Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies

Kciuk, Mateusz; Gielecińska, Adrianna; Mujwar, Somdutt; Marciniak, Beata; Drozda, Rafał; Kontek, Renata

doi:10.1080/14756366.2022.2052868

Cited by 48 publications

(40 citation statements)

References 211 publications

(240 reference statements)

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“…The inhibition of tumor isoforms of CA (CA-IX and XII) has been shown to significantly reduce the survival of hypoxic tumors. Nowadays, sulfonamide compounds have been tested in clinical trials, with SLC-0011 being one of the most prominent examples of this type of agents [ 22 ]. The best results against hCA-IX were observed with pyrazolo[4,3- e ][1,2,4]triazines with dissociation constants (KI values) of 23.7 and 26.5 nM, which were similar to reference sulfonamide compound acetazolamide (KI = 25 nM).…”

Section: Introductionmentioning

confidence: 99%

Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies

Kciuk

Mujwar

Szymanowska

et al. 2022

IJMS

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Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides constitute a novel class of heterocyclic compounds with broad biological activity, including anticancer properties. Investigated in this study, MM-compounds (MM134, MM136, MM137, and MM139) exhibited cytotoxic and proapoptotic activity against cancer cell lines (BxPC-3, PC-3, and HCT-116) in nanomolar concentrations without causing cytotoxicity in normal cells (L929 and WI38). In silico predictions indicate that tested compounds exhibit favorable pharmacokinetic profiles and may exert anticancer activity through the inhibition of BTK kinase, the AKT-mTOR pathway and PD1-PD-L1 interaction. Our findings point out that these sulfonamide derivatives may constitute a source of new anticancer drugs after optimization.

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Section: Introductionmentioning

confidence: 99%

Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies

Kciuk

Mujwar

Szymanowska

et al. 2022

IJMS

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“…Significant research activity to target CAIX with both antibodies and small molecule inhibitors has progressed to the clinic [ 6 ]. A CAIX specific monoclonal antibody, Girentuximab (trade name Rencarex), has been evaluated in Phase III clinical trials [ 7 ], but while the trial results did not meet the criteria for clinical approval, it was clear that some patients would see benefit from targeting CAIX.…”

Section: Immunotherapymentioning

confidence: 99%

Cancer Therapeutic Targeting of Hypoxia Induced Carbonic Anhydrase IX: From Bench to Bedside

McDonald¹,

Chafe

Supuran

et al. 2022

Cancers

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Carbonic Anhydrase IX (CAIX) is a major metabolic effector of tumor hypoxia and regulates intra- and extracellular pH and acidosis. Significant advances have been made recently in the development of therapeutic targeting of CAIX. These approaches include antibody-based immunotherapy, as well as use of antibodies to deliver toxic and radioactive payloads. In addition, a large number of small molecule inhibitors which inhibit the enzymatic activity of CAIX have been described. In this commentary, we highlight the current status of strategies targeting CAIX in both the pre-clinical and clinical space, and discuss future perspectives that leverage inhibition of CAIX in combination with additional targeted therapies to enable effective, durable approaches for cancer therapy.

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“…isoenzymes [38,39,34,35,40,41]. Lipinski's rules of ve, Veber's rule, and druggability were used to standardize these characteristics.…”

Section: Pharmacokinetic and Toxicological Evaluationmentioning

confidence: 99%

Establishing Veranoside-A2 as a Potential Antiretroviral Agent for the Treatment of HIV-AIDS: A Computational Analysis

Agrawal

Rani

Shah

et al. 2022

Preprint

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Immunocompromised human ailment commonly acknowledged as acquired immunodeficiency syndrome (AIDS) is instigated on by human immunodeficiency virus (HIV). HIV infection spreads through the exchange of bodily fluids including blood, sperm, vaginal fluid, and breast milk because these fluids include both free virus particles and virus that has already infected immune cells. It has been one of the most widely communicable human diseases by sexual transmission. HIV directly affects the human immune system resulting in the gradual loss of immunity in response to the pathogenic invasion responsible for life-threatening infections and malignancies to proliferate. HIV infect vital immune cells like CD4 T-cells and macrophages in the human body in a number of ways, including by pyroptosizing infected T-cells, which causes a slow decline in their population. Herbal plants are used for the therapy of HIV infection since the traditional time. Some of the commonly used herbs for the treatment of HIV infection are Vernonia amygdalina, Rheum officinale, Hypoxis hemerocallidea, Rheum palmatum, Cinnamomum tamala, Cassia abbreviata, Cinnamomum zeylanicum, Sutherlandia frutescens, Artemisia annua, Calendula officinalis, etc. These plants are supposed to be investigated further for isolation of anti-viral agents against HIV.

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Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies

Cited by 48 publications

References 211 publications

Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies

Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies

Cancer Therapeutic Targeting of Hypoxia Induced Carbonic Anhydrase IX: From Bench to Bedside

Establishing Veranoside-A2 as a Potential Antiretroviral Agent for the Treatment of HIV-AIDS: A Computational Analysis

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