tumor suppressor p53

p53 tumor suppressor fragment (232-240) is a peptide with the sequence H2N-Lys-Tyr-Met-Cys-Asn-Ser-Ser-Cys-Met-OH, MW= 1066.3. p53 is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where i

Pentamidine dimesylate is an inhibitor of calcium-dependent complex formation with p53 [(Ca)S100B-p53) in malignant melanoma (MM). Pentamidine dimesylate restores p53 tumor suppressor activity in vivo.

Kevetrin hydrochloride (4-Isothioureidobutyronitrile hydrochloride) 是一种小分子，是肿瘤抑制蛋白 p53 的激活剂，具有潜在的抗肿瘤活性。

TLBC, 一种硼烷-查尔酮衍生物，可在多种胶质瘤细胞系中表现出剂量依赖性抑制效应，其IC50值范围为5.5-25.5 μM。此外，TLBC能诱导细胞凋亡，且其作用并不依赖肿瘤抑制因子p53的变化。

SDU-071 是具有口服活性的 BRD4-p53 抑制剂，抑制 MDA-MB-231 细胞增殖，抑制 BRD4 与 p53 肿瘤抑制因子的相互作用，通过下调 BRD4 靶向基因的表达来抑制细胞增殖、迁移和侵袭，诱导细胞周期停滞和凋亡，可用于研究三阴乳腺癌。

CB2receptor agonist 8 (Compound 17) 是一种大麻素受体 2 (CB2 receptor) 激动剂。它在 U87、RPMI 8226、HL-60 和 L929 细胞系中表现出细胞毒性，IC50分别为 91.03、16.29、23.51 和 564.6 μM。该化合物激活 caspase3 7，增加促凋亡基因 BAX、BAD、BIM 和肿瘤抑制基因 p53 的表达，并在 U87 细胞中诱导细胞凋亡 (apoptosis)，同时抑制 U87 细胞的迁移。

Milademetan (DS-3032b or DS-3032) is a potent and selective MDM2 inhibitor with potential antineoplastic activity. Milademetan (p.o.) binds to and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protei

FL118 inhibits human survivinion expression and activates tumor suppressor p53 as a MOA in p53 wild-type cancer cells.

Milademetan is a potent and selective MDM2 inhibitor. MDM2 inhibitor DS-3032b binds to and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53 upon oral administration. By preventing this MDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis.

Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of yeast silent information regulator 2 (Sir2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis. Small molecule activators of SIRT1, such as resveratrol, extend lifespan in yeast and C. elegans in a manner that resembles caloric restriction. CAY10591 has been identified as an activator of the enzyme SIRT1. This compound increases fluorescence by 233% in a SIRT1 activity assay. [Activator activity was defined as the percentage of signal increase relative to signal window in the following formula: 100 x (Sample - Signallow)/(Signalhigh - Signallow)]. CAY10591 suppresses TNF-α in a dose-dependent manner. In THP-1 cells, TNF-α levels decreased from 325 pg/ml (control) to 104 and 53 pg/ml with 20 and 60 µM CAY10591, respectively. This activator also has a significant dose-dependent effect on fat mobilization in differentiated adipocytes, which would indicate the potential of SIRT1 activators for anti-obesity or anti-diabetic purposes.

Inactivation of the tumor suppressor p53 commonly coincides with increased signaling through NF-κB in cancer. CAY10681 is a dual modulator of p53-MDM2 interaction and NF-κB signaling. It potently binds MDM2 (Ki = 250 nM), reducing MDM2-mediated turnover of p53. CAY10681 also inhibits phosphorylation of IκBα and dose-dependently reduces nuclear accumulation of p65. It blocks the proliferation of cancer cell lines (IC50s range from 33 to 37 μM). CAY10681 exhibits excellent oral bioavailability and inhibits tumor growth in A549 xenografts in nude mice.

