Pyrithione zinc is an antibacterial and antifungal agent developed by scientists in the 1930's. Since then it has been used to treat seborrheic dermatitis of the scalp and other skin conditions such as eczema, athlete's foot, and vitiligo, as well as psoriasis. Because of its antifungal properties, it is commonly found in dandruff shampoo. Products containing pyrithione zinc are available today with and without prescription, and it is the main ingredient in many over-the-counter creams, lotions, soaps, and shampoos. It also has antibacterial properties and is effective against many pathogens from the Streptococcus and Staphylococcus genera. Pyrithione zinc`s other medical applications include treatments of psoriasis, eczema, ringworm, fungus, athletes foot, dry skin, atopic dermatitis, tinea, and vitiligo. Its antifungal effect is thought to derive from its ability to disrupt membrane transport by blocking the proton pump that energizes the transport mechanism.

Lificiguat (YC-1) [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole], a chemically synthetic benzylindazole compound, is a direct soluble guanylate cyclase activator. It possessed antiplatelet activity. YC-1 inhibits Hypoxia-inducible factor-1 (HIF-1). YC-1 demonstrated antineoplastic potential both in vitro and in vivo in animal models.

Echinomycin is a cyclic peptide of the family of quinoxaline antibiotics that was originally isolated from Streptomyces echinatus. It is thought to act as a bifunctional DNA intercalator. Echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. Echinomycin interferes with HIF-1 DNA binding in a sequence-specific fashion. It was brought into clinical trials by the NCI 20 years ago based on its antitumor activity. It has been extensively tested in phase I-II clinical trials. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. However, minimal or no antitumor activity was found in phase II clinical trials.

PX-478 is a highly potent and selective Hypoxia-inducible Factor-1α (HIF-1α) inhibitor. It lowers HIF-1α protein levels and HIF-1 transactivation in hypoxia and in normoxia in a variety of cancer cell lines, but has a more pronounced effect on translation of proteins, such as HIF-1α in hypoxia. PX-478 also enhances the radiosensitivity of prostate carcinoma PC3 cells. Its inhibition is independent of the tumor suppressor genes VHL and p53, and may be related to derangements in glucose uptake and metabolism due to inhibition of glucose transporter-1 (Glut-1). PX-478 has excellent activity against established human tumor xenografts, inducing tumor regressions with prolonged growth delays which correlate positively with HIF-1 levels. In high-fat-diet mice, PX-478 causes reduced fibrosis and fewer inflammatory infiltrates in their adipose tissues. PX-478 had been in phase I clinical trials by for the treatment of lymphoma and solid tumors. However, this research has been discontinued.

BAY-87-2243 is a potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor. BAY 87-2243 inhibits HIF-1 reporter gene activity and CA9 protein expression with IC50 of 0.7 nM and 2 nM, respectively. In hypoxic lung cancer H460 cells, BAY-87-2243 suppresses HIF target gene expression, and inhibits HIF-1α protein accumulation. BAY-87-2243 showed dose-dependent in vivo antitumor efficacy in the H460 lung tumor xenograft model accompanied by a suppression of HIF-1a protein and HIF-1 target genes without any signs of toxicity or body weight loss. Further mode-of-action analyses revealed that BAY-87-2243 exerts its effect on the HIF pathway by blocking mitochondrial complex I activity and thereby reducing HIF protein levels under hypoxia. BAY-87-2243 had been in phase I clinical trials by Bayer for the treatment of malignancies. However, this study has been terminated for the drug-related adverse events.

Kaempferide (3,5,7-trihydroxy-4′-methoxyflavone, Kae) is a naturally occurring flavonoid that is isolated from the roots of Alpinia officinarum (lesser galangal). Like other flavonoids, Kae also has a very good antioxidant properties and Kae can effectively reduce 1,1- diphenyl-2-picrylhydrazyl (DPPH). Studies have shown that Kae has anticancer and antihypertension effects. Kaempferide protects against myocardial Ischemia/reperfusion Injury through activation of the PI3K/Akt/GSK-3β pathway. Kaempferide inhibited potent antioxidant activity. Kaempferide is one of the candidates for active compound in propolis. Kaempferide, the most active among the four flavonoids isolated and characterized from Chromolaena odorata, induces apoptosis in cervical cancer cells while being pharmacologically safe.

Bufexamac is a nonsteroidal antiinflammatory drug (NSAID) used in topical formulations to treat dermatological diseases (eczema and dermatitis) and proctological conditions (haemorrhoids and anal fissure). Bufexamac-containing medicines have been available in EU Member States since the 1970s. In 2010 European Medicines Agency recommends revocation of marketing authorisations for bufexamac due to high risk of contact allergies. The phenolic bufexamac decomposition products could be the reason for its eczema-provoking properties frequently described in the literature. Bufexamac is a class IIb histone deacetylase (HDAC6, HDAC10) inhibitor. Bufexamac also triggered an HDAC6-independent, hypoxia-like response by stabilizing Hypoxia-inducible factor 1-alpha, providing a possible mechanistic explanation of its adverse, pro-inflammatory effects. Bufexamac was capable of specifically inhibiting leukotriene A4 hydrolase and attenuating lung inflammation in acute lung injury mouse model.

Acriflavine (ACF) is a topical antiseptic. The hydrochloride form is more irritating than the neutral form. It is derived from acridine. Commercial preparations are often mixtures with proflavine. Acriflavine was developed in 1912 by Paul Ehrlich, a German medical researcher, and was used during the First World War against sleeping sickness. ACF has known trypanocidal, antibacterial, and antiviral activities. Effects of ACF on cancer cells were first reported 50 years ago. By present time was demonstrated that ACF a drug, that binds directly to HIF-1 alpha and HIF-2 alpha and inhibits HIF-1 dimerization and transcriptional activity and thus has potent inhibitory effects on tumor growth and vascularization. Also Acriflavine in combination with 3,6-diaminoacridine (proflavine) could prove to be a potential antimalarial drug and its pharmacological action can be due to inhibition of gyrase activity. This is achieved through interaction of the ACF with the DNA substrate. This interaction may lead to conformation change in DNA unsuitable for binding of gyrase with DNA.

Pyrithione zinc is an antibacterial and antifungal agent developed by scientists in the 1930's. Since then it has been used to treat seborrheic dermatitis of the scalp and other skin conditions such as eczema, athlete's foot, and vitiligo, as well as psoriasis. Because of its antifungal properties, it is commonly found in dandruff shampoo. Products containing pyrithione zinc are available today with and without prescription, and it is the main ingredient in many over-the-counter creams, lotions, soaps, and shampoos. It also has antibacterial properties and is effective against many pathogens from the Streptococcus and Staphylococcus genera. Pyrithione zinc`s other medical applications include treatments of psoriasis, eczema, ringworm, fungus, athletes foot, dry skin, atopic dermatitis, tinea, and vitiligo. Its antifungal effect is thought to derive from its ability to disrupt membrane transport by blocking the proton pump that energizes the transport mechanism.