GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Abstract 494: BPI-452080: A potent and selective HIF-2α inhibitor for the treatment of clear cell renal cell carcinoma, von Hippel-Lindau disease, and other solid tumors
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 494-494
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 494-494
    Abstract: The most observed alteration in clear cell renal cell carcinoma (ccRCC) is the inactivation of the tumor suppressor von Hippel-Lindau (VHL) E3 ligase due to genetic predisposition, somatic mutations, or methylation. Loss of VHL can lead to hypoxia-inducible factor 2α (HIF-2α) accumulation and elevated expression of HIF target genes, such as VEGFA, many of which facilitate angiogenesis, proliferation, and metastasis of ccRCC. Therefore, inhibiting HIF-2α has become a new strategy for the treatment of ccRCC. Here, we present the discovery of BPI-452080, a selective small molecule HIF-2α inhibitor. In VHL defective ccRCC cell lines, BPI-452080 potently and selectively blocked the heterodimerization of HIF-2α with HIF-1β, but not that of HIF-1α with HIF-1β. It inhibited the downstream hypoxia-responsive gene transcription and VEGFA protein secretion. In multiple xenograft mouse models, oral administration of BPI-452080 significantly inhibited tumor growth in a dose-dependent manner. BPI-452080 demonstrated good PK/PD correlation in the 786-O xenograft model after a single dosing, as shown by a concentration-dependent inhibition of VEGFA secretion in plasma and a reduction of the mRNA levels of VEGFA, CXCR4, CCND1, and GLUT1 genes in tumor tissue. Moreover, BPI-452080 exhibited good bioavailability in multiple pre-clinical species, favorable ADME properties, and good tolerance in toxicology studies. In conclusion, BPI-452080 is a potent, selective, and orally bioavailable HIF-2α inhibitor which presents a novel therapeutic option for ccRCC, von Hippel-Lindau disease, and other solid tumors. BPI-452080 is planned to enter Phase I clinical trial in China in early 2023. Citation Format: Pingping Wang, Rongwen Yang, Yun Sun, Xuepeng Ju, Jiayu Zhao, Yanju Liu, Xiaoyun Liu, Zhengyao Zou, Jialin Ren, Min Wang, Haibo Chen, Xuegang Yi, Jian Zhang, Teng Ma, Gaoliang Cheng, Lijia Liu, Jing Guo, Xiangyong Liu, Hong Lan, Lieming Ding, Jiabing Wang. BPI-452080: A potent and selective HIF-2α inhibitor for the treatment of clear cell renal cell carcinoma, von Hippel-Lindau disease, and other solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 494.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-494
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract 501: Discovery of BPI-460372, a potent and selective inhibitor of TEAD for the treatment of solid tumors harboring Hippo pathway aberrations
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 501-501
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 501-501
    Abstract: The Hippo signaling pathway is critical for the regulation of organ development, tissue homeostasis, and tumorigenesis by controlling the activation status of yes-associated protein (YAP) or its homolog PDZ-binding motif (TAZ). As a major downstream effector, the transcription factor TEAD is activated by forming a complex with YAP/TAZ. Hippo pathway aberrations, such as NF2-deficiency or LATS1/2 mutations leading to hyperactivation of YAP/TAZ and subsequent activation of TEAD, have been reported in many cancers, including mesothelioma, meningioma, soft tissue sarcoma and non-small cell lung cancer. Inhibiting TEAD auto-palmitoylation by directly blocking the palmitoylation pocket of TEAD is a potential therapeutic approach for cancer treatment. Here we present BPI-460372, a novel small molecule that directly blocks the TEAD auto-palmitoylation. BPI-460372 covalently and irreversibly binds to the cysteine residue in the TEAD palmitoylation pocket, preventing TEAD palmitoylation and inhibiting its biological function. BPI-460372 significantly inhibits the expression of a TEAD-responsive element reporter, as well as the mRNA of downstream target genes such as CTGF and CYR61 in NF2-deficient cells. At the cellular level, BPI-460372 strongly inhibited the proliferation of tumor cells harboring Hippo pathway aberrations. BPI-460372 also significantly suppressed tumor growth in NF2-deficient or LATS1/2 mutation xenograft models. In addition, BPI-460372 exhibited excellent oral bioavailability, high exposure across multiple species, and adequate ADME properties. In conclusion, BPI-460372 is a potent and selective TEAD palmitoylation inhibitor for the treatment of solid tumors harboring Hippo pathway aberrations. It is planned to enter Phase I clinical trial in China in early 2023. Citation Format: Hongling Shen, Xiaofeng Xu, Hongfei Rong, Xizhen Song, Jinheng Gao, Jie Chen, Di Zhu, Xiangdong Zhao, Jun Tong, Zhengyao Zou, Xiaoyun Liu, Jin Guo, Yan Xu, Yabin Li, Xiangyong Liu, Hong Chen, Jiayu Zhao, Yanju Liu, Xuepeng Ju, Haibo Chen, Hong Lan, Lieming Ding, Jiabing Wang. Discovery of BPI-460372, a potent and selective inhibitor of TEAD for the treatment of solid tumors harboring Hippo pathway aberrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 501.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-501
