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更新于：2025-06-21
PLX-51107
更新于：2025-06-21
概要
基本信息
原研机构 |
在研机构- |
非在研机构 |
权益机构- |
最高研发阶段终止临床1/2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C26H22N4O3 |
InChIKeyAMSUHYUVOVCWTP-INIZCTEOSA-N |
CAS号1627929-55-8 |
关联
3
项与 PLX-51107 相关的临床试验NCT04910152
A Single Arm, Open Label, Phase 1b/2 Study of Novel BET Inhibitor PLX51107 for Steroid-Refractory Acute GVHD
NCT04022785
A Phase I Study of PLX51107 (A Novel Bromodomain Inhibitor) in Combination With Azacytidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia (AML)
NCT02683395
A Phase 1b/2a, Two-Part, Dose Escalation and Expansion Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX51107 in Subjects With Advanced Hematological Malignancies and Solid Tumors
100 项与 PLX-51107 相关的临床结果
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100 项与 PLX-51107 相关的转化医学
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100 项与 PLX-51107 相关的专利（医药）
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27
项与 PLX-51107 相关的文献（医药）2024-12-05LEUKEMIA & LYMPHOMA
Targeted BET inhibition with OPN-51107 synergizes with venetoclax in chronic lymphocytic leukemia
Article
作者: Skupa, Sydney A. ; Eiken, Alexandria P. ; Mavis, Cory ; El-Gamal, Dalia ; Ghione, Paola ; Gu, Juan (Jenny) ; Torka, Pallawi ; Sundaram, Suchitra ; Hernandez-Ilizaliturri, Francisco J. ; Zablonski, Kevin G.
Chronic lymphocytic leukemia (CLL) remains incurable and its ability to acquire resistance to front-line therapeutics has proved challenging. Bromodomain and extra-terminal proteins, particularly bromodomain-containing protein 4 (BRD4), are integral to gene expression in CLL and offer a promising therapeutic target. In this study, we examined the activity of the BRD4 inhibitor OPN-51107 alone and in combination with the BCL-2 inhibitor, venetoclax, in CLL cell lines and patient-derived CLL samples. We demonstrate that OPN-51107 induces anti-tumor activity in both CLL cell lines and patient-derived samples, including relapsed/refractory (R/R) samples and those with high-risk features (i.e. ATM and/or TP53 deletions). Importantly, the combination of OPN-51107 and venetoclax exhibited synergistic cytotoxicity in ibrutinib-resistant CLL cells and patient-derived CLL samples regardless of R/R or deletion status. This study establishes the preclinical efficacy of using OPN-51107 and venetoclax in combination in therapy-resistant and/or high-risk CLL, lending support for its further development as a combination therapy.
2024-10-01BIOORGANIC & MEDICINAL CHEMISTRY
Novel inhibitors of bromodomain and extra-terminal domain trigger cell death in breast cancer cell lines
Article
作者: Karttunen, Vilma ; Lahtela-Kakkonen, Maija ; Adla, Santosh Kumar ; Rahnasto-Rilla, Minna ; Puumalainen, Tatu
Small molecule inhibitors targeting the bromodomain and extra-terminal domain (BET) family proteins have emerged as a promising class of anti-cancer drugs. Nevertheless, the clinical advancement of these agents has been significantly hampered by challenges related to their potency, oral bioavailability, or toxicity. In this study, virtual screening approaches were employed to discover novel inhibitors of the bromodomain-containing protein 4 (BRD4) by analyzing their comparable chemical structural features to established BRD4 inhibitors. Several of these compounds exhibited inhibitory effects on BRD4 activity ranging from 60 % to 70 % at 100 µM concentrations, while one compound also exhibited an 84 % inhibition of Sirtuin 2 (SIRT2) activity. Furthermore, a subset of structurally diverse compounds from the BRD4 inhibitors was selected to investigate their anti-cancer properties in both 2D and 3D cell cultures. These compounds exhibited varying effects on cell numbers depending on the specific cell line, and some of them induced cell cycle arrest in the G0/G1 phase in breast cancer (MDA-MB-231) cells. Moreover, all the compounds studied reduced the sizes of spheroids, and the most potent compound exhibited a 90 % decrease in growth at a concentration of 10 µM in T47D cells. These compounds hold potential as epigenetic regulators for future studies.
