Dilazep is a coronary and cerebral vasodilator as an adenosine reuptake inhibitor. Dilazep is an inhibitor of platelet aggregation and of membrane transport of nucleosides. Dilazep is also known to have a vasodilating effect on renal vessels and is often used in patients with ischaemic heart disease, cerebral ischemia or renal dysfunction to improve tissue circulation.

Cefpimizole is an antibiotic of broad spectrum developed in Japan for the treatment of such conditions as uncomplicated gonorrhea and gynecologic infections. The drug was tested in clinical trials, however, its development was terminated.

Aclarubicin (INN) or aclacinomycin A is an anthracycline drug is primarily indicated in conditions like Acute non-lymphoblastic leukemia, Breast cancer, Gastric cancer, Lymphoma, Ovarian coma, Small cell lung cancer, Thyroid cancer. Soil bacteria Streptomyces galilaeus can produce aclarubicin. Aclarubicin (HCl) is used in combination with different anticancerous drugs to obtain best therapeutic results and to reduce toxicity or side effects. Aclarubicin (HCl) is administered intravenously. Aclarubicin is antagonistic to other agents that inhibit topoisomerase II, such as etoposide, teniposide and amsacrine. This agent is less cardiotoxic than doxorubicin and daunorubicin.

Buformin (1-butylbiguanide) is an oral antidiabetic drug of the biguanide class. AMPK activator. AMPK is a potential therapeutic target in the prevention and the treatment of type 2 diabetes and insulin resistance. Major classes of antidiabetic drugs have been reported to activate AMPK. Buformin exerts its anti-tumorigenic activity via activation of AMPK and inhibition of the mTOR signaling pathways in endometrial cancer cells. Toxicity: guinea pig LD50 subcutaneous 18 mg/kg; mouse LD50 intraperitoneal 140 mg/kg and 300 mg/kg oral. Buformin was withdrawn from the market in many countries due to an elevated risk of causing lactic acidosis.

Taurocholic acid is a bile acid and is the product of conjugation of cholic acid with taurine. Its sodium salt is the chief ingredient of the bile of carnivorous animals. Taurocholic acid, as with all bile acids, acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and cholerectic (a bile purging agent). Hydrolysis of taurocholic acid yields taurine, a nonessential amino acid. Taurocholic acid is one of the main components of urinary nonsulfated bile acids in biliary atresia. Raised levels of the bile acid taurocholate in the fetal serum in obstetric cholestasis may result in the development of a fetal dysrhythmia and in sudden intra-uterine death. In medical use, it is administered as a cholagogue and choleretic. Taurocholic acid is a potent TGR5 ligand, and in dogs, colonic perfusion with TCA induces PYY secretion. TCA enemas could stimulate GLP-1 and PYY secretion in obese patients with type 2 diabetes receiving the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin. Satiogen Pharmaceuticals is developing rectally administered taurocholic acid, a bile acid, for the treatment of obesity and type 2 diabetes mellitus.

Taurocholic acid is a bile acid and is the product of conjugation of cholic acid with taurine. Its sodium salt is the chief ingredient of the bile of carnivorous animals. Taurocholic acid, as with all bile acids, acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and cholerectic (a bile purging agent). Hydrolysis of taurocholic acid yields taurine, a nonessential amino acid. Taurocholic acid is one of the main components of urinary nonsulfated bile acids in biliary atresia. Raised levels of the bile acid taurocholate in the fetal serum in obstetric cholestasis may result in the development of a fetal dysrhythmia and in sudden intra-uterine death. In medical use, it is administered as a cholagogue and choleretic. Taurocholic acid is a potent TGR5 ligand, and in dogs, colonic perfusion with TCA induces PYY secretion. TCA enemas could stimulate GLP-1 and PYY secretion in obese patients with type 2 diabetes receiving the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin. Satiogen Pharmaceuticals is developing rectally administered taurocholic acid, a bile acid, for the treatment of obesity and type 2 diabetes mellitus.

