IKKε inhibitors(inhibitor of nuclear factor kappa B kinase subunit epsilon inhibitors), PDK1 inhibitors(3-phosphoinositide-dependent protein kinase 1 inhibitors), TBK1 inhibitors(Serine/threonine-protein kinase TBK1 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Berlex Biosciences

Active Organization

Berlex Biosciences

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC23H26IN7O2S

InChIKeyVAVXGGRQQJZYBL-UHFFFAOYSA-N

CAS Registry702675-74-9

100 Clinical Results associated with BX795

100 Translational Medicine associated with BX795

100 Patents (Medical) associated with BX795

228

Literatures (Medical) associated with BX795

11 Mar 2025·Environmental Science & Technology

IodoFinder: Machine Learning-Guided Recognition of Iodinated Chemicals in Nontargeted LC-MS/MS Analysis

Article

Author: Zhao, Tingting ; Li, Xing-Fang ; Shen, Qiming ; Huan, Tao

Iodinated disinfection byproducts (I-DBPs) pose significant health concerns due to their high toxicity. Current approaches to recognize unknown I-DBPs in mass spectrometry (MS) analysis rely on negative ionization mode, in which the characteristic I^- fragment can be observed in tandem mass spectra (MS/MS). Still, many I-DBPs ionize exclusively in positive ionization mode, where the I^- fragment is absent. To address this gap, this work developed a machine learning-based strategy to recognize iodinated compounds (I-compounds) from their MS/MS in both electrospray positive (ESI+) and negative ionization (ESI-) modes. Investigating over 6000 MS/MS spectra of 381 I-compounds, we first identified five characteristic I-containing neutral losses and one diagnostic I^- fragment in ESI+ and ESI- modes, respectively. We then trained Random Forest models and integrated them into IodoFinder, a Python program, to streamline the recognition of I-compounds from raw LC-MS data. IodoFinder accurately recognized over 96% of the 161 I-compound standards in both ionization modes. In its application to DBP mixtures, IodoFinder discovered 19 I-DBPs with annotated structures and an additional 17 with assigned formulas, including 12 novel and 3 confirmed I-DBPs. We envision that IodoFinder will advance the identification of both known and unknown I-compounds in exposome studies.

01 Mar 2025·Journal of Biotechnology

Interferon inhibitors increase rAAV production in HEK293 cells

Article

Author: Yoon, Seongkyu ; Fu, Qiang ; Sha, Sha ; Wang, Yongdan

Recombinant adeno-associated viruses (rAAVs) comprise a promising viral vector for therapeutic gene delivery to treat disease. However, the current manufacturing capability of rAAVs must be improved to meet commercial demand. Previously published omics studies indicate that rAAV production through transient transfection triggers antiviral responses and endoplasmic reticulum stress responses in the host cell. Both responses negatively regulate viral production. We demonstrate that the modulation of the antiviral immune response (by blocking interferon signaling pathways) can effectively lower the production of interferon and enhance viral genome production. The use of interferon inhibitors before transfection can significantly increase rAAV production in HEK293 cells, with up to a 2-fold increase in productivity and up to a 6-fold increase in specific productivity. Compared to the untreated groups, the addition of these small molecules generally reduced viable cell density but increased vector productivity. The positive candidates were BX795 (a TBK inhibitor), TPCA-1 (an IKK2 inhibitor), Cyt387 (a JAK1 inhibitor), and ruxolitinib (another JAK1 inhibitor). These candidates were identified using deep well screening, and reproducible titer improvement was achieved in a 30 mL shake flask scale. Additionally, genome titer improvement is feasible and scalable in two different media, but the extent of improvement may vary.

01 Feb 2025·Immunity

The cGAS-STING pathway activates transcription factor TFEB to stimulate lysosome biogenesis and pathogen clearance

Article

Author: Wang, Jun ; Wang, Yusha ; Lu, Sheng ; Qian, Chuying ; Liu, Wei ; Xu, Yinfeng ; Wan, Wei ; Wang, Qian ; Song, Lijiang ; He, Zhengfu

Induction of autophagy is an ancient function of the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway through which autophagic cargoes are delivered to lysosomes for degradation. However, whether lysosome function is also modulated by the cGAS-STING pathway remains unknown. Here, we discovered that the cGAS-STING pathway upregulated lysosomal activity by stimulating lysosome biogenesis independently of the downstream protein kinase TANK-binding kinase 1 (TBK1). STING activation enhanced lysosome biogenesis through inducing the nuclear translocation of transcription factor EB (TFEB) as well as its paralogs transcription factor E3 (TFE3) and microphthalmia-associated transcription factor (MITF). STING-induced lipidation of GABA type A receptor-associated protein (GABARAP), an autophagy-related protein, on STING vesicles was responsible for TFEB activation. Membrane-bound GABARAP sequestered the GTPase-activating protein folliculin (FLCN) and FLCN-interacting protein (FNIP) complex to block its function toward the Rag GTPases Ras-related GTP-binding C and D (RagC and RagD), abolishing mechanistic target of rapamycin (mTOR) complex 1 (mTORC1)-dependent phosphorylation and inactivation of TFEB. Functionally, STING-induced lysosome biogenesis within cells facilitated the clearance of cytoplasmic DNA and invading pathogens. Thus, our findings reveal that induction of lysosome biogenesis is another important function of the cGAS-STING pathway.

100 Deals associated with BX795

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	United States	Berlex Biosciences	01 May 2005

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