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KDDF-201512-02 Development of Cancer Therapeutics Targeting Mitochondrial TRAP1(Oncology, Chemical) [2019-03-29]

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Ongoing Project
Section Lead
Generation
Lead
Optimization
Preclinical Phase I Phase II Phase III

Development and Market Objectives

Development of mitochondria TRAP1 inhibitor as cancer therapeutics

Unmet Medical Need & Target Patients

Target patients:

Cancer patients with malignancies exhibiting a TRAP1 overexpression phenotype

Unmet medical needs:

- Despite increases in cancer incidence due to an aging population, effective anti-cancer drugs are still lacking.

- Anticancer drugs with noble mechanism of action are required to treat patients who do not respond to conventional anticancer therapeutics and to overcome drug resistance against conventional chemotherapy

- Novel therapeutics are required to improve combination therapy with current anticancer drugs

Status

Tumors often overexpress mitochondrial chaperone TRAP1 which is closely related to poor prognosis of cancer patients. We have developed two different classes of lead compounds (different MOA) targeting mitochondrial TRAP1: SMTINs and Panvotinibs. TRAP1 inhibitors are conjugated with the mitochondrial targeting moiety, triphenylphosphonium, to afford SMTINs which efficiently accumulate inside mitochondria. Panvotinibs are mitochondria-permeable Hsp90 inhibitors inactivating Hsp90 and Grp94 as well as TRAP1. The simultaneous inactivation of all the Hsp90 family proteins by Panvotinibs dramatically augment cancer-specific cytotoxic activity. Currently, we are optimizing SMTINs and Panvotinibs to improve DMPK properties of the drugs.

Intellectual Property

Patent application of a SMTIN class inhibitor, SMTIN-P01, was filed. Several SMTIN inhibitors with better anticancer activity than SMTIN-P01 have been developed and patent application of the inhibitors will be filed soon. We did not disclose drug information on Panvotinib at all, and the patent application will be finished soon.

Competitive Advantages

- In addition to target inhibition, we consider “subcellular drug distribution” and whereby are able to develop novel MOA drug with much improved anticancer activity.

- In case of Panvotinib, as an example, it inactivates Hsp90 and Grp94 similar to current Hsp90 inhibitors and degrades client proteins to increase cell death. However, different from Hsp90 inhibitors, Panvotinib never triggers heat shock response such as pro-survival Hsp70 induction, a well-known adverse effect of Hsp90 inhibitors. Therefore, Panvotinib shows dramatically improved cytotoxicity against cancer cells in vitro and in vivo compared with Hsp90 inhibitors.

Contact & Company Overview

Related Project

Related Project
Development of cancer therapeutics targeting mitochondrial TRAP1 Project view
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