A PHASE 3, EXTERNAL AND SYNTHETIC PLACEBO-CONTROLLED RANDOMIZED STUDY WITH DOSE-UP FOR NON-RESPONDERS TO INVESTIGATE SAFETY AND EFFICACY OF RITLECITINIB 50 MG AND 100 MG ONCE DAILY IN ADULT AND ADOLESCENT PARTICIPANTS 12 YEARS OF AGE AND OLDER WITH ALOPECIA AREATA

The purpose of the study is to learn about the safety and effects of the study medicine (called ritlecitinib) for the treatment of alopecia areata. Alopecia areata is a disease that causes hair loss on the scalp, face, and areas of the body.
Ritlecitinib is approved in many countries at a dose of 50 mg (milligram) taken by mouth once a day for the treatment of patients 12 years and older with severe alopecia areata. This study will look at both the 50 mg dose and a 100 mg dose.
This study is seeking participants who:
* Are 12 years of age or older
* Have a diagnosis of alopecia areata
* Have lost 50% or more of the hair on their scalp
* Do not have any other conditions that causes hair loss
* Are willing to stop all other treatments that they may be taking for alopecia areata
About 550 participants will take part in in this study.
Participants will be chosen by chance, like drawing names out of a hat, to receive 1 of 2 different amounts of ritlecitinib (50 mg and 100 mg) taken by mouth once daily.
The 2 doses of ritlecitinib in this study will be compared to each other and also to data from previous studies. This will help to see if the 100 mg dose of ritlecitinib is safe and effective.
People will be in this study for about 13 months. During the study, participants will need to visit the study site up to 9 times. Participants will undergo various tests and procedures such as:
* alopecia areata assessment,
* physical examinations,
* hearing tests,
* blood tests,
* x-ray,
* ECG (electrocardiogram),
* photographs of the scalp and eyes. Participants will also be asked to complete questionnaires about their alopecia areata.

开始日期2025-03-19

申办/合作机构

Pfizer Inc.

NCT06795373

/ Recruiting临床2期IIT

A Single-center, Single-arm, Open-label Phase IIA Clinical Trial to Investigate Efficacy and Safety of Ritlecitinib (PF-06651600) in Participants With Chronic Spontaneous Urticaria

The purpose of this research study is to see if a drug called ritlecitinib is safe and effective for treating chronic spontaneous urticaria (CSU). CSU is hives and itching lasting over six weeks. Ritlecitinib is approved by the Food and Drug Administration (FDA) to treat another condition, but it is not approved for treating CSU. Participation is expected to last 20 weeks and include 7 clinic visits. This study will involve physical examinations, blood tests, looking at and taking pictures of participant's skin and hives, optional skin biopsies, and hearing tests. Eligible participants for this study will take ritlecitinib for 12 weeks and complete a daily diary about their skin and hives. The main risks of being in this study are side effects from ritlecitinib. Less than 1 in 10 people taking ritlecitinib experience diarrhea, acne, hives, rash, inflammation of hair follicles, dizziness, and increased blood levels of creatine phosphokinase (a muscle protein). Participants could also experience a rare but serious side effect, such as shingles, unusual infection, cancer, or blood clot. Benefits of participating in this study include a potential improvement in participant's condition and quality of life. Participating in this study may also help researchers develop new ways of helping future patients.

开始日期2025-02-01

申办/合作机构

Icahn School of Medicine at Mount Sinai

ChiCTR2500095989

/ Suspended临床4期IIT

Real-world study on the efficacy and safety of Ritlecitinib in Chinese patients with severe alopecia areata: A single-center, prospective, observational study

开始日期2025-02-01

申办/合作机构

中南大学湘雅医院

100 项与甲苯磺酸利特昔替尼相关的临床结果

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100 项与甲苯磺酸利特昔替尼相关的转化医学

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100 项与甲苯磺酸利特昔替尼相关的专利（医药）

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143

项与甲苯磺酸利特昔替尼相关的文献（医药）

2025-04-01·CLINICAL IMMUNOLOGY

Novel janus kinase 3 inhibitor ritlecitinib suppresses T and B cell responses to prevent acute cardiac allograft rejection in mice

Article

作者: Xu, Jian ; Hui, Jialiang ; Deng, Wenfeng ; Xia, Renfei ; Yan, Ziyan ; Wang, Yuchen ; Miao, Yun ; Zeng, Wenli ; Liu, Rumin ; Mo, Liqian ; Liao, Tao ; Shi, Xiaoyi

