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TH

theophylline

✓ Approved

Bausch Health Companies Inc. · ADORA1 · Small Molecule

What is theophylline?

theophylline is a small molecule developed by Bausch Health Companies Inc.. It is approved for therapeutic indications via oral (po).

Drug Profile

CompanyBausch Health Companies Inc.
Drug ClassSmall Molecule
Molecular TargetADORA1, ADORA2A
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Bausch Health Companies Inc.

Mechanism of Action

Molecular Targets

theophylline acts on 2 molecular targets:

ADORA1adenosine A1 receptor (RDC7)
ADORA2Aadenosine A2a receptor (A2aR, RDC8)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

theophylline is developed for 3 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Respiratory, thoracic and mediastinal disordersAsthma✓ Approved
Respiratory, thoracic and mediastinal disordersBronchitis chronic✓ Approved
Respiratory, thoracic and mediastinal disordersEmphysema✓ Approved

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PubMedACS omega2026-10-17

ChemODE: A Physics-Informed Neural Surrogate for Robust Pharmacokinetics and Biochemical Dynamics.

Kulvutiroj Wit W

The automated discovery of governing kinetic laws from observational data is a critical challenge in systems biology, pharmacology, and chemical engineering. In these experimental domains, data-driven mechanism discovery is complicated by sparse sampling, measurement noise (e.g., blood assays), and the prevalence of nonlinear saturation limits (Michaelis-Menten kinetics). Existing symbolic regression methods, such as SINDy, rely on polynomial basis functions that fundamentally fail to extrapolate physical saturation, and their reliance on numerical differentiation degrades catastrophically in high-noise regimes (>5%). In this work, we introduce ChemODE, a physics-informed gray-box framework tailored for biochemical and pharmacokinetic (PK) networks. ChemODE integrates (1) Constrained Rational Layers to autonomously enforce physical saturation laws, (2) On-the-fly Feature Normalization to resolve magnitude bias in multicompartment scale separations, and (3) a noise-robust integral-based optimization scheme. We validate ChemODE on fundamental biological benchmarks, including the nonlinear Brusselator limit cycle and a synthetic 3-compartment pharmacokinetic model. To demonstrate clinical applicability, ChemODE successfully extracts physiological absorption and elimination rates from real-world human theophylline pharmacokinetic assays. Furthermore, rigorous uncertainty quantification (10-seed ensembles) proves that ChemODE recovers enzyme kinetics with high precision (V max error ≈ 1%), significantly outperforming unconstrained baselines. This work establishes that integral-based minimization, combined with rational architectural constraints and a neural residual paradigm, provides a robust surrogate modeling path for interpretable mechanism discovery in noise-dominated biochemical settings.

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PubMedInternational immunopharmacology2026-10-16

Ensifentrine inhibits lipopolysaccharide-induced production of cytokines by human lung macrophages: a comparison with roflumilast, and an interaction with adenosine.

Brollo M M, Salvator H H, Glorion M M, Marquant Q Q et al.

The dual phosphodiesterase (PDE) 3/4 inhibitor ensifentrine was recently approved for the maintenance treatment of chronic obstructive pulmonary disease in adults. Ensifentrine anti-inflammatory effects have not been studied in human lung macrophages (LMs), which are critically involved in respiratory disease. The main objectives of the present study were to compare the inhibitory effects of ensifentrine, the PDE4 inhibitor roflumilast, and the non-selective PDE inhibitor theophylline on the lipopolysaccharide (LPS)-induced production of cytokines by LMs and to assess interactions with the adenosine analogue 5´-N-ethyl-carboxamidoadenosine (NECA). LMs isolated from resected human lungs were incubated with a range of concentrations of ensifentrine, roflumilast, theophylline, NECA, and formoterol, and stimulated with LPS for 24 h. The levels of tumour necrosis factor-alpha (TNF-α), CCL2, CCL3, and CCL4 in the culture supernatants were measured using ELISAs. Ensifentrine reduced the LPS-stimulated production of TNF-α by LMs in a concentration-dependent manner, with a 100-fold lower potency but a 20-30% higher efficacy than roflumilast. Theophylline and formoterol were essentially inactive. The relative reductions in the LPS-induced production of TNF-α and the three CCL chemokines associated with treatment with the two selective inhibitors was further accentuated by NECA and resulted in similar levels of cytokine production inhibition (between 65% and 95%) with the two PDE inhibitors. Clinically relevant concentrations of ensifentrine and roflumilast partially inhibited the LPS-induced production of cytokines by LMs - cytokine production that might be enhanced during inflammatory flare-ups of respiratory diseases.

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PubMedMolecules (Basel, Switzerland)2026-10-16

Evaluation of Interleukin-8 (IL-8) Expression in Human Aortic Endothelial Cells (HAECs) and Antioxidant Activity of Isolated Compounds from the Endemic Hawaiian Plant Pipturus albidus (Māmaki).

Meesakul Pornphimon P, Kim Kyung Ah KA, Si Yaru Y, Kuroki Yutaka Y et al.

