更新于：2024-11-01

CYP11A1

更新于：2024-11-01

基本信息

别名

Cholesterol desmolase、cholesterol monooxygenase (side-chain-cleaving)、Cholesterol side-chain cleavage enzyme, mitochondrial

+ [9]

简介

A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:21636783). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:21636783).

关联

项与 CYP11A1 相关的药物

Opevesostat

靶点

CYP11A1

作用机制

CYP11A1抑制剂

在研机构

Merck Sharp & Dohme LLC [+5]

原研机构

Orion Oyj

在研适应症

转移性前列腺癌 [+3]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

ODM-209

靶点

CYP11A1

作用机制

CYP11A1抑制剂

在研机构

Orion Corp

原研机构

Orion Oyj

在研适应症

晚期乳腺癌 [+3]

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

INV-9956

靶点

CYP11A1

作用机制

CYP11A1抑制剂

在研机构

深圳市原力生命科学有限公司初创企业 [+1]

原研机构

深圳市原力生命科学有限公司初创企业

在研适应症

转移性去势抵抗性前列腺癌 [+1]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 CYP11A1 相关的临床试验

NCT06633419 / Not yet recruiting临床1期

A Phase 1, Open-Label, Fixed-Sequence Study to Evaluate the Effects of Multiple Doses of Carbamazepine on the Single-Dose Pharmacokinetics of MK-5684 in Healthy Adult Male Participants

Researchers have designed a study medicine called opevesostat as a new way to treat prostate cancer.
The purpose of this study is to learn what happens to opevesostat in a person's body over time (a pharmacokinetic or PK study). Researchers will compare what happens to opevesostat in the body when it is given with and without another medicine called carbamazepine.

开始日期2024-10-24

申办/合作机构

Merck Sharp & Dohme Corp.

NCT06609005 / Not yet recruiting临床1期

A Phase 1, Multi-Center, Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Evidence of Antitumor Activity of INV-9956 in Adult Patients with Advanced Metastatic Castration Resistant Prostate Cancer

This is a Phase 1a, first-in-human, open-label dose-escalation study to determine the RDR and/or MTD, and to assess the DLT of INV-9956. The safety, tolerability, PK/PD, and preliminary antitumor activity of INV-9956 will be assessed in adult patients with advanced mCRPC.

开始日期2024-10-16

申办/合作机构

Shenzhen Ionova Life Sciences Co., Ltd.

NCT06566989 / Completed临床1期

An Open-label Phase 1 Study to Evaluate Metabolism, Excretion, and Mass Balance of [¹⁴C]MK-5684 in Healthy Male Participants

This is a study of opevesostat in healthy adult male participants. The purpose of this study is to understand the absorption, distribution, metabolism, and elimination of opevesostat in humans, as well as its pharmacokinetics (PK), metabolic profile, and safety and tolerability.

开始日期2024-09-19

申办/合作机构

Merck Sharp & Dohme LLC

[+1]

100 项与 CYP11A1 相关的临床结果

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100 项与 CYP11A1 相关的转化医学

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0 项与 CYP11A1 相关的专利（医药）

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6,814

项与 CYP11A1 相关的文献（医药）

2025-01-01·Theriogenology

Paternal trans fatty acid and vitamin E diet affect the expression pattern of androgen signaling pathway genes in the testis of rat offspring

Article

作者: Shams, Amir Abbas ; Alizadeh, AliReza ; Karoii, Danial Hashemi ; Vesali, Samira ; Shahhoseini, Maryam ; Vesal, Soheil

Numerous studies have shown that an improper diet in parents has a negative impact on offspring's health. Furthermore, the negative effects of trans fatty acids (TFA) in maternal diets on fertility and health and their impact on future generations have been documented. However, there is limited research on the negative effects of TFA in paternal diets on male children. The current work used qRT-PCR to investigate the effects of trans fatty acids and vitamin E in the paternal diet on the expression pattern of androgen signaling pathway genes such as STAR, CYP11a1, HSD3B, SRD5a2, and SCARB1 in offspring testes. In this experiment, parental rats were randomly separated into four groups, each with ten father rats, and were fed for eight weeks (60 days) as follows. 1: Standard diet group plus liquid sunflower oil (control). 2: Standard diet group containing trans fatty acids (CTH). 3: The regular diet group received 2.5 times the recommended quantity of vitamin E supplement. 4: Standard diet group with vitamin E and trans fatty acid supplementation (ETH). The testis tissue samples from 35 offspring were then used. Following RNA extraction from tissues and cDNA synthesis, quantitative real-time PCR was used to evaluate the expression levels of androgen signaling pathway genes such as STAR, CYP11A1, HSD3B, SCARB1, and SRD5A2. Our findings showed that the expression of CYP11A1 was considerably reduced in the progeny of paternal rats given ETH compared to the CTH group. The expression levels of the STAR gene were significantly lower in the progeny of paternal rats administered TFA, ETH, and vitamin E compared to the controls. Although the CTH group had lower SCARB1 expression than the other groups, the difference was not statistically significant. Paternal vitamin E consumption substantially affected SRD5A2 expression when compared to offspring of paternal rats fed vitamin E + trans fatty acid or those fed a conventional diet containing trans fatty acid. Furthermore, the vitamin E group showed a statistically significant increase in HSD3B expression compared to the other groups. Bioinformatics analyses, such as protein-protein interaction networks and gene ontology term enrichment, revealed that these genes play roles in lipid biosynthesis, hormone metabolism, male sex differentiation, reproductive development, and steroid biosynthesis. Our data indicate that paternal trans fatty acid consumption influences the expression of particular androgen signaling pathway genes in offspring testis, with vitamin E potentially mitigating some of these effects.

