Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light and during wound healing or tissue remodeling. Many members of this group perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). HSPs are found in virtually all living organisms, from bacteria to humans.
The 70 kilodalton heat shock proteins are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an important part of the cell's machinery for protein folding, performing chaperoning functions, and helping to protect cells from the adverse effects of physiological stresses. Additionally, membrane-bound Hsp70s have been identified as a potential target for cancer therapies and their extracellularly localized counterparts have been identified as having both membrane-bound and membrane-free structures.
Hsp90 is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs.
Geldanamycin is a 1,4-benzoquinone ansamycin antitumor antibiotic that inhibits the function of Hsp90 by binding to the unusual ADP/ATP-binding pocket of the protein. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis.
Vernalis Research develops and applies fragment and structure-based methods to drug discovery, and has generated cell active lead compounds and development candidates against biological targets in oncology, neurodegeneration, anti-infectives and inflammation.
Heat shock protein HSP 90-alpha is a protein that in humans is encoded by the HSP90AA1 gene.
Eribulin, sold under the brand name Halaven, is an anticancer medication used to treat breast cancer and liposarcoma.
Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonproprietary Names for MMAE-MAB-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody. It is a potent antimitotic drug derived from peptides occurring in marine shell-less mollusc Dolabella auricularia called dolastatins which show potent activity in preclinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors. These drugs show potency of up to 200 times that of vinblastine, another antimitotic drug used for Hodgkin lymphoma as well as other types of cancer.
Dactolisib is an imidazoquinoline derivative acting as a PI3K inhibitor. It also inhibits mTOR. It is being investigated as a possible cancer treatment.
ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4-ALK translocation. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involved in the abnormal growth of tumour cells. All the current approved ALK inhibitors function by binding to the ATP pocket of the abnormal ALK protein, blocking its access to energy and deactivating it. A majority of ALK-rearranged NSCLC harbour the EML4-ALK fusion, although as of 2020, over 92 fusion partners have been discovered in ALK+ NSCLC. For each fusion partner, there can be several fusion variants depending on the position the two genes were fused at, and this may have implications on the response of the tumour and prognosis of the patient.
Volasertib is an experimental small molecule inhibitor of the PLK1 protein being developed by Boehringer Ingelheim for use as an anti-cancer agent. Volasertib is the second in a novel class of drugs called dihydropteridinone derivatives.
An Hsp90 inhibitor is a substance that inhibits that activity of the Hsp90 heat shock protein. Since Hsp90 stabilizes a variety of proteins required for survival of cancer cells, these substances may have therapeutic benefit in the treatment of various types of malignancies. Furthermore, a number of Hsp90 inhibitors are currently undergoing clinical trials for a variety of cancers. Hsp90 inhibitors include the natural products geldanamycin and radicicol as well as semisynthetic derivatives 17-N-Allylamino-17-demethoxygeldanamycin (17AAG).
Paul Workman is a British scientist noted for his work on the discovery and development of pharmaceutical agents in the field of oncology. He is President and CEO of The Institute of Cancer Research In London.
Ceritinib is a prescription-only drug used for the treatment of non-small cell lung cancer (NSCLC). It was developed by Novartis and received FDA approval for use in April 2014..Ceritinib is also sold under the brand name Spexib in few countries by Novartis.
PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer.
Said Sebti (Arabic: سيد سبتي, (first name is an American cancer researcher who is Professor and Chairman of the Department of Drug Discovery at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fl. Sebti is noted for his work to rehabilitate the 'failed' cancer drug Triciribine, now under development at the pharmaceutical company Prescient Therapeutics. Sebti is currently Chief Scientific Officer at Prescient Therapeutics.
Emactuzumab (RG-7155) is a humanized monoclonal antibody directed against colony stimulating factor 1 receptor (CSF-1R) expressed on macrophages and has demonstrated a profound antitumor effect through interference with the CSF-1/CSF-1R axis, along with a manageable safety profile in patients with diffuse-type tenosynovial giant cell tumors (d-TGCT).
Brolucizumab sold under trade name Beovu among others, is a humanized single-chain antibody fragment for the treatment of neovascular (wet) age-related macular degeneration (AMD).
Silmitasertib (INN), codenamed CX-4945, is a small-molecule inhibitor of protein kinase CK2, a constitutively active serine/threonine-specific protein kinase that is overexpressed in several types of tumors.
Mehdi Mollapour is a British-American Biochemist and Cancer Biologist. He is a Professor, Vice Chair for Translational Research and Director of Renal Cancer Biology Program for the Department of Urology, and Adjunct Professor at the Department of Biochemistry and Molecular Biology at SUNY Upstate Medical University.
