tumor metabolism

Berberine (Umbellatine) 属于生物碱类天然产物，可以激活 AMPK、抑制 DNA 拓扑异构酶、诱导 ROS 生成。Berberine 具有抗肿瘤、抗菌、降血糖、降血脂等生物学活性。

Exo-1 (Methyl 3-(4-fluorobenzoyl)-6-methyl-2-pyridinecarboxylate) 是一种合成化合物，已被证明会影响各种营养物质的代谢，以及各种激素的调节。它还被证明具有抗炎和抗肿瘤作用。

N-Desethyl Sunitinib（SU012662,N-去乙基-舒尼替） 是 Sunitinib 由细胞色素P450酶3A4 （CYP3A4）代谢产生的主要活性代谢物。Sunitinib是一种口服的抑制剂，可抑制多种酪氨酸激酶参与肿瘤增殖和血管生成，包括 VEGFR、PDGFR、KIT 和 FLT3 等，被批准用于治疗晚期/转移性肾细胞癌（RCC）

HFI-142 是一种小分子抑制剂，能够特异性结合氨肽酶 N 的活性位点并抑制其酶活性。HFI-142 已被证明可抑制红细胞中白三烯 A4 的生物合成，该作用通过调控与肿瘤生长和进展相关的炎症及代谢通路，可能在癌症研究中具有治疗潜力。HFI-142 还可抑制其他氨肽酶的活性，包括氨肽酶 N 以及与蛋白质代谢相关的多种酶。

Lon-TK 是一种 LTB 的糖酵解抑制剂与 linker 的偶联物。LTB 是通过硫代缩酮 (thioketal) 连接的 Lonidamine (Lon) 和 PD-L1 抑制剂 (BMS-1) 的前药，能够有效地抑制肿瘤细胞的糖酵解代谢，同时阻断 PD-1/PD-L1 的免疫逃逸路径。Lon-TK 具有光动力增强免疫研究的潜在应用前景。

Triphenyl phosphate 可通过激活MAOA/ROS/NFκB破坏胎盘色氨酸代谢，诱发异常神经行为，促进核因子 κ B (NFκB)、白细胞介素-6、肿瘤坏死因子α等炎症因子诱导氧化应激，并可能导致过敏性接触性皮炎。

1-Methyladenosine-d3 hydriodide 是 1-Methyladenosine 的氘代物。1-Methyladenosine 是一种 RNA 修饰，其水平升高与癌症的发生有关，并可作为肿瘤标志物。甲基化的 1-Methyladenosine 能通过提高 PPARδ 的表达，调节胆固醇代谢，并激活 Hedgehog 信号通路，推动肝脏肿瘤的形成。

human TDO2-IN-1 (Cpd-2) 是一种高效的人TDO2抑制剂，IC50为14.8 nM。在代谢、炎症以及肿瘤免疫监视的研究中发挥关键作用。

Anticanceragent 239 (Compound 5) 是 hTERT 启动子 G-四链体 DNA 结构 (hTERT G4) 的一种配体 (Kd = 1.1 μM)，可下调 hTERT 的表达。它能够降低端粒酶活性、缩短端粒长度，并诱导 DNA 损伤、细胞急性衰老和细胞凋亡 (apoptosis)。此外，Anticanceragent 239 还会引发线粒体功能障碍、干扰铁代谢，并激活癌细胞中的铁死亡 (Ferroptosis)。在 MDA-MB-231 异种移植小鼠模型中，该化合物能有效抑制肿瘤生长。

Trivalent hydroxyarsinothricn (R-AST-OH) 是一种共价且不可逆的肾型谷氨酰胺酶 (KGA) 抑制剂。它通过与谷氨酰胺结合位点结合并与活性位点半胱氨酸残基形成共价键来起作用。Trivalent hydroxyarsinothricn 能选择性地杀死三阴性乳腺癌 (TNBC) 细胞，而对照细胞系则没有细胞毒性。KGA 作为控制谷氨酰胺代谢的酶，与肿瘤的恶性程度相关。

Glutathione arsenoxide (GSAO) TFA 是一种有潜力的抗癌活性分子和肿瘤代谢抑制剂。它靶向线粒体内膜上的腺嘌呤核苷酸转移酶 (ANT)，并导致细胞增殖停滞和细胞死亡。此外，该化合物可用于识别细胞表面蛋白质，如蛋白质二硫异构酶。

Oligomycin 是一种由链霉菌 (Streptomyces) 产生的大环内酯类抗生素。Oligomycin 常用于研究线粒体功能和细胞能量代谢，具有抗真菌和抗肿瘤活性。

DRB18是一种高效的广谱葡萄糖转运蛋白(GLUT)抑制剂。它通过诱导与葡萄糖相关途径有关的代谢物含量的变化，显著调节A549细胞中与能量相关的代谢。DRB18通过促进G1/S期阻滞、增加氧化应激和促进坏死性细胞死亡发挥其效果，最终表现出显著的抗肿瘤活性[1]。

NHI-2 是一种乳酸脱氢酶 A (LDHA) 抑制剂，其 IC50 值为 14.7 µM，对 LDHB 的 IC50 为 55.8 µM，对 LDHA 有高选择性。NHI-2 作为高效的抗糖酵解剂，可增强细胞凋亡、诱导 S 和 G2 期细胞周期阻滞，并在癌细胞中产生广谱抗增殖作用。NHI-2 还影响细胞外酸化速率及 ATP 生成，并在小鼠 B78 黑色素瘤模型中显示肿瘤生长抑制效果，凸显其在癌症代谢研究中的作用。

