Staurosporine is an alkaloid isolated from the culture broth of Streptomyces staurosporesa. It exerts antimicrobial, hypotensive, and cytotoxic activity. The main biological activity of staurosporine is the inhibition of protein kinases through the prevention of ATP binding to the kinase. This is achieved through the stronger affinity of staurosporine to the ATP-binding site on the kinase. Staurosporine is a prototypical ATP-competitive kinase inhibitor in that it binds to many kinases with high affinity, though with little selectivity. It is a potent, cell permeable protein kinase C inhibitor with an IC50 of 0.7 nM. At higher concentration (1-20 nM), staurosporine also inhibits other kinases such as PKA, PKG, CAMKII and Myosin light chain kinase (MLCK). At 50-100 nM, it is a functional neurotrophin agonist, promoting neurite outgrowth in neuroblastoma, pheochromocytoma and brain primary neuronal cultures. At 0.2- 1 uM, staurosporine induces cell apoptosis. Staurosporine is also a potent GSK-3β inhibitor with a reported IC50 value of 15 nM. In research, staurosporine is used to induce apoptosis. It has been found that one way in which staurosporine induces apoptosis is by activating caspase-3. Staurosporine was discovered to have biological activities ranging from anti-fungal to anti-hypertensive. The interest in these activities resulted in a large investigative effort in chemistry and biology and the discovery of the potential for anti-cancer treatment. Staurosporine induces apoptosis by multiple pathways and that the inhibition of more than one kinase is responsible for its potent activity. Because the mechanism of action of staurosporine is distinct from traditional anticancer drugs, this may warrant further preclinical evaluations of the antitumor potential of new staurosporine derivatives either alone or in combination with death ligands or conventional chemotherapeutic drugs.

Ginsenoside Rb3 is a protopanaxadiol ginsenoside that can be isolated from several different Panax species. Ginsenoside Rb3 exerts antidepressant and antidiabetic activities as well as cardio- and neroprotective action in ischemic tissue injury in animal models. Ginsenoside Rb3 inhibits apoptosis and cell proliferation, in addition it demonstrates antiaxidant properties. Ginsenoside Rb3 may modulate activity of GABA-A and NMDA receptors.

1-(2-methoxyphenyl)piperazine is an effective blocker of striatal dopaminergic receptors in rat brain and is apparently the simplest chemical structure known to exert dopaminergic blocking activity. It is exhibited pronounced antihypertensive and weak sympatholytic activities in experimental animals. Blood pressure was also lowered in hypertensive patients and this effect was sometimes accompanied by a strong sedation, and after large repeated doses, by disorientation and stupor. In a filter paper bioassay 1-(2-methoxyphenyl)piperazine demonstrated acaricidal activity. 1-(2-methoxyphenyl)piperazine is a building block of many serotonergic and dopaminergic agents. Some of them have antidepressant activity.

OPC-21268, a non-peptide vasopressin V1 receptor antagonist, inhibited oxytocin- and vasopressin-induced contractions of myometrial strips from rats and from full-term pregnant women. OPC-21268, because of its non-peptide structure, is orally active and has been shown to lower blood pressure in a patient with congestive heart failure and in spontaneously hypertensive rats. It also attenuates vasopressin induced bradycardia in rabbits and pressor responses in rats. It has been demonstrated that OPC-21268 exerts its inhibitory action through binding to the vasopressin V1 receptors in rat liver and kidney. Finally, OPC-21268 was reported to be safe and non-toxic in healthy humans. Merck scientists showed that OPC-21268 had significant affinity for the rOTR and the hOTR. OPC-21268 has been in phase II clinical trials by Otsuka for the treatment of heart failure and hypertension. However, this research has been discontinued.