2023-11-01Clinical cancer research : an official journal of the American Association for Cancer Research
Phase I Results of Bromodomain and Extra-Terminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies
Article
作者: Borthakur, Gautam ; Burger, Jan ; Daver, Naval ; Sasaki, Koji ; Bhalla, Kapil N ; Jain, Nitin ; Pierce, Sherry ; DiNardo, Courtney D ; Short, Nicholas J ; Kadia, Tapan ; Fiskus, Warren C ; Khoury, Joseph D ; Qiao, Wei ; Ravandi, Farhad ; Masarova, Lucia ; Issa, Ghayas C ; Senapati, Jayastu ; Miller, Darla ; Pemmaraju, Naveen ; Konopleva, Marina ; Jabbour, Elias ; Garcia-Manero, Guillermo ; Wilson, Nathaniel R ; Alvarado, Yesid
Abstract:
Purpose::
Treatment outcomes in patients with relapsed/refractory (R/R) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remains dismal. On the basis of both extensive preclinical data and emerging clinical data, treatment with bromodomain and extra-terminal domain inhibitors (BETi) is a potential approach for patients with high-risk myeloid malignancies.
Patients and Methods::
We conducted a phase I trial to study the safety and efficacy of PLX51107 (BETi) and azacitidine combination therapy in patients with R/R AML and high-risk (HR) MDS and studied mechanisms of resistance to the combination therapy.
Results::
Thirty-seven patients with HR R/R MDS (n = 4) and R/R AML (n = 33) were treated. Sixteen patients (43%) had MECOM gene rearrangement and 7 other patients had TP53 mutation. Median prior number of therapies was three (range 1–9); 97% had received prior hypomethylating agent and 84% prior venetoclax. Overall response rate was 8/37 (22%): complete remission with incomplete platelet recovery (n = 1); morphologic leukemia-free state (n = 2); hematologic improvement (n = 5). The most common nonhematologic toxicities were febrile neutropenia and pneumonia in 12 (32%) patients each; 6 patients (17%) had severe hyperbilirubinemia. RNA-sequencing analysis of mononuclear cells harvested on treatment (day 3) versus pretreatment showed significant changes in mRNA expressions in responders: downregulation of MYC, BCL2, IL7R, and CDK6 and upregulation of HEXIM1, CD93, DCXR, and CDKN1A. Immunoblot analyses confirmed reduction in protein levels of c-Myc, CDK6, BCL2, and BCL-xL, and induction of BRD4 and HEXIM1 protein levels in responders.
Conclusions::
In a heavily pretreated patient cohort with R/R MDS and AML, PLX51107+ azacitidine was well-tolerated and resulted in modest clinical benefit.
1
项与 PLX-51107 相关的新闻（医药）2025-03-25
·精准药物
申请上市临床结果临床2期
100 项与 PLX-51107 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 急性移植物抗宿主病 | 临床2期 | 美国 | 2022-04-19 | |
| 类固醇难治性移植物抗宿主病 | 临床2期 | 美国 | 2022-04-19 | |
| 急性髓性白血病 | 临床1期 | 美国 | 2016-03-01 | |
| 晚期恶性实体瘤 | 临床1期 | 美国 | 2016-03-01 | |
| 骨髓增生异常综合征 | 临床1期 | 美国 | 2016-03-01 | |
| 非霍奇金淋巴瘤 | 临床1期 | 美国 | 2016-03-01 |
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临床结果
临床结果
适应症
分期
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临床1/2期 | 2 | 觸夢醖鬱構積齋簾製廠 = 積築糧齋窪觸獵獵願憲 簾憲夢繭夢簾醖鹹選餘 (顧築範憲窪醖蓋淵構廠, 窪廠鹹憲構鹹膚製鑰壓 ~ 觸衊顧壓窪餘鏇窪願蓋) 更多 | - | 2025-01-28 | |||
临床1期 | 37 | 鹹憲鑰鬱網蓋鬱構繭觸(觸夢齋窪製糧願築願築) = non-hema ~ logic ~ xicities: 9 (24%) pts had elevated bilirubin/liver function tests (n=2 Grade 4 and n=7 Grade 3) and n=24 had infections. 鬱廠繭選鹽壓廠獵選觸 (淵艱鹹壓餘選繭襯餘蓋 ) 更多 | 积极 | 2021-11-05 | |||
临床1/2期 | 36 | 製艱膚鹽範壓淵鑰範壓(範廠鬱蓋衊糧鹽膚齋顧) = 17% 鑰憲膚廠糧齋膚衊選窪 (蓋襯鹽壓範鏇淵艱願蓋 ) 更多 | - | 2018-06-01 |
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