rifampicin

P1, N=32, Completed, Cascade Pharmaceuticals, Inc | Trial primary completion date: Feb 2027 --> Mar 2026 | Not yet recruiting --> Completed | Trial completion date: Feb 2027 --> Apr 2026

While modulating Bcl-2 pathways can be effective in MS, future research should aim to provide greater clarification and to design precision-based drugs capable of neuroprotective effects.

Among 5 255 randomized patients, 374 (7.1%) had LTBI and received preventive treatment, most commonly isoniazid (82.1%) and rifampicin (11.8%). From Year 1-5 (after ~98% of LTBI+ patients completed preventive treatment), transaminase elevations were generally similar among LTBI+ and LTBI- patients. The absence of observed TB risk in guselkumab-treated patients suggests IL-23 inhibitors may be better treatment options than TNFi in high-risk patients, including those in TB-endemic regions.

P1, N=48, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

Treatment of LS180 human colon adenocarcinoma cells, a commonly used human PXR (hPXR) experimental model, with a hPXR agonist (rifampicin, T0901317, SR12813, ritonavir, or paclitaxel) increased AOX1 mRNA expression by 5.2-, 10.2-, 4.7-, 2.2-, and 6.5-fold, respectively, and increased a prototypic hPXR target gene (CYP3A4 mRNA) expression by 9.5-, 13.5-, 7.2-, 3.4-, and 18.0-fold, respectively...It was abolished by actinomycin D, indicating the mRNA increase occurred by a transcriptional mechanism...Control analysis indicated that PCN increased mouse PXR-regulated Cyp3a11 mRNA and Cyp3a-mediated enzyme activity. Overall, our novel data provide evidence for a role of PXR in AOX1 gene expression.

P1, N=14, Not yet recruiting, Merck Sharp & Dohme LLC

P1, N=32, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting --> Completed

However, when acting as a victim, co-administration with strong CYP3A4 inhibitors (itraconazole, ketoconazole) increased flumatinib AUC0-72h by approximately 12-fold (AUCR = 11.65-12.96), whereas rifampicin decreased Cmax and AUC0-72h by 2.4- and 4.7-fold (CmaxR = 0.41, AUCR = 0.21), respectively. Flumatinib shows negligible perpetrator potential but is highly sensitive to CYP3A4 modulation. PBPK-informed DDI assessment supports cautious co-administration with strong CYP3A4 inhibitors or inducers and guides its rational clinical use.

P1, N=32, Active, not recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting --> Active, not recruiting | N=72 --> 32

P4, N=5, Terminated, West Virginia University | N=20 --> 5 | Enrolling by invitation --> Terminated; The study was stopped because all five participants were lost to follow-up before completing treatment or any assessments, leaving no outcome data available and making continuation of the trial infeasible.

DDI simulations indicated that vcMMAE-based ADCs act as victims with low-to-moderate sensitivity; coadministration with ketoconazole increased MMAE exposure by 45%-85%, whereas rifampin reduced it by 49%-56%. Conversely, as perpetrators, the ADCs exhibited a negligible impact on the PK of midazolam and digoxin, suggesting a low risk of MMAE-mediated inhibition or induction of CYP3A4 and P-gp...By quantitatively assessing the drug-drug interaction potential of valine-citrulline-monomethyl auristatin E-based antibody-drug conjugates as both victims and perpetrators, this work provides a scientifically justified tool to guide regulatory labeling. Importantly, this framework supports clinical drug-drug interaction trial waivers, thereby streamlining the development of next-generation targeted therapeutics.

This review discusses the current knowledge of natural products in terms of their antimicrobial actions through autophagy regulation, particularly the roles of distinct natural product classes, such as polyphenols, alkaloids, terpenoids, quinones, peptides, and macrolides in modulating autophagy for potentially contributing to control various infectious diseases. Exploring the intricate molecular interplay between natural products and autophagy in limiting infections may provide valuable insights that could inform the development of innovative host-directed antimicrobial treatments based on autophagy regulation.Abbreviations: 3-MA: 3-methyladenine; AM: alveolar macrophages; AMP: antimicrobial peptides; AMPK: 5' adenosine monophosphate-activated protein kinase; ARDS: acute respiratory distress syndrome; ART: artemisinin; ASFV: African swine fever virus; ATG: autophagy related; AZM: azithromycin; BafA1: bafilomycin A1; BECN1: beclin 1; BMDM: bone marrow-derived macrophage; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2; CBD: cannabidiol; CF: cystic fibrosis; CGA: chlorogenic acid; CGAS: cyclic GMP-AMP synthase; CHUK/IKKα: component of inhibitor of nuclear factor kappa B kinase complex; CLP: cecal ligation and puncture; CLR: clarithromycin; CMA: chaperone-mediated autophagy; CoV: coronavirus; DHT: dihydrotanshinone I; EGCG: epigallocatechin-3-gallate; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK2: eukaryotic translation initiation factor 2 alpha kinase 2; ESKAPE: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.; ESRRA: estrogen related receptor alpha; FOXO1: forkhead box O1; FUNDC1: FUN14 domain containing 1; HBV: hepatitis B virus; HCV: hepatitis C virus; HDT: host-directed therapy; HIV: human immunodeficiency virus; HMGB1: high mobility group box 1; HSV: herpes simplex virus; IAV: influenza A virus; ICT: isocryptotanshinone; IFN: interferon; IKBKB/IKKβ: inhibitor of nuclear factor kappa B kinase subunit beta; IL: interleukin; INH: isoniazid; IRF3: IFN regulatory factor 3; KEAP1: kelch like ECH associated protein 1; LAMP: lysosomal associated membrane protein; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MDM: monocyte-derived macrophage; MDR: multidrug-resistant; MON: monotropein; Mtb: Mycobacterium tuberculosis; MTOR: mechanistic target of rapamycin kinase; mtROS: mitochondrial ROS; NET: neutrophil extracellular trap; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; NFKB/NF-κB: nuclear factor kappa B; NLRP3: NLR family pyrin domain containing 3; NLRX1: NLR family member X1; NOTCH1: notch receptor 1; NTM: nontuberculous mycobacteria; OMS: ohmyungsamycin; PAK1: p21 (RAC1) activated kinase 1; PINK1: PTEN induced kinase 1; PKM/PKM2: pyruvate kinase M1/2; PLD: phospholipase D; PM: peritoneal macrophage; PPM1A: protein phosphatase, Mg2+/Mn2+ dependent 1A; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PTEN: phosphatase and tensin homolog; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RELA/p65: RELA proto-oncogene, NF-kB subunit; RIF: rifampicin; ROS: reactive oxygen species; RSV: resveratrol; RUBCN/rubicon: rubicon autophagy regulator; SAR: selective autophagy receptor; SIRT: sirtuin; STING1: stimulator of interferon response cGAMP interactor 1; STX17: syntaxin 17; Tat: trans-activator of transcription; TB: tuberculosis; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TLR: toll like receptor; TNA: tanshinone IIA; TNF: tumor necrosis factor; UA: ursolic acid; ULK1/Atg1: unc-51 like autophagy activating kinase 1; UPR: unfolded protein response; UVRAG: UV radiation resistance associated; VAMP8: vesicle associated membrane protein 8; VDR: vitamin D receptor; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1; ZIKV: Zika virus.