9(Z),11(E),13(E)-Octadecatrienoic Acid ethyl ester (α-ESA) is a conjugated polyunsaturated fatty acid commonly found in plant seed oil. This fatty acid accounts for about 60% of the total fatty acid composition of bitter gourd seed oil and about 70% in tung oil. α-ESA is metabolized and converted to conjugated linoleic acid (9Z,11E-CLA) in rats. It has shown potential as a tumor growth suppressor. In colon cancer Caco-2 cells, α-ESA induced apoptosis through up-regulation of GADD45, p53, and PPARγ. In DLD-1 cells supplemented with α-ESA, apoptosis was induced via lipid peroxidation with an EC50 of 20 μM. It also inhibits DNA polymerases and topoisomerases with IC50s ranging from ~5-20 μM for different isoforms of the enzymes. α-ESA ethyl ester is a neutral, more lipid soluble form of the free acid.

Methyl alpha-eleostearate (α-ESA) is a conjugated polyunsaturated fatty acid commonly found in plant seed oil. This fatty acid accounts for about 60% of the total fatty acid composition of bitter gourd seed oil and about 70% in tung oil. α-ESA is metabolized and converted to conjugated linoleic acid (9Z,11E-CLA) in rats. It has shown potential as a tumor growth suppressor. In colon cancer Caco-2 cells, α-ESA induced apoptosis through up-regulation of GADD45, p53, and PPARγ. In DLD-1 cells supplemented with α-ESA, apoptosis was induced via lipid peroxidation with an EC50 of 20 μM. It also inhibits DNA polymerases and topoisomerases with IC50s ranging from ~5-20 μM for different isoforms of the enzymes. α-ESA methyl ester is a neutral, more lipid soluble form of the free acid.

The protein p53, often called the 'guardian of the genome,' is a transcription factor that is activated in response to cellular stress (low oxygen levels, heat shock, DNA damage, etc.) and acts to prevent further proliferation of the stressed cell by promoting cell cycle arrest or apoptosis. Its role as a tumor suppressor is evident by the observation that approximately 50% of human tumors have mutated or non-functional p53. PK7242 is an inducer of reactivation of mutant p53 in cancer cells. In cancer cells carrying the Y220C mutant, PK7242 binds to the p53-Y220C core domain and induces growth inhibition, cell-cycle arrest, and apoptosis.

MMRi62 (7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol) 是一种铁死亡 (ferroptosis) 诱导剂，靶向 MDM2-MDM4 (抑癌基因 p53 负调控因子)。MMRi62 对胰腺导管腺癌 (PDAC) 细胞显示出 p53 独立的促凋亡 (apoptosis) 活性，并诱导其自噬 (autophagy)。MMRi62 诱导铁死亡，伴随着活性氧增加和铁蛋白重链 (FTH1) 溶酶体降解。MMRi62 还可导致突变型 p53 的蛋白酶体降解，并对具有 KRAS 和 TP53 高频突变特征的原位异种移植 PDAC 小鼠模型具有体内药效。

GEM-5为基于吉西他滨且含HIF-1α抑制剂(YC-1)的偶联物，IC50值为30 nM。此化合物能有效降低HIF-1α表达，并提高肿瘤抑制因子p53的表达量。GEM-5可诱导A2780细胞的凋亡(apoptosis)，进而抑制肿瘤生长。

MDM2-IN-26 (compound A3) is an inhibitor of MDM2 that facilitates the activation of p53's tumor suppressor functions by inhibiting the MDM2-p53 interaction, with MDM2 being the primary negative regulator of p53. This compound is utilized in cancer research [1].

p53 (232-240) 是由人类肿瘤抑制蛋白 p53 中第 232 到 240 位氨基酸组成的肽。该肽段能增强与主要组织相容性复合体 (MHC) 的结合亲和力，提高自身的免疫原性，从而增强免疫系统对肿瘤抗原的响应。p53 (232-240) 可以应用于癌症疫苗的开发，并用于研究免疫系统识别和清除肿瘤细胞的过程。