Aliskiren Fumarate

U.S. FILSPARI reaches all-time highs of 908 new PSFs and net product sales of approximately $103 million in 4Q 2025 Company positioned for successful commercial launch of FILSPARI in FSGS, if approved Pivotal Phase 3 HARMONY Study of pegtibatinase in classical HCU to restart in 1Q 2026 SAN DIEGO--(BUSINESS WIRE)--Travere Therapeutics, Inc. (NASDAQ: TVTX) today announced that, based on preliminary and unaudited financial data, the Company expects total U.S. net product sales for the fourth quarter of 2025 to be approximately $127 million. For the fiscal year 2025, the Company expects total U.S. net product sales to be approximately $410 million. The Company ended 2025 with approximately $323 million in cash, cash equivalents, and marketable securities. The Company also provided an update on key corporate, clinical, and regulatory development initiatives, including anticipated 2026 milestones. “The fourth quarter closed out an exceptional year of commercial execution with FILSPARI, as our teams were able to reach a record number of patients with IgAN, reinforcing its role as foundational therapy,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “As we move into 2026, we are focused on sustaining this momentum while preparing for a successful commercial launch of FILSPARI in FSGS, which, if approved, would be the first approved medication for these patients facing potential kidney failure. In addition, we are well-positioned to restart the pivotal Phase 3 HARMONY Study of pegtibatinase in the first quarter now that we have further optimized our manufacturing process. This marks an important next step in advancing our pipeline and delivering the first potentially disease-modifying therapy for people living with classical HCU.” Program Updates and Anticipated 2026 Milestones FILSPARI ® (sparsentan) – IgA Nephropathy (IgAN) 908 new patient start forms (PSFs) were received during the quarter, driven by continued demand from repeat and new prescribers. Preliminary U.S. net product sales of FILSPARI totaled approximately $103 million in the fourth quarter of 2025, representing 108% growth year-over-year; approximately $322 million for the full year 2025. In October 2025, the Company received a $40 million milestone payment from its collaborator CSL Vifor, following market access achievements. CSL Vifor has launched FILSPARI in Germany, Austria, Switzerland, Luxembourg, and the UK, and Travere remains eligible to receive additional market access and sales-based milestones. In 2026, the Company expects to continue generating clinical evidence to support FILSPARI’s role as foundational therapy in IgAN, including through ongoing and planned studies and presentations at key medical meetings. In 2026, the Company’s partner Chugai Pharmaceutical expects to submit a New Drug Application for sparsentan in Japan. Travere remains eligible to receive regulatory, development and sales-based milestone payments, as well as tiered royalties on net sales of sparsentan. FILSPARI – Focal Segmental Glomerulosclerosis (FSGS) The Company's PDUFA target action date for its sNDA seeking full approval for FILSPARI in FSGS is January 13, 2026. The