Radiosensitization of human pancreatic cancer by piperlongumine analogues

Ma, Hao; Wu, Yang‐Chang; Zhang, Wannian; Zhang, Huojun; Miao, Zhenyuan

doi:10.1016/j.cclet.2020.08.049

Cited by 22 publications

(20 citation statements)

References 21 publications

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“…DARTS experiments for identifying the targets of 25 were performed as our previous reports 28 , 38 . Cells were lysed and treated with 25 (50 μmol/L) followed by digestion with 0.1% pronase for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy

Zhu

Meng

et al. 2021

Acta Pharmaceutica Sinica B

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Receptor-interacting protein (RIP) kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis (UC) by regulating necroptosis and inflammation. Our group previously identified TAK-632 ( 5 ) as an effective necroptosis inhibitor by dual-targeting RIP1 and RIP3. In this study, using ligand-based substituent-anchoring design strategy, we focused on the benzothiazole ring to obtain a series of TAK-632 analogues showing significantly improving on the anti-necroptosis activity and RIP1 selectivity over RIP3. Among them, a conformational constrained fluorine-substituted derivative ( 25 ) exhibited 333-fold selectivity for RIP1 ( K d = 15 nmol/L) than RIP3 ( K d > 5000 nmol/L). This compound showed highly potent activity against cell necroptosis (EC 50 = 8 nmol/L) and systemic inflammatory response syndrome (SIRS) induced by TNF- α in vivo. Especially, it was able to exhibit remarkable anti-inflammatory treatment efficacy in a DSS-induced mouse model of UC. Taken together, the highly potent, selective, orally active anti-necroptosis inhibitor represents promising candidate for clinical treatment of UC.

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Section: Methodsmentioning

confidence: 99%

Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy

Zhu

Meng

et al. 2021

Acta Pharmaceutica Sinica B

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“…Recombinant wild-type p66/p51 HIV-1 RT was expressed and purified as described. , The RT assay was performed with the EnzCheck Reverse Transcriptase Assay kit (Molecular Probes, Invitrogen), as described by the manufacturer. The assay is based on the dsDNA quantitation reagent PicoGreen.…”

Section: Experimental Sectionmentioning

confidence: 99%

Improving Druggability of Novel Diarylpyrimidine NNRTIs by a Fragment-Based Replacement Strategy: From Biphenyl-DAPYs to Heteroaromatic-Biphenyl-DAPYs

et al. 2021

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A series of novel heteroaromatic-difluoro-biphenyl-diarylpyrimidines were designed as non-nucleoside anti-HIV inhibitors targeting reverse transcriptase by a fragment-based replacement strategy with the purpose of improving the druggability. Hopping fiveor six-membered heterocycle groups on the biphenyl moiety as bioisosterism for intrinsically cyanophenyl gave 23 derivatives. All of these compounds possessed excellent HIV-1 inhibitory activity in the nanomolar range. Among them, 12g with a 4-pyridine group displayed excellent inhibitory activity toward WT and mutant HIV virus possessing significant selectivity. Moreover, this compound exhibited a decent improvement in druggability than etravirine and rilpivirine: (1) The hydrochloric acid salt of 12g exhibited significantly improved water solubility in different pH conditions. (2) 12g did not show apparent CYP enzymatic inhibitory activity or acute toxicity. (3) Excellent oral bioavailability was also revealed (F = 126%, rats) in 12g.Collectively, these novel heteroaromatic-biphenyl-DAPYs represent promising drug candidates for HIV clinical therapy.

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“…In this study, we applied brachytherapy for the treatment of orthotopic HNSCC tumors using intratumoral injection of 177 Lu-DTPA-pAuNS. This local chemoradiotherapy method can deliver a relatively precise quantity of high-dose-rate radiopharmaceutical to specific tumor positions so that the risk of side effects is minimized [30][31][32]. Brachytherapy has also been applied in different types of HNSCC, including nasopharyngeal cancer, and oral cancer [33,34].…”

Section: Discussionmentioning

confidence: 99%

Brachytherapy Approach Using 177Lu Conjugated Gold Nanostars and Evaluation of Biodistribution, Tumor Retention, Dosimetry and Therapeutic Efficacy in Head and Neck Tumor Model

et al. 2021

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Brachytherapy can provide sufficient doses to head and neck squamous cell carcinoma (HNSCC) with minimal damage to nearby normal tissues. In this study, the β−-emitter 177Lu was conjugated to DTPA-polyethylene glycol (PEG) decorated gold nanostars (177Lu-DTPA-pAuNS) used in surface-enhanced Raman scattering and photothermal therapy (PTT). The accumulation and therapeutic efficacy of 177Lu-DTPA-pAuNS were compared with those of 177Lu-DTPA on an orthotopic HNSCC tumor model. The SPECT/CT imaging and biodistribution studies showed that 177Lu-DTPA-pAuNS can be accumulated in the tumor up to 15 days, but 177Lu-DTPA could not be detected at 24 h after injection. The tumor viability and growth were suppressed by injected 177Lu-DTPA-pAuNS but not nonconjugated 177Lu-DTPA, as evaluated by bioluminescent imaging. The radiation-absorbed dose of the normal organ was the highest in the liver (0.33 mSv/MBq) estimated in a 73 kg adult, but that of tumorsphere (0.5 g) was 3.55 mGy/MBq, while intravenous injection of 177Lu-DTPA-pAuNS resulted in 1.97 mSv/MBq and 0.13 mGy/MBq for liver and tumorsphere, respectively. We also observed further enhancement of tumor-suppressive effects by a combination of 177Lu-DTPA-pAuNS and PTT compared to 177Lu-DTPA-pAuNS alone. In conclusion, 177Lu-DTPA-pAuNS may be considered as a potential radiopharmaceutical agent for HNSCC brachytherapy.

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Radiosensitization of human pancreatic cancer by piperlongumine analogues

Cited by 22 publications

References 21 publications

Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy

Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy

Improving Druggability of Novel Diarylpyrimidine NNRTIs by a Fragment-Based Replacement Strategy: From Biphenyl-DAPYs to Heteroaromatic-Biphenyl-DAPYs

Brachytherapy Approach Using 177Lu Conjugated Gold Nanostars and Evaluation of Biodistribution, Tumor Retention, Dosimetry and Therapeutic Efficacy in Head and Neck Tumor Model

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