nonselective

PD 089828 is a competitive inhibitor of the receptor tyrosine kinases FGFR1, PDGFRβ, and EGFR (IC50s = 0.15, 1.76, and 5.47 µM, respectively) and a noncompetitive inhibitor of the nonreceptor tyrosine kinase c-Src (IC50 = 0.18 µM)

Apyramide is an anti-inflammatory agent (NSAID) that acts as a prodrug of indomethacin, a potent, blood-brain permeable, and nonselective inhibitor of COX1 and COX2.

Pilocarpine Hydrochloride (NSC 5746 HCl) , a nonselective muscarinic acetylcholine receptor agonist, is utilized to produce an experimental model of epilepsy.

Phentolamine mesylate (Phentolamine methanesulfonate) is a nonselective alpha-adrenergic antagonist used to treat hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of [RAYNAUD DISEASE] and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.

Carteolol hydrochloride (Abbott-43326) is a synthetic quinolinone derivative, antihypertensive Carteolol Hydrochloride is a nonselective beta-adrenoceptor blocking agent for beta-1 and beta-2 receptors with no membrane-stabilizing activity but moderate intrinsic sympathomimetic effects. It is used for the treatment of hypertension and certain arrhythmias and as an anti-angina and antiglaucoma agent.

Aminophylline (Phyllocontin) is a competitive nonselective phosphodiesterase inhibitor giving a bronchodilatory effect.

Ibudilast (MN-166)(KC-404;AV-411;MN-166) is a relatively nonselective phosphodiesterase inhibitor. It is approved for use as an anti-inflammatory in Japan.

2,6-Dichlorodiphenylamine, an analogue of Diclofenac Sodium, exhibits anti-Candida albicans activity. Diclofenac Sodium, a potent and nonselective COX inhibitor, has IC50 values of 4 and 1.3 nM for human COX-1 and COX-2 in CHO cells. [1]. Makoto Urai, et al. Potent Drugs That Attenuate anti-Candida albicans Activity of Fluconazole and Their Possible Mechanisms of Action. J Infect Chemother. 2014 Oct;20(10):612-5.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8 9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26 DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630 624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20 2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

Yohimbine is a nonselective alpha 2-adrenergic receptor (AR) antagonist(IC50 : 0.6 μM)

Phentolamine Analogue 1 is a nonselective α-adrenergic antagonist, similar to phentolamine.

Enprofylline (Enprofilina), a bronchodilator, acts primarily as a competitive nonselective phosphodiesterase inhibitor. Enprofylline is used in asthma, chronic obstructive pulmonary disease, and in the management of sickle cell disease, diabetic neuropathy, and cerebrovascular insufficiency.

Ampiroxicam (Flucam) is a nonselective cyclooxygenase inhibitor uesd as anti-inflammatory drug.

LUN42518 HCl is an analogue of phentolamine. Phentolamine is a nonselective alpha-adrenergic antagonist.

4-Aminopyridine (Dalfampridine) is a nonselective potassium (K+) channel blocker that binds to the cytoplasmic side of the cell membrane.

Arotinolol is a nonselective α β-adrenergic receptor blocker and a vasodilating β-blocker. Arotinolol also shows potency for inhibiting the binding of the radioligand [125I-ICYP] to [5HT1B-serotonergic] receptor sites. It is an antihypertensive agent.

Indomethacin-D4 is a deuterium labeled Indomethacin. Indomethacin is a potent and nonselective inhibitor of COX1 and COX2, with IC50s of 18 nM and 26 nM for human COX-1 and COX-2, respectively, in CHO cells.

Ketorolac D5, a deuterium-labeled version of Ketorolac, is a non-steroidal anti-inflammatory agent that functions as a nonselective COX inhibitor. It exhibits IC50 values of 20 nM for COX-1 and 120 nM for COX-2.

Penbutolol is a nonselective beta-blocker utilized as an antihypertensive and an antianginal.

Propranolol D7 hydrochloride is a deuterium labeled Propranolol hydrochloride. Propranolol hydrochloride is a nonselective antagonist of β-adrenergic receptor (βAR).

(rel)-Tranylcypromine D5 hydrochloride is a deuterium labeled (rel)-Tranylcypromine hydrochloride. (rel)-Tranylcypromine hydrochloride is an irreversible, nonselective inhibitor of monoamine oxidase (MAO) used in the treatment of depression.

Talabostat isomer mesylate, an isomer of talabostat mesylate, is a potent, nonselective, and orally available inhibitor of dipeptidyl peptidase IV (DPP-IV) with a Ki of 0.18 nM. Talabostat (PT100, Val-boroPro) is notable for its efficacy in inhibiting DPP-IV.

Glisoxepide is a sulphonamide derivative and is an orally available nonselective K(ATP) channel blocker. It has antihyperglycemic activity and cardiovascular regulation effect.

CP-640186 is an isozyme-nonselective Acetyl-CoA carboxylase (ACCase) inhibitor. The IC50s of CP-640186(CP 640186) is 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively.