Burlingame, CA, United States
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Patent
Cleave Biosciences | Date: 2017-08-23

Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.


Patent
Cleave Biosciences | Date: 2015-07-09

The invention relates to detection of drug insensitivity by detecting mutations in the p97 gene or the p97 gene product following treatment with a p97 inhibitor, and identification of drugs to overcome such drug insensitivity.


Patent
Cleave Biosciences | Date: 2015-01-19

The present invention is directed to certain fused pyrimidines having a homo or hetero cyclopentyl, cyclohexyl or cycloheptyl ring as the pyrimidine fusion partner; having an amino benzyl or substituted amino benzyl group at the 4 position of the pyrimidine ring; and a 5:6 heterobicyclo ring with at least one N, O or S at the 2 position of the pyrimidine ring. These compounds are useful for treatment of cancer by inhibition of the p97 complex.


Patent
Cleave Biosciences | Date: 2013-07-19

A group of fused two ring pyrimidine compounds having a heterocycles substituent at the 2 position and a substituted amine at the 4 position as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine and other ring are disclosed. In addition a group of quinazoline compounds having similar substituents at the 2 and 4 positions as well as at other positions are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity.


Patent
Cleave Biosciences | Date: 2016-06-03

Nitrogen hexacycle compounds having an arylalkyl amine substituent at the P4 position and a substituted 5:6 bicyclic group at the P2 position of the nitrogen hexacycle as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the nitrogen hexacycle, the aryl alkyl group and the 5:6 bicyclic group are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.


Patent
Cleave Biosciences | Date: 2013-07-19

Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.


Patent
Cleave Biosciences | Date: 2014-12-10

Monocyclic pyrimidine and pyridine compounds having a benzyl amine substituent at the 4 position and a 5:6 bicyclic heteroaryl substituent at the 2 position of the pyrimidine or pyridine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.


Patent
Cleave Biosciences | Date: 2012-05-10

Compounds, pharmaceutical compositions, and methods of using such compounds to treat or prevent diseases or disorders associated with or mediated by JAMM proteins are disclosed. The compounds and compositions inhibit the enzymatic activity of a JAMM domain, including the JAMM domain of the CSN5 subunit of the COP9-signalsome (CSN), the JAMM domain of the Rpn11/Poh1/Psmd14 subunit of the 26S proteasome, the JAMM domain of AMSH, the JAMM domain of AMSH-LP, the JAMM domain of BRCC36, among other JAMM domains.


Over the last few decades, investigators have developed a number of methods to treat multiple myeloma. With surgery and radiation therapy being equally ineffective and not viable for the majority of cancer cases, chemotherapy has been often used in treating multiple myeloma. However, the latter treatment type exhibits modest pharmacological efficacy, which necessitates the discovery of better treatment options with reduced side effects and the potential to increase average survival rates. A number of innovative multiple myeloma therapeutic agents are available in the market, offering higher efficacy and safety levels. Forecasts suggest innovative therapeutics will provide better pharmacological benefit to patients and generate significant revenues moving forward. Monoclonal antibodies (mAbs) have been usefully used for a number of malignancies owing to their high specificity and superior therapeutic effectiveness. The ability of targeted mAbs to bind to specific cells plays key part in minimising side effects of cancer treatment. Currently, researchers are developing targeted mAbs for the treatment of multiple myeloma, which are expected to offer better therapeutic effects. Novel cancer treatment modalities such as vaccination are also under study for exploring their pharmacological efficacy. Vaccines for treating multiple myeloma are likely to overcome relapse by activating cancer patients’ immune system; they are presently under various stages of development and reliable clinical findings are required for them to receive FDA marketing approval. New report “Global Multiple Myeloma Drug Market & Pipeline Insight 2015” developed by Kuick Research is now available at MarketPublishers.com. The report offers an unrivalled guide to the worldwide multiple myeloma drug universe. It provides a deep overview of the disease and reviews the mechanism of drugs for treating multiple myeloma. The study presents a deep investigation of the current state of the market and presents a shrewd look at the clinical pipeline; analyses the market dynamics covering key market drivers and challenges for commercialization of the respective drugs; provides a detail outlook for the market with in-depth forecasts. The report explores the multiple myeloma drug development pipeline, on the basis of indication, stage and company; as well as reviews the drugs available in the market; suspended and discontinued multiple myeloma drugs in clinical pipeline. The competitive landscape is also analysed including profiles of the top 15 market players. More new reports by the publisher can be found at Kuick Research page.


REDWOOD CITY, Calif.--(BUSINESS WIRE)--REVOLUTION Medicines, Inc., a company focused on frontier cancer targets and drug discovery inspired by nature’s lessons, today announced that noted chemical biologist and cancer investigator Kevan Shokat, Ph.D. has joined the company as an academic co-founder and member of the company’s scientific advisory board, along with co-founders Martin Burke, M.D., Ph.D. and Michael Fischbach, Ph.D. The company also appointed accomplished industry veteran Julian Adams, Ph.D., leading structural biologist John Kuriyan, Ph.D., and noted clinical and translational oncologist Trever Bivona, M.D., Ph.D., to its scientific advisory board. “REVOLUTION Medicines has established significant momentum in deploying our product engine to advance multiple oncology drug discovery programs,” said Mark A. Goldsmith, M.D., Ph.D., president and chief executive officer of REVOLUTION Medicines. “Dr. Shokat is a leader and pioneer in the design of small molecules to modulate signal transduction pathways that control cellular growth exploited by cancer cells. Drs. Adams, Kuriyan and Bivona are also exceptionally accomplished scientists who bring additional creativity, experience and insights to help us fulfill our mission to engage frontier targets on behalf of cancer patients.” Dr. Shokat currently serves as professor and vice-chair in the department of cellular and molecular pharmacology at University of California, San Francisco, professor in the department of chemistry at University of California, Berkeley and investigator at the Howard Hughes Medical Institute. He is the recipient of numerous awards and grants, including election to the National Academy of Science and the Institute of Medicine. Dr. Shokat and his research laboratory are widely recognized for exploiting tools of chemistry, protein engineering and genetics to reveal the functions of individual kinases within a cell, and thus identify critical signaling molecules as candidates for drug development. He is a founder of Intellikine (acquired by Takeda) and Cellular Genomics (acquired by Gilead); co-founder of Araxes Pharmaceuticals, eFFECTOR Therapeutics and Mitokinin, LLC and a scientific advisor at Kura Oncology. Dr. Adams currently serves as president, research and development at Infinity Pharmaceuticals. He is a highly successful and noted drug hunter, having discovered and developed Velcade® (bortezomib), a proteasome inhibitor for cancer therapy while at ProScript Inc. (acquired by Millennium Pharmaceuticals). Earlier in his career, while at Boehring Ingelheim, he discovered the drug Viramune® (nevirapine) for HIV. Dr. Adams has received many awards, including the 2012 Warren Alpert Foundation Prize for his role in the discovery and development of bortezomib, the 2012 C. Chester Stock Award Lectureship from Memorial Sloan-Kettering Cancer Center and the 2001 Ribbon of Hope Award for Velcade® from the International Myeloma Foundation. He is an inventor on more than 40 patents and has authored over 100 papers and book chapters in peer-reviewed journals. Dr. Adams is on the board of directors of Warp Drive Bio and the Princess Margaret Cancer Foundation, as well as a member of the scientific advisory boards of Cleave Biosciences and Stand Up to Cancer. Dr. Kuriyan currently serves as professor of biochemistry and molecular biology in the department of molecular and cell biology at the University of California, Berkeley. Dr. Kuriyan’s research focuses on the structure and mechanism of the enzymes and molecular switches that carry out cellular signal transduction. He is internationally recognized for his groundbreaking work in structural biology, including elucidation of foundational insights about the dynamics of protein kinases that have been highly impactful in the drug discovery field. He is an investigator at the Howard Hughes Medical Institute and member of the National Academy of Sciences, which awarded him the 2005 Richard Lounsbery Award. Dr. Kuriyan is an academic founder of Nurix, Inc. and a member of the advisory boards of Carmot Therapeutics and Amgen, Inc. Dr. Bivona is an associate professor at the University of California, San Francisco. He is a medical oncologist and accomplished cell and molecular biologist. He maintains an active academic clinical practice and leads a basic and translational research laboratory focused on cancer genetics, precision medicine and the molecular basis of targeted therapy response and resistance. Dr. Bivona’s research has led to the elucidation of important mechanisms of resistance to EGFR-targeted therapy, BRAF- and MEK-targeted therapy and ALK-targeted therapy in lung and other cancers. He is the recipient of an NIH Director’s New Innovator Award and an elected member of the American Society for Clinical Investigation. About REVOLUTION Medicines The mission of REVOLUTION Medicines is to discover and develop new drugs directed toward frontier oncology targets for cancer patients. The company draws inspiration from nature’s lessons including natural products that are inherently rich with biological function. REVOLUTION Medicines deploys an innovative toolkit including REVBLOCKS™, an integrated suite of modular synthesis methodologies applied to simple chemical “building blocks,” and the REVEAL™ computational platform, which uses evolution’s lessons to inform selection of chemical scaffolds and guide drug design for non-classical drug targets. Headquartered in Redwood City, Calif. at the intersection of Silicon Valley and the birthplace of biotechnology, REVOLUTION Medicines is a private company financed by top-tier investor Third Rock Ventures. For more information, please visit www.revolutionmedicines.com.

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