Delving into the Latest Updates on Carbonic anhydrase inhibitors(CSIRO) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

CA2

Action

inhibitors

Mechanism

CA2 inhibitors(Carbonic anhydrase II inhibitors)

Therapeutic Areas

Eye Diseases

Active Indication

Glaucoma

Inactive Indication-

Originator Organization

Fundación CSIRO Chile Research

Active Organization

Fundación CSIRO Chile Research

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

High Altitude Renal Syndrome (HARS) is a clinical syndrome characterized by polycythemia, hyperuricemia, hypertension, and albuminuria at high altitudes. This review emphasizes hypoxia-induced High Altitude Polycythemia (HAPC) as its core driver. In 2014, the 6th Qinghai International Conference on Mountain Medicine and High Altitude Physiology established international diagnostic criteria for HAPC (hemoglobin ≥210g/L in males, ≥190g/L in females). HAPC triggers systemic hypoxia, leading to hyperuricemia via uric acid overproduction and reduced renal excretion, hypertension from hemodynamic changes, and glomerular injury through erythrocytosis. Pathological mechanisms involve HIF-2α-mediated glomerular hypertrophy and podocyte damage. Treatment strategies target HAPC and downstream effects. Carbonic anhydrase inhibitors (e.g., acetazolamide) reduce hematocrit and improve oxygen saturation, but newer agents like methazolamide and dichlorphenamide offer equivalent efficacy with fewer side effects (e.g., reduced central nervous system toxicity). For severe cases, descending to lower altitudes remains the gold standard. Additional interventions include calcium channel blockers (nifedipine), urate-lowering drugs, and experimental therapies such as HIF-2α inhibitors (PT2385) and endothelin receptor antagonists (matitan). This analysis underscores HAPC as the primary etiology of HARS, advocating revised diagnostic criteria and treatment prioritization.

01 Nov 2025·JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY

Fenton reaction-enhanced mild photothermal therapy for cancer suppression with a multifunctional platform

Article

Author: Li, Na ; Tang, Bo ; Wang, Kaiye ; Liu, Xiaohan ; Jia, Yuting ; Pan, Limeng ; Shi, Mingwan ; Pan, Wei

Mild photothermal therapy effectively reduces hyperthermia-related tissue injuries; however, its low therapeutic efficiency presents a significant limitation. Herein, we developed an organic multifunctional photothermal platform with enhanced Fenton catalytic activity to increase tumor sensitivity to mild photothermal therapy. This platform incorporated a self-augmented Fenton molecule integrating carbonic anhydrase inhibitor and ferrocene, which was co-encapsulated with the photothermal agent IR 825 via an amphiphilic polymer. Under near-infrared laser irradiation, IR 825 generated heat for mild photothermal therapy, while the inhibitor blocked carbonic anhydrase IX, resulting in intracellular acidosis due to the H⁺ accumulation. The combination of acidosis and controlled heating facilitated the Fenton reaction, increasing oxidative damage to cells and heightening their sensitivity to heat. Consequently, this synergistic effect enhanced the therapeutic efficacy of mild photothermal therapy against tumor cells, as demonstrated by significant tumor inhibition in our experimental results. This study represents a promising approach towards advancing mild photothermal therapy for cancer treatment.

11 Sep 2025·JOURNAL OF MEDICINAL CHEMISTRY

Hit-to-Lead Optimization of Acetazolamide-Based Bacterial Carbonic Anhydrase Inhibitors with Efficacy In Vivo for Treatment of Vancomycin-Resistant Enterococci Septicemia

Article

Author: Tharra, Prabhakara R. ; An, Weiwei ; Supuran, Claudiu T. ; Seleem, Mohamed N. ; Nocentini, Alessio ; Youse, Molly S. ; Flaherty, Daniel P. ; Abouelkhair, Ahmed A. ; Holly, Katrina J. ; Marapaka, Anil Kumar ; Drummond, Faith L. ; S. Abdelsattar, Abdallah ; Snell, Olivia C. ; Abutaleb, Nader S.

As one of the leading causes of hospital-acquired infections reported by the National Healthcare Safety Network, vancomycin-resistant enterococci (VRE) continue to afflict patients in healthcare facilities, with limited FDA-approved drugs available for treating systemic infections. Our group previously showed the 1,3,4-thiadiazole acetazolamide human carbonic anhydrase inhibitor scaffold can be repositioned with potent in vitro efficacy against enterococcal pathogens. However, only acetazolamide has been explored for in vivo efficacy in murine septicemia models. Herein, we report a hit-to-lead account in which we expand the structure-activity relationship for the 1,3,4-thiadiazole scaffold, identified lead candidates with favorable in vitro ADME profiles, and advanced a promising lead analog forward into in vivo pharmacokinetic studies. Ultimately, we demonstrated efficacy in a murine septicemic peritonitis infection model after oral dosing. Overall, we demonstrate a successful example of an acetazolamide-based lead compound with in vivo therapeutic potential for the treatment of septicemic vancomycin-resistant VRE infection.

1

News (Medical) associated with Carbonic anhydrase inhibitors(CSIRO)

06 Jul 2024

·pharma.economictimes.indiatimes.com

Drugs body flags side effects of heart, Glaucoma medications

New Delhi: Drug standards body Indian Pharmacopoeia Commission (IPC) has issued a drug safety alert on commonly used drugs amlodipine and acetazolamide , saying both these medicines cause adverse reactions. Amlodipine - used for treatment of fatal coronary heart disease and non-fatal myocardial infarction and to reduce the risk of stroke - causes lichenoid keratosis, an inflammatory reaction, IPC said. According to IPC, amlodipine is also used to reduce the risk of coronary revascularisation procedures and need for hospitalisation due to angina in patients with coronary artery disease. The medicine is used alone or in combination with other medications. The lesions generally appear on the forearms, hands, chests of middle-aged women, or areas exposed to the sun, it said. Acetazolamide - a carbonic anhydrase inhibitor used to treat glaucoma - may lead to choroidal effusion or choroidal detachment, which is fluid buildup in the choroid layer of the eye. IPC, which comes under the health and family welfare ministry, has cautioned healthcare professionals to "diligently monitor" the potential occurrence of adverse drug reactions (ADRs) when administering these drugs. It has also advised patients and consumers to closely monitor the possibility of the above ADRs when using the suspected drugs. "Companies manufacturing these drugs may be asked to insert warnings in their package so that patients and doctors know about the adverse event," a government official said on the condition of anonymity. The IPC warning is based on preliminary analysis of adverse drug reactions (ADRs) from the Pharmacovigilance Programme of India (PvPI) database. By Teena Thacker ,