Canbas Co., Ltd.

Takeda Pharmaceutical Company Limited

General Incorporated Association Pharma Valley Project Supporting Organization

Takumi Kawabe

Hidetaka Kobayashi

Takuji Sato

Sayaka Yamamoto

Machiyo Ishigaki

Yoko Hasegawa

Masashi Suganuma

Akira Asai

Naohisa Ogo

Daisuke Muraoka

Osamu Takikawa

Naoki Mine

Naoya Saito

Tatsuya Kibe

Keiichi Sakakibara

Jonathan M Friedman

Toshiyuki Hibino

Chikako Suda

Presented herein, in certain aspects, are conjugates capable of binding phosphatidylserine (PS) and toll-like receptors (TLRs), and their uses for the treatment of selected diseases and disorders, such as cancer.

Phosphatidylserine-binding conjugates

A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, an aliphatic ring and a heterocyclic ring; X, Rand Rrepresent a substituent on a ring atom constituting ring A; m represents an integer of 0 to 6; X represents, for example, a halogen atom; and Rand Rare the same or different and are selected from, for example, the group consisting of groups of formula (a) or formula (b); and in the following formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1 to 8, r represents an integer of 1 to 8, s represents an integer of 1 to 8, Rrepresents, for example, —C(═NH)—HN, and Rrepresents, for example, a substituted or unsubstituted aryl group].

IDO/TDO inhibitor

This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells, and combinations of T cell activating agents and/or an immune checkpoint inhibitors with and without peptides and peptidimimetics. The invention compounds and combinations can be used to inhibit cell growth, such as treat a tumor or cancer.

Peptides and peptidomimetics in combination with t cell activating and/or checkpoint inhibiting agents for cancer treatment

This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells. While the invention is not limited to any particular mechanism, the compounds of the invention appear to function at least in part by inhibiting G2 cell cycle checkpoint. Thus, invention compounds can be used to inhibit cell growth alone or be used in combination with a nucleic acid damaging treatment to inhibit cell growth.

Peptides and peptidomimetics in combination uses and treatments for cancer patient subpopulations

Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.

Compounds with anti-cancer activity

The invention provides compositions and methods for inhibiting Chk1 and/or Chk2 kinases. Also provided are compositions and methods for inhibiting G2 cell arrest checkpoint, particularly in mammalian, e.g., human, cells. The compositions and methods of the invention are also used to treat disorders of cell growth, such as cancer. In particular, the invention provides methods for selectively sensitizing G1 checkpoint impaired cancer cells to DNA damaging agents and treatments. Also provided are methods for screening for compounds able to interact with, e.g., inhibit, enzymes involved in the G2 cell cycle arrest checkpoint, such as Chk1 and/or Chk2/Cds1 kinase.

Compositions and methods for inhibiting G2 cell cycle arrest and sensitizing cells to DNA damaging agents

The invention provides compositions and methods to inhibit the cell cycle G2 checkpoint, in particular the DNA-damage-induced G2 checkpoint, in mammalian cells including human cells. Specifically, the invention provides compositions and methods to sensitize cells to DNA-damaging agents by abrogating the cell cycle G2 checkpoint. Compounds of the invention are used to treat proliferative disorders such as cancer. The invention provides compositions and methods for selectively sensitizing G1 checkpoint impaired cancer cells to DNA-damaging agents and treatments.

Compounds that abrogate DNA damage induced cell cycle G2 checkpoint and/or augment anti-cancer activity of DNA-damaging treatments

Compounds that abrogate DNA-damage-induced cell cycle G2 checkpoint and/or augment anti-cancer activity of DNA-damaging treatments

The invention provides compounds having immune-modulating and/or anti-inflammatory and/or anti-viral activity, wherein compounds of the invention include peptides and peptidomimetics. The invention further provides methods of using immune-modulating and/or anti-inflammatory and/or anti-viral compounds of the invention. In particular, the invention provides methods for treating a disease related to an immune disorder or inflammation or viral infection by administering an amount of a G2-checkpoint-abrogating peptide or peptidomimetic sufficient to inhibit the disease.

Peptides and peptidomimetics having immune-modulating, anti-inflammatory, and anti-viral activity

Peptides and peptidomimetics having anti-proliferative activity and/or that augment nucleic acid damaging agents or treatments

The present disclosure provides methods for determining the sensitivity of cancerous cells to various anti-cancer therapies and predicting the efficacy of these therapies. Specifically, the present disclosure provides methods for predicting the efficacy of one or more candidate anti-cancer therapies in a patient, based on determining the sensitivity of the patient's cancerous cells after exposure to candidate anti-cancer therapies in vitro. The disclosure further provides methods for predicting the efficacy of candidate anti-cancer therapies by using an in vitro sensitivity test of the patient's cancerous cells and a surrogate in vivo efficacy test of the patient's cancerous cells grafted into a surrogate host. The disclosure further provides methods for selecting the most efficacious anti-cancer therapy(s) for a patient, thereby avoiding ineffective or unnecessary treatments.

Sensitivity test to predict efficacy of anti-cancer therapies

The invention relates to compounds including peptides and peptidomimetics having anti-fungal activity alone, and in combination with other agents that have anti-fungal activity. The invention includes the use of cell cycle G2 checkpoint abrogators as anti-fungal agents, such as anti-fungal medicine.

Growing community of inventors

Numazu, Japan

Takumi Kawabe