Acute rejection is the main contributor to early allograft failure. Current immunosuppressive regimens have shortcomings, such as toxicity and minimal inhibitory effects on B cells. Hence, developing novel, effective, and selective anti-acute rejection drugs is crucial. Therefore, this study aimed to investigate the inhibitory effect of ritlecitinib (PF-06651600), a new janus kinase 3 inhibitor, on T and B cells, as well its preventive effects on acute allograft rejection. A murine cardiac transplantation model coupled with cell culture- and immunohistochemistry-based techniques was used. In vitro assays demonstrated that ritlecitinib inhibits naïve CD4⁺ T cell differentiation into T helper (Th)1 and Th17 cells, reduces relative inflammatory cytokines, and suppresses CD4⁺ and CD8⁺ T cell proliferation. Furthermore, ritlecitinib inhibited B cell activation and differentiation and antibody production. In vivo experiments revealed that ritlecitinib significantly prolongs allograft survival, decreases serum donor-specific antibody immunoglobulin G levels, alleviats allograft damage, and reduces C4d deposition and T, B, and plasma cell infiltration in allografts. Moreover, B and plasma cell percentages and counts were significantly decreased in recipient spleen, lymph nodes, bone marrow, and blood. Overall, ritlecitinib prevented acute rejection in cardiac transplantation by inhibiting T and B cells, suggesting its potential as a novel clinical immunosuppressant.

2025-04-01·JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Response to ritlecitinib with or without narrow-band ultraviolet B add-on therapy in patients with active nonsegmental vitiligo: Results from a phase 2b extension study

Article

作者: Adiri, Roni ; Napatalung, Lynne ; Shore, Ronald N ; Guttman-Yassky, Emma ; Pandya, Amit G ; Peeva, Elena ; Ezzedine, Khaled ; Hamzavi, Iltefat ; Ghosh, Pranab ; Yamaguchi, Yuji

BACKGROUND:

Ritlecitinib demonstrated efficacy in a phase 2b trial of nonsegmental vitiligo.

OBJECTIVE:

To evaluate the efficacy and tolerability of ritlecitinib with add-on narrow-band ultraviolet B (nbUVB) phototherapy in patients with nonsegmental vitiligo.

METHODS:

Following a 24-week, placebo-controlled, dose-ranging period, patients received ritlecitinib 200 mg for 4 weeks then 50 mg for 20 weeks, with or without nbUVB phototherapy 2x/week. Missing data were handled using last observation carried forward and observed case (OC).

RESULTS:

Forty-three patients received ritlecitinib + nbUVB and 187 received ritlecitinib-monotherapy. Nine patients receiving ritlecitinib + nbUVB discontinued due to nbUVB group-specific efficacy criteria requiring >10% improvement in % change from baseline (% change from baseline) in Total-Vitiligo Area Scoring Index at week 12. At week 24, mean % change from baseline in Facial-VASI score was -57.0 vs -51.5 (last observation carried forward; P = .158) and -69.6 vs -55.1 (OC; P = .009), for ritlecitinib + nbUVB vs ritlecitinib-monotherapy, respectively. Mean % change from baseline in Total-Vitiligo Area Scoring Index at week 24 was -29.4 vs -21.2 (last observation carried forward; P = .043) and -46.8 vs -24.5 (OC; P < .001), respectively. nbUVB addition to ritlecitinib was well tolerated with no new safety signals.

LIMITATIONS:

Exploratory analysis; discontinuation criterion applied only to the ritlecitinib + nbUVB group; small sample size.

CONCLUSION:

Ritlecitinib alone and with nbUVB therapy improved facial and total body repigmentation and was well tolerated. Adding nbUVB may improve ritlecitinib efficacy.

2025-04-01·MOLECULAR DIVERSITY

Identification of novel covalent JAK3 inhibitors through consensus scoring virtual screening: integration of common feature pharmacophore and covalent docking

Article

作者: Qiu, Genhong ; Xu, Lei ; Jia, Lei ; Zhu, Jingyu ; Yu, Li ; Chen, Yun ; Jin, Jian ; Cai, Yanfei

Accumulated research strongly indicates that Janus kinase 3 (JAK3) is intricately involved in the initiation and advancement of a diverse range of human diseases, underscoring JAK3 as a promising target for therapeutic intervention. However, JAK3 shows significant homology with other JAK family isoforms, posing substantial challenges in the development of JAK3 inhibitors. To address these limitations, one strategy is to design selective covalent JAK3 inhibitors. Therefore, this study introduces a virtual screening approach that combines common feature pharmacophore modeling, covalent docking, and consensus scoring to identify novel inhibitors for JAK3. First, common feature pharmacophore models were constructed based on a selection of representative covalent JAK3 inhibitors. The optimal qualitative pharmacophore model proved highly effective in distinguishing active and inactive compounds. Second, 14 crystal structures of the JAK3-covalent inhibitor complex were chosen for the covalent docking studies. Following validation of the screening performance, 5TTU was identified as the most suitable candidate for screening potential JAK3 inhibitors due to its higher predictive accuracy. Finally, a virtual screening protocol based on consensus scoring was conducted, integrating pharmacophore mapping and covalent docking. This approach resulted in the discovery of multiple compounds with notable potential as effective JAK3 inhibitors. We hope that the developed virtual screening strategy will provide valuable guidance in the discovery of novel covalent JAK3 inhibitors.

