g-15

G15 is a cell-permeable non-steroidal antagonist of GPER (Ki = 20 nM)

STO-609 is a specific and cell-permeable inhibitor of the Ca2+ calmodulin-dependent protein kinase kinase (CaM-KK) for recombinant CaM-KKα KKβ (Ki: 80 15 ng mL).

Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993). Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4 References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993).

Deltorphin II is a peptide agonist of δ2-opioid receptors.1,2It is selective for δ-opioid receptors over μ- and κ-opioid receptors in radioligand bindings assays (Kis = 0.0033, >1, and >1 μM, respectively) and induces [35S]GTPγS binding in mouse brain membrane preparations (EC50= 0.034 μM). Deltorphin II (0.12 mg/kg) decreases the infarction zone:risk zone ratio in a rat model of myocardial ischemia-reperfusion injury induced by coronary occlusion, an effect that can be reversed by the δ2-opioid receptor antagonist naltriben but not the δ1-opioid receptor antagonist BNTX.3Intrathecal administration of deltorphin II (15 μg/animal) increases latency to withdraw in the paw pressure and tail-flick tests in rats.4 1.Raynor, K., Kong, H., Chen, Y., et al.Pharmacological characterization of the cloned κ-, δ-, and μ-opioid receptorsMol. Pharm.45(2)330-334(1994) 2.Scherrer, G., Befort, K., Contet, C., et al.The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: A parallel study of mu, delta and combinatorial opioid receptor knockout miceEur. J. Neurosci.19(8)2239-2248(2004) 3.Maslov, L.N., Barzakh, E.I., Krylatov, A.V., et al.Opioid peptide deltorphin II simulates the cardioprotective effect of ischemic preconditioning: role of δ2-opioid receptors, protein kinase C, and KATP channelsBull. Exp. Biol. Med.149(5)591-593(2010) 4.Labuz, D., Toth, G., Machelska, H., et al.Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin II in rat spinal cord: A search for selectivity of delta receptor subtypesNeuropeptides32(6)511-517(1998)

Kaurenoic acid (kaurenoate) has anti-inflammatory potential in acetic acid-induced colitis, decreases in MDA level. Kaurenoic acid exerts a uterine relaxant effect acting principally through calcium blockade and in part, by the opening of ATP-sensitive potassium channels. Kaurenoic acid exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of cytokine production and activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway. Kaurenoic acid derivatives have an antimicrobial activity of substituted on carbon-15 at concentrations greater than or equal to 250 μg/ml. Kaurenoic acid has inhibitory effects on the LPS-induced inflammatory response in RAW264.7 macrophages.

Rec 15/2615 is an antagonist of α1B-adrenergic receptors (α1B-ARs; Ki = 0.45 nM for the recombinant human receptor).1 It selectively inhibits α1B-ARs over α1A-, α1D-, and α1L-ARs (Kis = 7.59, 10.23, and 49 nM, respectively). Rec 15/2615 inhibits norepinephrine-induced contractions of isolated rabbit prostate and urethral strips (Kis = 100 and 316.2 nM, respectively), as well as reduces norepinephrine-induced contractions of chloroethylclonidine-precontracted isolated rabbit aortic rings (Ki = 50 nM).2 It decreases diastolic blood pressure (ED25 = 183 μg/kg, i.v.) and increases intracavernous pressure in anesthetized dogs when administered intracavernously at doses ranging from 30 and 1,000 μg/kg.1,2 |1. Sironi, G., Colombo, D., Poggesi, E., et al. Effects of intracavernous administration of selective antagonists of α1-adrenoceptor subtypes on erection in anesthetized rats and dogs. J. Pharmacol. Exp. Ther. 292(3), 974-981 (2000).|2. Testa, R., Guarneri, L., Angelico, P., et al. Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): Role of the alpha-1L adrenoceptor in tissue selectivity, part II. J. Pharmacol. Exp. Ther. 281(3), 1284-1293 (1997).

