Most of the sound frequencies used in these recordings
correspond either to the molar mass or equivalent scalar
octave of the related products.

This work is dedicated to the public domain and
may be reproduced without authorization.

Algorithmic piano music mixed with sound frequencies.


* 5-NOT or 5-nonyloxytryptamine oxalate (5-NOT)  a PSA mimetic, is a small molecule that has been shown to be effective in vitro. 5-NOT promotes in-vitro neuritogenesis of motor neurons, as well as in vitro myelination and Schwann cell motility, all of which are critical to peripheral nervous repair.
( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992320/ )

* Alendronate administration reduced bone resorption and increased mineralized tissue formation inside the bone tunnel. Thus, the capacity of alendronate to protection from tendon deterioration and also reduce of bone loss may act synergistically to improve tendon-bone integration.
( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992320/ )

* Allergy-Antihistamines Mix plays the sound frequencies of fexofenadine, desloratadine and levoceterizine. Fexofenadine is used in the treatment of allergy symptoms, such as hay fever and urticaria. Therapeutically, fexofenadine is a selective peripheral H1-blocker. Desloratadine is a tricyclic H1 antagonist used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (hives). Levoceterizine acts as an inverse agonist that decreases activity at histamine H1 receptors. It is used for the treatment of allergic rhinitis (hay fever) and long term hives of unclear cause.

* Bay-11-7082 has been shown to significantly decrease MMP activities in injured anterior cruciate ligament (ACL) fibroblasts and thus hold promise as small molecule drugs to facilitate ACL repair. These recent efforts have remarkably improved the understanding of the effects of small molecules on ACL repair and tendon-to-bone interface healing. Regeneration or replacement of a ruptured/torn ligament or tendon is one of the most common procedures performed by sports medicine surgeons. Anterior cruciate ligament (ACL) rupture is one of the most common injuries of the knee due to trauma or disease.
( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992320/ )

* Betulin is a small molecule whose inhibition of SREBP decreased the biosynthesis of cholesterol and fatty acid. In vivo, betulin ameliorated diet-induced obesity, decreased the lipid contents in serum and tissues, and increased insulin sensitivity. Furthermore, betulin reduced the size and improved the stability of atherosclerotic plaques. Inhibition of the SREBP pathway can be employed as a therapeutic strategy to treat metabolic diseases including type II diabetes and atherosclerosis. Betulin, which is abundant in birch bark, could be a leading compound for development of drugs for hyperlipidemia. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors activating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride.

* BGP-15 is a small molecule that improves cardiac function in two mouse models of heart failure. Atrial fibrillation, which is the most common abnormal heart rhythm, and heart failure are increasing in incidence, but current drugs show limited efficacy. BGP-15 can prevent or reduce episodes of irregular heartbeats and significantly improve heart function in mouse models of heart failure and atrial fibrillation. BGP-15 has already been tested for human use as a treatment for other disorders and is known to be well-tolerated with a good safety profile. The drug works via an unexpected molecular pathway by increasing activation of a receptor, called the insulin-like growth factor 1 receptor. A shortage of this receptor has previously been associated with an increased risk of cardiovascular disease. Understanding the mechanisms through which BGP-15 exerts its effects may further aid the development of new therapies for heart disease.

* Breathing Difficulty-Heliox Therapy. Heliox is a mixture of helium and dioxygen. Heliox is a medical treatment for patients with difficulty breathing. Helium is an odorless, non-explosive and biologically inert gas. It has been used for a long time as a mixture with oxygen, known as heliox, in the treatment of upper and lower airway obstruction, such as asthma, chronic obstructive pulmonary disease, bronchiolitis and bronchopulmonary dysplasia. Heliox has the following benefits: Reduces resistance to flow within the airways and consequently decreases the work of breath during spontaneous and non-invasive positive-pressure ventilation; provides an optimal patient-ventilator interaction; and reduces destructive hemodynamic effects. Additionally, heliox is used in children during bronchoscopy, even as a treatment for pneumothorax and hyperammonemia. The helium–oxygen mixture was used in the treatment of severe asthma, cystic fibrosis, bronchoalveolitis, post-extubation pathologies and pharyngo–laryngeal edema. Also, it is usually less known that heliox can be used as a therapeutic agent in the treatment of acute respiratory distress or ventilatiory-induced lung inflammation.


* Camphor relieves itching from insect bites, minor skin irritation, or joint pain. It is absorbed in the skin epidermis, where it stimulates nerve endings sensitive to heat and cold. The action on nerve endings also induces a slight local analgesia. Camphor inhibits coughing and relieves upper airway congestion due to the common cold. Camphor has been used in traditional medicine over centuries, probably most commonly as a decongestant. Camphor was used in ancient Sumatra to treat sprains, swellings, and inflammation.

* CHIR-99021, an AMPK activator led to the mobilization of resident mesenchymal stem cells in the tooth pulp that had been exposed via the drilling of holes in mice molars. This GSK3beta inhibitor-induced stem cell mobilization promoted a natural process of reparative dentin formation that completely restored dentin, leading the authors to conclude that stimulation of mesenchymal stem cell mobilization and differentiation into odontoblast-like cells may represent a novel approach to clinical tooth restoration.

* CHIR99021-Valproic acid, both of which activate AMPK, significantly expanded cochlear supporting cells (i.e. “inner ear stem cells”) that expressed and maintained the epithelial stem cell marker Lgr5. Treatment with CHIR and VPA also led to the differentiation of Lgr5-expressing cells into hair cells in high yield, providing additional evidence that AMPK activation promotes differentiation of adult stem cells including inner ear stem cells, possibly leading to treatments for hearing loss. Interestingly, the authors demonstrated in a previous study that CHIR and VPA also promoted the multilineage differentiation of Lgr5+ intestinal stem cells into mature enterocytes, goblet cells and Paneth cells. AMPK activation has also been shown to improve gut epithelial differentiation and metformin increases goblet and Paneth cell differentiation from intestinal epithelial cells, further indicating that AMPK activation likely represents a common mechanism of action linking structurally dissimilar compounds that enhance inner ear and intestinal stem cell maintenance and differentiation.

* EMA401 is a drug under development for the treatment of peripheral neuropathic pain. It was initially established as a potential drug option for patients suffering pain caused by postherpetic neuralgia. It may also be useful for treating various types of chronic neuropathic pains caused by lesions and other diseases affecting the somatosensory system in addition to postherpetic neuralgia. EMA401 has been implicated in alleviating pains associated with a host of neural abnormalities, ranging from excessive nerve sprouting due to damaged nerve caused by shingles, diabetes, osteoarthritis, HIV and chemotherapy. EMA401 is more effective and has virtually no central nervous system side effects in comparison to current drugs for pain relief. Pain pathways of the other functional systems have major molecular and mechanistic differences compared to pain pathways of the peripheral nervous system. EMA401 target proteins, angiotensin II type 2 receptors, are extremely important for nociception within the peripheral nervous system and less so for nociception within other functional systems. EMA401 is the first drug on the market that targets angiotensin II type 2 receptors (AT2R) with high affinity but has a low affinity for angiotensin II type 1 receptors.

* Epalrestat is a carboxylic acid derivative and a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy, which is one of the most common long-term complications in patients with diabetes mellitus. It reduces the accumulation of intracellular sorbitol which is believed to be the cause of diabetic neuropathy, retinopathy and nephropathy  It is well tolerated, with the most commonly reported adverse effects being gastrointestinal issues such as nausea and vomiting, as well as increases in certain liver enzymes. Eparestalt may help improvement of subjective neuropathy symptoms, abnormality of vibration sense, and abnormal changes in heart beat associated with diabetic peripheral neuropathy.

* ETC-1002 or Bempedoic acid is a small molecule inhibitor of ATP citrate lyase that also activates
5'-adenosine monophosphate-activated protein kinase, effectively reducing low-density lipoprotein cholesterol and inducing some other positive metabolic changes. Recent evidence from phase I and II clinical trials in humans has shown a positive efficacy and safety profile of ETC-1002, with low-density lipoprotein cholesterol reductions similar to those attainable by usual doses of many statins and with no major apparent side effects. Bempedoic acid is an oral, nonstatin therapy designed to primarily work in the liver to inhibit cholesterol biosynthesis. Bempedoic acid is a prodrug that is complementary to—yet distinct from—other lipid-lowering therapies, including statins. Bempedoic acid is converted to its active moiety primarily in the liver, and inhibits adenosine triphosphate citrate lyase (ACL)—an enzyme two steps upstream from HMG-CoA reductase, the target of statins—along the cholesterol biosynthesis pathway. Bempedoic acid is converted to its active moiety by very long-chain acyl-CoA synthetase-1 (ACSVL1), which is not present in skeletal muscle. By inhibiting ACL, bempedoic acid is designed to reduce cholesterol synthesis, resulting in LDL receptor upregulation.