2024-12-01·Comparative Biochemistry and Physiology Part D: Genomics and Proteomics

Genome-wide analysis of the cytochrome P450 gene family in Pacific oyster Crassostrea gigas and their expression profiles during gonad development

Article

作者: He, Cheng ; Wu, Xuanbing ; Chen, Meizhen ; Wang, Weili ; Li, Huiqi ; Zhang, Chuanxu ; Zheng, Huaiping ; Zhang, Hongkuan

The cytochrome P450 (CYP) gene superfamily plays a significant role in various physiological processes, producing different compounds such as hormones, fatty acids, and biomolecules. However, little information is known their roles during gonad development in Pacific oyster (Crassostrea gigas). In this study, total of 116 CgCYP (Crassostrea gigas cytochrome P450) genes were identified and their expression pattern was analyzed for the first time. The relative molecular weights of these CgCYP genes ranged from 63.52 to 113.41 kDa, and the length of encoded amino acids ranged from 103 to 993. And total 26 cis-acting elements of these CgCYP genes were identified. GO and KEGG enrichment analysis showed some CgCYP genes are essential for the metabolism of male and female sex hormones. Additionally, expression anslysis showed 69 CgCYP genes were over-expressed in early gonad development and triploid infertile individuals. More importantly, expression levels of CgCYP1, CgCYP15, CgCYP34, CgCYP46, CgCYP69, CgCYP87, CgCYP88, and CgCYP103, were found to be significantly higher in female gonad, suggesting their important roles in female gonad development. The results of this study will provide a better understanding of the CgCYP genes in the gonad development of Pacific oyster.

2024-12-01·Molecular and Cellular Endocrinology

High concentrations of progesterone inhibit the expression of genes related to steroid metabolism in MA-10 Leydig cells

Article

作者: Martin, Luc J ; Basque, Audrey ; Martin, Luc J. ; Izichkis, Liel-Sarah

Leydig cells are the main testosterone-producing cells in males. During androgen synthesis, cholesterol enters the mitochondria via the STAR protein and is converted into pregnenolone by the CYP11A1 enzyme. This steroid is then exported from the mitochondria to be metabolized to progesterone by the HSD3B1 enzyme in the endoplasmic reticulum. In this study, we used 3'Tag-RNA-Seq to identify progesterone-regulated genes in MA-10 Leydig cells. Our results indicate that high concentrations of progesterone (30 μM) are involved in a negative feedback loop that inhibits cAMP/PKA-dependent activation of Star and Cyp11a1 expression and participate in cAMP/PKA-dependent down-regulation of genes related to the metabolism of steroid hormones. Linked to activation of the MAPK signaling pathway, endoplasmic reticulum stress and apoptosis, most of the genes encoding bZIP transcription factors are upregulated by progesterone in MA-10 Leydig cells. However, only DDIT3 protein levels are increased in response to progesterone in MA-10 Leydig cells. Like normal Leydig cells, MA-10 cells very weakly express the classical nuclear receptor for progesterone, suggesting that gene regulation by progesterone is rather mediated by one of the non-classical membrane receptors for progesterone However, current findings suggest that the inhibitory effect of progesterone on STAR protein increase in response to forskolin is not dependent on PGRMC1/2 or PAQR9. Furthermore, the increase in progesterone synthesis in response to activation of the cAMP/PKA pathway is rather inhibited by siRNA-mediated knockdown of PAQR9. Overall, this study shows that progesterone produced by Leydig cells participates in the regulation of steroidogenesis through autocrine action involving negative feedback upon activation of the cAMP/PKA pathway.

