Pol beta inhibitor and application thereof

A technology of β inhibitors and uses, which is applied in the field of medicine, can solve the problems that inhibitors cannot be approved, lack potential or specificity, etc., and achieve the effect of fast blood clearance, high affinity and specificity, and low production cost

Inactive Publication Date: 2021-10-08
南京科瑞斯生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of these inhibitors cannot be approved for clinical use due to lack of potency or specificity

Method used

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  • Pol beta inhibitor and application thereof
  • Pol beta inhibitor and application thereof
  • Pol beta inhibitor and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0035] 1. Materials and Methods

[0036] 1.1 Cell lines and cell culture

[0037] The colorectal cancer cell line SW480 was derived from ATCC (Manassas, VA, USA). All these cells were cultured under standard conditions.

[0038] 1.2 Antibody

[0039] The antibodies used in the examples of the present invention are as follows: anti-tubulin (AM103A; Bio-world, Dublin, OH, USA), anti-γH 2 AX (Ser139, #9718, Cell Signaling Technology, Danvers, MA, USA), anti-cleavage caspase-3 (Asp175, #9664, Cell Signaling Technology, Danvers, MA, USA), anti-Ki67 (D2H10, Cell Signaling Technology, Danvers , MA, USA), anti-DNA polβ (Q324, Bioworld, Dublin, OH, USA), anti-M13 (45001419, R37119, Life Technologies).

[0040] 1.3 Preparation of lentivirus and stable cell lines

[0041] A stable polβ knockout cell line was obtained by infecting SW480 cells with a recombinant lentiviral vector (SHC203) containing the polβ shRNA sequence. Cultured with lentivirus-containing medium plus 4 μg / ml poly...

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Abstract

The invention discloses a pol beta inhibitor and application thereof, belongs to the technical field of medicines. The invention provides the pol beta inhibitor which is a small molecule polypeptide with an amino acid sequence as shown in SEQ ID No.1. The pol beta inhibitor has a close relationship with temozolomide drug resistance and can be used for preparing drugs for treatment and/or adjuvant treatment of tumors, or can be used for enhancing the chemosensitivity of temozolomide or reducing the chemoresistance of temozolomide. A small peptide 10D provided by the invention can be used as a novel pol beta inhibitor, which can enhance the anti-tumor effect of TMZ on colorectal cancer. Therefore, the small peptide 10D is expected to become a candidate drug for improving TMZ treatment and auxiliary optimization of brain metastatic CRC chemotherapy.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a polβ inhibitor and its application. Background technique [0002] Temozolomide (TMZ) is an oral chemotherapy drug that causes cell death by inducing DNA damage and disrupting DNA replication. Clinical studies have shown that patients receiving TMZ have good tolerance and response. However, the disadvantages of chemotherapy, such as low selectivity, side effects, systemic toxicity, and drug resistance of cancer cells, cannot be ignored. A growing body of research has shown that DNA repair pathways enable tumor cells to survive chemotherapeutic drug-induced DNA damage. [0003] TMZ is an alkylating agent of imidazotetrazine with anti-tumor activity. It is rapidly converted into the active product MTIC (3-methyl-(triazine-1-)imidazole-4-carboxamide) in the physiological pH state of the systemic circulation. MTIC causes cancer cell toxicity through methylation of guanine on N7 ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08A61K38/10A61K31/4188A61P35/00A61P35/04
CPCC07K7/08C12N15/1037A61K38/10A61K31/4188A61P35/00A61P35/04A61K2300/00
Inventor 潘飞燕高源隆
Owner 南京科瑞斯生物科技有限公司
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