Thiocysteine 是一种半胱氨酸衍生物， 氨基酮戊酸盐合成酶的激活剂，可用于半胱氨酸代谢的研究。它也是一种抗肿瘤化合物。

Motexafin gadolinium, also known as PCI 0120, is a synthetic metallotexaphyrin with radiosensitizing and chemosensitizing properties. Motexafin gadolinium accumulates in tumor cells preferentially due to their increased rates of metabolism, generating rea

Rostaporfin (also known as REM-001, tin ethyl etiopurpurin, Sn(IV) etiopurpurin, Purlytin, SnET2), is a synthetic purpurin with photosensitizing activity. Rostaporfin preferentially accumulates in tumor cells due to an increased rate of metabolism. Upon e

MTI-31 (LXI-15029) 是口服有效的，高度选择性的mTORC1和mTORC2抑制剂，对 mTOR 的Kd 为 0.20 nM，IC50为 39 nM。MTI-31可用于乳腺癌的研究。

Cytochrome P450 metabolism of polyunsaturated fatty acids produces numerous bioactive epoxide regioisomers. (±)10(11)-EpDPA is a docosahexaenoic acid epoxygenase metabolite, derived via epoxidation of the 10,11-double bond of DHA. It has been detected in rat brain and spinal cord, as well as human serum, and acts as a substrate for soluble epoxide hydrolase with a Km value of 5.1 μM. (±)10(11)-EpDPA and other epoxy metabolites of DHA are reported to demonstrate antihyperalgesic activity in inflammatory and neuropathic pain models and to potently inhibit angiogenesis and tumor growth in in vitro assays.

Cytochrome P450 metabolism of polyunsaturated fatty acids produces numerous bioactive epoxide regioisomers. (±)13(14)-EpDPA is a docosahexaenoic acid epoxygenase metabolite, derived via epoxidation of the 13,14-double bond of DHA. It has been detected in rat brain and spinal cord and is a preferred substrate for soluble epoxide hydrolase with a Km value of 3.2 μM. (±)13(14)-EpDPA demonstrates antihyperalgesic activity in inflammatory and neuropathic pain models. (±)13(14)-EpDPA and other epoxy metabolites of DHA are also reported to potently inhibit angiogenesis and tumor growth in in vitro assays.

CC260 is a selective PI5P4Kα and PI5P4Kβ inhibitor with Kis of 40 nM and 30 nM, respectively. CC260 does not inhibit or weakly inhibits other protein kinases, such as Plk1 and RSK2. CC260 can be used for cell energy metabolism, diabetes and cancer research[1]. In cultured C2C12 myotubes, CC260 (20 μM) enhances Insulin-induced Akt phosphorylation at both Thr-308 and Ser-473 but suppresses S6K phosphorylation (Thr-389) by mTORC1[1]. CC260 (2.5 μM, 5 μM, 10 μM, 20 μM) significantly increases phosphorylation of acetyl-CoA carboxylase (ACC) in a dose-dependent manner[1]. CC260 treatment reduces the ability of BT474 cells to survive serum starvation, which could be rescued by expressing the PI5P4Kβ refractory mutant[1]. In BT474 cells, CC260 treatment causes an increase in glycolytic ATP production[1]. [1]. Song Chen, et al. Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53- tumor cells. Proc Natl Acad Sci U S A. 2021 May 25;118(21):e2002486118.

16,16-dimethyl PGA2 is a metabolism-resistant analog of PGA2 with a prolonged in vivo half-life. It inhibits the proliferation of Sendai virus in cultured African green monkey kidney cells by >90% at a concentration of 4 μg/ml. Daily infusion of 10 μg of 16,16-dimethyl PGA2 methyl ester into mice infected with influenza A virus increased survival by 40%. Similar treatment of mice inoculated with erythroleukemia cells delayed tumor growth and increased survival time.

Aspulvinone O is a fungal metabolite that has been found in P. variotti and has antioxidant and anticancer activities.1,2 It scavenges 2,2-diphenyl-1-picrylhydrazyl radicals in a cell-free assay (IC50 = 11.6 μM).1 Aspulvinone O inhibits aspartate transaminase 1 (GOT1; Kd = 3.32 μM) and is cytotoxic to PANC-1, AsPC-1, and SW1990 pancreatic cancer cells (IC50s = 20.54-26.8 μM).2 It reduces the oxygen consumption rate (OCR) and induces apoptosis in SW1990 cells. Aspulvinone O (2.5 and 5 mg/kg) reduces tumor growth in an SW1990 mouse xenograft model. |1. Zhang, P., Li, X.-M., Wang, J.-N., et al. New butenolide derivatives from the marine-derived fungus Paecilomyces variotii with DPPH radical scavenging activity. Phytochem. Lett. 11, 85-88 (2015).|2. Sun, W., Luan, S., Qi, C., et al. Aspulvinone O, a natural inhibitor of GOT1 suppresses pancreatic ductal adenocarcinoma cells growth by interfering glutamine metabolism. Cell Commun. Signal. 17(1), 111 (2019).

12(S)-HETE is a product of arachidonic acid metabolism through the 12-lipoxygenase pathway. It is primarily found in platelets, leukocytes, and to a lesser extent in smooth muscle cells. It enhances tumor cell adhesion to endothelial cells, fibronectin, and the subendothelial matrix. tetranor-12(S)-HETE is the major β-oxidation product resulting from peroxisomal metabolism of 12(S)-HETE in numerous tissues, and Lewis lung carcinoma cells. No biological function has yet been determined for tetranor-12(S)-HETE. Some data indicate it may play a role in controlling the inflammatory response in injured corneas. In some diseases (e.g., Zellweger's Syndrome) peroxisomal abnormalities result in the inability of cells to metabolize 12(S)-HETE, which may be responsible for symptoms of the disease. The tetranor derivative of 12(S)-HETE is available as a research tool for the elucidation of the metabolic fate of its parent compound.