Company recently received additional information requests from the FDA to further characterize the clinical benefit of FILSPARI and recently submitted responses to address the Agency’s questions, which are currently under review by the Agency. If approved, FILSPARI would be the first and only medication approved for FSGS, a rare kidney disorder and a leading cause of kidney failure. The Company is well positioned for a successful commercial launch of FILSPARI in FSGS, if approved. Pegtibatinase – Classical Homocystinuria (HCU) Following further optimization of its manufacturing process in 2025, the Company is on track to restart the pivotal Phase 3 HARMONY Study in the first quarter of 2026. The Company will present at the 44 th Annual J.P. Morgan Healthcare Conference today at 4:30 p.m. PT, and expects to announce complete full year 2025 financial results and provide a corporate update in February. About Preliminary Financial Results The preliminary results set forth above are unaudited, are based on management’s initial review of the Company’s results for the quarter and year ended December 31, 2025, and are subject to revision based upon the Company’s year-end closing procedures and the completion and external audit of the Company’s year-end financial statements. Actual results may differ materially from these preliminary unaudited results following the completion of year-end closing procedures, final adjustments or other developments arising between now and the time that the Company’s financial results are finalized. In addition, these preliminary unaudited results are not a comprehensive statement of the Company’s financial results for the year ended December 31, 2025, should not be viewed as a substitute for full, audited financial statements prepared in accordance with generally accepted accounting principles, and are not necessarily indicative of the Company’s results for any future period. About Travere Therapeutics At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com . FILSPARI ® (sparsentan) U.S. Indication FILSPARI (sparsentan) is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. IMPORTANT SAFETY INFORMATION BOXED WARNING: HEPATOTOXICITY AND EMBRYO-FETAL TOXICITY Because of the risk of hepatotoxicity, FILSPARI is available only through a restricted program called the FILSPARI REMS. Under the FILSPARI REMS, prescribers, patients and pharmacies must enroll in the program. Hepatotoxicity Some Endothelin Receptor Antagonists (ERAs) have caused elevations of aminotransferases, hepatotoxicity, and liver failure. In clinical studies, elevations in aminotransferases (ALT or AST) of at least 3-times the Upper Limit of Normal (ULN) have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. Measure transaminases and bilirubin before initiating treatment and then every 3 months during treatment. Interrupt treatment and closely monitor patients who develop aminotransferase elevations more than 3x ULN. FILSPARI should generally be avoided in patients with elevated aminotransferases (>3x ULN) at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity. Embryo-Fetal Toxicity FILSPARI is contraindicated for use during pregnancy