227

项与甲苯磺酸利特昔替尼相关的新闻（医药）

2025-03-13

·研发客

自免战歌起，强生口服多肽站上C位，多家中国公司闪亮登场｜2025 AAD

// • 强生口服多肽icotrokinra展现出重塑中重度斑块状银屑病治疗标准的潜力； • 多家中国公司也展示各自在研产品治疗中重度斑块状银屑病的研究成果； • BMS尝试突破突围，寻求氘可来昔替尼更广阔的适应症； • Q32 Bio治疗斑秃的核心产品被医生看好，但投资人并不买账； • 特应性皮炎治疗领域将迎来OX40抑制剂新生力军。随着自免领域的研发热度持续升温，一众参赛选手开始亮出阶段性研究成果。在刚刚落幕的2025年美国皮肤病学会（AAD）年会上，或许能窥见这个赛道未来将诞生哪些“重磅炸弹”。银屑病可能是今年大会最受关注的治疗领域之一。其中，强生的IL-23受体（IL-23R）靶向拮抗多肽icotrokinra站上舞台C位，不仅显著疗效，对比BMS的TYK2变构抑制剂氘可来昔替尼也不落下风，展现出重塑中重度斑块状银屑病治疗标准的潜力。来自诺诚健华、益方生物和翰森制药/荃信生物等中国公司的新药也纷纷闪亮登场。氘可来昔替尼四面受敌，不过BMS没有退缩，而是转战银屑病关节炎、红斑狼疮等其他疾病领域。此外，Q32 Bio、礼来、恒瑞医药等竞相布局斑秃市场，安进/协和麒麟和赛诺菲则在特应性皮炎上争夺“first-in-class”的宝座。大获全胜作为银屑病巨头，强生在该领域的新药研发经验毋庸置疑。与此前推出的英夫利西单抗、戈利木单抗、乌司奴单抗、古塞奇尤单抗等均为注射液不同，icotrokinra（JNJ-2113）采用更为便利的口服给药方式。早在去年11月，强生就宣布icotrokinra在关键性3期研究ICONIC-LEAD中取得积极结果。此次大会公布了该研究的完整结果，显示该产品每日一次在12岁及以上中重度斑块状银屑病患者中显著的皮肤清除率与良好安全性。数据显示，第16周时，icotrokinra组65%的患者达到IGA 0/1，即皮肤症状清除或几乎清除，50%患者达到PASI 90，即银屑病面积与严重程度指数改善至少90%。在第24周时，PASI 90应答率提升至65%，74%达到IGA 0/1，近半数患者实现皮肤完全清除（46%达IGA 0，40%达PASI 100）。另外，icotrokinra还在Ⅲ期ICONIC-ADVANCE 1/2研究中，在第16周达到IGA 0/1与PASI 90的共同主要终点，并在所有关键次要终点中显著优于氘可来昔替尼。氘可来昔替尼是过去10余年来首个获批治疗中重度斑块状银屑病的口服疗法，其他创新疗法以注射用的单抗为主。现在，这种治疗格局可能很快就要被打破。据悉，强生将启动首个斑块状银屑病头对头研究ICONIC-ASCEND，以证明口服给药的icotrokinra相较于注射用生物制剂乌司奴单抗的优效性。神仙打架在BMS和强生后面奋起直追的还有多家中国公司。其中，诺诚健华与益方生物都在本次大会亮出各自开发的口服TYK2抑制剂治疗中重度斑块状银屑病的Ⅱ期研究成果。其中，诺诚健华ICP-488经12周治疗后，每天一次6mg和9mg剂量组的PASI 75应答率分别为77.3%和78.6%，PASI 90应答率分别达到36.4%和50.0%，sPGA 0/1（即皮损完全清除或基本清除）应答率分别为70.5%和71.4%。益方生物D-2570经12周治疗后，18mg、27mg、36mg剂量组的PASI 75应答率分别为90.0%、85.4%和85.0%，PASI 90应答率分别为75.0%、70.7%和77.5%，PASI 100应答率分别为40.0%、39.0%和50.0%，sPGA 0/1应答率分别为82.5%、80.5%和87.5%。单从数值来看，ICP-488的PASI 90应答率在第12周时与icotrokinra第16周时旗鼓相当，而D-2570则更胜一筹。益方生物在新闻稿中表示，D-2570的疗效数据优于已上市的同类TYK2抑制剂，并且在效果上可与IL-17A、IL-23等抗体生物药相媲美。在注射疗法方面，翰森制药与荃信生物合作开发的长效疗法HS-20137也值得关注。这是一款靶向IL-23的人源化IgG1单抗，翰森制药于2024年4月获得其独家权益。 Ⅱ期临床数据显示，HS-20137在中重度斑块状银屑病患者中起效迅速，200mg每八周给药一次剂量组治疗16周后PASI 75、PASI 90应答率分别为92.3%和76.9%，该比例在第20、24和28周时分别达到84.6%、89.7%和87.2%。试验还设置了200mg每十二周给药一次剂量组，16周时PASI 100高达40%。 BMS的守与攻眼下，全球银屑病市场获批疗法众多，针对TNF-α、IL-12/23、IL-23、IL-17A、IL-36等靶点的新药层出不穷，生物类似药来势汹汹，新一代的口服、长效疗法也试图杀出重围。在这种背景下，氘可来昔替尼的处境可谓前有狼后有虎。不过BMS并未坐以待毙，而是在更广阔的适应症中找寻出路。本次大会上，BMS首度公布了氘可来昔替尼治疗活动性银屑病关节炎（PsA）成人患者的Ⅲ期POETYK PsA-2（IM011-055）试验结果，证实了其在改善关节及皮肤症状、提升患者报告生活质量方面的潜力。数据显示，治疗组在16周后ACR20（疾病体征和症状至少改善20%）应答比例达到54.2%，显著高于安慰剂组的39.4%。此外，研究还达到了多个关键次要终点，并展现良好的耐受性和安全性特征。除了POETYK PsA-2，氘可来昔替尼另一项针对PsA的Ⅲ期研究POETYK PsA-1也在去年12月达到了主要终点和关键次要终点。这些研究结果均表明，口服氘可来昔替尼有可能成为PsA患者的首个TYK2抑制剂。此外，该药还在开展治疗红斑狼疮的全球Ⅱ期PAISLEY CLE研究，同样可能帮助这款口服TYK2抑制剂摆脱“银屑病专药”的标签。下一位斑秃克星作为仅次于雄激素性脱发的第二大脱发类疾病，斑秃市场潜力巨大。随着礼来的巴瑞替尼、辉瑞的利特昔替尼和太阳制药的deuruxolitinib等JAK抑制剂相继获批，这个领域的参与者也在加紧步伐。比如Q32 Bio。在今年2月经历大幅裁员、重组并砍掉肾脏管线后，这家Biotech正全力推进其核心资产bempikibart用于中重度斑秃的Ⅱ期研究。bempikibart是一款IL-7/TSLP双功能受体拮抗剂，通过阻断IL-7和TSLP信号重新调节适应性免疫功能。在本次AAD大会上，Q32 Bio公布了2a期斑秃试验SIGNAL-AA的结果，bempikibart用于重度及极重度斑秃患者，第24周SALT评分（头皮脱发）显著改善，且停药后疗效持续。尽管只有24周的给药，多名患者在36周的随访期间获得持续的反应，甚至超过55周。目前，bempikibart的开发计划进展顺利，开放标签扩展研究将于2025年上半年启动，SIGNAL-AA Part B研究预计于2025年上半年开始给药，关键数据2026年上半年公布。康涅狄格州皮肤病医生Brett King博士评论道：“重症患者在治疗24周后甚至停药数周仍显示疗效，这一现象非常引人注目。若bempikibart的活性（包括诱导长期缓解的潜力）及安全性在后续试验中得以验证，它有望改变斑秃的治疗范式。” 不过这一数据并未说服投资人，消息公布后，Q32 Bio股价已连续两日下跌7%以上。部分分析师认为bempikibart在斑秃中的疗效可能不及现有疗法。礼来的JAK1/2抑制剂巴瑞替尼则瞄准了12岁至18岁的严重斑秃青少年这一群体。大约40%的斑秃患者在20岁前首次发病。在AAD上公布的3期BRAVE-AA-PEDS研究结果显示，在第36周接受每日一次口服巴瑞替尼 4mg和2mg治疗后，患者头皮、眉毛和睫毛的头发再生得到了临床意义上的改善。42.4%的患者接受巴瑞替尼4mg治疗后，第36周头皮头发覆盖率达到80%以上。如果巴瑞替尼在这一年轻群体中获批，将直接对垒辉瑞的JAK3/TEC抑制剂利特昔替尼，这是全球首款获批同时用于治疗12岁及以上青少年及成人重度斑秃患者的创新药物。此外，恒瑞医药也携其JAK1抑制剂硫酸艾玛昔替尼片的Ⅲ期成果加入斑秃战场。数据显示，该药在第8周即可改善成人重度斑秃患者症状，4mg和8mg剂量组24周时分别有34.9%和40.6%的患者达到SALT评分≤20，显著优于安慰剂组。在治疗核心期和延长期间，达到SALT评分≤20的患者比例持续增加。 OX40抑制剂在AD中的突破目前，全球范围内尚未有OX40抑制剂获批上市，而安进/协和麒麟的rocatinlimab及赛诺菲的amlitelimab，是自免领域临床进度较快的两个选手。在本次AAD大会上公布的Ⅲ期IGNITE试验的最新数据显示，rocatinlimab有望争夺特应性皮炎（AD）领域“first-in-class”的宝座。在为期24周的研究中，rocatinlimab达到了共同主要终点和所有关键次要终点，两种剂量均显示具有统计学意义的疾病活动性降低。高剂量组中42.3%的患者湿疹面积和严重程度指数评分较基线降低≥75%（EASI 75），低剂量组中36.3%的患者达到EASI 75。这支持了rocatinlimab作为特应性皮炎一种新治疗选择的潜力。安进计划在ASCEND试验中进一步探索该药超过24周的效果，并在ASTRO和ORBIT试验中评估其在青少年患者中的作用。尽管取得了积极的成果，专家和分析人士预计，rocantinlimab的应用将被降至二线治疗领域，而且它可能必须面对来自赛诺菲OX40L单抗amlitelimab的竞争。后者也在本次大会上海报展示了针对中重度AD患者的STREAM-AD与RIVER-AD研究结果。 RIVER-AD是一项单臂长期扩展Ⅱ期研究。此次大会首次公布了该研究的中期分析结果，主要针对Ⅱb期STREAM-AD试验中第24周未达到EASI-75或IGA 0/1应答的患者，统一予以amlitelimab 250mg Q4W，并于治疗28周评估有效性和安全性。结果显示，试验组和安慰剂组患者进入这项扩展研究时的EASI评分与STREAM-AD研究基线时的EASI评分相比，平均降低了35.8%和18.3%；治疗第28周，EASI评分分别较基线下降了83.4%和85.2%；同时，治疗28周时的EASI-75、EASI-90、IGA 0/1应答率与STREAM-AD研究第24周的应答率相当。这一数据展现了amlitelimab在特应性皮炎中的潜力。它提供了一种独特的作用机制，可以帮助使过度活跃的免疫系统正常化，并在不消耗T细胞的情况下恢复免疫平衡。编辑 | 姚嘉 yao.jia@PharmaDJ.com 总第2360期访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

临床3期申请上市临床成功

2025-03-09

·Firstwordpharma

AAD25: Lilly, Incyte's Olumiant gains ground in severe adolescent alopecia with late-stage success

Eli Lilly and Incyte’s once-daily oral JAK1/2 inhibitor Olumiant (baricitinib) demonstrated notable improvements in hair regrowth on the scalp, eyebrows and eyelashes in a Phase III study of adolescents with severe alopecia areata (AA), moving the drug a step closer to taking on Pfizer’s JAK3/TEC kinase inhibitor Litfulo (ritlecitinib) — the first alopecia medication approved for the younger age group in the US and EU. The findings were presented over the weekend at the American Academy of Dermatology (AAD) annual meeting.Backed by the BRAVE-AA1 and BRAVE-AA2 trials, Olumiant secured FDA authorisation in 2022 for adults with severe AA, making it the first systemic treatment approved in the US for the condition.The BRAVE-AA-PEDS study randomised 257 participants aged 12 to under 18 to receive daily baricitinib 2 mg, 4 mg or placebo — the primary efficacy goal being Severity of Alopecia Tool (SALT) score ≤20 at 36 weeks. Results showed that at this timepoint, 42.4% of patients receiving the 4-mg dose achieved the main goal, compared with 4.5% in the placebo group. Moreover, Olumiant 4 mg led to at least a 50% disease improvement in 60% of patients, while the 2 mg dose achieved the same in 36.9%, and placebo in 5.7%.Specifically, Olumiant 4 mg achieved 90% scalp hair coverage in 36.5% of patients, significant eyebrow regrowth in 50.0%, and eyelash regrowth in 42.9%, while the 2 mg dose showed 21.4%, 24.1%, and 25.5% improvement, respectively. In contrast, placebo results were 2.3% for scalp, 0% for eyebrows and 14.0% for eyelashes. Notably, outcomes in adolescents achieved at 36 weeks were comparable to those seen in adult studies at 52 weeks, suggesting faster hair regrowth in the former. Meanwhile, the safety profile in adolescents was consistent with previous Olumiant trials in juvenile idiopathic arthritis and atopic dermatitis. "With these data, baricitinib is the most well-studied JAK inhibitor in severe alopecia areata," remarked Anabela Cardoso, senior vice president of immunology medical affairs at Lilly. The drugmaker plans to present additional data from BRAVE-AA-PEDS later this year, whilst also discussing the findings with global regulators.Following the footsteps of Olumiant and Litfulo, Sun Pharmaceutical’s oral JAK1/2 inhibitor Leqselvi (deuruxolitinib) entered the severe AA market last year, albeit only approved for adults. Also at AAD this year, Q32 Bio unveiled upbeat mid-stage data for its IL-7/TSLP bifunctional receptor antagonist, bempikibart, in severe to very severe disease. For more on the severe AA space, read: Spotlight On: AAD25 – Lilly's data puts Pfizer on notice while Q32 Bio plays long game in alopecia areata.

临床结果上市批准临床3期

2025-01-26

·化学经纬

新药研发新趋势：融合氮杂环的使用

药物研发新趋势：融合氮杂环的兴起在现代药物研发的舞台上，融合氮杂环化合物正逐渐成为一颗耀眼的新星。随着科学技术的不断进步，药物的结构和性质也在快速演变。最近美国亚利桑那大学的一项研究对2013年至2023年间美国FDA批准的小分子药物进行了深入分析，揭示了融合氮杂环化合物在新药研发中的重要性。本文将为您系统总结这项研究的主要内容，带您走进药物化学的新视野。研究背景 2013年至2023年间，FDA批准了321种新小分子药物，其中82%含有至少一个氮杂环，这一比例相较于过去几十年的59%有了惊人的增长。此外，每种药物的氮杂环数目也显著增加，大量药物含有两个(33%)、三个(23%)或四个(8%)氮杂环，并且有两个药物含六个氮杂环的结构。 From:J. Med. Chem. 2024, 67, 11622–11655 下图是美国FDA批准的独特新小分子药物集中出现的前35个氮杂环，排名前五位的是吡啶，哌啶，吡咯烷，哌嗪和嘧啶。与从FDA成立到2012年12月的前25种氮杂环化合物进行比较，揭示了一些显著变化。在前五种最常见的氮杂环化合物中，吡啶已经取代了哌啶，成为第一位，后者降至第二位；吡咯烷已经从第五位跃升至与哌啶并列的第二位；哌嗪从第三位降至第四位；而嘧啶则是一个新面孔，跻身第五位，较之前的第十位大幅上升。 From:J. Med. Chem. 2024, 67, 11622–11655 融合氮杂环对2013年到2023年间美国FDA批准的小分子药物中的氮杂环结构分析表明，一个关键的新的显著增长趋势是使用不同类型的融合氮杂环，其中大多数在早期的研究中是不存在的，这一趋势主要受到新批准的抗癌药物的推动。融合氮杂环的优势融合氮杂环化合物因其在药物中的多功能性和结构多样性而备受青睐。这些化合物不仅增强了药物的效力和选择性，还提高了药物的生物利用度和稳定性。在新批准的药物中，融合氮杂环的出现频率和多样性都有显著提升，尤其是在抗癌领域。融合氮杂环的应用实例在这项研究中，多个新药的成功案例展示了融合氮杂环化合物的巨大潜力。以下是融合氮杂环在最近十年FDA批准药物中的具体应用： 01 吡咯并嘧啶共有六种新的吡咯并嘧啶类药物获得批准，所有这些药物都是激酶抑制剂，其中三种用于治疗癌症。Abrocitinib（2022年1月批准）和Baricitinib（2018年5月批准）分别包含张力性环丁烷和氮杂环丁烷环作为其结构的一部分，其中Abrocitinib用于治疗湿疹，Baricitinib用于治疗类风湿性关节炎。Ritlecitinib（2023年6月批准），其结构中含有活性丙烯酰胺取代基和4-取代的吡咯并嘧啶，与Abrocitinib和Baricitinib类似，用于治疗斑秃（脱发）。 From:J. Med. Chem. 2024, 67, 11622–11655 02 吡唑并嘧啶五种新的含有吡唑并嘧啶的药物已经获得批准，它们都是用于治疗癌症的激酶抑制剂。值得注意的是，这些吡唑并嘧啶中有三种是吡唑并[3,4-d]嘧啶，另外两种是异构体吡唑并[1,5-a]嘧啶。其中Larotrectinib是用于治疗实体肿瘤的一种首创新药，它具有两个手性吡咯烷取代基，而快速批准用于治疗非小细胞肺癌药物Repotrectinib最引人注目的地方是其吡唑并嘧啶结构被包含在一个手性大环酰胺中。 From:J. Med. Chem. 2024, 67, 11622–11655 03 吡咯并吡啶吡咯并吡啶是另一种新兴的融合氮杂环类化合物，已有五种新的成员获得批准，其中四种属于吡咯并[2,3-b]吡啶，还有一种是HIV/AIDS药物Fostemsavir（2020年7月批准），属于吡咯并[2,3-c]吡啶类。该类别的两种药物，即抗癌药物Venetoclax（2016年4月批准），用于治疗慢性淋巴细胞白血病（CLL）、小淋巴细胞淋巴瘤（SLL）和急性髓性白血病（AML））以及肽类药物Zilucoplan（2023年10月批准），用于治疗重症肌无力。最后，激酶抑制剂Pexidartinib（2019年8月批准）和Pemigatinib（2020年4月批准）分别用于治疗腱鞘巨细胞肿瘤（TGCT）和胆管癌。 From:J. Med. Chem. 2024, 67, 11622–11655 04 吲唑吲唑是另一种新兴的融合氮杂环，有五个成员被批准，包括Belumosudil，Lenacapavir，Zavegepant，Entrectinib和Niraparib。Entrectinib (2019年8月批准)是一种含吡唑的酪氨酸激酶抑制剂，用于治疗非小细胞肺癌，而Niraparib(2017年3月批准)以聚(ADP-核糖)聚合酶(PARP)为靶点，并被用于治疗卵巢癌。 From:J. Med. Chem. 2024, 67, 11622–11655 05 吡唑并吡啶在此期间，已有三种含吡唑并吡啶的药物获得批准，包括Riociguat和它的去甲基含氟衍生物Vericiguat。Selpercatinib(2020年5月批准)是一种新的富含氮杂环的激酶抑制剂，用于治疗RET基因突变的癌症患者。 From:J. Med. Chem. 2024, 67, 11622–11655 未来展望随着新药的不断涌现，我们可以预见，融合氮杂环化合物将在未来的药物治疗中扮演更加重要的角色。这些复杂的化学结构不仅为患者带来了新的希望，也为药物化学家提供了新的挑战和机遇。随着对融合氮杂环的深入研究，我们有望开发出更有效、更安全的药物，以应对各种复杂的疾病挑战。乐研密切跟踪新药研发的最近进展，目前已开发出众多结构新颖的融合氮杂环分子砌块，部分产品展示如下：参考文献 Marshall, C. M.; et al. An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023). J. Med. Chem. 2024, 67, 11622–11655

加速审批医药出海

100 项与甲苯磺酸利特昔替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14924

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
斑秃	美国	Pfizer Inc.	2023-06-23

未上市

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适应症	最高研发状态	国家/地区	公司	日期
非节段型白癜风	临床3期	美国	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	中国	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	日本	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	澳大利亚	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	保加利亚	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	加拿大	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	德国	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	印度	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	意大利	Pfizer Inc.	2022-12-01
非节段型白癜风	临床3期	墨西哥	Pfizer Inc.	2022-12-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04006457 (ALLEGRO-LT, Pubmed \| J Eur Acad Dermatol Venereol)	临床3期	斑秃	449	Ritlecitinib 200mg loading dose followed by 50mg daily	餘醖鑰餘鬱鏇窪繭醖選(壓鹹壓築餘醖餘網繭製) = occurred in six patients 蓋製淵鏇壓窪鏇糧糧憲 (廠鑰襯壓蓋壓衊憲鹹淵 ) 更多	积极	2025-01-23
NCT03395184 (CTgov)	临床2期	克罗恩病	244	Placebo (Induction Period: Placebo QD)	憲鹹壓齋鬱鏇製願憲憲 = 獵鹹鬱鏇築鑰範簾鏇醖廠餘窪齋憲鏇襯範鑰廠 (積獵簾鬱蓋醖鑰網遞遞, 襯鏇淵鹹選鏇鏇衊醖襯 ~ 網鏇願蓋淵糧鬱膚艱繭) 更多	-	2024-10-30
				Ritlecitinib (Induction Period: Ritlecitinib 200 mg/50 mg QD)	憲鹹壓齋鬱鏇製願憲憲 = 衊遞鹹願鬱範鹽鏇壓鏇廠餘窪齋憲鏇襯範鑰廠 (積獵簾鬱蓋醖鑰網遞遞, 醖顧範繭選製艱醖糧構 ~ 製顧艱顧築鬱廠夢糧餘) 更多
NCT03732807 (ALLEGRO, Pubmed \| Am J Clin Dermatol)	临床2/3期	斑秃	718	Ritlecitinib 50 mg	齋觸鏇壓獵獵顧壓遞選(齋膚夢餘範鏇願廠餘鬱) = 艱窪觸獵膚獵遞築鬱醖鹹艱糧製顧鹹簾衊獵積 (壓衊積鏇夢選顧簾積憲 )	积极	2024-10-23
				Ritlecitinib 30 mg	齋觸鏇壓獵獵顧壓遞選(齋膚夢餘範鏇願廠餘鬱) = 膚願鏇窪鑰鬱醖構鏇膚鹹艱糧製顧鹹簾衊獵積 (壓衊積鏇夢選顧簾積憲 )
NCT03732807 \| NCT04006457 (ALLEGRO-2b/3 \| ALLEGRO Phase 2b/3 \| ALLEGRO phase 2b/3 study \| ALLEGRO, Pubmed \| Br J Dermatol) 人工标引	临床2/3期	斑秃	385	Ritlecitinib 50 mg	顧構窪顧壓顧遞膚憲範(鹹築願遞醖鑰獵築簾觸) = 餘獵簾獵觸艱遞壓壓鹹醖積選鬱簾鹽艱鹹蓋蓋 (醖鹹糧繭製築鏇蓋醖憲 ) 更多	积极	2024-10-21
				Ritlecitinib 200/50 mg	顧構窪顧壓顧遞膚憲範(鹹築願遞醖鑰獵築簾觸) = 製衊膚鑰壓鑰觸積夢積醖積選鬱簾鹽艱鹹蓋蓋 (醖鹹糧繭製築鏇蓋醖憲 ) 更多
NCT05650333 (CTgov)	临床1期	斑秃	15	Ritlecitinib 20 mg	顧鑰鏇糧製顧壓夢醖膚(夢糧鏇願廠憲鹽糧範糧) = 襯繭窪鹹糧鏇簾獵簾糧衊壓齋糧餘鹽窪網範鏇 (獵繭積鬱壓積觸鹹遞醖, 30) 更多	-	2024-10-08
NCT03732807 (ALLEGRO phase 2b/3, Pubmed \| Dermatol Ther (Heidelb))	临床2/3期	斑秃	522	Ritlecitinib 30 mg	夢鬱襯範廠願範夢鏇餘(製衊襯鑰觸襯壓選齋鏇): OR = 2.12 (95% CI, 1.23 ~ 3.65), P-Value = < 0.05	积极	2024-09-10
				Ritlecitinib 50 mg
NCT05128058 (CTgov)	临床1期	-	16	RITLECITINIB (RITLECITINIB 50 MG CAPSULE)	蓋膚觸繭淵鹽網夢獵壓(築製繭遞鏇廠構窪築鏇) = 鑰夢範壓獵襯鹹憲顧鹽蓋鬱糧鏇積艱衊衊遞襯 (遞製憲鹽製範窪鬱願遞, 鹹獵壓製鬱選廠鏇糧壓 ~ 範齋壓齋蓋網窪廠膚繭) 更多	-	2023-11-13
				RITLECITINIB (RITLECITINIB 200 MG CAPSULE)	蓋膚觸繭淵鹽網夢獵壓(築製繭遞鏇廠構窪築鏇) = 齋窪網壓鑰範願餘窪範蓋鬱糧鏇積艱衊衊遞襯 (遞製憲鹽製範窪鬱願遞, 窪鏇願築鏇窪憲夢繭鏇 ~ 夢製壓衊淵襯製窪齋膚) 更多
NCT04006457 (ALLEGRO-LT, EADV2023)	临床3期	斑秃	447	Ritlecitinib 200 mg	衊築網衊齋鏇糧觸積構(糧餘觸網襯壓觸繭膚築) = 鑰選獵膚顧遞衊繭鬱製醖鹽簾鏇願齋鹹夢鹹簾 (鬱齋鏇憲築鑰鹹鬱範艱 ) 更多	-	2023-10-11
				Ritlecitinib 50 mg	衊築網衊齋鏇糧觸積構(糧餘觸網襯壓觸繭膚築) = 廠襯壓構繭壓積簾襯遞醖鹽簾鏇願齋鹹夢鹹簾 (鬱齋鏇憲築鑰鹹鬱範艱 ) 更多
NCT03732807 (ALLEGRO phase 2b/3, EADV2023)	临床2/3期	斑秃	191	Ritlecitinib 50mg QD	夢膚築壓製獵顧廠蓋壓(艱膚窪醖鏇積築繭網獵) = 積醖顧願糧蓋積網鬱繭齋願憲繭製製襯醖鬱糧 (窪遞願鏇壓網鬱範鬱選 ) 更多	-	2023-10-11
NCT05040295 (CTgov)	临床1期	-	12	Ritlecitinib (Treatment A: Ritlecitinib 30 mg Intact Adult Capsule)	簾選窪繭鹽鑰醖構積糧(鑰鬱築繭鬱獵繭壓壓糧) = 範鹹鑰顧網鹹糧觸製選憲淵築鏇鹹遞醖壓衊淵 (網範醖膚淵淵構顧築積, 39) 更多	-	2023-08-21
				Ritlecitinib (Treatment B: Ritlecitinib 3*10 mg Pediatric Capsules)	簾選窪繭鹽鑰醖構積糧(鑰鬱築繭鬱獵繭壓壓糧) = 鹽廠鹽獵蓋築鹹餘膚襯憲淵築鏇鹹遞醖壓衊淵 (網範醖膚淵淵構顧築積, 40) 更多