JNJ-26854165 (Serdemetan) is a p53-activating agent with antiproliferative activity in various p53 wild-type (WT) tumor cell lines. JNJ-26854165 inhibited clonogenic survival in all cell lines, but in a lower extent in p53-null-HCT116. JNJ-26854165 also inhibited proliferation, capillary tube formation and migration of HMEC-1 cells. JNJ-26854165 demonstrated cytotoxic activity in vitro. In vivo, JNJ-26854165 (Serdemetan) caused a greater than additive increase in tumor growth delay. 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 in vivo. JNJ-26854165 (Serdemetan) treatment at 0.25μM in H460 and at 5μM in A549 cells resulted in a sensitivity-enhancement ratio of 1.18 and 1.36, respectively. JNJ-26854165 treatment induced p53-mediated apoptosis in acute leukemia cells with wild-type p53, in which p53 rapidly drives transcription-independent apoptosis followed by activation of a transcription-dependent pathway. JNJ-26854165 accelerated the proteasome-mediated degradation of p21 and antagonized the transcriptional induction of p21 by p53. JNJ-26854165 is currently being evaluated in Phase I clinical trials.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 60 mg/mL|
Preclinical assessment of JNJ-26854165 (Serdemetan), a novel tryptamine compound with radiosensitizing activity in vitro and in tumor xenografts.
Chargari C, et al. Cancer Lett. 2011 Dec 22;312(2):209-18. PMID: 21937165.
Initial testing of JNJ-26854165 (Serdemetan) by the pediatric preclinical testing program.
Smith MA, et al. Pediatr Blood Cancer. 2012 Aug;59(2):329-32. PMID: 21922647.
The novel tryptamine derivative JNJ-26854165 induces wild-type p53- and E2F1-mediated apoptosis in acute myeloid and lymphoid leukemias.
Kojima K, et al. Mol Cancer Ther. 2010 Sep;9(9):2545-57. PMID: 20736344.
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