Pipturus albidus (commonly known as māmaki) is an endemic Hawaiian plant traditionally consumed as a medicinal herbal tea; however, its comprehensive potential for phytochemical composition and biological activities remains underexplored. In this study, we present the first comprehensive phytochemical characterization of the ethanol extract of P. albidus, identifying twelve compounds through chromatographic and spectroscopic analyses. The isolated compounds were subjected to a series of antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC). Cinchonain Ia (2), vitexin (6), and (7S,8R)-dihydrodehydro diconiferyl alcohol (11) demonstrated strong free radical-scavenging and reducing capacities. Evaluation of Interleukin-8 (IL-8) expression in TNF-α-stimulated human aortic endothelial cells (HAECs) revealed that catechin-(7,8-bc)-4a-(3,4-dihydroxyphenyl)-dihydro-2(3H)-pyranone (3) and trans-ferulic acid (9) significantly increased IL-8 mRNA expression (p < 0.05), indicating potential pro-inflammatory effects of these isolated constituents. In contrast, neither the crude extract (PE) nor vitexin (6) produced a statistically significant difference in IL-8 mRNA levels compared to the TNF-α control (p < 0.05). Quantitative LC-MS/MS analysis confirmed that caffeine, theobromine, theophylline, and EGCG were below the limit of detection in P. albidus leaf extracts, indicating that P. albidus possesses a phytochemical constituent distinct from that of green tea. In summary, P. albidus leaves contain unique phytochemicals with cell-free antioxidant activity, while cell-based assays indicate potential pro-inflammatory risks for compounds 3 and 9 and no significant anti-inflammatory suppression by PE or vitexin (6).

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PubMedArchiv der Pharmazie2026-10-15

Synthesis of Some New Xanthine Derivatives and Evaluation of DPP IV Inhibitory Activities.

Akgün Erol E, Yurttaş Leyla L, Kaleli Sevde Nur Biltekin SNB, Osmaniye Derya D et al.

Dipeptidyl peptidase IV (DPP IV) inhibition prolongs incretin activity and represents an established therapeutic strategy for the management of type 2 diabetes mellitus. To investigate the underexplored combination of benzyl groups at the N7 position and a piperazine-linked arylthiazole moiety at the C8 position of the xanthine scaffold, 15 novel compounds (6a-6o) were synthesised. The synthetic route involved bromination at the C8 position of theophylline, introduction of benzyl groups at the N7 position, replacement of the bromine atom at the C8 position with piperazine, and subsequent cyclocondensation with phenacyl thiocyanate derivatives. All final compounds were characterised by 1H and 13C NMR spectroscopy, high-resolution accurate-mass mass spectrometry, and analytical HPLC. All derivatives inhibited DPP IV in the low-nanomolar range, with compounds 6c and 6b showing the highest activities, with IC50 values of 3.95 ± 0.53 and 4.04 ± 0.65 nM, respectively. NIH3T3 cytotoxicity IC50 values ranged from 28.52 to 397.63 µM, indicating substantial preliminary concentration margins relative to DPP IV inhibition. Molecular docking, 100 ns molecular dynamics simulations, interaction-fingerprint analyses and trajectory-based MM/PBSA calculations supported persistent interactions with key DPP IV active-site residues. These results identify the synthesised derivatives, particularly 6b and 6c, as promising lead structures for further optimisation.

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PubMedFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2026-10-15

Evaluating the biological effects of caffeine-related compounds methylliberine and theacrine by integrated in silico and in vitro new approach methods (NAMs).

Santillo Michael F MF, Sprando Robert L RL, Yourick Jeffrey J JJ

Methylliberine (1,O2,7,9-tetramethyluric acid; 1,2,7,9-MU) and theacrine (1,3,7,9-tetramethyluric acid; 1,3,7,9-MU) are purine alkaloids found in a variety of botanicals and products marketed as dietary supplements. Despite their widespread use, extensive data on their human health effects are lacking. Therefore, methylliberine and theacrine were profiled using multiple new approach methods (NAMs): in silico metabolite predictions, in silico blood-brain barrier (BBB) permeability predictions, and in vitro assays for adenosine receptor binding (A1, A2A), functional activity (A2A), cytochrome P450 inhibition (CYP1A2), and phosphodiesterase inhibition (PDE3A, PDE4B, PDE4D). Like caffeine, methylliberine and theacrine were predicted to be metabolized via desmethylation by multiple in silico models. In silico predictions and cluster analysis also suggested that methylliberine and theacrine may permeate the BBB like caffeine. In vitro assays revealed that methylliberine and its metabolite 1,2,9-MU were CYP1A2 inhibitors (IC50, 9.6 and 27 μM, respectively) that agreed with clinical observations and could lead to interactions with drugs and xenobiotics. Both methylliberine and theacrine were A2A receptor antagonists, suggesting a potential for stimulant effects, although their potencies (52-62% inhibition at 100 μM) were weaker than theophylline, paraxanthine, and caffeine (IC50, 4.9-23.3 μM). Overall, this study highlights integration of multiple NAMs for profiling two purine alkaloids relevant to human health.

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PubMedPloS one2026-10-08

A modular toolkit for theophylline-dependent synthetic auxotrophs via riboswitch-gated essential genes.

Gonzalez-Lopez Carlos C, Overly Adrian A, Singh Saahil S, Huang Charlie C et al.

Synthetic auxotrophs are a useful means for developing genetically encoded biocontainment systems. Current methods for developing synthetic auxotrophs are complicated or expensive, limiting access and adoption of biocontainment technologies. To address this gap, we developed a simple and modular platform for creating synthetic auxotrophs based on ligand-dependent translational gating of essential genes. By inserting a theophylline-responsive riboswitch upstream of essential genes in Escherichia coli, we created strains whose viability depends on the presence of theophylline. We systematically applied this approach to 29 essential genes, obtained ligand-dependent growth phenotypes for 19 targets, and found that 18 of these essential genes yielded stringent live-die synthetic auxotrophs. These strains exhibited robust theophylline dependence with escape frequencies ranging from 1 × 10-5 to 1 × 10-6 (most below limit of detection). Our modular design allows for the rapid (<1 week), low-cost, and reliable generation of synthetic auxotrophs. This work introduces ligand-dependent translational control as a new mechanism for engineering synthetic auxotrophy and provides an accessible platform that expands the biocontainment toolkit.

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