项与 CYP11A1 相关的新闻（医药）

2024-10-17

·今日头条

12周肿瘤缩小91%！12款一类抗癌新药/新技术首次在中国获批临床

据中国国家药监局药品审评中心（NMPA）消息，近期（2024年9月23日~2024年10月6日）共有11款一类创新药/新技术，首次在中国获得临床试验默示许可（IND），其中包括ADC药物、双抗类药物、CAR-T细胞疗法、TCR-T细胞疗法等。下面全球肿瘤医生网帮大家简单汇总一下，以供癌友们参考。一、首次在中国获批临床的一类新药大汇总（一）ABBV-706 1、药品信息 ①药物名称： ABBV-706注射用冻干粉。 ②研发公司： AbbVie（艾伯维）。 ③治疗靶点：靶向SEZ6。 ④适应证：复发/难治小细胞肺癌。 2、药物介绍 ABBV-706注射用冻干粉是一款靶向SEZ6（是一种跨膜蛋白，在小细胞肺癌、中枢神经系统肿瘤、其他神经内分泌肿瘤中表达）的ADC药物，与拓扑异构酶1抑制剂有效载荷结合，在治疗小细胞肺癌(SCLC)、其他神经内分泌肿瘤(NEN)、中枢神经系统肿瘤(CNS)方面展现出了良好的疗效。在2024 ASCO大会上，公布了ABBV-706的1期临床研究数据（NCT05599984），本次共入组49例患者（包括22例小细胞肺癌、5例中枢神经系统肿瘤、22例其他神经内分泌肿瘤），既往接受过2.5线治疗（范围1-6）。结果显示：对于33名RECIST可评估患者，客观缓解率（ORR）达到21%（详见下图），其中7例达到部分缓解（PR）。除了ABBV-706这款在研的ADC药物外，2024全球还获批上市了多款ADC药物，阅读原文了解详情：【速览】2024年全球15款获批ADC药物大汇总，一文掌握！ ▲图源“NMPA”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除值得一提的是，其中一位76岁高级别胃神经内分泌肿瘤（胃部G3 NET转移）患者，既往曾接受过术前肿瘤切除手术+标准一线化疗，入组接受ABBV-706 治疗6周后，达到部分缓解（PR），肿瘤缩小78% ；治疗第12周，肿瘤进一步缩小至91% （详见下图）！ ▲图源“NMPA”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除（二）INV-9956胶囊 1、药品信息 ①药物名称： INV-9956胶囊。 ②研发公司：原力生命科学。 ③治疗靶点： CYP11A1。 ④适应证：晚期转移性去势抵抗性前列腺癌。 2、药物介绍 INV-9956是原力生命科学自主研发的一款强效且高选择性的口服CYP11A1抑制剂，可用于治疗去势抵抗性前列腺癌（CRPC），具有卓越的体内抗肿瘤疗效。2024年9月30日，INV-9956胶囊的新药IND申请获中国国家药监局药品审评中心（NMPA）批准，拟用于治疗晚期转移性去势抵抗性前列腺癌。在此之前（2024年7月16日）INV-9956就已获得美国食品药品监督管理局（FDA）批准，开展临床研究。（三）JNJ-78278343 1、药品信息 ①药物名称： JNJ-78278343注射液。 ②研发公司：强生公司。 ③治疗靶点： KLK2-CD3。 ④适应证：成年男性晚期前列腺癌。 2、药物介绍 JNJ-78278343注射液是由强生公司研发的一款KLK2-CD3双特异性抗体在研新药，通过与T细胞上的CD3结合，从而诱导T细胞活化，并将T细胞重定向至肿瘤细胞，最终导致T细胞介导的KLK2表达肿瘤细胞的裂解。目前JNJ-78278343的新药IND申请已获得中国NMPA的批准，拟用于成年男性的晚期前列腺癌的治疗。（四）BT8009 1、药品信息 ①药物名称： BT8009。 ②研发公司： Bicycle公司。 ③治疗靶点： Nectin-4。 ④适应证：尿路上皮癌。 2、药物介绍 BT8009是一种双环毒素结合物（BTC），由一种高度选择性的双环肽组成，该肽靶向nectin-4（是一种粘附分子，在尿路上皮癌等多种肿瘤中表达），通过可裂解的连接体与MMAE连接，可以高亲和性和选择性与靶标结合，具有高肿瘤渗透性。（五）CG009301 1、药品信息 ①药物名称：注射用CG009301。 ②研发公司： Cullgen Inc。 ③治疗靶点： GSPT1。 ④适应证：复发/难治性血液恶性肿瘤。 2、药物介绍 CG009301是一种高选择性GSPT1降解剂，用于治疗复发或难治性血液系统恶性肿瘤[包括但不限于急性髓系白血病（AML）、急性淋巴细胞白血病（ALL）、高风险骨髓增生异常综合征（MDS）]。2024年10月8日，中国国家药品监督管理局(NMPA)已批准CG009301的临床试验(IND)申请，Cullgen将很快在中国启动CG009301的I期临床试验。（六）SYN818 1、药品信息 ①药物名称： SYN818片。 ②研发公司：圣域生物。 ③适应证：晚期实体瘤。 2、药物介绍 SYN818片是由圣域生物自主研发的一款新型强效且高选择性的1类小分子化合物，可精准靶向并高效抑制Polθ（DNA聚合酶θ）的活性，从而抑制肿瘤细胞的DNA损伤修复，最终达到抗肿瘤的目的。2024年9月30日，——SYN818片的新药IND申请，获得中国NMPA批准，用于晚期实体瘤的治疗。（七）GTA182 1、药品信息 ①药物名称： GTA182片。 ②研发公司： PRMT5。 ③适应证： MTAPnull/lost晚期实体瘤。 2、药物介绍 GTA182是一种是一款可穿透血脑屏障的第二代蛋白质精氨酸甲基转移酶5(PRMT5)抑制剂，具有甲硫腺苷(MTA)协同作用，对MTAP缺失的癌细胞具有高度选择性，而且不针对MTAP正常表达的非癌细胞，这种选择性有望为MTAP缺失型癌症患者提供更有效、更安全的治疗选择。约有10%的实体瘤存在MTAP缺失，包括胶质母细胞瘤、肺癌、胰腺癌和膀胱癌等，这些肿瘤的治疗选择很有限，患者的大量临床需求尚未得到满足。而GTA182对MTAP缺失型肿瘤的高选择性及其穿透血脑屏障的能力，使其成为可能治疗中枢神经系统肿瘤和非中枢神经系统适应症的临床开发的best-in-class药物，已在先前的研究中展现出具有抑制肿瘤生长和肿瘤消退的显著效果。（八）PTX-912 1、药品信息 ①药物名称：注射用PTX-912。 ②研发公司：博致生物。 ③适应证：局部晚期/转移性实体瘤。 2、药物介绍注射用PTX-912是由博致生物自主研发的新一代免疫细胞靶向的IL-2前药融合蛋白，显示出对 PD-1 通路的剂量依赖性抑制，可使IL-2前药在肿瘤微环境中被特异性激活，有助于改善IL-2的外周毒性问题，还可充分发挥IL-2的免疫激活及抗肿瘤功效。2024年10月12日，注射用PTX-912的临床试验默示许可获中国国家药品监督管理局批准，拟用于治疗局部晚期/转移性实体瘤。（九）YY2201 1、药品信息 ①药物名称： YY2201片。 ②研发公司：亚尧生物。 ③治疗靶点： ATR。 ④适应证：晚期实体瘤。 2、药物介绍 YY2201片是由亚尧生物自主研发的一款口服ATR小分子抑制剂，在此前的研究中，展现出良好的体内/体外活性。该药已获得中国NMPA及美国食品药品监督管理局（FDA）的IND临床批件（IND173030），用于晚期实体瘤的治疗。二、首次在中国获批临床的新技术大汇总（十）IM96 CAR-T 1、药品信息 ①药物名称： IM96 CAR-T细胞注射液。 ②治疗靶点： GUCY2C。 ③适应证：结直肠癌。 2、药物介绍 IM96 CAR-T细胞注射液是由我国自主研发的一款靶向GUCY2C的CAR-T细胞产品，目前新药IND申请已获我国NMPA批准，用于治疗晚期结直肠癌。值得欣慰的是，在2024年美国临床肿瘤学会（ASCO）年会上，我国研究团队携IM96 CAR-T的I期临床数据（NCT05287165）惊艳亮相！结果显示：在19例可评估患者中，疾病控制率（DCR）高达73.7%，客观缓解率（ORR）达到26.3%（详见下图），可见IM96 CAR-T在转移性结直肠癌患者中，具有持久的疗效且安全性可控。此外，在DL3亚组中，无论有无肝转移，客观缓解率（ORR）均能达到40.0%，可见该药在肝转移患者中显示出很高的治疗潜力！ ▲图源“ASCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除（十一）IPM001 1、药品信息 ①药物名称： IPM001注射液。 ②研发公司：臻知医学。 ③治疗靶点：多抗原靶点。 ④适应证：进展期原发性肝细胞癌。 2、药物介绍 IPM001注射液是由北京臻知医学自主研发的一款多抗原靶点的自体工程化T细胞（TCR-T）注射液，可靶向数十种肝癌相关抗原与新生抗原。2024年10月9日，IPM001注射液的新药临床研究申请，正式获得国家药品监督管理局（NMPA）默示许可，用于经二线系统性抗肿瘤治疗失败或不耐受的进展期原发性肝细胞癌的治疗，有望成为中国晚期肝癌患者的重要治疗选择之一。（十二）IX001 TCR-T 1、药品信息 ①药物名称： IX001 TCR-T注射液。 ②研发公司：镔铁生物。 ③治疗靶点： KRAS G12V突变。 ④适应证：晚期胰腺癌。 2、药物介绍 IX001 TCR-T注射液是一款针对KRAS G12V突变的创新型TCR-T细胞疗法，可将特异性识别KRAS G12V突变的TCR基因序列，转入T细胞中，使其精准识别并杀伤胰腺癌细胞。2024年10月9日，该药的临床试验默示许可获中国国家药品监督管理局（NMPA）批准，拟用于HLA-A*11:01基因型、KRASG12V抗原表达阳性晚期胰腺癌的治疗。三、小编寄语以上新药/新技术仅为众多研发热点中的一小部分，还有多款抗癌新药或新型免疫疗法正在研发中，而且目前有多款在研药物已相继开展临床试验。对现有治疗方案不满意的患者，可将近期影像学及病理检查报告、治疗经历等资料，提交至全球肿瘤医生网医学部，进行初步评估或了解详细的入排标准。四、参考资料 [1]QI C,et al.Phase I study of GUCY2C CAR-T therapy IM96 in patients with metastatic colorectal cancer[J]. 2024. https://meetings.asco.org/abstracts-presentations/234018 [2]Chandana S R,et al.First-in-human study of ABBV-706, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced solid tumors[J]. 2024. https://ascopubs-org.libproxy1.nus.edu.sg/doi/10.1200/JCO.2024.42.16_suppl.3001 [3]https://www.cde.org.cn/ 本文为全球肿瘤医生网原创，未经授权严禁转载

抗体药物偶联物细胞疗法临床申请免疫疗法ASCO会议

2024-10-13

·医药观澜

21款1类新药首次在中国获批临床！来自强生、艾伯维、恒瑞等

▎药明康德内容团队报道根据中国国家药监局药品审评中心（CDE）官网以及公开资料，近两周（9月30日~10月12日），有21款1类创新药首次在中国获得临床试验默示许可（IND），药物类型包括了双抗、抗体偶联药物（ADC）双抗、ADC、核药、蛋白降解疗法、基因编辑疗法、TCR-T细胞疗法、间充质干细胞药物、治疗实体瘤的CAR-T细胞药物、双环肽偶联药物以及小分子药物等等。本文将根据公开资料对这些产品进行介绍。图片来源：123RF 瑞核医药：镥[177Lu]PSMA-0057注射液、镓[68Ga]PSMA-0057注射液作用机制：靶向PSMA的核药适应症：前列腺癌瑞核医药1类新药镥[177Lu]PSMA-0057注射液获批临床，拟用于前列腺特异性膜抗原（PSMA）阳性前列腺癌的治疗。同时该公司的镓[68Ga]PSMA-0057注射液获批临床，拟用于筛选适合接受镥[177Lu]PSMA-0057注射液治疗的PSMA阳性的前列腺癌患者。公开资料显示，PSMA在超过90%的前列腺癌细胞表面都出现了过表达，以其为靶点的放射性药物治疗前列腺癌已经得到临床研究验证。广东省创新药转化医学研究院有限公司；原力生命科学：INV-9956胶囊作用机制：CYP11A1抑制剂适应症：前列腺癌广东省创新药转化医学研究院有限公司和原力生命科学联合申报的INV-9956胶囊获批临床，拟开发用于晚期转移性去势抵抗性前列腺癌。根据原力生命科学新闻稿，这是其自主研发的一款强效且高选择性的口服CYP11A1抑制剂，此前已经在美国获批IND。类固醇激素是驱动前列腺癌的关键因素之一，细胞色素P450 11A1（CYP11A1）是类固醇合成过程中的重要限速酶，靶向CYP11A1提供了抑制类固醇激素生产的有效手段。艾伯维（AbbVie）：ABBV-706注射用冻干粉作用机制：靶向SEZ6的ADC 适应症：小细胞肺癌艾伯维研发的1类新药ABBV-706注射用冻干粉获批临床，拟单药治疗复发/难治小细胞肺癌。公开资料显示，ABBV-706是一种靶向SEZ6的抗体偶联药物（ADC），有效载荷为TOP1i，目前正在国际范围内处于1期临床研究阶段。该产品有望用于治疗小细胞肺癌、中枢神经系统肿瘤和神经内分泌癌。睿跃生物：注射用CG009301 作用机制：GSPT1靶向蛋白降解剂适应症：血液恶性肿瘤睿跃生物1类新药注射用CG009301获批临床，拟开发治疗复发/难治性血液恶性肿瘤（包括但不限于AML、ALL、高危型MDS等）。根据睿跃生物新闻稿介绍，CG009301是高选择性GSPT1靶向蛋白降解剂。公开资料显示，GSPT1是一种在许多癌症中高度表达的蛋白质，包括血液学和实体瘤。圣域生物：SYN818片作用机制：靶向DNA聚合酶θ（Polθ）的小分子抑制剂适应症：晚期实体瘤圣域生物1类创新药物SYN818片获批临床，拟用于治疗晚期实体瘤。根据圣域生物新闻稿介绍，SYN818是一种新型强效、高选择性的抑制剂药物，其通过精准靶向DNA聚合酶θ（Polθ），有效抑制肿瘤细胞的DNA损伤修复，从而有选择性的杀死肿瘤细胞。研究表明，SYN818不仅对同源重组修复缺陷（HRD）肿瘤细胞具有单独成药的潜力，还具有与PARP抑制剂、放化疗、抗体偶联药物等联合用于多种肿瘤治疗的潜质。湃隆生物：GTA182片作用机制：脑通透性PRMT5抑制剂适应症：MTAPnull/lost晚期实体瘤湃隆生物1类新药GTA182片获批临床，拟开发治疗MTAPnull/lost晚期实体瘤。根据湃隆生物公开资料，GTA182片是一款可穿透血脑屏障的蛋白精氨酸甲基转移酶5（PRMT5）抑制剂，具有甲硫腺苷 (MTA) 协同作用，对MTAP缺失的癌细胞具有高度选择性，不针对MTAP正常表达的非癌细胞。这种选择性有望为MTAP缺失型癌症患者提供更有效、更安全的治疗选择。镔铁生物：IX001 TCR-T注射液作用机制：针对KRAS G12V突变TCR-T细胞疗法适应症：胰腺癌镔铁生物1类新药IX001 TCR-T注射液获批临床，拟开发适应症为基因型为HLA-A*11:01，肿瘤抗原KRAS G12V表达为阳性的晚期胰腺癌。