type and mutant p53 tumors indicating that the mechanism involves both p53 dependent and independent functions [59].”
BackgroundInitial testing of the MDM2 inhibitor RG7112 by the pediatric preclinical testing program
Carol, H., Reynolds, C. P., Kang, M. H., Keir, S. T., Maris, J. M., Gorlick, R. G., Kolb, E. A., Billups, C. A., Geier, B., Kurmasheva, R. T., et al. (2012) · Pediatric Blood & Cancer · doi:10.1002/pbc.24235 · Cited by 64 · see citing works
“Furthermore, in vitro sensitivity to serdemetan did not segregate with p53 status, and in vivo responses to serdemetan were noted in xenografts with both mutant and wild-type p53 [52].”
BackgroundResultSelf-citationRole of de novo cholesterol synthesis enzymes in cancer
Yang, J., Wang, L., & Jia, R. (2020) · Journal of Cancer · doi:10.7150/jca.38598 · Cited by 63 · see citing works
Cam, M., Bid, H. K., Xiao, L., Zambetti, G. P., Houghton, P. J., & Çam, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.530303 · Cited by 58 · see citing works
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“In the PPTP testing, this agent demonstrated tumor growth inhibition in the OS models (Smith et al., 2012a).”
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Jones, R. J., Gu, D., Bjorklund, C. C., Kuiatse, I., Remaley, A. T., Bashir, T., Vreys, V., & Orlowski, R. Z. (2013) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.204958 · Cited by 26 · see citing works
“…reported to act as a human double minute protein (HDM)-2 inhibitor with preclinical efficacy in acute myeloid and lymphoid leukemias (Kojima et al., 2010; Smith et al., 2012), as well as various solid tumors (Chargari et al., 2011), and has completed phase I trials (Tabernero et al., 2011).”
BackgroundSelf-citationLessons learned from 20 years of preclinical testing in pediatric cancers
Smith, M. A., Houghton, P. J., Lock, R. B., Maris, J. M., Gorlick, R. G., Kurmasheva, R. T., Li, X., Teicher, B. A., Chuang, J. H., Cruz, F. S. D., et al. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108742 · Cited by 19 · see citing works
Self-citationYou, L., Liu, H., Huang, J., Xie, W., Wei, J., Ye, X., & Qian, W. (2016) · Oncotarget · doi:10.18632/oncotarget.13951 · Cited by 11 · see citing works
“However, recent pre-clinical studies have demonstrated antiproliferative activity in various p53 wt and mutant cancer models [20, 23, 24], implying p53-independent activities.”
BackgroundMethodNenkov, M., Ma, Y., Haase, D., Zhou, Z., Li, Y., Petersen, I., Lu, G., & Chen, Y. (2020) · Oncology Reports · doi:10.3892/or.2020.7546 · Cited by 7 · see citing works
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Ouyang, M., Gui, Y., Li, N., & Zhao, L. (2024) · Scientific Reports · doi:10.1038/s41598-024-81503-x · Cited by 4 · see citing works
“Furthermore, Serdemetan, an antagonist of the HDM2 ubiquitin ligase, triggers early apoptosis in p53 wild-type cells 36 .”
Jeong, S., An, S.-C., An, H., Lim, S. Y., Kim, J. M., & Lee, S. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118686 · Cited by 4 · see citing works
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Inchiosa, M. A. (2023) · Journal of Pharmacy and Pharmacology Research · doi:10.26502/fjppr.073 · Cited by 2 · see citing works
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Mattern, M. R., Eddins, M. J., Agarwal, S., Sterner, D. E., Kodrasov, M. P., Kumar, S., Wu, J., & Nicholson, B. (2014) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-319-06752-0_12 · Cited by 1 · see citing works
The ubiquitin/proteasome pathway in neoplasia
van Waardenburg, R. C. A. M., & Bjornsti, M. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139046947.041
- Authors
- Smith, M. A., Gorlick, R., Kolb, E. A., Lock, R., Carol, H., Maris, J. M., Keir, S. T., Morton, C. L., Reynolds, C. P., Kang, M. H., Arts, J., Bashir, T., Janicot, M., Kurmasheva, R. T., & Houghton, P. J.
- Affiliations
- National Institutes of Health (US)
- Children's Hospital at Montefiore (US)
- Alfred I. duPont Hospital for Children (US)
- Children's Cancer Institute Australia (AU)
- Children's Hospital of Philadelphia (US)
- Duke Medical Center (US)
- St. Jude Children's Research Hospital (US)
- Texas Tech University Health Sciences Center (US)
- Janssen (Belgium) (BE)
- Nationwide Children's Hospital (US)
- Corresponding author
- Smith, Malcolm A.
- ORCID
- Venue
- Pediatric Blood & Cancer
- Publisher
- Wiley
- Published
- 2011-09-15
- Volume
- 59
- Issue
- 2
- Pages
- 329-332
- ISSN
- 1545-5009 (ISSN-L)
- 1545-5017
- PMC
- PMC4504194
- OpenAlex
- W2050013428
- Cited by
- 26
- References
- 17
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2021: 2 · 2020: 3 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pediatric Blood & Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- Funders
- The National Cancer Institute (NO1-CM-42216, CA21765, CA108786)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53 activators, acute lymphoblastic leukemia, pediatric solid tumors, xenografts, cytotoxicity, objective response, mutant p53
- MeSH terms
- Animals, Brain Neoplasms, Child, Drug Evaluation, Preclinical, Female, Humans, Mice, Inbred BALB C, Neuroblastoma, Radiation-Sensitizing Agents, Sarcoma, Tryptamines, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Mice, SCID, Mice, Inbred NOD, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Proliferation, Mice, Proto-Oncogene Proteins c-mdm2, Precursor Cell Lymphoblastic Leukemia-Lymphoma
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