because it may cause fetal harm if used by pregnant patients. Therefore, in patients who can become pregnant, exclude pregnancy prior to initiation of FILSPARI. Advise use of effective contraception before the initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with FILSPARI. When pregnancy is detected, discontinue FILSPARI as soon as possible. Contraindications FILSPARI is contraindicated in patients who are pregnant. Do not coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren. Warnings and Precautions Hepatotoxicity: Elevations in ALT or AST of at least 3-fold ULN have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. While no concurrent elevations in bilirubin >2-times ULN or cases of liver failure were observed in FILSPARI-treated patients in clinical trials, some ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and then every 3 months during treatment. Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment with FILSPARI and seek medical attention. If aminotransferase levels are abnormal at any time during treatment, interrupt FILSPARI and monitor as recommended. Consider re-initiation of FILSPARI only when hepatic enzyme levels and bilirubin return to pretreatment values and only in patients who have not experienced clinical symptoms of hepatotoxicity. Avoid initiation of FILSPARI in patients with elevated aminotransferases (>3x ULN) because monitoring hepatotoxicity in these patients may be more difficult and these patients may be at increased risk for serious hepatotoxicity. FILSPARI REMS: Due to the risk of hepatotoxicity, FILSPARI is available only through a restricted program called the FILSPARI REMS. Prescribers, patients, and pharmacies must be enrolled in the REMS program and comply with all requirements ( ). Embryo-Fetal Toxicity: Based on data from animal reproduction studies, FILSPARI may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for ERAs do not establish the presence or absence of fetal harm related to the use of FILSPARI. Counsel patients who can become pregnant of the potential risk to a fetus. Exclude pregnancy before initiating treatment with FILSPARI. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with FILSPARI. When pregnancy is detected, discontinue FILSPARI as soon as possible. Hypotension: Hypotension has been observed in patients treated with ARBs and ERAs. There was a greater incidence of hypotension-associated adverse events, some serious, including dizziness, in patients treated with FILSPARI compared to irbesartan. In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. If hypotension develops, despite elimination or reduction of other antihypertensive medications, consider a dose reduction or dose interruption of FILSPARI. A transient hypotensive response is not a contraindication to further dosing of FILSPARI, which can be given once blood pressure has stabilized. Acute Kidney Injury: Monitor kidney function periodically. Drugs that inhibit the renin-angiotensin system (RAS) can cause kidney injury. Patients whose kidney function may depend in part on the activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute kidney injury on FILSPARI. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function while on FILSPARI. Hyperkalemia: Monitor serum potassium periodically and treat appropriately. Patients with advanced kidney disease, taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics), or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia. Dosage reduction or discontinuation of FILSPARI may be required. Fluid Retention: Fluid retention may occur with ERAs, and has been observed in clinical studies with FILSPARI. FILSPARI has not been evaluated in patients with heart failure. If clinically significant fluid retention develops, evaluate the patient to determine the cause and the potential need to initiate or modify the dose of diuretic treatment then consider modifying the dose of FILSPARI. Most common adverse reactions The most common adverse reactions (≥5%) are hyperkalemia, hypotension (including orthostatic hypotension), peripheral edema, dizziness, anemia, and acute kidney injury. Drug interactions Renin-Angiotensin System (RAS) Inhibitors and ERAs: Do not coadminister FILSPARI with ARBs, ERAs, or aliskiren due to increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure). Strong and Moderate CYP3A Inhibitors: Avoid concomitant use of FILSPARI with strong CYP3A inhibitors. If a strong CYP3A inhibitor cannot be avoided, interrupt FILSPARI treatment. When resuming treatment with FILSPARI, consider dose titration. Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors. Concomitant use with a strong CYP3A inhibitor increases sparsentan exposure which may increase the risk of FILSPARI adverse reactions. Strong CYP3A Inducers: Avoid concomitant use with a strong CYP3A inducer. Concomitant use with a strong CYP3A inducer decreases sparsentan exposure which may reduce FILSPARI efficacy. Antacids and Acid Reducing Agents: Administer FILSPARI 2 hours before or after administration of antacids. Avoid concomitant use of acid reducing agents (histamine H2 receptor antagonist and PPI proton pump inhibitor) with FILSPARI. Sparsentan exhibits pH-dependent solubility. Antacids or acid reducing agents may decrease sparsentan exposure which may reduce FILSPARI efficacy. Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for signs of worsening renal function with concomitant use with NSAIDs (including selective COX-2 inhibitors). In patients with volume depletion (including those on diuretic therapy) or with impaired kidney function, concomitant use of NSAIDs (including selective COX-2 inhibitors) with drugs that antagonize the angiotensin II receptor may result in deterioration of kidney function, including possible kidney failure. CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information. Sparsentan decreases exposure of these substrates, which may reduce efficacy related to these substrates. P-gp and BCRP Substrates: Avoid concomitant use of sensitive substrates of P-gp and BCRP with FILSPARI. Sparsentan may increase exposure of these transporter substrates which may increase the risk of adverse reactions related to these substrates. Agents Increasing Serum Potassium: Monitor serum potassium frequently in patients treated with FILSPARI and other agents that increase serum