根据镔铁生物公开资料，这是该公司首个申报注册临床试验的在研产品，是一款针对KRAS G12V突变TCR-T细胞疗法。该产品通过基因修饰技术，将能够特异性识别KRAS G12V突变的TCR基因序列转入T细胞，使其能够精准识别并有效杀伤胰腺癌细胞。臻知医学：IPM001注射液作用机制：多抗原靶点自体免疫细胞注射液适应症：原发性肝细胞癌臻知医学申报的IPM001注射液获批临床，拟开发用于治疗经二线系统性抗肿瘤治疗失败或不耐受的进展期原发性肝细胞癌。根据臻知医学新闻稿介绍，IPM001是其自主研发的多抗原靶点自体免疫细胞注射液，为一种工程化T细胞注射液，可靶向数十种中国人群肝癌相关抗原与新生抗原。在前期研究者发起的临床试验（IIT）中，该产品展现了良好的药物安全性，对于经多线系统性抗肿瘤治疗失败的进展期原发性肝细胞癌患者表现出良好的临床疗效。原天生物：YT001注射液作用机制：间充质干细胞治疗产品适应症：膝骨关节炎（KOA）原天生物1类生物制品新药YT001注射液获批临床，拟开发治疗膝骨关节炎（KOA）。根据原天生物新闻稿介绍，这是其研发的一款间充质干细胞治疗产品。间充质干细胞具有免疫调节作用，能够缓释炎症反应，促进损伤修复，其免疫调节和损伤修复功能可帮助调节关节腔内紊乱微环境，缓解软骨的降解。恒瑞医药、拓界生物：SHR-6934注射液作用机制：生物制品新药适应症：心力衰竭恒瑞医药和拓界生物联合申报的SHR-6934注射液获批临床，拟开发用于治疗心力衰竭。目前尚未从公开渠道查询到该产品的作用机制，从受理号可知这是一款治疗用生物制品。心力衰竭的发病率和致死率都极高，并且预后不良，约一半的心衰患者在确诊后五年内死亡。随着心脏疾病、糖尿病等患者的生存期延长、老龄化程度加深，全球心衰患者数量将持续增长。思道医药：注射用DM001 作用机制：EGFR/TROP2双抗ADC 适应症：实体瘤思道医药1类新药注射用DM001获批临床，拟开发用于晚期或转移性HR+、HER2-乳腺癌、转移性三阴性乳腺癌、晚期或转移性EGFRmut或EGFRwt非小细胞肺癌和其他实体瘤。根据思道医药新闻稿介绍，DM001是一款注射用EGFR/TROP2双抗ADC。该产品此前获得美国FDA IND批准，目前正在美国和澳洲开展临床1期研究。瑞风生物：RM-101注射液作用机制：基于AAV的基因编辑类药物适应症：Usher综合征2型相关RP 瑞风生物申报的RM-101注射液获批临床，拟开发用于治疗USH2A基因外显子13突变所致的Usher综合征2型相关RP（视网膜色素变性）或非综合征型RP。根据瑞风生物公开资料介绍，RM-101是基于AAV的基因编辑类药物，能特异靶向USH2A RNA，调控可变剪接生物学过程，诱导功能正常蛋白的表达恢复。该产品通过视网膜下注射给药，有望实现一次性给药并长期有效。Usher综合征是与视网膜色素变性有关的最常见综合征，USH2A基因突变导致视网膜色素变性，患者通常在青少年时期逐渐出现夜盲和周边视野缺失，最终可能导致全盲。瑞宏迪医药：RGL-193注射液作用机制：AAV双基因药物适应症：帕金森病恒瑞医药子公司瑞宏迪医药申报的1类新药RGL-193注射液获批临床，拟开发治疗帕金森病。公开资料显示，这是瑞宏迪医药针对帕金森病自主研发的一款AAV双基因药物，采用立体定向技术注入患者脑内。它可以提高左旋多巴的转化效率，同时还起到保护和修复受损多巴胺能神经元的作用，具有潜在的延缓病情进展、减少口服抗帕金森病药量的效果。艺妙医疗：IM96嵌合抗原受体T细胞注射液（IM96 CAR-T细胞注射液）作用机制：靶向GUCY2C的CAR-T疗法适应症：结直肠癌艺妙医疗申报的IM96 CAR-T细胞注射液获批临床，拟开发用于治疗结直肠癌。根据艺妙医疗新闻稿介绍，这是其与北京大学肿瘤医院合作开发的用于治疗转移性结直肠癌的全新一代抗肿瘤药物，是一款靶向鸟苷酸环化酶2C（GUCY2C）的CAR-T疗法。该产品的临床前研究数据于今年6月入选美国临床肿瘤学会（ASCO）年会，研究显示IM96针对结直肠癌的最佳客观缓解率（ORR）达到50%，且仅有5.0%的患者出现神经毒性和≥3级的细胞因子释放综合征（CRS）。 