预约演示
更新于：2025-05-08
PF-4136309
更新于：2025-05-08
概要
基本信息
在研机构- |
权益机构- |
最高研发阶段终止临床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C29H31F3N6O3 |
InChIKeyZNSVOHSYDRPBGI-LXWOLXCRSA-N |
CAS号1341224-83-6 |
关联
5
项与 PF-4136309 相关的临床试验NCT02732938
PHASE 1B/2 STUDY OF PF-04136309 IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
NCT02598206
A Phase 1, Randomized, Open Label, Single Dose, 2-period Crossover Study To Evaluate Food Effect On The Pharmacokinetics Of Pf-04136309 In Healthy Subjects
NCT01413022
Phase IB Study of FOLFIRINOX Plus PF-04136309 in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma
100 项与 PF-4136309 相关的临床结果
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100 项与 PF-4136309 相关的转化医学
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100 项与 PF-4136309 相关的专利（医药）
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9
项与 PF-4136309 相关的文献（医药）2024-02-25Journal of biochemistry
Identification of effective CCR2 inhibitors for cancer therapy using humanized mice
Article
作者: Sugiyama, Shigeaki ; Yumimoto, Kanae ; Fujinuma, Shun ; Nakayama, Keiichi I
Abstract:
C-C chemokine receptor type 2 (CCR2) is the receptor for C-C motif chemokine 2 (CCL2) and is associated with various inflammatory diseases and cancer metastasis. Although many inhibitors for CCR2 have been developed, it remains unresolved which inhibitors are the most effective in the clinical setting. In the present study, we compared 10 existing human CCR2 antagonists in a calcium influx assay using human monocytic leukemia cells. Among them, MK0812 was found to be the most potent inhibitor of human CCR2. Furthermore, we generated a human CCR2B knock-in mouse model to test the efficacy of MK0812 against a lung metastasis model of breast cancer. Oral administration of MK0812 to humanized mice did indeed reduce the number of monocytic myeloid-derived suppressor cells and the rate of lung metastasis. These results suggest that MK0812 is the most promising candidate among the commercially available CCR2 inhibitors. We propose that combining these two screening methods may provide an excellent experimental method for identifying effective drugs that inhibit human CCR2.
2021-01-01Journal of Cancer3区 · 医学
GOLM1 Drives Colorectal Cancer Metastasis by Regulating Myeloid-derived Suppressor Cells
3区 · 医学
ArticleOA
作者: Yu, Jiao ; Cao, Ximing ; Jin, Long ; Zhao, Shuhong ; Dang, Yunzhi ; Wang, Qing
Colorectal cancer (CRC) is the most common digestive neoplasms worldwide, metastasis and recurrence still account for the leading cause for the high mortality rate, but the exact mechanisms remain unclear. More and more evidence has indicated that the deregulation of GOLM1 plays a crucial role in cancer progression. Here, we reported a novel role of GOLM1 in promoting CRC metastasis. In this study, the expression of GOLM1 was detected in human CRC cohort. The function of GOLM1 in CRC metastasis was analyzed by in vivo cecum orthotopic model. We found that the expression of GOLM1 was significantly increased in CRC tissues than adjacent nontumor. Overexpression GOLM1 can promote CRC immune escape and metastasis by recruiting of myeloid-derived suppressor cells (MDSCs) at the same time. PF-04136309, a small molecule and specific inhibitor of CCR2 can largely suppressed GOLM1-mediated CRC metastasis. These results suggest that GOLM1 can promote CRC metastasis and is a prognostic biomarker in human CRC.
2020-06-01Investigational new drugs
Phase 1b study of a small molecule antagonist of human chemokine (C-C motif) receptor 2 (PF-04136309) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic ductal adenocarcinoma
Article
作者: Ryan, David P ; Ganguly, Bishu ; Jacobs, Ira A ; Yin, Donghua ; Gamelin, Eric C ; Wolpin, Brian M ; O'Reilly, Eileen M ; Lowery, Maeve A ; Britten, Carolyn D ; Linehan, David C ; Taylor, Carrie T ; Belt, Brian A ; Joh, Tenshang ; Bullock, Andrea J ; