更新于：2024-11-01

Congenital Thrombotic Disease, Due to Protein C Deficiency

由于蛋白C缺乏导致的先天性血栓性疾病

更新于：2024-11-01

基本信息

别名

Congenital thrombotic disease, due to Protein C deficiency、PROC deficiency、Thrombophilia, hereditary, due to pc deficiency

+ [1]

简介-

关联

项与由于蛋白C缺乏导致的先天性血栓性疾病相关的药物

TUB-040

靶点

NaPi-2b

作用机制

NaPi-2b 调节剂

在研机构

Tubulis GmbH

原研机构

Tubulis GmbH

在研适应症

由于蛋白C缺乏导致的先天性血栓性疾病 [+2]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

项与由于蛋白C缺乏导致的先天性血栓性疾病相关的临床试验

NCT06303505 / Recruiting临床1/2期

A First-in-human Dose Escalation and Optimization Phase I/IIa Study to Investigate Safety, Tolerability, PK, and Efficacy of the NaPi2b ADC TUB-040 in Patients with Platinum-resistant High-grade Ovarian Cancer (PROC) or R/r Adenocarcinoma Non-small Cell Lung Cancer (NSCLC)

The purpose of this multicentric, open label trial (NAPISTAR 1-01) is to evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040 and to find the best dose of TUB-040 in patients with ovarian cancer and Non Small Cell Lung Cancer. TUB-040 is an antibody-drug-conjugate which delivers a topoisomerase I inhibitor to tumor cells which overexpress the target NaPi2b. The study consists of two parts: In dose escalation, ovarian cancer patients and lung cancer patients receive increasing doses of TUB-040 until the maximal tolerated dose is found. In dose optimization, at least two doses are compared with each other to determine which dose is optimal for patients.
TUB-040 is given IV every 3 weeks until the disease progresses or the patient has to stop due to side effects.

开始日期2024-06-12

申办/合作机构

Tubulis GmbH

100 项与由于蛋白C缺乏导致的先天性血栓性疾病相关的临床结果

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100 项与由于蛋白C缺乏导致的先天性血栓性疾病相关的转化医学

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0 项与由于蛋白C缺乏导致的先天性血栓性疾病相关的专利（医药）

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项与由于蛋白C缺乏导致的先天性血栓性疾病相关的文献（医药）

2019-10-01·Journal of Cellular and Molecular Medicine2区 · 医学

Pathogenic variants of PROC gene caused type I activity deficiency in a familial Chinese venous thrombosis

2区 · 医学

ArticleOA

作者: Xiao, Lu ; Fu, Yingyun ; Liu, Shengguo ; Yue, Yongjian ; Huang, Qijun ; Zhuang, Kaixue ; Yang, Mo ; Zou, Chang ; Li, Shulin ; Han, Xuemei

AbstractPathogenic mutation of protein C (PROC) gene results into the deficiency of PROC activity. This study aimed to identify the pathogenic genetic variants and to explore the functional consequence in Chinese familial venous thrombosis (VTE). Whole exome sequencing was performed to identify the pathogenic variants of anticoagulant factors. Serum coagulation and anti‐coagulation factors activity were assayed to evaluate the genetic association. Functional study of PROC antigen secretion deficiency was conducted in VTE subjects and in vitro cell lines. One rare pathogenic variant (p.Ala178Pro) was identified in the four VTE subjects but not in the normal subjects from the family. An inframeshift variant (rs199469469) was also identified in a paediatric subject of the pedigree. Further evaluation of serum PROC activity levels in p.Ala178Pro variants VTE carriers showed significantly lower PROC activity compared to non‐carriers. Furthermore, in vitro study showed that the p.Ala178Pro mutant cells had a consistent reduction in concentration of PROC antigen. In conclusions, our study demonstrated the pathogenic variant (p.Ala178Pro) contributed to PROC type I activity deficiency, which may be due to decreased secretion of PROC.

2002-05-01·Hamostaseologie4区 · 医学

Molekularbiologische Grundlagen und Diagnostik der hereditären Defekte von Antithrombin III, Protein C und Protein S.

4区 · 医学

Review

作者: Witt I

Recent progress in molecular biology enabled the elucidation of the nucleotide sequences of the genes for antithrombin III (AT III), protein C (PROC) and protein S (PROS). Furthermore numerous mutations were identified causing genetic defects of the important inhibitors of blood coagulation. As the genes for AT III (13.8 kb) and PROC (11.2 kb) are small and easy to analyze a great number of molecular defects already are described in extensive databases (50, 73): 79 different mutations for AT III and 160 for PROC are included. The identification of mutations leading to AT III and PROC deficiency has given important information on the structure-function relationships of the proteins. In case of protein C deficiency the clinical relevance of DNA analyses is most important because the diagnosis at the protein level is often uncertain. The gene for PROS is not so easy to analyze like the other two genes. The PROS gene is large and also a PROS pseudogene exists. Although a number of mutations have been identified, there has not been published a database until now. The clinical relevance to identify gene defects in PROS deficiency is as important as for PROC deficiency. Presumably the elucidation of PROS gene defects will advance in the near future.

2001-07-01·Thrombosis Research3区 · 医学

Combined Occurrence of a Heterozygous Missense Mutation in the Protein C Gene and Allelic Exclusion of One Protein S Allele Leading to Severe Venous Thrombosis

3区 · 医学

Article

作者: Daniela Häring ; Viola Hach-Wunderle ; Christine Mannhalter ; Bernadette Knoll ; Sandra Rieger

Individuals with more than one defect in the natural anticoagulant system exhibit an increased risk for thrombosis. We report on a family with two cases of combined protein C (PROC) and protein S (PROS) deficiency, five cases of isolated PROC deficiency Type I, and two cases of isolated PROS deficiency Type I. PROC and PROS deficiency were documented by functional and immunologic tests. The sequencing of all exons and splice junctions of the PROC gene led to the identification of a new, unpublished G-->A transition at nt 8490, leading to an exchange of alanine 259 by threonine. The mutation was present in all family members with PROC deficiency. The carriers of the isolated PROC mutation were asymptomatic at ages of 4, 7, 10, 11, and 80 years. The combination of the PROC mutation with a PROS deficiency in two family members triggered venous thromboembolism at age 31 and 6 years, respectively. The PROS deficiency was associated with complete exclusion of one PROS allele. Two family members with isolated PROS deficiency are still asymptomatic at age 21 and 9 years, respectively. Our findings in this family suggest that the heterozygous mutation at codon 259 of the PROC gene represents a mild thrombotic risk factor and only confers a high thrombotic risk in combination with a second defect, such as the complete exclusion of one PROS allele.