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Dual-Signal Cascaded Nucleic Acid Amplification Circuit-Loaded Metal-Organic Frameworks for Accurate and Robust Imaging of Intracellular MicroRNA
    American Chemical Society (ACS) ; 2023
    In:  Langmuir Vol. 39, No. 30 ( 2023-08-01), p. 10453-10463
    Details
    In: Langmuir, American Chemical Society (ACS), Vol. 39, No. 30 ( 2023-08-01), p. 10453-10463
    Type of Medium: Online Resource
    ISSN: 0743-7463 , 1520-5827
    URL: Article
    URL: Article
    DOI: 10.1021/acs.langmuir.3c00897
    DOI: 10.1021/acs.langmuir.3c00897.s001
    RVK:
    VA 5760
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2023
    detail.hit.zdb_id: 2005937-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Chemiluminescence resonance energy transfer-based multistage nucleic acid amplification circuits for MiRNA detection with low background
    Royal Society of Chemistry (RSC) ; 2023
    In:  The Analyst Vol. 148, No. 12 ( 2023), p. 2683-2691
    Details
    In: The Analyst, Royal Society of Chemistry (RSC), Vol. 148, No. 12 ( 2023), p. 2683-2691
    Abstract: Chemiluminescence resonance energy transfer (CRET)-based assays have shown great potential in biosensing due to their negligible background autofluorescence, yet are still limited by their low sensitivity and short half-life luminescence. Herein, a multistage CRET-based DNA circuit was constructed with amplified luminescence signals for accurate miRNA detection and fixed reactive oxygen species (ROS) signals for cell imaging. The DNA circuit is designed through an ingenious programmable catalytic hairpin assembly (CHA), hybridization chain reaction (HCR), and the use of DNAzyme to realize target-triggered precise regulation of distance between the donor and acceptor for CRET-mediated excitation of photosensitizers. In detail, the analyte catalyzes the hybridization of CHA reactants, which leads to the assembly of multiple HCR-mediated DNAzyme nanowires. Subsequently, DNAzymes catalyze the oxidation of luminol by H 2 O 2 , and the adjacent photosensitizer chlorin e6 (Ce6) anchored on the DNA nanostructure is stimulated by the CRET process, resulting in the amplified long-wavelength luminescence and the generation of single oxygen signals through further energy transfer to oxygen. The biomarker miRNA can be detected with great sensitivity by integrating the recognition module into a universal platform. Furthermore, the DNA circuit enables CRET-mediated intracellular miRNA imaging, by detecting singlet oxygen signals through a ROS probe. The significant amplification effect is attributed to the robust multiple recognition of the target and the guaranteed transduction of the CRET signal through programmable engineering of DNA nanostructures. The CRET-based DNA circuit achieves amplified long-wavelength luminescence for accurate miRNA detection with low background and ROS-mediated signal fixation for cell imaging, making it a promising candidate for early diagnosis and theranostics.
    Type of Medium: Online Resource
    ISSN: 0003-2654 , 1364-5528
    URL: Article
    DOI: 10.1039/D3AN00594A
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2023
    detail.hit.zdb_id: 1472713-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract 495: Discovery of BPI-221351, a potent, selective, orally available, and brain penetrating dual inhibitor of mutant IDH1/2
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 495-495
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 495-495
    Abstract: Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are critical enzymes of the tricarboxylic acid cycle, which convert isocitrate into α-ketoglutarate (α-KG). IDH1 or IDH2 mutations are observed in more than 80% of low- to mid-grade gliomas and in ~20% of acute myeloid leukemia (AML). Tumor-related IDH1/2 mutants acquire a novel function of using α-KG as a substrate to produce R-2-hydroxyglutarate (2-HG). 