Fresenius Kabi · TUBB · 小分子
paclitaxel 是一种小分子，由Fresenius Kabi研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。
| 商品名 | PNP, Dabur, DO/NDR/02, PNP, Dabur |
| 公司 | Fresenius Kabi |
| 药物类别 | 小分子 |
| 分子靶点 | TUBB |
| 给药途径 | Injectable (Others), Intravenous (IV) |
| 状态 | Approved |
paclitaxel 作用于 1 个分子靶点：
| TUBB | tubulin beta class I (TUBB1, CSCSC1) |
paclitaxel 针对 4 个适应症，涉及 1 个治疗领域。
| 治疗领域 | 疾病/病症 | 分期 |
|---|---|---|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Breast cancer | ✓ Approved |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-small cell lung cancer stage IV | ✓ Approved |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Ovarian cancer | ✓ Approved |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-small cell lung cancer metastatic | ✓ Approved |
Bao Yuling Y, Guo Yuanyuan Y, Zhuang Xiangting X, Li Dan D et al.
Xia Shuai S, Sheng Tao T, Li Jia-Min JM, Zhang Bing-Feng BF et al.
The aim of this research was to design nanostructured lipid carriers co-delivering paclitaxel and ubenimex to improve the tumor microenvironment and enhance efficacy against breast cancer. Nanostructured lipid carriers (NLC) offer unique advantages for co-delivery of anti-tumor drugs, including high drug-loading capacity, controlled-release performance, and facile functionalization. This study developed a nanostructured lipid carrier (NLC) co-loaded with paclitaxel and ubenimex to achieve synergistic therapeutic effects on breast cancer by improving the immunosuppressive tumor microenvironment. Ubenimex (Uben) was conjugated to vitamin E polyethylene glycol succinate (TPGS) via ester bonds, after which the synthetic conjugate, paclitaxel, and lipid materials were formulated into the nanostructured lipid carrier (PTX/Uben-NLC) by the emulsified solvent evaporation-low-temperature curing method and subsequently characterized and evaluated for improved anti-tumor efficacy. The prepared PTX/Uben-NLC was approximately spherical with a negative potential and a particle size of about 161 nm. The formulation demonstrated sustained drug release. Uben exhibited pH-responsive release in the weakly acidic tumor microenvironment (TME) and induced immune cell activation and secretion of anti-tumor cytokines (IFN-γ, TNF-α, IL-12), while secretion of immunosuppressive cytokines (TGF-β and IL-10) was concurrently inhibited. PTX exerted direct anti-tumor effects on tumor cells. Consequently, the PTX/Uben-NLC alleviated TME immunosuppression and enhanced anti-breast-cancer activity. Dual-drug-loaded nanostructured lipid carriers alleviated TME immunosuppression to enhance synergistic anti-breast cancer therapy and provided a feasible solution for breast cancer treatment.
Han Hai-Li HL, Yang Xue-Qiong XQ, Xie Yun-Xia YX, Zhang Long-Yue LY et al.
Fifteen new metabolites were isolated from Clonostachys rosea, a biocontrol fungus derived from Taxus yunnanensis. Among these, clonostachydimers A and B (14-15) are unprecedented anthrone-furanone hybrid dimers with a unique 6/6/6/6/5 pentacyclic framework, presumably biosynthesized via a [4 + 2] cycloaddition reaction. Their structures and absolute configurations were established by spectroscopic analyses, X-ray crystallography, ECD calculations, Snatzke's method, and DP4+ analysis. Bioassays indicated that several metabolites exhibited significant antimicrobial activity against drug-resistant pathogens as well as cytotoxic activity. Compound 3 showed potent cytotoxicity against A549/Taxol cells (IC50 = 0.542 μM), exceeding that of doxorubicin and paclitaxel, while also displaying activity against MRSA and Candida albicans. Molecular docking suggested potential dual targeting of Topoisomerase II and P-glycoprotein, supporting its activity against paclitaxel-resistant cells.
Demirkıran Aykut A, Araz Murat M, Eryılmaz Melek Karakurt MK, Karaağaç Mustafa M et al.
