JNJ 26854165

• 产品号: S1172
• CAS号: 881202-45-5
• 分子式: C21H20N4
• 分子量: 328.4103
• 保 存: -20°C

产品别名

• 标题: JNJ 26854165
• IUPAC标准名: 1-N-[2-(1H-indol-3-yl)ethyl]-4-N-(pyridin-4-yl)benzene-1,4-diamine
• IUPAC传统名: 1-N-[2-(1H-indol-3-yl)ethyl]-4-N-(pyridin-4-yl)benzene-1,4-diamine

产品登记号

• CAS号: 881202-45-5

产品性质

• 作用靶点: p53
• 成盐信息: Free Base
• 溶解度: DMSO
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Solid tumours,Prostate cancer, Non-small cell lung

Biological Activity

• Description: JNJ 26854165 (Serdemetan) is an orally bioavailable HDM2 antagonist.
• Targets: HDM2; Mdm2
• In Vitro: JNJ 26854165 is a novel tryptamine derivative which activates p53 and acts as a HDM2 ubiquitin ligase antagonist. JNJ 26854165 inhibits cell growth and induces apoptosis in leukemia cell lines with IC50 values of 0.24, 0.33, 0.32 and 0.44 μM at 72 hours for OCI-AML-3, MOLM-13, NALM-6 and REH cells, respectively. In addition, JNJ 26854165 accelerates proteasome-mediated degradation of p21 and antagonizes the transcriptional induction of p21 by p53. It also induces S-phase delay and upregulates E2F1 expression in p53 mutant cells, resulting in preferential apoptosis of S-phase cells. ^[1] JNJ 26854165 is an oral Mdm2 inhibitor which can inhibit the interaction of Mdm2-p53 complex with the proteasome and increase p53 levels by binding to RING domain of Mdm2. ^[2] A recent study shows that JNJ 26854165 inhibits clonogenic survival in four human cancer cell lines: H460, A549, p53-WT-HCT116, and p53-null-HCT116. ^[3]
• In Vivo: JNJ 26854165 leads to significant differences in EFS distribution in 17 of the 36 (47%) evaluable solid tumor xenografts and in 5 of 7 (71%) of the evaluable ALL xenografts using a dose of 20 mg/kg administered via oral gavage daily for 5 days, repeated for 6 weeks. ^[4]
• Clinical Trials: JNJ 26854165 is currently being evaluated in Phase I clinical trials in patients with Neoplasms.

Combination Therapy

• Description: JNJ 26854165 is an orally bioavailable, small-molecule and a HDM2 antagonist with potential antineoplastic activity.

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: OCI-AML-3, MOLM-13, NB4 and U937 cells
• Concentrations: 0-10 μM
• Incubation Time: 72 hours
• Methods: Cell lines are maintained in RPMI 1640 medium containing 10% heat-inactivated fetal calf serum (FCS). OCI-AML-3, MOLM-13, NB4 and U937 cells are derived from acute myelogenous leukemia (AML) patients, K562 from a chronic myelogenous leukemia (CML) patient in blast crisis, and NALM-6, REH, P12-ICHIK
• Protocol: Animal Study ^[4]
• Animal Models: CB17SC scid^-/- female mice.
• Formulation: JNJ-26854165 is dissolved in DMSO and then diluted in water.
• Doses: ≤20 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Kojima K, et al. Mol Cancer Ther. 2010, 9(9), 2545-2557.http://www.ncbi.nlm.nih.gov/pubmed/20736
• References: [2] Yuan Y, et al. J Hematol Oncol. 2011, 4:16.
• References: [3] Chargari C, et al. Cancer Lett. 2011, 312(2), 209-218.
• References: [4] Smith MA, et al. Pediatr Blood Cancer. 2011, doi: 10.1002/pbc.23319.

参考文献

• Kojima K, et al. Mol Cancer Ther. 2010, 9(9), 2545-2557.http://www.ncbi.nlm.nih.gov/pubmed/20736
• Chargari C, et al. Cancer Lett. 2011, 312(2), 209-218.
• Smith MA, et al. Pediatr Blood Cancer. 2011, doi: 10.1002/pbc.23319.
• Yuan Y, et al. J Hematol Oncol. 2011, 4:16.