2-HG is an oncogenic metabolite, and reducing it by inhibiting mutant IDH1 or IDH2 has been shown to be an effective treatment approach. Although agents targeting IDH1 or IDH2 have been approved to treat IDH-mutant cancers, existing IDH1 inhibitors do not cross the blood-brain barrier, a feature needed for treating glioma. Furthermore, resistant mutations do occur, including cross-isoform mutations, which call for the development of dual IDH1/2 inhibitors with good brain penetration. However, IDH1/2 dual inhibitors are rarely discovered. Here we report the discovery of BPI-221351, a potent inhibitor of mutant IDH1 and mutant IDH2. BPI-221351 shows excellent inhibitory activities against both IDH1 and IDH2 enzymes, and potently suppresses 2-HG levels in tumor cells harboring IDH1 or IDH2 mutants. In an IDH-mutant xenograft model, BPI-221351 reduced 2-HG to baseline level up to 24 h after a single oral dose administration. In addition, BPI-221351 possesses excellent blood-brain-barrier penetration with a higher drug concentration in the brain than that in plasma. In conclusion, BPI-221351 exhibits strong activity towards both IDH1 and IDH2 mutants in vitro and in vivo with favorable pharmacological properties, presenting a new therapeutic opportunity for treating glioma and other relevant cancers. Citation Format: Hongling Shen, Xiaofeng Xu, Yabin Li, Xizhen Song, Jie Chen, Yunting Bi, Jing Guo, Tong Xu, Huijuan Zhang, Lijia Liu, Zhengyao Zou, Jialin Ren, Jun Tong, Xiaoyun Liu, Hongfei Rong, Teng Ma, Chao Wang, Xiangyong Liu, Hong Chen, Jiayu Zhao, Xuepeng Ju, Haibo Chen, Haidi Shen, Hong Lan, Lieming Ding, Jiabing Wang. Discovery of BPI-221351, a potent, selective, orally available, and brain penetrating dual inhibitor of mutant IDH1/2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 495.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-495
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Modeling analysis of COVID-19 based on morbidity data in Anhui, China
    American Institute of Mathematical Sciences (AIMS) ; 2020
    In:  Mathematical Biosciences and Engineering Vol. 17, No. 4 ( 2020), p. 2842-2852
    Details
    In: Mathematical Biosciences and Engineering, American Institute of Mathematical Sciences (AIMS), Vol. 17, No. 4 ( 2020), p. 2842-2852
    Abstract: 〈abstract〉 〈p〉Since the first case of coronavirus disease (COVID-19) in Wuhan Hubei, China, was reported in December 2019, COVID-19 has spread rapidly across the country and overseas. The first case in Anhui, a province of China, was reported on January 10, 2020. In the field of infectious diseases, modeling, evaluating and predicting the rate of disease transmission is very important for epidemic prevention and control. Different intervention measures have been implemented starting from different time nodes in the country and Anhui, the epidemic may be divided into three stages for January 10 to February 11, 2020, namely. We adopted interrupted time series method and develop an SEI/QR model to analyse the data. Our results displayed that the lockdown of Wuhan implemented on January 23, 2020 reduced the contact rate of epidemic transmission in Anhui province by 48.37%, and centralized quarantine management policy for close contacts in Anhui reduced the contact rate by an additional 36.97%. At the same time, the estimated basic reproduction number gradually decreased from the initial 2.9764 to 0.8667 and then to 0.5725. We conclude that the Wuhan lockdown and the centralized quarantine management policy in Anhui played a crucial role in the timely and effective mitigation of the epidemic in Anhui. One merit of this work is the adoption of morbidity data which may reflect the epidemic more accurately and promptly. Our estimated parameters are largely in line with the World Health Organization estimates and previous studies.〈/p〉 〈/abstract〉
    Type of Medium: Online Resource
    ISSN: 1551-0018
    URL: Article
    DOI: 10.3934/mbe.2020158
    Language: Unknown
    Publisher: American Institute of Mathematical Sciences (AIMS)
    Publication Date: 2020
    detail.hit.zdb_id: 2265126-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    An Intelligent Laser‐Free Photodynamic Therapy Based on Endogenous miRNA‐Amplified CRET Nanoplatform**
    Wiley ; 2023
    In:  Chemistry – A European Journal Vol. 29, No. 33 ( 2023-06-13)
    Details
    In: Chemistry – A European Journal, Wiley, Vol. 29, No. 33 ( 2023-06-13)
    Abstract: Laser‐free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep‐seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA‐responsive laser‐free PDT was developed through metal‐organic frameworks (MOFs)‐mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)‐loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)‐mimicking hemin/G‐quadruplex DNAzyme on MOFs. Simultaneously, the on‐MOF assembled DNAzymes efficiently catalyzed chemiluminescence reaction to stimulate adjacent Ce6 in the presence of luminol and H 2 O 2 , thus allowing the CRET‐mediated Ce6 luminescence and reactive oxygen species (ROS) generation for self‐illuminating PDT. The CRET nanoplatform achieved significant malignant cell apoptosis and tumor inhibition effects without external laser irradiation. It is envisioned that the miRNA‐amplified CRET nanoplatform might be a selective and highly efficient antitumor nanomedicine for precise theranostic.