Clinical outcomes remain heterogeneous among patients with unresectable stage III non-small cell lung cancer treated with definitive chemoradiotherapy. We evaluated the prognostic value of the systemic immune-inflammation index (SII) and explored survival outcomes according to the concurrent chemotherapy backbone in this setting. This retrospective study included 101 patients treated with definitive chemoradiotherapy before consolidation durvalumab became standard practice. Baseline SII was calculated using routine blood counts. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and Cox proportional hazards models. With a median follow-up of 40.6 months, patients with low SII had significantly longer OS (26.1 vs. 10.9 months, p = 0.004) and PFS (15.6 vs. 7.2 months, p = 0.018) than those with high SII. Elevated SII remained independently associated with inferior OS in multivariable analysis (HR 1.99, 95% CI 1.21-3.27, p = 0.007). Although survival was numerically longer with cisplatin/etoposide than with carboplatin/paclitaxel, the difference was not statistically significant. Subgroup analysis according to SII level and chemotherapy regimen showed the poorest outcomes among patients with high SII receiving carboplatin/paclitaxel. These findings support the prognostic value of SII and suggest a potential role for risk stratification in patients with unresectable stage III NSCLC undergoing definitive chemoradiotherapy in the pre-durvalumab era.
Wickramarachchi Upul U, Corballis Natasha N, Gilbert Timothy T, Ryding Alisdair A et al.
Percutaneous coronary intervention (PCI) using drug-coated balloons (DCBs) may provide outcomes comparable to drug-eluting stents (DESs) due to the absence of a permanent implant and improved coronary artery remodelling. This study compared clinical outcomes of DCB-only angioplasty with DESs in a real-world setting. All patients undergoing PCI with DCBs or DESs for de novo disease were included in a propensity score-matched analysis using prospective and retrospective collected data from a single centre. The primary outcome was target lesion revascularisation (TLR) at 12 months. The secondary outcomes were major adverse cardiac events (MACEs) defined as a composite of all-cause death, myocardial infarction, or TLR at 12 months. Propensity matching produced 904 DCB lesions (719 patients) matched to 1424 DES lesions (1271 patients). The DCB group had smaller coronary arteries, shorter treated segments, and more bifurcation lesions. The mean age was 65 years, 22% of patients had prior MI, 16% had diabetes, and 58% had acute coronary syndromes. The rate of TLR at 12 months was as follows: 2.3% with DCBs; 2.5% with DESs (OR 0.86, p = 0.726, 95% CI 0.37-2.02). MACE was 8.2% with DCBs and 7.3% for DESs (OR 1.04, 95% CI 0.73-1.47). Results suggest comparable outcomes in patients who received paclitaxel DCBs compared to DESs without excess MACE, highlighting the need for randomised controlled trials.
Li Huan H, Cheng Yu Y, Meng Yanyun Y, Nan Liang L et al.
Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, closely associated with an imbalanced tumor immune microenvironment. Tumor-associated macrophages (TAMs) play a crucial role in tumor progression. This study aimed to investigate whether glycine combined with β-elemene inhibits TNBC progression by suppressing M2 macrophage polarization through the IL-6/JAK2/STAT3 pathway. UPLC-Q-Exactive HRMS was used to identify glycine and β-elemene. In vitro, 4T1 cell viability was determined by CCK-8 assay. RAW264.7 cells were polarized to M2 macrophages and co-cultured with 4T1 cells. Colony formation, wound healing, and Transwell assays were performed. Western blot and immunohistochemistry were used to detect protein expression. In vitro experiments were performed with at least three independent biological replicates. In vivo, 4T1 xenograft mouse models were established (n=10 per group) to evaluate anti-tumor efficacy. Glycine combined with β-elemene significantly suppressed proliferation, colony formation, and migration of 4T1 cells. Mechanistically, the combination inhibited M2 macrophage polarization by downregulating IL-6, p-JAK2, and p-STAT3. In vivo, the combination with paclitaxel showed the strongest anti-tumor effect, with reduced tumor volume and weight, decreased Ki-67 expression, and suppressed M2 polarization. Glycine combined with β-elemene inhibits M2 macrophage polarization by suppressing the IL-6/JAK2/STAT3 pathway, thereby exerting anti-TNBC effects. Its combination with paclitaxel demonstrates synergistic anti-tumor efficacy.
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