BicycleTx：BT8009 作用机制：靶向Nectin-4的双环肽偶联药物适应症：尿路上皮癌 Bicycle公司申报的BT8009获批临床，拟开发治疗尿路上皮癌。公开资料显示，BT8009是Bicycle Therapeutics公司研发的第二代双环肽偶联毒素在研疗法，靶向Nectin-4。Bicycle公司致力于利用诺贝尔化学奖获得者Gregory Winter爵士的科研成果以及双环肽技术开发变革性药物。双环肽是由9-20个氨基酸组成的多肽，能以高亲和性和选择性与靶标结合，具有高肿瘤渗透性特性，且肽类的性质提供了“可调控”的药物动力学半衰期和肾脏清除途径。在全球范围内，BT8009已启动在转移性尿路上皮癌症中的2/3期注册试验。康抗生物：KGX101 作用机制：细胞因子IL-12前药产品适应症：晚期或转移性实体瘤康抗生物在研新药KGX101（注射用肿瘤特异性重组IL-12 Fc融合蛋白）获批临床，拟开发用于晚期或转移性实体瘤。根据康抗生物公开资料介绍，KGX101为一款新一代细胞因子IL-12前药产品。它通过肿瘤特异性蛋白酶切Linker融合掩蔽蛋白，既提高了活性药物在肿瘤区域的富集程度，又降低了细胞因子的系统性毒性。一旦Linker被肿瘤微环境中的特异性金属基质蛋白酶切除，KGX101就能够像IL-12一样，有效刺激肿瘤中的免疫细胞，重塑肿瘤微环境，从而达到治疗目的。恒瑞医药：HRS-9563注射液作用机制：化药新药适应症：高血压恒瑞医药HRS-9563注射液获批临床，拟用于治疗高血压。目前尚未从公开渠道查询到该产品的适应症，从受理号可知这是一款化药新药。武汉人福创新药物研发中心：HW211026软膏作用机制：化药适应症：光化性角化病武汉人福创新药物研发中心申报的1类新药HW211026软膏获批临床，拟用于光化性角化病的治疗。从受理号可知这是一款化药新药。光线性角化病（日光性角化病）是长期暴晒所引起的癌前增生，会导致皮肤粗糙、有鳞屑，呈各种颜色，并且可进展为鳞状细胞癌。强生：JNJ-78278343注射液作用机制：KLK2-CD3双抗适应症：前列腺癌强生公司（Johnson & Johnson）1类新药JNJ-78278343注射液获批临床，拟开发用于治疗晚期前列腺癌成人男性患者。根据强生公开资料，这是一款KLK2-CD3双特异性抗体在研新药，在国际范围内处于1期临床研究阶段。KLK2是一种高度前列腺特异性抗原。JNJ-78278343被设计用于靶向KLK2，并通过与T细胞上的CD3结合而诱导T细胞活化。该产品给药后可结合T细胞上的CD3和表达KLK2的肿瘤细胞上的KLK2，将T细胞重定向到肿瘤细胞，产生T细胞介导的KLK2表达肿瘤细胞的裂解。博致生物：注射用PTX-912 作用机制：IL-2前药融合蛋白适应症：局部晚期/转移性实体瘤博致生物申报的注射用PTX-912获批临床，拟开发用于治疗局部晚期/转移性实体瘤。根据博致生物公开资料，PTX-912是该公司自主开发的新一代免疫细胞靶向的IL-2前药融合蛋白，利用独创的前药技术，使IL-2前药在肿瘤微环境中被特异性激活，从而解决IL-2的外周毒性问题。同时，PTX-912可将激活后的IL-2靶向定位至肿瘤特异性的效应T细胞亚群中，以充分发挥IL-2的激活免疫和抗肿瘤的功效。目前，该产品已经启动美国1期临床试验。亚尧生物：YY2201片作用机制：ATR激酶抑制剂适应症：晚期实体瘤亚尧生物申报的YY2201片获批临床，拟开发治疗晚期实体瘤。公开资料显示，这是亚尧生物研发的ATR激酶抑制剂小分子药物。ATR是一种DNA修复的关键激酶，也是一种“合成致死”抗肿瘤靶点。在已完成的系列非临床研究中，YY2201片展现出良好的体内、外活性、药代动力学特征及安全性。参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved Oct 13，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]各公司官网及公开资料本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

抗体药物偶联物临床申请细胞疗法临床1期免疫疗法

2024-10-10

·PRNewswire

Metastatic Castration-Resistant Prostate Cancer Clinical Trial Pipeline Appears Robust With 90+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

Metastatic Castration-Resistant Prostate Cancer (mCRPC) refers to prostate cancer that has spread (metastasized) to other parts of the body and continues to progress despite treatments that lower testosterone levels (androgen deprivation therapy or ADT) major pharmaceutical companies are heavily investing in research and development of new treatments, including immunotherapy (e.g., sipuleucel-T) and targeted therapies, which are seen as the next frontier in treating mCRPC. The use of precision medicine to identify genetic profiles in patients has further expanded the potential for targeted treatment. LAS VEGAS , Oct. 10, 2024 /PRNewswire/ -- DelveInsight's ' Metastatic Castration-Resistant Prostate Cancer Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mCRPC therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mCRPC pipeline domain. Key Takeaways from the Metastatic Castration-Resistant Prostate Cancer Pipeline Report DelveInsight's mCRPC pipeline report depicts a robust space with 90+ active players working to develop 100+ pipeline therapies for mCRPC treatment. Key mCRPC companies such as Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others are evaluating new mCRPC drugs to improve the treatment landscape. Promising mCRPC pipeline therapies such as REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others are under different phases of mCRPC clinical trials. In October 2024, Curium announced that it had entered into a strategic partnership with PDRadiopharma Inc, a wholly-owned subsidiary of PeptiDream, for the clinical development, regulatory filing, and commercialization in Japan of 177Lu-PSMA-I&T and 64Cu-PSMA-I&T. The two agents 177Lu-PSMA-I&T and 64Cu-PSMA-I&T target prostate-specific membrane antigen (PSMA) expressed on prostate cancer cells and are being investigated for prostate cancer treatment and diagnostics. In July 2024, the US FDA granted fast-track designation to the prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical 225Ac-FL-020 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). In July 2024, Merck and Orion Corporation announced the mutual exercise of option providing Merck global exclusive rights to Opevesostat, an investigational CYP11A1 inhibitor, for the treatment of Metastatic Castration-Resistant Prostate Cancer. In July 2024, the US FDA granted fast-track designation to the antibody-drug conjugate (ADC) BNT324/DB-1311 to potentially treat patients with unresectable advanced or metastatic castration-resistant prostate cancer (mCRPC) whose disease had progressed on or after standard systemic regimens. In July 2024, FutureChem announced that the FC-705 has received orphan drug designation from the Ministry of Food and Drug Safety (MFDS) for the treatment of prostate cancer. In June 2024, CAR T-Cell Therapy demonstrated promising results for mCRPC according to Phase I trial results. In January 2024, Lava Therapeutics announced that it has signed a clinical trial collaboration and supply agreement with Merck to evaluate its prostate cancer therapy LAVA-1207 as a combination treatment with MSD's Keytruda (pembrolizumab). In July 2024, Blue Earth Therapeutics announced the signing of a clinical research collaboration with University College London (UCL). The collaboration is centered on a Phase I/II trial designed to evaluate the safety, tolerability, radiation dosimetry, and antitumor activity of the 225Ac-rhPSMA-10.1 in men with metastatic castrate-resistant prostate cancer who have previously responded to lutetium 177 (177Lu)-PSMA therapy. Request a sample and discover the recent advances in mCRPC treatment drugs @ Metastatic Castration-Resistant Prostate Cancer Pipeline Report The mCRPC pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mCRPC drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mCRPC clinical trial landscape. Metastatic Castration-Resistant Prostate Cancer Overview Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer that continues to grow and spread despite hormone therapy aimed at lowering testosterone levels. The term "metastatic" refers to cancer spreading to other parts of the body, such as the bones, lymph nodes, or distant organs, while "castration-resistant" indicates that the cancer no longer responds to treatments that reduce testosterone, a key driver of prostate cancer growth. mCRPC is typically more aggressive and challenging to treat than earlier stages of prostate cancer. The causes of mCRPC stem from genetic and environmental factors. Genetic mutations in the androgen receptor pathway can make cancer cells less dependent on testosterone, allowing them to thrive even under hormone-suppressing treatments. Environmental factors like diet, lifestyle, and exposure to certain chemicals may also contribute to the development and progression of prostate cancer. Symptoms of mCRPC often include pain in bones, fatigue, difficulty urinating, weight loss, and general weakness. As the cancer spreads, it can impair the function of other organs, depending on the site of metastasis. Diagnosis of mCRPC usually involves a combination of tests, including prostate-specific antigen (PSA) blood tests, imaging studies like CT scans, MRIs, or bone scans, and sometimes biopsies to confirm the spread and resistance to treatment. Treatment options for mCRPC are more complex and may include newer hormonal therapies (e.g., abiraterone, enzalutamide), chemotherapy (docetaxel or cabazitaxel), immunotherapy (e.g., sipuleucel-T), or targeted therapies such as PARP inhibitors. Bone-targeting therapies, radiation, and palliative care can also be used to manage symptoms and improve the quality of life. Treatment is typically tailored to the individual based on the extent of the disease and the patient health. Find out more about mCRPC treatment drugs @ Drugs for Metastatic Castration-Resistant Prostate Cancer Treatment A snapshot of the mCRPC Pipeline Drugs mentioned in the report: Learn more about the emerging mCRPC pipeline therapies @ Metastatic Castration-Resistant Prostate Cancer Clinical Trials Metastatic Castration-Resistant Prostate Cancer Therapeutics Assessment The mCRPC pipeline report proffers an integral view of the mCRPC emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Metastatic Castration-Resistant Prostate Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous Therapeutics Assessment By Molecule Type: Small molecule, Cell therapy, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Androgen receptor degradation enhancers, Antibody-dependent cell cytotoxicity, Proto-oncogene protein c-akt inhibitors, Androgen receptor antagonists, Bromodomain and extraterminal domain protein inhibitors, Cyclin-dependent kinase 4 inhibitors, Cyclin-dependent kinase 6 inhibitors, Ionizing radiation emitters, PPAR alpha antagonists. Key Metastatic Castration-Resistant Prostate Cancer Companies: Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others. Key Metastatic Castration-Resistant Prostate Cancer Pipeline Therapies: REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others. Dive deep into rich insights for new drugs for mCRPC treatment, visit @ Metastatic Castration-Resistant Prostate Cancer Drugs Table of Contents For further information on the mCRPC Cancer pipeline therapeutics, reach out @ Metastatic Castration-Resistant Prostate Cancer Treatment Drugs Related Reports Metastatic Castration-Resistant Prostate Cancer Market Metastatic Castration-Resistant Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCRPC companies including AstraZeneca, Merck Sharp & Dohme, Hinova Pharmaceuticals, Pfizer, Astellas Pharma, Modra Pharmaceuticals, AB Science, Eli Lilly and Company, Zr Pharma & GmbH, Bristol-Myers Squibb, Ipsen, Exelixis, Takeda, Janssen Research & Development, Tesaro, Lantheus Holdings, Kintor Pharmaceutical, MacroGenics, Daiichi Sankyo, Madison Vaccines, Novartis, Point Biopharma, Xencor, Essa Pharma, Telix International, Bayer, Arvinas, among others. Metastatic Prostate Cancer Market Metastatic Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key metastatic prostate cancer companies including AstraZeneca, Arvinas, Madison Vaccines, Phosplatin Therapeutics, Hinova Pharmaceuticals, Bristol Myers Squibb, Merck, MacroGenics, Daiichi Sankyo, Seagen, Taiho Pharmaceutical, Modra Pharmaceuticals, Xencor, Point Biopharma, Lantheus Holdings, Zenith Epigenetics, Essa Pharma, Telix Pharmaceuticals, Kintor Pharmaceutical, AB Science, Eli Lilly and Company, Exelixis among others. Metastatic Castration-Sensitive Prostate Cancer Market Metastatic Castration-Sensitive Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCSPC companies including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. Metastatic Castration-Sensitive Prostate Cancer Pipeline Metastatic Castration-Sensitive Prostate Cancer Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key mCSPC companies, including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED