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Methods and compounds for targeting sortilin receptors and inhibiting vasculogenic mimicry

An angiogenesis mimetic, compound technology, applied in the fields of peptide/protein components, chemical instruments and methods, immunoglobulin, etc., can solve the problems of poor prognosis of ovarian cancer patients

Pending Publication Date: 2021-08-20
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The presence of both angiogenic mimicry and positive CD133 expression is associated with advanced tumors, high-grade ovarian cancer, and chemotherapy unresponsiveness, leading to poor prognosis in ovarian cancer patients

Method used

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  • Methods and compounds for targeting sortilin receptors and inhibiting vasculogenic mimicry
  • Methods and compounds for targeting sortilin receptors and inhibiting vasculogenic mimicry
  • Methods and compounds for targeting sortilin receptors and inhibiting vasculogenic mimicry

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0836] Example 1: Composition

[0837] Peptides targeting Sortilin

[0838] The first family of Katana peptides targeting Sortilin was derived from bacterial cell penetrant proteins, while the second family was based on optimized primary sequences derived from Sortilin ligands, progranulin, and neurotensin (Table 1 ). These peptides have been described in: PCT / CA2016 / 051379: PEPTIDE COMPOUNDS AND CONJUGATE COMPOUNDS FOR THE TREATMENT OF CANCERTHROUGH RECEPTOR-MEDIATED CHEMOTHERAPY and US Patent Application Serial No. 62 / 510,381 ): CONJUGATES AND USES THEREOF FOR TREATING INFLAMMATORY DISEASES), which are incorporated herein by reference.

[0839] Table 1 Amino acid sequences of the Katana peptide family.

[0840]

[0841]

[0842] method

[0843] Generation of Katana-peptide drug conjugates

[0844] Docetaxel and doxorubicin were first chosen as proof of principle for cytotoxic drugs, whereas curcumin was chosen among phytochemicals. Docetaxel is a semi-syn...

example 2

[0868] Example 2: Sortilin Receptor-Mediated Cancer Therapy: A Targeted Pathway for Angiogenesis Mimicry Inhibition in Ovarian and Breast Cancer

[0869] background

[0870]Angiogenic mimicry is defined as the formation of microvascular channels by invasive, metastatic and genetically deregulated tumor cells. This microcirculatory system is independent of endothelial cells and provides oxygen and nutrients to tumor cells. Angiogenesis mimicry has been identified in ovarian cancer and triple-negative breast cancer (TNBC) and shown to be associated with decreased overall survival in cancer patients. This process contributes in part to current chemoresistance and promotes tumor progression and dissemination of cancer metastases. Therefore, targeting angiogenic mimicry in ovarian and TNBC tumors may aid in cancer therapy. Sortilin, a scavenger receptor, is known to have a major function in cancer cells; however, it is reported here that it further plays a novel role in angiogen...

example 3

[0877] Example 3: Sortilin receptor-mediated cancer therapy increases anticancer drug efficacy and safety: a targeted approach to ovarian cancer

[0878] background

[0879] In current modern oncology, the development of personalized therapies for ovarian cancer remains extremely challenging. One strategy to achieve higher selectivity and better delivery of anticancer drugs into cancer cells is to conjugate cytotoxic agents to specific peptide ligands that selectively target these cells Abundant and / or exclusively expressed receptors. Increased expression of sortilin, a clearance receptor, was observed clinically in aggressive ovarian cancer biopsies and correlated with tumor grade. With this in mind, we developed a peptide conjugation platform and a sortilin receptor-mediated vectorization strategy to increase the cell-targeting selectivity and cell-delivery efficacy of anticancer agents.

[0880] method

[0881] As a proof-of-concept, doxorubicin was conjugated to a sort...

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Abstract

The present disclosure relates to peptide compounds and conjugate compounds, processes, methods and uses thereof for treatment of cancer or aggressive cancer. For example, the compounds can comprise compounds of formula X1 X2X3X4X5GVX6AKAGVX7NX8FKSESY (I) (SEQ ID NO: 1) (X9)nGVX10AKAGVX11NX12FKSESY (II) (SEQ ID NO: 2) YKX13LRRX14APRWDX15PLRDPALRX16X17L (III) (SEQ ID NO: 3) YKX18LRR(X19)nPLRDPALRX20X21L (IV) (SEQ ID NO: 4) IKLSGGVQAKAGVINMDKSESM (V) (SEQ ID NO: 5) IKLSGGVQAKAGVINMFKSESY (VI) (SEQ ID NO: 6) IKLSGGVQAKAGVINMFKSESYK (VII) (SEQ ID NO: 7) GVQAKAGVINMFKSESY (VIII) (SEQ ID NO: 8) GVRAKAGVRNMFKSESY (IX) (SEQ ID NO: 9) GVRAKAGVRN(Nle)FKSESY (X) (SEQ ID NO: 10) YKSLRRKAPRWDAPLRDPALRQLL (XI) (SEQ ID NO: 11) YKSLRRKAPRWDAYLRDPALRQLL (XII) (SEQ ID NO: 12) YKSLRRKAPRWDAYLRDPALRPLL (XIII) (SEQ ID NO: 13) wherein X1 to X21 and n can have various different values and wherein at least one protecting group and / or at least one labelling agent is optionally connected to said peptide compound at an N- and / or C-terminal end, for use in inhibiting vasculogenic mimicry and / or for treating a cancer.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 722,726, filed August 24, 2018, and U.S. Provisional Application No. 62 / 804,063, filed February 11, 2019, both of which are incorporated by reference in their entirety This article. technical field [0003] The present disclosure relates to methods and compositions for targeting the sortilin receptor and inhibiting angiogenic mimicry. Background technique [0004] According to a recent World Health Organization report, 8.2 million patients died of cancer in 2012 (1). Cancer is thus a growing health problem in both developing and developed countries. It is estimated that the number of cancer cases per year will increase over the next two decades (1). Commonly used general treatments for cancer are surgery, endocrine therapy, chemotherapy, and radiotherapy (2). A recent hope, however, has been placed on generating "targeted therapies" that look a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28A61K47/64A61K47/68A61P35/00A61P9/00C07K14/00C07K14/705C07K16/18C07K7/08C40B30/04
CPCA61K47/64A61P9/00A61P35/00C40B30/04C07K7/083C07K14/47C07K16/286C07K2317/76C07K2317/77C07K2317/34A61K38/164
Inventor R·贝利沃B·阿纳比M·德梅勒A·拉罗克J-C·柯里A·兹格海布
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