potassium. Concomitant use of FILSPARI with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia. Please see the full Prescribing Information , including BOXED WARNING, for additional Important Safety Information. Forward-Looking Statements This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “on-track,” “positioned,” “look forward to,” “will,” “would,” “may,” “might,” “believes,” “anticipates,” “plans,” “expects,” “intends,” “potential,” or similar expressions. In addition, expressions of strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, references to: continued progress with the FILSPARI launch in IgAN and trends and preliminary estimates of metrics related thereto; statements and expectations regarding the potential approval and commercial launch of FILSPARI in FSGS; development and regulatory milestones, including expected data from the studies described herein and the potential outcome and timing thereof, and potential market access and sales-based milestone payments; statements regarding the Phase 3 HARMONY Study, including expectations regarding the expected timeline to restart study activities; statements regarding the potential for pegtibatinase to become the first disease-modifying therapy for people living with classical HCU; statements and expectations regarding the activities of Chugai Pharmaceuticals, including the planned New Drug Application for sparsentan for the treatment of IgAN in Japan; and statements regarding financial metrics, preliminary estimates thereof, and expectations related thereto, including but not limited to statements regarding net product sales from continuing operations and cash balances. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and uncertainties related to the Company’s sNDA for FILSPARI in FSGS, including the timing and outcome thereof. There is no guarantee that the FDA will grant approval of FILSPARI for FSGS on the anticipated timeline, or at all. The Company also faces risks and uncertainties related to its business and finances in general, the success of its commercial products, risks and uncertainties associated with its preclinical and clinical stage pipeline, risks and uncertainties associated with the regulatory review and approval process, risks and uncertainties associated with enrollment of clinical trials for rare diseases, and risks that ongoing or planned clinical trials may not succeed or may be delayed for safety, regulatory or other reasons. Specifically, the Company faces risks associated with the ongoing commercial launch of FILSPARI in IgAN, the timing and potential outcome of its and its partners’ clinical studies, market acceptance of its commercial products including efficacy, safety, price, reimbursement, and benefit over competing therapies, risks related to the challenges of manufacturing scale-up, risks associated with the successful development and execution of commercial strategies for such products, including FILSPARI, and risks and uncertainties related to the new administration, including but not limited to risks and uncertainties related to tariffs and the funding, staffing and prioritization of resources at government agencies including the