* Hair regeneration requires reactivating dormant hair follicle stem cells. Pharmacological induction of autophagy is sufficient to activate quiescent telogen hair follicles, initiating new anagen hair growth. Hair loss resulting from shortened anagen, lengthened telogen, and/or impeded anagen induction may thereby be rescued by activating autophagy. Quiescent (telogen) hair follicles can be stimulated to initiate anagen and hair growth by small molecules that activate autophagy, including the metabolites alpha-ketoglutarate (alpha-KG) and alpha-ketobutyrate (alpha-KB), and the prescription drugs rapamycin and metformin, which impinge on mTOR and AMPK signaling. Anagen can be pharmacologically activated in telogen skin when natural anagen-inducing signal(s) are absent has implications for the treatment of hair loss patients. ( https://doi.org/10.1016/j.celrep.2019.05.070 )

* Hypoxia-Hypoxemia Therapy. The application of positive-pressure mechanical ventilation is one of the cornerstones of support for patients with acute respiratory failure. Unfortunately, the clinical condition of some patients does not improve, despite escalating ventilatory support. Adjunctive therapies to mechanical ventilation such as nitric oxide and heliox have been explored for the purposes of minimizing injurious settings and supporting adequate gas exchange. The combined use of nitric oxide and heliox could be a rescue therapy for a critically ill infants with localized interstitial pulmonary emphysema and pulmonary hypertension. All the while conventional interventions were ineffective, not feasible, or unlikely to take effect in time, heliox and nitric oxide  improved oxygenation, after echocardiographic evidence of high right-ventricular pressure. Regarding the coronavirus, doctors make different hypotheses about what happens inside the body of a patient with COVID-19. One of the hypotheses is that inflammation of the lungs, which develops under the influence of the coronavirus, leads to a thrombosis of small vessels in the lungs. Nitrogen monoxide allows these vessels to open and relieve patients.

* IDE-1 is an inducer of definitive endoderm 1. IDE1 activates the TGF-beta signaling pathway and induces definitive endoderm formation in human and mouse embryonic stem cells. It is also reported to increase the levels of Nodal expression, induce Smad2 phosphorylation and SOX17 expression. Beta cells are the major cells (70% of the total cells) in the islet of Langerhans of the pancreas, critical to store and release the hormone insulin to maintain glucose homeostasis. Irregularities with the normal functioning of beta cells can lead to either type 1 diabetes mellitus (T1DM), where the islets are completely destroyed by the patient’s own immune system (autoimmune response), or type 2 diabetes mellitus (T2DM), where patients are unable to respond to insulin due to insulin resistance and inadequate production.

* Inclisiran is a small interfering ribonucleic acid (siRNA) molecule being investigated for the treatment of hypercholesterolemia. Inclisiran may be an option in the future as a cholesterol-lowering medication, where it would likely be used in patients who are unable to achieve their LDL-C targets despite maximally tolerated statin therapy or who are intolerant to statin therapy. Inclisiran works by targeting the PCSK9 enzyme; however, as opposed to PCSK9 inhibitors, which are antibodies that inhibit circulating PCSK9, inclisiran is a chemically synthesized small interfering RNA (siRNA) molecule that reduces the production of PCSK9 through gene silencing. Once bound, inclisiran is rapidly taken in by the cell where it then binds to the RNA-induced silencing complex as well as the messenger RNA (mRNA) encoding PCSK9. The siRNA RISC complex cleaves the PCSK9 mRNA, preventing the synthesis of the PCSK9 protein. One siRNA RISC complex can do this degradation process with multiple PCSK9 mRNA. Without PCSK9 enzymes, there will be no lysosomal degradation of the LDL receptor, so LDL-C will bind the receptor, be recycled in the hepatocyte, and result in a lower serum LDL-C level.

* J-2156 is a somatostatin receptor 4 agonist which reduces mechanosensitivity of peripheral nerve afferents and spinal neurons in an inflammatory pain model. The analgesic effect of J-2156
in acute neurogenic/non-neurogenic inflammatory reactions and chronic arthritis   is mediated mainly via peripheral SST4 receptors. Chronic Low Back Pin (LBP) is a debilitating condition that ranks among the most common reasons for patient visits to healthcare providers. J-2156 alleviated both primary and secondary hyperalgesia in the lumbar axial deep tissues at L4/L5 and L1 respectively. This was accompanied by a reduction in the otherwise augmented lumbar DRG (L4-L6) expression levels of the putative pro-nociceptive markers, pp38 MAPK and pp44/pp42 MAPK and a reduction in pp38 MAPK in the lumbar enlargement of the spinal cord. J-2156 is also a pharmacological target for relief of breast cancer-induced bone pain (BCIBP).

* KU-32 a novel drug for diabetic neuropathy, is safe for human islets and Improves In vitro insulin secretion and viability. KU-32 can stop and even reverse diabetic peripheral neuropathy, or DPN, in mice. The condition leads to death of nerves in the extremities of individuals with diabetes. KU-32 is also a potential new treatment for 'chemo brain'.  As many as 1 in 3 patients with cancer who undergo chemotherapy experience cognitive impairment as a result of the treatment. The cognitive dysfunction associated with chemotherapy is commonly referred to as “chemo brain.” The symptoms of chemo brain include difficulty remembering things, trouble concentrating and processing information, and overall confusion. Chemotherapy increases levels of hydrogen peroxide in the brain and KU-32 can counter the negative effects of this excessive substance. Hydrogen peroxide is a reactive oxygen species and potentially damaging which may have an effect on cognitive function. Additionally, it may serve as a preventative in order to treat it. KU-32 prevents cognitive impairment, and our preliminary neurochemical data suggest that it may prevent increases in hydrogen peroxide production.


* LM22A-4 is a small molecule used for nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in those older than 50 years. LM22A-4, also can lead to improvements in respiratory problems, spatial memory, motor skill defects and brain performance iassociated with Rett Syndrome. Finally, this compound (LM22A-4) may have potential as a therapeutic to reduce compulsive alcohol drinking without a generalized effect on motivation.

* MCC950 is a specific inhibitor of the NOD-like receptor family pyrin-domain-containing protein 3 (NLRP3) inflammasome. NLRP3 blockade can help attenuate asthma, neuropathic pain, colitis, stroke, chikungunya infection and more—including Parkinson’s. Parkinson's disease is the second-most common neurodegenerative disease worldwide, with 10 million sufferers, whose control of body movements is affected. The disease is characterised by the loss of brain cells that produce dopamine, which is a chemical that co-ordinates motor control, and is accompanied by chronic inflammation in the brain. MCC950, given orally once a day, blocked NLRP3 activation in the brain and prevented the loss of brain cells, resulting in markedly improved motor function. MCC950 effectively 'cooled the brains on fire', turning down microglial inflammatory activity, and allowing neurons to function normally.

* Microgabalin is an effective drug for for post-herpetic neuralgia and diabetic peripheral neuropathic pain.

* N106 is a small molecule which increases SUMOylation of SERCA2a. This compound directly activates the SUMO-activating enzyme, E1 ligase, and triggers intrinsic SUMOylation of SERCA2a. We identified a pocket on SUMO E1 responsible for N106 effects. The incidence of heart failure (HF) continues to increase in the United States despite significant advances in pharmacological therapies and novel devices. There is an acute need for novel treatment strategies for heart failure. A key abnormality in HF is defective handling of calcium that has been partially related to abnormal sarcoplasmic reticulum (SR) function in cardiac myocytes. Reduced expression and altered activity of the cardiac sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), have been found in human and animal models of HF.

* Photoregulin3 alters the activity of a transcription factor that regulates rod genes. In follow-up experiments, mice with a mutation that replicates many of the features of retinitis pigmentosa were given Photoregulin3 to see if it could slow the progression of the disease. Indeed, Photoregulin3 could stop many of the rod cells from degenerating in the treated mice. At the end of the experiment, the mice treated with this small molecule had about twice as many rods as the control mice. The treated mice also responded better to flashes of light.

* PM-43I can inhibit STAT6-dependent allergic airway disease in mice. Moreover, PM-43I reversed preexisting allergic airway disease in mice. Importantly, PM-43I was efficiently cleared through the kidneys and had no long-term toxicity. PM-43I represents the first of a class of small molecules that may be suitable for further clinical development as a therapeutic drug against asthma. Steroids prevent inflammation as well as other immune responses. The researchers' work shows that treating asthma with PM-43I may control asthma without impairing the ability of the body to fight pathogens. Steroids drive down all the immune system, but this small molecule specifically targets the pathway that leads to asthma, uncompromising the other pathways that allow the body to fight disease. Treatment alone would be able to control the asthma. PM-43I prevents the induction of fungal-induced asthma and, more importantly, reverses many of the hallmark features of asthma including airway constriction, lung inflammation, and lung mucus production.

* SB-216763 is a small molecule that generated mesenchymal stem cell-derived functional endothelial cells (MDFECs) and facilitated rapid transmural coverage of injured blood vessels. Small molecules with 1H-pyrrole-2,5-dione as a core structure have great potential to improve the efficacy of MSC-based cell therapy for vascular diseases, such as atherosclerosis and restenosis. SB216763 also promotes axonal regeneration and remyelination, thereby providing a promising therapeutic approach for peripheral nerve injury. Furthermore, may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease.


* Tissue Regeneration. Inducing stem cell differentiation is a promising means to aid in muscle regeneration. Three small molecules induced myoblast dedifferentiation, BIO (glycogen synthase-3 kinase inhibitor), SB203580 (p38 MAP kinase inhibitor), and lysophosphatidic acid.  Additionally, these compounds did not affect the potential of the dedifferentiated cells to redifferentiate into myoblasts at a later date. ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992320/ )

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