(R)-Alprenolol is a less active stereoisomer of antihypertensive beta-blocker alprenolol. Its activity against beta-adrenoreceptor is 100 times lower than the activity of (S)-alprenolol. In a model of ventricular arrhythmias produced by ligation of the left coronary artery, (R)-alprenolol was effective at 15.5 mg/kg, whereas (S)-alprenolol abolished the ventricular arrhythmia by cumulative dose of 7.5 mg/kg.

(S)-Alprenolol is a more active stereoisomer of antihypertensive beta-blocker alprenolol. Its activity against beta-adrenoreceptor is 100 times greater than the activity of (R)-alprenolol. In a model of ventricular arrhythmias produced by ligation of the left coronary artery, (S)-alprenolol was effective at 7.5 mg/kg, whereas (R)-alprenolol abolished the ventricular arrhythmia by cumulative dose of 15.5 mg/kg. As a most active enantiomer of alprenolol, the compound was used as a tool to study beta-adrenergic receptors.

Veratramine, a steroidal alkaloid originating from Veratrum nigrum L. CYP2D6 and SULT2A1 mediating hydroxylation and sulfation were identified as the major biotransformation for veratramine. Veratramine significantly inhibits the hedgehog pathway in NIH/3T3 cells. Veratramine is both a release and uptake inhibitor of serotonin. Veratramine exhibits cytotoxic activity against human tumor cell lines A549, PANC-1, SW1990 and NCI-H249. Veratramine has demonstrated distinct anti-hypertension effects in spontaneously hypertensive rats.

S-aranidipine or (S)-MPC-1304 is an enantiomer of MPC-1304 (methyl 2-oxopropyl 1,4-dihydro-2,6-di-methyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate), a calcium entry blocker. The Ca2+ entry blocking activity of the (S) enantiomer of MPC-1304 was approximately 150 times greater than that of its (R) enantiomer. Likewise, the antihypertensive effect of the (S) enantiomer was twice as great as that of MPC-1304 (racemate) in conscious spontaneously hypertensive rats, while the (R) enantiomer was ineffective. Thus, most of the pharmacological activity of MPC-1304 resides in its (S) configuration.

HC-030031 is a substituted theophylline derivative. Potent and selective TRPA1 inhibitor. HC-030031 inhibits human and rat TRPA1 with IC50 of 6.2 and 7.6 uM, respectively. It is selective against several TRP channels (IC50 >10 or 20 uM). HC-030031 can block both inward and outward currents elicited by AITC or formalin rapidly and reversibly and also blocks the activation of TRPA1 by N-methylmaleimide and by electrophillic prostaglandins. It does not block currents mediated by TRPV1, TRPV3, TRPV4 hERG, or NaV1.2 channels. HC-030031 exhibited efficacy in CFA, SNL, and other pain models. HC-030031 was shown to attenuate cold hyperalgesia in CFA (inflammatory), spared never injury (SNI, neuropathic), and paclitaxelmediated cold hyperalgesia. Also HC-030031 was found to decrease heat hyperalgesia in the paclitaxel model of chemotherapy-induced neuropathic pain.In an ovalbumin-induced mouse asthma model, gene KO and treatment with HC-030031 reduced the induction of cytokines, chemokines, neurotransmitters, as well as leukocyte infiltration and airway hyperactivity. Furthermore, HC-030031 and genetic deletion of mast cells attenuated itch-scratching behaviors. In oxazolone-induced contact dermatitis models, TRPA1 KO and HC-030031 decreased pro-inflammatory cytokines, T cell infiltration, dermatitis score, and edema, indicating that TRPA1 may play a central role in inflammation and pruritus.

Glyceryl 2-nitrate (G-2-N) is the major metabolite of glyceryl trinitrate. Strips of rat aorta contracted with potassium chloride or with norepinephrine were relaxed by G-2-N. After oral administration to the anaesthetized rat or to the conscious dog G-2-N exhibited antianginal and hypotensive activity. The hypotensive and also cardiovascular activity of G-2-N lasted much longer than that of glyceryl trinitrate.