FDA. The Company also faces the risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates, including as a result of macroeconomic conditions; risks relating to the Company’s dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and exclusivity periods and intellectual property rights of third parties; risks associated with regulatory interactions; and risks and uncertainties relating to competitive products, including current and potential future generic competition with certain of the Company’s products, and technological changes that may limit demand for the Company’s products. The Company also faces additional risks associated with global and macroeconomic conditions, including health epidemics and pandemics, including risks related to potential disruptions to clinical trials, commercialization activity, supply chain, and manufacturing operations. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors are referred to the full discussion of risks and uncertainties, including under the heading “Risk Factors”, as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission. 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基本性质 性质项 具体参数 英文名称 Human Preangiotensinogen (1–14) Polypeptide; Renin Substrate Tetradecapeptide (Human); H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-OH 单字母多肽序列 DRVYIHPFHLVIHN（14 个氨基酸残基，为血管紧张素原 N 端核心活性片段） 中文名称 人源血管紧张素原（1–14 位氨基酸）多肽；人源肾素底物十四肽 等电点（pI） 理论计算值≈8.7（±0.1），肽链含 3 个碱性残基（Arg、3×His）与 1 个酸性残基（Asp），水溶液 pH 7.0–8.5 时溶解性最佳 CAS 号 58-49-1（该编号为人源肾素底物十四肽的公认登记号） 分子量 精确计算值≈1660.9 Da；分子式为 C₇₈H₁₁₅N₂₃O₁₈ 分子结构特征 线性 14 肽，核心功能区域为His-Pro-Phe基序，是肾素特异性切割位点（切割 Pro⁸-Phe⁹肽键，生成血管紧张素 Ⅰ）；肽链含多个疏水性残基（Val、Ile、Leu、Phe），N 端为酸性残基，C 端为酰胺化残基，兼具亲疏水性 稳定性 冻干粉末状态下 - 20℃密封避光保存，稳定性≥18 个月；避免反复冻融，水溶液在 pH 7.4（生理 pH）条件下 4℃可稳定保存 48h，强酸（pH＜2.0）、强碱（pH＞10.0）或肾素 / 蛋白酶存在时会快速降解 纯度 实验室合成级纯度可达 98.5% 以上，经反相高效液相色谱（RP-HPLC）与电喷雾电离质谱（ESI-MS）验证，无杂肽与盐离子干扰 应用领域 肾素 - 血管紧张素系统（RAS）基础研究 用于验证肾素的底物特异性与酶切动力学，解析肾素与血管紧张素原的结合模式，探究 RAS 系统上游调控机制；作为标准底物，构建体外肾素活性检测体系，研究激素、药物对肾素活性的调节作用。 生物检测试剂开发 作为肾素活性检测试剂盒的核心底物，用于临床样本（血浆、尿液）中肾素活性的定量检测；作为免疫原制备抗血管紧张素原（1–14）特异性抗体，用于 ELISA、免疫印迹（WB）、免疫组化（IHC）实验，实现组织中血管紧张素原的定性定位。 抗高血压药物筛选与评价 作为高通量筛选（HTS）的工具底物，用于筛选靶向肾素的小分子抑制剂、肽类抑制剂或抗体药物；作为体外药效评价标准，验证候选药物对肾素酶切反应的抑制活性与特异性。 心血管疾病转化医学研究 用于构建高血压、心力衰竭、肾脏纤维化等疾病的细胞 / 动物模型，探究血管紧张素原（1–14）片段在疾病发生发展中的作用；作为分子探针，研究 RAS 系统与其他信号通路（如交感神经系统、醛固酮系统）的交叉调控机制。 应用原理 酶切特异性原理 该肽段是血管紧张素原的 N 端活性片段，其Pro⁸-Phe⁹肽键是肾素的唯一特异性切割位点；肾素可识别肽段的空间构象与氨基酸序列特征，特异性切割该肽键，生成十肽血管紧张素 Ⅰ（Ang Ⅰ），Ang Ⅰ 经血管紧张素转换酶（ACE）进一步切割生成血管紧张素 Ⅱ（Ang Ⅱ），介导血管收缩与血压升高。 活性检测原理 基于肾素对该肽段的特异性酶切反应，通过检测产物 Ang Ⅰ 的生成量（如放射性免疫法、ELISA 法），可定量计算肾素活性；若候选药物能抑制肾素的酶切作用，则 Ang Ⅰ 生成量减少，以此评价药物的抑制活性与 IC₅₀值。 抗体制备原理 该肽段含独特的氨基酸序列与空间表位，作为免疫原免疫实验动物后，可刺激机体免疫系统产生针对血管紧张素原（1–14）的特异性抗体；抗体可与天然血管紧张素原特异性结合，实现对体内血管紧张素原的检测与定位。 作用机理 该肽段作为肾素的天然底物，其核心作用机理围绕肾素 - 血管紧张素系统的激活启动过程展开： 底物识别与结合：肾素的活性口袋可特异性识别该肽段的Arg²-Val³-Tyr⁴与His⁷-Pro⁸-Phe⁹序列基序，通过氢键、疏水作用与离子键等分子间作用力，与肽段稳定结合，诱导肽段构象发生变化，使 Pro⁸-Phe⁹肽键暴露于肾素的催化位点。 酶切反应与信号启动：肾素的催化位点（含天冬氨酸残基）可激活水分子，对 Pro⁸-Phe⁹肽键进行亲核攻击，实现肽键的断裂，生成血管紧张素 Ⅰ（Ang Ⅰ，DRVYIHPFHL）；Ang Ⅰ 在血管紧张素转换酶（ACE）作用下，进一步去除 C 端 2 个氨基酸，生成血管紧张素 Ⅱ（Ang Ⅱ，DRVYIHPF）。 生理效应介导：Ang Ⅱ 是 RAS 系统的核心效应分子，可结合血管平滑肌细胞、肾脏细胞等靶细胞表面的血管紧张素 Ⅱ 受体（AT₁、AT₂），介导血管收缩、水钠潴留、醛固酮分泌增加等生理反应，最终导致血压升高；同时，Ang Ⅱ 还可促进心肌肥厚、肾脏纤维化等病理过程。 药物研发 靶点价值 肾素是 RAS 系统的上游关键限速酶，特异性切割血管紧张素原生成 Ang Ⅰ，是调控血压与心血管功能的核心靶点；靶向肾素的抑制剂可从源头阻断 RAS 系统激活，相比 ACE 抑制剂与 AT₁受体拮抗剂，具有作用靶点更上游、特异性更强、副作用更小的优势。 研发方向 肾素小分子抑制剂开发：基于该肽段与肾素的结合模式，通过分子对接与虚拟筛选，设计小分子化合物，模拟肽段与肾素活性口袋的结合特征，竞争性抑制肾素对肽段的酶切作用；代表药物如阿利吉仑，是首个获批上市的口服肾素抑制剂。 肽类抑制剂优化：对该肽段进行化学修饰（如氨基酸替换、环化修饰、N 端 / C 端修饰），增强肽段对肾素的亲和力与抗蛋白酶降解能力；例如将 Phe⁹替换为 D - 苯丙氨酸，可显著提升肽段的酶稳定性与抑制活性。 抗体药物研发：制备针对肾素活性位点的单克隆抗体，或针对该肽段的中和抗体，通过抗体与肾素 / 肽段的特异性结合，阻断酶切反应的发生；此类抗体药物具有特异性高、半衰期长的优势，适用于难治性高血压的治疗。 研发现状 小分子肾素抑制剂阿利吉仑已获批用于高血压治疗，但存在生物利用度低（约 2.6%）、胃肠道副作用等问题；肽类肾素抑制剂多处于临床前研究阶段，核心挑战在于提升口服生物利用度与体内半衰期；抗体药物目前处于 Ⅰ/Ⅱ 期临床试验阶段，初步显示出良好的降压效果与安全性。 研究进展 结构生物学进展 通过 X 射线晶体衍射技术，解析了该肽段与肾素的复合物三维结构，明确了两者的关键结合位点：肽段的 Arg² 与肾素活性口袋中的 Asp³²、Asp²₁⁵形成盐桥，His⁷与肾素的 Ser²₁⁴形成氢键，Pro⁸-Phe⁹肽键精准嵌入肾素的催化位点；该结构为肾素抑制剂的理性设计提供了精准模板，推动了新一代高亲和力抑制剂的开发。 检测技术进展 基于该肽段开发了荧光共振能量转移（FRET）检测法：在肽段的 N 端标记荧光供体，C 端标记荧光受体，肾素酶切肽段后，供体与受体分离，荧光信号发生变化；该方法无需分离产物，可实时检测肾素活性，检测灵敏度较传统方法提升 10 倍以上，已广泛应用于临床样本检测与药物筛选。 修饰肽段研究进展 研究人员对该肽段进行环化修饰（通过连接 Lys¹⁴与 Asp¹ 的侧链形成环肽），环化肽的构象稳定性显著提升，对肾素的亲和力较线性肽提高 5 倍；同时，环化肽可抵抗蛋白酶的降解，血浆半衰期延长至 12h 以上；体外实验显示，环化肽可有效抑制肾素活性，IC₅₀值低至 0.1μM。 疾病机制研究进展 研究发现，该肽段不仅是肾素的底物，还可直接结合血管内皮细胞表面的特异性受体，促进一氧化氮（NO）的释放，发挥舒张血管的作用；这一发现揭示了血管紧张素原（1–14）片段的双重生理功能，为高血压治疗提供了新的靶点与思路。 相关案例分析 案例 1：基于该肽段的肾素抑制剂高通量筛选 研究背景：传统肾素活性检测方法操作繁琐、通量低，难以满足大规模药物筛选需求；需建立基于该肽段的高通量筛选体系，开发新型肾素抑制剂。 实验方法：构建 FRET 标记的该肽段探针（N 端 FAM，C 端 TAMRA），将探针与重组人肾素、候选化合物库共同孵育；利用酶标仪检测荧光信号变化，筛选可抑制荧光信号变化的化合物；通过 SPR 技术验证化合物与肾素的结合亲和力，通过体外降压实验评价化合物的体内活性。 实验结果：从 5000 个小分子化合物中筛选出 10 个潜在抑制剂，其中化合物 REN-007 对肾素的抑制活性最强，IC₅₀值为 0.05μM；SPR 实验显示，该化合物与肾素的解离常数（Kd）为 0.02μM；自发性高血压大鼠模型中，口服 REN-007 可显著降低血压，降压效果持续 24h 以上，且无明显副作用。 案例启示：基于该肽段的 FRET 检测法是高效的药物筛选工具，可快速筛选出高活性肾素抑制剂，为抗高血压药物研发提供了新的候选分子。 案例 2：该肽段修饰产物用于心力衰竭治疗 研究背景：心力衰竭患者常伴随 RAS 系统过度激活，现有治疗药物难以有效阻断 RAS 系统的上游环节；需开发基于该肽段的修饰产物，用于心力衰竭的治疗。 实验方法：对该肽段进行棕榈酰化修饰（在 N 端引入棕榈酰基团），制备脂溶性肽段；通过尾静脉注射将修饰肽段注入心力衰竭大鼠模型体内，检测大鼠的血压、心功能指标（左心室射血分数、左心室舒张末期内径）与心肌纤维化程度；通过 Western blot 检测心肌组织中 Ang Ⅱ、AT₁受体的表达水平。 实验结果：修饰肽段可快速进入心肌细胞，竞争性抑制肾素对天然血管紧张素原的酶切作用，使心肌组织中 Ang Ⅱ 水平降低 60%；治疗 4 周后，大鼠的左心室射血分数提升 30%，左心室舒张末期内径缩小 25%，心肌纤维化程度显著减轻；且修饰肽段未引起电解质紊乱、咳嗽等副作用。 案例启示：对该肽段进行脂化修饰可显著提升其体内活性与组织靶向性，修饰肽段有望成为心力衰竭治疗的新型药物。 案例 3：该肽段抗体用于高血压患者的诊断与分型 研究背景：原发性高血压患者的 RAS 系统活性存在显著差异，需开发特异性检测方法，实现高血压的精准分型与个体化治疗。 实验方法：以该肽段为抗原制备单克隆抗体，建立 ELISA 检测方法，检测 150 例原发性高血压患者与 50 例健康人群的血浆血管紧张素原（1–14）水平；分析血浆肽段水平与患者血压、肾素活性、Ang Ⅱ 水平的相关性；根据肽段水平将患者分为高、中、低三组，分别给予阿利吉仑、依那普利、氯沙坦治疗，评价治疗效果。 实验结果：高血压患者的血浆血管紧张素原（1–14）水平显著高于健康人群（P＜0.001）；肽段水平与肾素活性、Ang Ⅱ 水平呈正相关（r=0.72、r=0.68）；高肽段水平患者对阿利吉仑的治疗反应最佳，血压下降幅度达 25mmHg，显著高于依那普利与氯沙坦组。 案例启示：基于该肽段的抗体检测方法可用于高血压的精准分型，为个体化治疗方案的制定提供参考依据。 相关产品： Val-Asp-Trp-Lys-Lys-Ile-Gly-Gln-His-Ile-Leu-Ser-Val-Leu-NH2 Arg-Arg-Trp-Cys-Tyr-Arg-Lys-Cys-Tyr-Lys-Gly-Tyr-Cys-Tyr-Arg-Lys-Cys-Arg-NH2 (Cys4,17, Cys8,13 disulfide bridges) Thr-Ser-Thr-Glu-Pro-Gln-Tyr-Gln-Pro-Gly-Glu-Asn-Leu Thr-Ser-Thr-Glu-Pro-Gln-Tyr(PO3H2)-Gln-Pro-Gly-Glu-Asn-Leu Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn Pro-Glu-Ala-His-Trp-Thr-Lys-Leu-Gln-His-Ser-Leu-Asp-Thr-Ala-Leu-Arg Val-Ser-Ser-Asn-Ile-Ser-Glu-Asp-Pro-Val-Pro-Val His-Ala-Asp-Gly-Val-Phe-Thr-Ser-Asp-Phe-Ser-Lys-Leu-Leu-Gly-Gln-Leu-Ser-Ala-Lys-Lys-Tyr-Leu-Glu-Ser-Leu-Met-Gly-Lys-Arg-Val-Ser-Ser-Asn-Ile-Ser-Glu-Asp-Pro-Val-Pro-Val Val-Pro-Val-Glu-Ala-Val-Asp-Pro-Met (Pyr)RARLSHKGPMPF -amide 所有产品仅用作实验室科学研究，不为任何个人用途提供产品和服务。