3(Z),6(Z),9(Z),12(Z),15(Z)-Octadecapentaenoic acid, a microalgal polyunsaturated fatty acid (PUFA), is identified in G. kowalevskii and serves as a chemotaxonomic biomarker for microalgae and dinoflagellates.

3-Hydroxyterphenyllin is a p-terphenyl fungal metabolite originally isolated from A. candidus that has diverse biological activities, including antioxidant, antiproliferative, antibacterial, and antiviral properties.1,2,3,4 It has a 96% scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals when used at a concentration of 100 μg/ml.2 3-Hydroxyterphenyllin inhibits the growth of HeLa cervical, A549 lung, and HepG2 liver cancer cells (IC50s = 23, 36, and 32 μM, respectively), as well as methicillin-resistant S. aureus (MRSA) and V. vulnificus bacteria (MIC = 31 μg/ml for both).3 It also inhibits HIV-1 integrase in both coupled and strand transfer assays (IC50s = 2.8 and 12.1 μM, respectively).4References1. Kurobane, I., Vining, L.C., McInnes, A.G., et al. 3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by 1H and 13C nuclear magnetic resonance spectroscopy. J. Antibiot. (Tokyo) 32(6), 559-564 (1979).2. Yen, G.-C., Chang, Y.-C., Sheu, F., et al. Isolation and characterization of antioxidant compounds from Aspergillus candidus broth filtrate. J. Agric. Food Chem. 49(3), 1426-1431 (2001).3. Wang, W., Liao, Y., Tang, C., et al. Cytotoxic and antibacterial compounds from the coral-derived fungus Aspergillus tritici SP2-8-1. Mar. Drugs 15(11), E348 (2017).4. Singh, S.B., Jayasuriya, H., Dewey, R., et al. Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites. J. Ind. Microbiol. Biotechnol. 30(12), 721-731 (2003). 3-Hydroxyterphenyllin is a p-terphenyl fungal metabolite originally isolated from A. candidus that has diverse biological activities, including antioxidant, antiproliferative, antibacterial, and antiviral properties.1,2,3,4 It has a 96% scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals when used at a concentration of 100 μg/ml.2 3-Hydroxyterphenyllin inhibits the growth of HeLa cervical, A549 lung, and HepG2 liver cancer cells (IC50s = 23, 36, and 32 μM, respectively), as well as methicillin-resistant S. aureus (MRSA) and V. vulnificus bacteria (MIC = 31 μg/ml for both).3 It also inhibits HIV-1 integrase in both coupled and strand transfer assays (IC50s = 2.8 and 12.1 μM, respectively).4 References1. Kurobane, I., Vining, L.C., McInnes, A.G., et al. 3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by 1H and 13C nuclear magnetic resonance spectroscopy. J. Antibiot. (Tokyo) 32(6), 559-564 (1979).2. Yen, G.-C., Chang, Y.-C., Sheu, F., et al. Isolation and characterization of antioxidant compounds from Aspergillus candidus broth filtrate. J. Agric. Food Chem. 49(3), 1426-1431 (2001).3. Wang, W., Liao, Y., Tang, C., et al. Cytotoxic and antibacterial compounds from the coral-derived fungus Aspergillus tritici SP2-8-1. Mar. Drugs 15(11), E348 (2017).4. Singh, S.B., Jayasuriya, H., Dewey, R., et al. Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites. J. Ind. Microbiol. Biotechnol. 30(12), 721-731 (2003).

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 μM), showing no effect on PAR-2, PAR-3, or PAR-4. It inhibits the aggregation of human platelets induced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), with high selectivity relative to U46619. RWJ-56110 dihydrochloride also blocks angiogenesis and the formation of new vessels in vivo, and induces cell apoptosis[1][2].

