biphasic

Melitracen hydrochloride (Thymeol hydrochloride) , an antidepressant, is used as potential dopamine D1/2 receptor antagonist to treat depression.

TT2-32 TFA induces a biphasic activation of phosphotyrosine phosphatase activity in human colon tumor cell line, SW620

RH1 (NSC 697726) is a bioreductive anticancer compound that exhibits dose-dependent biphasic effects in vitro, inducing apoptosis at higher doses and senescence at lower doses.

Rosmanol has antioxidant activity, it can activate the antioxidant response element. Rosmanol has biphasic modulation of GABAA receptors, demonstrates CNS activity in mouse models of antinociception, antidepressant and anxiolysis. Rosmanol potently induce

L-Albizziin (2-Methoxyidazoxan monohydrochloride) is a highly potent selective antagonist of the alpha 2r adrenergic receptor, with little or no antagonistic effect on imidazoline. It has a significantly higher affinity for the alpha 2D adrenergic receptor (pKd9.7) in guinea pigs than for the alpha 2A adrenergic receptor (pKd8.2) in rabbits.

Spirorenone is an androstadienone derivative as a highly effective aldosterone antagonist. Spirorenone is 8.6 times as potent as spironolactone, but showed a lower affinity for the mineralocorticoid receptors. In phase I clinical trials Spirorenone was absorbed with a half-life of 20-30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1-2 h. Disposition of the parent drug was biphasic with half-lives of 50-60 min (distribution) and 5-6 h (elimination). Neither significant accumulation nor enzyme induction was observed after prolonged treatment.

(−)-Apomorphine, a non-selective dopamine receptor agonist, demonstrates pKi values of 6.43 (D1), 7.08 (D2L), 7.59 (D3), 8.36 (D4), and 7.83 (D5) for human recombinant receptors. It induces biphasic effects on locomotor activity and possesses anti-Parkinsonian and neuroprotective properties.[1,2,3,4]

SOS1 agonist-1 (compound 79) serves as an agonist for the Son of sevenless homologue 1 (SOS1), a crucial guanine nucleotide exchange factor involved in catalyzing the GDP to GTP exchange on RAS proteins, thus regulating RAS activation. By increasing nucleotide exchange on RAS, SOS1 agonists enhance cellular RAS-GTP levels and induce biphasic signaling alterations in ERK1/2 phosphorylation, playing a pivotal role in anti-cancer activity [1].

Epinodosin induces significant DNA damage to HepG2 cells in a time- and dose-dependent manner.Epinodosin has a biphasic, dose-dependent effect on root growth and a strong inhibitory effect on root hair development in Lactuca sativa L. seedlings.

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.