Istaroxime is a novel intravenous agent with luso-inotropic properties that acts by inhibition of Na( )/K( ) adenosine triphosphatase and stimulation of sarco/ endoplasmic reticulum calcium ATPase isoform 2. It is significantly decreased left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, heart rate and increased systolic blood pressure and cardiac index with no change in neurohormones, renal function or troponin I. Istaroxime has successfully concluded phase II clinical trials in cardiac failure patients. Istaroxime induced apoptosis, affected the key proliferative and apoptotic mediators c-Myc and caspase-3 and modified actin cytoskeleton dynamics and RhoA activity in prostate cancer cells – this provides novel insights into the anti-cancer properties of istaroxime further supporting the development of this agent as a novel anti-cancer drug candidate.

Hydroxytamoxifen (Afimoxifene) is an active metabolite of tamoxifen exerting estrogen receptor modulatory function. In addition, hydroxytamoxifen binds to regulates transcriptional activity of the estrogen-related receptor gamma. ASCEND Therapeutics, Inc. was developing TamoGel (4-hydroxytamoxifen gel) for a variety of estrogen-dependent conditions, including breast cancer, cyclic breast pain and gynecomastia.

Angiotensin (1-7) [Ang 1-7] is a 7 amino acid peptide generated predominantly from Ang II by the action of Ang-converting enzyme 2. Ang 1-7 can act as a negative modulator of aldosterone secretion in vitro and in vivo. The endogenous heptapeptide angiotensin-(1-7) (Ang-(1-7)) is a RAS component that has a central role in the alternative axis. It is generated by the cleavage of Ang-II by the action of the angiotensin converting enzyme 2 (ACE 2) and acts via interaction with the G-protein coupled receptor Mas. Angiotensin (1-7) induces vasorelaxation through release of NO and prostaglandins, perhaps through activation of a non-AT1, non-AT2 receptor, Mas. Counteracts the vasoconstrictive and proliferative effects of angiotensin II and stimulates vasopressin (anti-diuretic hormone) release in vivo. Clinical uses range from treatment of cardiovascular-related diseases, ocular pathologies, metabolic dysfunctions, brain conditions and degenerative diseases to applications in cell differentiation and hematopoiesis, tumor therapy, acute lung injury, fibrosis, infection, among others. Tarix Orphan is developing TXA127 for rare neuromuscular and connective tissue diseases. TXA127 is a pharmaceutical formulation of the naturally occurring peptide, Angiotensin (1-7). TXA127 has been effective in animal models of Duchenne muscular dystrophy (DMD), Limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy MDC1A, Marfan syndrome, and Dystrophic Epidermolysis Bullosa (DEB). FDA granted rare pediatric disease designation to TXA127 from Tarix to treat recessive dystrophic epidermolysis bullosa (RDEB). TXA127 has been granted orphan drug status by FDA as a treatment for pulmonary arterial hypertension, to enhance engraftment in patients receiving a stem cell transplant, and for Myelodysplastic Syndrome (MDS). Tarix Orphan has broad IP protection for TXA127 and Orphan Drug Designations (ODDs) have been granted for DMD LGMD and DEB in the U.S., and for DMD in Europe. Tarix Orphan aims to initiate a clinical trials for both DMD and DEB in early 2018 and has an active IND for a Phase II trial in DMD, as well as Fast Track designation for DMD.

Mureletecan is a water-soluble prodrug, consisting of camptothecin covalently linked to polymeric backbone methacryloylglycynamide, with potential antineoplastic activity. After entering tumor cells, the active moiety camptothecin is slowly released from mureletecan via hydrolysis of the ester linkage. Camptothecin, the active moiety, is an alkaloid isolatable from the Chinese tree Camptotheca acuminata. Camptothecin itself suffers from poor solubility, which is why it is often investigated with a solubilizing conjugate; such as in Mureletecan. Camptothecin binds to and stabilizes the topoisomerase I-DNA covalent complex producing potentially lethal double-stranded DNA breaks when encountered by DNA replication machinery. Camptothecin has also been shown to inhibit HIF1a. Camptothecin has been investigated with a number of solubilizing conjugates as a potential treatment in various forms of cancer.