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg/ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg/ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg/kg, respectively). Zonisamide (40 mg/kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

mSIRK (G-Protein βγ Binding Peptide) is a cell-permeable activator of ERK 1 2 with an EC50 of 2.5-5 μM. It disrupts the interaction between the α and βγ subunits, facilitating α subunit dissociation without inducing nucleotide exchange [1].

Diosbulbin G is a natural product of Dioscorea, Dioscoreaceae. The catalog number is TMA0692 and the CAS number is 67567-15-1. Diosbulbin G can be used as a reference standard.

KRAS G12C inhibitor 15 is a potent inhibitor of the KRAS G12C protein.

L2H2-6OTD, a telomeric inhibitor analogue characterized by containing one to four G-quadruplex binding loops, exhibits telomerase inhibitory activity with an IC 50 value of 15 nM.

ARN-21934 is a potent, highly selective, blood-brain barrier (BBB) penetrant inhibitor for human topoisomerase II α over β. It inhibits DNA relaxation with an IC50 of 2 μM, compared to 120 μM for Etoposide. ARN-21934 exhibits favorable in vivo pharmacokinetic properties and shows promise in anticancer research, displaying affinity for topoIIα with an IC50 of 2 μM and for topoIIβ with an IC50 of 120 μM. It demonstrates activity against human cancer cell lines including melanoma (A375: 12.6 μM, G-361: 8.1 μM), breast (MCF7: 15.8 μM), endometrial (HeLa: 38.2 μM), lung (A549: 17.1 μM), and prostate (DU145: 11.5 μM) cancer cells. Following a single intraperitoneal injection of 10 mg kg, ARN-21934 achieves a peak plasma concentration of 0.68 μg mL in 15 minutes, with a half-life of 149 minutes, and remains detectable in plasma and the brain for up to 360 minutes. [1] Jose Antonio Ortega, et al. Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β. J Med Chem. 2020 Nov 12;63(21):12873-12886.

Ru360, an oxygen-bridged dinuclear ruthenium amine complex, is a selective mitochondrial calcium uptake inhibitor. Ru360 potently inhibits Ca2+ uptake into mitochondria with an IC50 of 0.184 nM. Ru360 binds to mitochondria with high affinity (Kd of 0.34 nM). Ru360 has antiarrhythmic and cardioprotective effects[1][2]. Ru360 permeates slowly into the cell, and specifically inhibits mitochondrial calcium uptake in intact cardiomyocytes and in isolated heart. 1 μm Ru360 is taken up by myocardial cells and accumulated in the cytosol in a biphasic manner[1]. During pelleting hypoxia, Ru360 (10 µM) significantly improves cell viability in wild type cardiomyocytes[3]. Ru360 (15-50 nmol/kg) treatment abolishes the incidence of arrhythmias and haemodynamic dysfunction elicited by reperfusion in a whole rat model. Ru360 administration partially inhibits calcium uptake, preventing mitochondria from depolarization by the opening of the mitochondrial permeability transition pore (mPTP)[1]. [1]. G de J García-Rivas, et al. Ru360, a Specific Mitochondrial Calcium Uptake Inhibitor, Improves Cardiac Post-Ischaemic Functional Recovery in Rats in Vivo. Br J Pharmacol. 2006 Dec;149(7):829-37. [2]. M A Matlib, et al. Oxygen-bridged Dinuclear Ruthenium Amine Complex Specifically Inhibits Ca2+ Uptake Into Mitochondria in Vitro and in Situ in Single Cardiac Myocytes. J Biol Chem. 1998 Apr 24;273(17):10223-31. [3]. Lukas J Motloch, et al. UCP2 Modulates Cardioprotective Effects of Ru360 in Isolated Cardiomyocytes During Ischemia. Pharmaceuticals (Basel). 2015 Aug 4;8(3):474-82.

