Merck KGaA

Technology for Lysophosphatidic Acid (LPA) Receptor antagonists

Posted by Merck KGaAResponsive · Innovative Products and Technologies · Germany

Summary of the technology

Merck has developed and patented the results of its intense R&D activities for the identification of small organic molecules as antagonists to certain LPA receptors (LPAR1, -R2, -R3). Herein described are LPA-R2 receptor selective inhibitors. Based upon a rational screening cascade established, compounds have been identified and characterized with regard to their specific in vitro and cellular activities. The package includes access to the IP, experimental results, and materials. Merck offers the unique chance to acquire this promising program.

Merck KGaA
Merck KGaA

Description of the technology

Figure 1:

A) Structure of LPA (16:0 species)

B) Signaling pathways of LPA-receptors LPA-R1, LPA-R2, and LPA-R3 and their biological responses

Lysophosphatidic Acid (LPA) Receptor


Lysophospholipids are membrane-derived bioactive lipid mediators. Lysophospholipids affect fundamental cellular functions, including proliferation, differentiation, survival, migration, adhesion, invasion and morphogenesis. These functions influence many biological processes that include, but are not limited to neurogenesis, angiogenesis, wound healing, fibrosis, immunity, inflammation and cancerogenesis.

Physiologic and pathophysiologic role of LPA-R

Lysophosphatidic acid (LPA, e.g. Fig. A) is a lysophospholipid known to act through sets of specific G protein coupled receptors (GPCRs) in an auto- and paracrine fashion (Fig. 1B). LPA binds to its cognate GPCRs (LPA1 – LPA6); it activates intracellular signaling pathways to produce a variety of biological responses.

Antagonists of the LPA receptors find use in the treat-mentof diseases, disorders or conditions, in which LPA plays a role, particularly in proliferative or inflammatory diseases, such as cancer, fibrosis or arthritis.

Therapeutic use of LPA-R antagonists

Increased LPA levels have been detected in ascites and plasma of ovarian cancer patients. LPA has been shown to promote tumor proliferation, survival, migration and invasion (Fig. 1B). Increased levels of LPA, altered receptor expression and altered responses to LPA may contribute to the initiation, progression and outcome of ovarian cancer.


LPA is potentially also involved in many other cancer types, e.g. prostate, breast, melanoma, head and neck, bowel and thyroid cancers.
Therefore, (selective) LPA receptor antagonists should be able to decrease the above listed effects, resulting in a positive outcome in cancer progression.


Innovation


Merck has developed and patented the results of its intense R&D activities for the identification of small organic molecules as antagonists to certain LPA receptors (LPAR1, -R2, -R3). Herein described are LPA-R2 receptor selective inhibitors. Based upon a rational screening cascade established, compounds have been identified and characterized with regard to their specific in vitro and cellular activities. The package includes access to the IP, experimental results, and materials. Merck offers the unique chance to acquire this promising program.

Patents

Merck has filed international patent applications in the field of LPA-R antagonists.

WO2012028243 (A1):

Figure : The invention relates to novel pyrazolopyridinone derivatives according to formula (I) and a process of manufacturing thereof. These pyrazolopyridinone derivatives can be used as LPA receptor antagonists for the treatment of various diseases, e.g. cancer.

WO 2013020622 (A1)

Figure: The invention relates to N-(benzimidazol-2-yl)cyclopropanecarboxamides of formula I as lysophosphatidic acid (LPA)
receptor antagonists; and their preparation and use in the treatment of proliferative or inflammatory diseases.

WO2013045028 (A1)

Figure: The invention provides novel substituted benzyl piperidine compounds according to Formula (I) as lysophosphatidic acid (LPA) receptor antagonists, their manufacture and use for the treatment of proliferative or inflammatory diseases, such as cancer, fibrosis or arthritis.

Terms:

  • Merck is seeking partners, who are interested in acquiring this technology. The Terms concerning the transfer of technology and rights to the IPm and further joint development (if desired) are to be negotiated.

Technology Owner

Merck KGaA

Large Enterprise

Related keywords

  • Biological Sciences
  • Medicine, Human Health
  • Cytology, Cancerology, Oncology
  • Medical Research
  • Pharmaceutical Products / Drugs
  • Biology / Biotechnology
  • Biochemistry / Biophysics Technology
  • Cellular and Molecular Biology Technology
  • In vitro Testing, Trials Technology
  • Molecular design Technology
  • In vitro Testing, Trials Market
  • Therapeutic
  • Clinical Medicine
  • Oncology
  • inflammation
  • arthritis
  • fibrosis
  • ovarian
  • prostate cancer
  • tumor proliferation
  • tumor survival
  • tumor migration
  • tumor invasion
  • ovarian cancer

About Merck KGaA

Large Enterprise from Germany

Merck KGaA, Darmstadt, Germany is a leading company for innovative and top-quality high-tech products in healthcare, life science and performance materials. Around 39,000 employees work in 65 countries to improve the quality of life for patients, to further the success of our customers and to help meet global challenges.

Legal Disclamer

There are two different, unaffiliated companies that use the name MERCK. Merck KGaA, Darmstadt, Germany, which operates this website, uses the firm name “Merck KGaA, Darmstadt, Germany,” in the United States and Canada, and also uses “EMD Serono” in biopharma, “MilliporeSigma” in life science and “EMD Performance Materials” in materials business. The other company, Merck & Co., Inc. holds the rights in the trademark MERCK in the United States and Canada. Merck & Co. is not affiliated with or related to Merck KGaA, Darmstadt, Germany, which owns the MERCK trademark in all other countries of the world. To reflect such fact and to avoid any confusion, certain logos, terms and business descriptions of the publications on this website have been substituted or modified, such as by referring to “Merck KGaA, Darmstadt, Germany” instead of “Merck” standing alone. Publications on this webpage, therefore, slightly deviate from the otherwise identical versions accessible outside the United States and Canada.

Send your request

By clicking "Send your request" you are signing up and accepting our Terms of Service and Privacy policy

Technology Offers on Innoget are directly posted and managed by its members as well as evaluation of requests for information. Innoget is the trusted open innovation and science network aimed at directly connect industry needs with professionals online.