Konruns Pharmaceutical Co., Ltd.

Beijing Konruns Pharmaceutical Co., Ltd.

Xijuan Wang

Zhiqiang Zhang

Xuehui Zhang

Peng Yao

Jiehe Yang

Xiaokai Zhang

Junxia Qiu

Di Sun

The present application provides a quinolyl-substituted carboxylic acid compound as shown in formula (I) or a pharmaceutically acceptable salt thereof, as well as a method for preparing the compound, a use of the compound, and a formulation containing the quinolyl-substituted carboxylic acid compound or the pharmaceutically acceptable salt thereof. This type of compounds are inhibitors for AXL and/or VEGFR2 protein kinase, and can be used to treat diseases caused by abnormality of the two protein kinases, such as, tumor, etc. 

Quinolyl-substituted carboxylic acid compound or pharmaceutically acceptable salt thereof, pharmaceutical composition of the same, and use of the same

A thrombin-like enzyme isolated fromvenom, comprising an alpha subunit having the sequence of SEQ ID No. 1 and a beta subunit having the sequence of SEQ ID No. 2, which are linked by seven disulfide bonds, is provided. The hemocoagulase ofin the present invention is a serine proteinase having a molecular weight of 29.3-29.5 kD and an isoelectric point of 5.5, and is able to hydrolyze the alpha chain of human fibrinogen. The invention also provides methods of purifying the thrombin-like enzyme from snake venom, which comprise removing insoluble substance by pretreatment, conducting twice of anion-exchange column chromatography, collecting active eluting peak, dialyzing, ultra-filtrating and desalinating so as to obtain a snake venom thrombin-like enzyme.

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The present invention provides a venene haemocoagulase gene and its expression for the functional protein. The haemocoagulase gene of the present invention has a nucleotide sequence shown by the sequence list SEQ ID NO: 1 or the mutated nucleotide sequence formed by replacement, depletion, or addition of one or more nucleotide based on the said nucleotide sequence with an equivalent function. The said haemocoagulase has amino acid sequence shown by SEQ ID NO: 2. Haemocoagulase of the present invention has an obvious hemostatic effect, a broad effective dose range, safe and reliable application, which creates good conditions for the development of genetic engineering products of recombinant haemocoagulase in the future.

Haemocoagulase

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Beijing, China

Xijuan Wang