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid .1,217R(18S)-EpETE is an activator of large-conductance calcium-activated potassium (BKCa) channels, increasing the potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells (VSMCs) at +60 mV when used at a concentration of 50 nM.2It has negative chronotropic effects in isolated neonatal rat cardiomyocytes (NRCMs; EC50= ~1-2 nM) and prevents calcium-induced increases in the spontaneous beating of NRCMs.3,4 1.Schwarz, D., Kisselev, P., Ericksen, S.S., et al.Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: Highly steroselective formation of 17(R), 18(S)-epoxyeicosatetraenoic acidBiochem. Pharmacol.67(8)1445-1457(2004) 2.Lauterbach, B., Barbosa-Sicard, E., Wang, M.H., et al.Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activatorsHypertension39(2 Pt. 2)609-613(2002) 3.Falck, J.R., Wallukat, G., Puli, N., et al.17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analoguesJ. Med. Chem.54(12)4109-4118(2011) 4.Arnold, C., Markovic, M., Blossey, K., et al.Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acidsJ. Biol. Chem.285(43)32720-32733(2010)

Spirotetramat is an insecticide that demonstrates efficacy against C. pyrinymphs in vitro (LC50= 6.51-12.53 mg AI/L) and achieves a 99.2% mortality rate in C. pyrinymphs within European pear (P. communis) fields 15 days post-application at a dosage of 27 g/hectare. Additionally, it reduces embryonic viability and nymph survival in O. insidiosus. Spirotetramat exhibits aquatic toxicity by altering protein levels in organisms, specifically by increasing glutathione peroxidase (GPX) and superoxide dismutase (SOD) levels, decreasing malondialdehyde (MDA) levels, and causing lethality in Chinese toad (B. gargarizans) tadpoles (LC50= 6.98 mg/L). Its formulations are utilized in agricultural insect control. Spirotetramat is marketed exclusively for research and analytical applications, formulated for controlled laboratory settings without the availability of bulk sizes.

The biological effects of prostaglandin D2 (PGD2) are transduced by at least two 7-transmembrane G protein-coupled receptors, designated DP1 and CRTH2/DP2. In humans, CRTH2/DP2 is expressed on Th2 cells, eosinophils, and basophils where it mediates the chemotactic activity of PGD2. CAY10597, as a racemic mixture, is a potent CRTH2/DP2 receptor antagonist that binds to the human receptor with a Ki value of 37 nM. The R enantiomer is slightly more potent exhibiting Ki values of 23 and 22 nM at the human and murine CRTH2/DP2 receptor, respectively. The R enantiomer of CAY10597 inhibits eosinophil chemotaxis induced by 13,14-dihydro-15-keto-prostaglandin D2 with an IC50 value of 40 nM.

3β-OH-7-Oxocholenic acid is a bile acid.1 It is also a metabolite of 7β-hydroxy cholesterol in rats. Conjugated forms of 3β-OH-7-oxocholenic acid have been found in the urine of patients with Neimann-Pick disease type C.2,3 |1. Norii, T., Yamaga, N., and Yamasaki, K. Metabolism of 7β-hydroxycholesterol-4-14C in rat. Steroids 15(3), 303-326 (1970).|2. Alvelius, G., Hjalmarson, O., Griffiths, W.J., et al. Identification of unusual 7-oxygenated bile acid sulfates in a patient with Niemann-Pick disease, type C. J. Lipid Res. 42(10), 1571-1577 (2001).|3. Maekawa, M., Omura, K., Sekiguchi, S., et al. Identification of two sulfated cholesterol metabolites found in the urine of a patient with Niemann-Pick disease type C as novel candidate diagnostic markers. Mass Spectrom. (Tokyo) 5(2), S0053 (2016).

Treprostinil Palmitil (TP), a prodrug of the DP1 and EP2 agonist Treprostinil (UT-15), exhibits EC50 values of 0.6 and 6.2 nM, respectively. It is a pure prodrug without any inherent binding affinity for G-protein coupled receptors, including prostanoid receptors.

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Zonisamide sodium is a 1,2 benzisoxazole derivative. It is the first agent of this chemical class to be developed as an antiepileptic drug.