    Type of Medium: Online Resource
    ISSN: 0947-6539 , 1521-3765
    URL: Issue
    URL: Article
    DOI: 10.1002/chem.v29.33
    DOI: 10.1002/chem.202300861
    RVK:
    VA 1120 ; VA 3507
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1478547-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Interleukin 33 in tumor microenvironment is crucial for the accumulation and function of myeloid-derived suppressor cells
    Informa UK Limited ; 2016
    In:  OncoImmunology Vol. 5, No. 1 ( 2016-01-02), p. e1063772-
    Details
    In: OncoImmunology, Informa UK Limited, Vol. 5, No. 1 ( 2016-01-02), p. e1063772-
    Type of Medium: Online Resource
    ISSN: 2162-402X
    URL: Article
    DOI: 10.1080/2162402X.2015.1063772
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2645309-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    The laser beamline in SULF facility
    Cambridge University Press (CUP) ; 2020
    In:  High Power Laser Science and Engineering Vol. 8 ( 2020)
    Details
    In: High Power Laser Science and Engineering, Cambridge University Press (CUP), Vol. 8 ( 2020)
    Abstract: In this paper, we report the recent progress on the $1~\text{PW}/0.1~\text{Hz}$ laser beamline of Shanghai Superintense Ultrafast Laser Facility (SULF). The SULF-1 PW laser beamline is based on the double chirped pulse amplification (CPA) scheme, which can generate laser pulses of 50.8 J at 0.1 Hz after the final amplifier; the shot-to-shot energy fluctuation of the amplified pulse is as low as 1.2% (std). After compression, the pulse duration of 29.6 fs is achieved, which can support a maximal peak power of 1 PW. The contrast ratio at $-80~\text{ps}$ before main pulse is measured to be $2.5\times 10^{-11}$ . The focused peak intensity is improved by optimizing the angular dispersion in the grating compressor. The maximal focused peak intensity can reach $2.7\times 10^{19}~\text{W}/\text{cm}^{2}$ even with an $f/26.5$ off-axis parabolic mirror. The horizontal and vertical angular pointing fluctuations in 1 h are measured to be 1.89 and $2.45~\unicode[STIX]{x03BC}\text{rad}$ , respectively. The moderate repetition rate and the good stability are desirable characteristics for laser–matter interactions. The SULF-1 PW laser beamline is now in the phase of commissioning, and preliminary experiments of particle acceleration and secondary radiation under 300–400 TW/0.1 Hz laser condition have been implemented. The progress on the experiments and the daily stable operation of the laser demonstrate the availability of the SULF-1 PW beamline.
    Type of Medium: Online Resource
    ISSN: 2095-4719 , 2052-3289
    URL: Article
    DOI: 10.1017/hpl.2020.3
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2723155-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Pulsed Laser Deposited Sns-Snse Composite Thin Film As a New Anode Material for Lithium Storage
    The Electrochemical Society ; 2015
    In:  ECS Meeting Abstracts Vol. MA2015-02, No. 7 ( 2015-07-07), p. 517-517
    Details
    In: ECS Meeting Abstracts, The Electrochemical Society, Vol. MA2015-02, No. 7 ( 2015-07-07), p. 517-517
    Abstract: In recent years tin-based materials has been subjected as promising anode materials due to a high theoretical capacity of Li 4.4 Sn (994mAh g -1 ). However, tin-based materials is still far away from practical use since it suffers from significant volume change. It has been demonstrated that nano-thin film have its unique characteristics than bulk materials. In this work, SnS-SnSe composite thin films are synthesized by plused laser deposition. Its first discharge capacity was 1225.8 mAh g -1 and capacity after three cycles maintained about 650 mAh g -1 . SnS-SnSe composite thin film firstly reacted with Li during discharge to form Li 2 SALi 2 Se and Sn, then Sn reacted with Li to form Li x Sn alloy. During the charge, Li x Sn firstly decomposed to form elementary Sn, then Sn catalyzed Li 2 S and Li 2 Se to decompose to rebuild SnS-SnSe composite thin film. Li 2 S and Li 2 Se produced during discharge can suffer a certain amount of volume change which enhanced the cycle performance. SnS-SnSe composite thin film had more grain boundary than SnS or SnSe thin film which could effectively enhance electrochemical activity and increase capacity. Fig.1 The first three CVs of SnS-SnSe composite thin film Fig.2 Galvanostatic charge-discharge curve of SnS-SnSe composite thin film electrodes Fig.3 Cycling performance of SnS-SnSe, SnS and SnSe thin films with 20 cycles Acknowledgements The authors appreciate the financial support of LPMT, CAEP (ZZ13007), Project 2013A030214 supported by CAEP. Figure 1
    Type of Medium: Online Resource
    ISSN: 2151-2043
    URL: Article
    DOI: 10.1149/MA2015-02/7/517
    Language: Unknown
    Publisher: The Electrochemical Society
    Publication Date: 2015
    detail.hit.zdb_id: 2438749-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...