Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.

The natural tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP also known as Goralatide) is generated from the N-terminus of thymosin-β4 through enzymatic cleavage by prolyl oligopeptidase (POP). AcSDKP regulation of proliferation of different cells is implicated in hematopoiesis and angiogenesis. This tetrapeptide present in almost all cells was recently detected at elevated concentrations in neoplastic diseases. However, previously reported in vitro and in vivo studies indicate that AcSDKP does not contribute to the pathogenesis of cancers. AcSDKP was in the phase II clinical trial for development of a new non-radioactive test for measuring glomerular filtration rate in patient with Chronic Kidney Disease. In addition, using mice models was concluded ,that AcSDKP might be an oral antifibrotic peptide drug that would be relevant to combating fibroproliferative kidney diseases such as diabetic nephropathy.

Elomotecan (BN 80927), a homocamptothecin derivative, inhibits both topoisomerase I and topoisomerase II mediated DNA relaxation. It potently inhibits proliferation of human tumor cells in vitro and in vivo. Elomotecan was being developed for the treatment of solid tumors.

Somatoprim (DG3173) is a heptapeptide somatostatin analog (SSA) that binds with high affinity to sstr2, sstr4 and sstr5 and shows a very low insulin suppression in contrast to other SSA. Initially developed by Ipsen, it is under active development by licensee Aspireo Pharmaceuticals, an Israeli company. In vitro as well as in vivo testing showed a dose-dependent GH lowering effect. Somatoprim has demonstrated a unique receptor binding and pharmacological profile which is differentiated from SSAs that are currently marketed or in clinical development. In particular, Somatoprim has shown an improved side effect profile with reduced adverse effects on the gastrointestinal tract and glucose metabolism. Furthermore, assessment of growth hormone secretion in cultured human somatotroph adenoma tissue treated with Somatoprim indicates that it has the potential to increase the response rate of acromegalic patients to SSA therapy. Somatoprim is currently in phase I/II of clinical development.

Rocepafant (also known as BN 50730 or LAU 8080) is a hetrazepinic derivative and a platelet-activating factor (PAF) receptor antagonist. PAF is a mediator of cerebral ischemic injury and administration of rocepafant in neonatal rats was found to have a neuroprotective role, attenuating hypoxic-ischemic brain injury in neonatal rats. Combined with two other types of compounds, rocepafant was shown to modulate the stress-induced up-regulation of cycloooxygenase-2 and prostaglandin E2 in humans, which may be of potential therapeutic value in the design of treatment for complex neuroinflammatory disorders. This compound has been evaluated for treatment of asthma, arrhytmias and rheumatic disorders, but development of rocepafant has been discontinued in 2003.

Ginkgolide B belongs to the class of organic compounds known as ginkgolides and bilobalides. These are diterpene lactones with a structure based either on the gingkolide or the bilobalide skeleton. The ginkgolide skeleton is a very rigid structure consisting of hexacyclic C20 trilactone. The cis-fused F/A/D/C ring junction forms an empty semi-ball hole, the D ring contains a cage form tetrahydrofuran ring which occupies the center of the empty hole, and the oxygen atoms of the D,C and F ring and 10-hydroxyl group consist of an analogous crown ether structure. Ginkgolide B is one of the ginkgolides isolated from the leaves of the Ginkgo biloba tree. The Ginkgolide B is the most potent antagonist of platelet activating factor (PAF) and exhibits therapeutic action in a variety of diseases mainly by the PAF receptor. The ginkgolide B possesses a number of beneficial effects such as anti-inflammatory, anti-allergic, antioxidant, and neuroprotective effects. It promotes the proliferation, migration and adhesion of endothelial progenitor cells, and the induction of angiogenesis through vascular endothelial factor (VEGF). Ginkgolide B is considered a valid non-pharmacological (or nutraceutical) approach to the prophylaxis of both migraine with and without aura. Effects of ginkgolide B include reduction of Ca2+-stimulated intracellular events, scavenging of free radicals, modulation of central nervous system glutamatergic transmission and reduction of antiplatelet activating factor (PAF) levels in brain. Ginkgolide B is an active component of EGb, a standardised extract of Ginkgo biloba leaves. Ginkgolide B is one of the major components of EGb-761.

Cicletanine is a diuretic, developed by Ipsen for the treatment of hypertension. The drug was marketed in France by Recordati under the name Tenstaten. The mechanism(s) by which cicletanine exerts its biological effects has not been definitely established. The salidiuretic activity appears to be the result of an action of the sulfoconjugated metabolite of cicletanine, which inhibits the apical Na+-dependent Cl-/HCO3- anion exchanger in the distal convoluted tubule. The mechanism of the vasodilating effect of cicletanine may include stimulation of vascular prostaglandin synthesis, inhibition of the low Km cyclic GMP phosphodiesterases, and blockade of Ca2+ channels either directly or indirectly. The drug has also been shown to interact with other proteins, including alpha-adrenergic, vascular histamine, and muscarinic receptors.

Taspoglutide is a glucagon-like peptide-1 agonist was studied in phase III clinical trials for the treatment patients with type 2 diabetes. However, in September 2010 Roche halted Phase III clinical trials due to gastrointestinal intolerability and serious hypersensitivity reactions experienced by some trial participants.

Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.

Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.