Russell Dahl | |
---|---|
Born | 1974 |
Nationality | American |
Alma mater | University of California San Diego Santa Clara University |
Occupation(s) | Organic chemist, academic and biotechnology entrepreneur |
Russell Dahl (born 1974) is an American organic chemist, academic and biotechnology entrepreneur. Dahl is mainly known for his work in pharmaceutical research. He is the founder of biopharmaceutical startup Neurodon.
Dahl was raised in San Jose, California. He completed his undergraduate studies at Santa Clara University, graduating in 1997 with a bachelor's degree in chemistry and combined science. [1] In 2002, he obtained his master's degree in chemistry from the University of California San Diego (UCSD). Dahl earned his PhD in chemistry in 2004 from UCSD. [2] [3] During his doctoral studies, Dahl had a fellowship at DuPont Pharmaceuticals where he and his team developed some of the first poly-ADP ribose polymerase (PARP) inhibitors for the treatment of cancers. [4] [5] His thesis research at UCSD culminated in the development of new reaction methodology for the synthesis of biologically relevant oligosaccharides. [6] [7] [8]
From 2006 to 2012, he was the Director of Medicinal Chemistry Sanford-Burnham Medical Research Institute. Dahl has held faculty positions at University of Southern California, UC San Diego School of Medicine, Palomar College, Rosalind Franklin University of Medicine and Science, University of Illinois at Chicago, University of New England and Purdue University. [9] [10]
His main area of work is pharmaceutical research and drug discovery. Most of his research is focused on the discovery and development of small molecules that inhibit ER stress-induced cell death and dysfunction, which plays a role in multiple diseases, including diabetes and neurodegenerative conditions. Dahl invented and patented small molecule activators of the sarco/endoplasmic reticulum Ca2+-ATPase, [11] or SERCA, a protein whose major function is to maintain calcium homeostasis in the cell. [12] [13] One compound Dahl created, CDN1163, is utilized by researchers as a tool molecule to probe the effects of SERCA in various disease models. [14] [15] [16] Dahl has authored or co-authored over 100 peer-reviewed articles. [17] [18]
During 2003 and 2006, Dahl discovered a series of alpha-ketoamides as selective inhibitors of the p38 mitogen-activated protein kinase that became drug candidates for inflammatory diseases. [19] [20] [21] [22]
In 2015, Dahl founded Neurodon, a biopharmaceutical startup, with a focus on discovery of neuroprotective drugs for treatment of conditions such as diabetes, Alzheimer's disease and amyotrophic lateral sclerosis (ALS). [23] [24] [25] [26] [27] [28] [29] [30]
Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases such as CSF1R, ABL, c-KIT, FLT3, and PDGFR-β. Specifically, it is used for chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL) that are Philadelphia chromosome–positive (Ph+), certain types of gastrointestinal stromal tumors (GIST), hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), systemic mastocytosis, and myelodysplastic syndrome.
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.
Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosemide. It is given by mouth or by injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to a day.
Thiazide refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available.
Fingolimod, sold under the brand name Gilenya, is an immunomodulating medication, mostly used for treating multiple sclerosis (MS). Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. It has been reported to reduce the rate of relapses in relapsing-remitting multiple sclerosis by approximately one-half over a two-year period.
Chelerythrine is a benzophenanthridine alkaloid present in the plant Chelidonium majus. It is a potent, selective, and cell-permeable protein kinase C inhibitor in vitro. And an efficacious antagonist of G-protein-coupled CB1 receptors. This molecule also exhibits anticancer qualities and it has served as a base for many potential novel drugs against cancer. Structurally, this molecule has two distinct conformations, one being a positively charged iminium form, and the other being an uncharged form, a pseudo-base.
Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation, apoptosis and autophagy. Persistent activation of the p38 MAPK pathway in muscle satellite cells due to ageing, impairs muscle regeneration.
The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1, Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4). The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor.
Glucose-6-phosphate exchanger SLC37A4, also known as glucose-6-phosphate translocase, is an enzyme that in humans is encoded by the SLC37A4 gene.
Glucagon-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists(GLP-1-RA), incretin mimetics, or GLP-1 analogs, are agonists of the GLP-1 receptor. This class of medications is used for the treatment of type 2 diabetes. One of their advantages over older insulin secretagogues, such as sulfonylureas or meglitinides, is that they have a lower risk of causing hypoglycemia. GLP-1 has a short duration of action, so to overcome this limitation several modifications in either the drugs or the formulations are being developed. The 2022 ADA standards of medical care in diabetes include GLP-1-RA as a first line pharmacological therapy for type 2 diabetes, specifically in patients with atherosclerotic cardiovascular disease or obesity.
Lipidology is the scientific study of lipids. Lipids are a group of biological macromolecules that have a multitude of functions in the body. Clinical studies on lipid metabolism in the body have led to developments in therapeutic lipidology for disorders such as cardiovascular disease.
The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at eleven conserved sites. It is a cysteine protease and a member of the PA clan of proteases. It has a cysteine-histidine catalytic dyad at its active site and cleaves a Gln–(Ser/Ala/Gly) peptide bond.
A deuterated drug is a small molecule medicinal product in which one or more of the hydrogen atoms contained in the drug molecule have been replaced by its heavier stable isotope deuterium. Because of the kinetic isotope effect, deuterium-containing drugs may have significantly lower rates of metabolism, and hence a longer half-life.
SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that modulate sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium-glucose transport protein 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type II diabetes mellitus (T2DM). Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in patients with type II diabetes (T2DM). Several medications of this class have been approved or are currently under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.
Targeted covalent inhibitors (TCIs) or Targeted covalent drugs are rationally designed inhibitors that bind and then bond to their target proteins. These inhibitors possess a bond-forming functional group of low chemical reactivity that, following binding to the target protein, is positioned to react rapidly with a proximate nucleophilic residue at the target site to form a bond.
A proteolysis targeting chimera (PROTAC) is a heterobifunctional molecule composed of two active domains and a linker, capable of removing specific unwanted proteins. Rather than acting as a conventional enzyme inhibitor, a PROTAC works by inducing selective intracellular proteolysis. PROTACs consist of two covalently linked protein-binding molecules: one capable of engaging an E3 ubiquitin ligase, and another that binds to a target protein meant for degradation. Recruitment of the E3 ligase to the target protein results in ubiquitination and subsequent degradation of the target protein via the proteasome. Because PROTACs need only to bind their targets with high selectivity, there are currently many efforts to retool previously ineffective inhibitor molecules as PROTACs for next-generation drugs.
Halicin (SU-3327) is an experimental drug that acts as an enzyme inhibitor of c-Jun N-terminal kinase (JNK). Originally, it was researched for the treatment of diabetes, but development was discontinued for this application due to poor results in testing. In 2019, this molecule was found by an artificial intelligence (AI) model to show antibiotic properties against a number of bacteria.
Hagit Eldar-Finkelman is an Israeli scientist and a principal investigator of an active research laboratory at the Sackler School of Medicine at Tel Aviv University. Eldar-Finkelman’s research is focused on the signal transduction field and drug development targeting protein kinases. She is well known for her pioneering work on the functions of GSK-3 and its contribution to diabetes and other pathogenies, including depressive behavior, Alzheimer’s diseases, and Huntington’s diseases. Novel findings also include the unique evolution of GSK-3 isozymes. Eldar-Finkelman is a leading figure in developing novel substrate competitive inhibitors (SCIs) for GSK-3 with significant benefits as drug candidates.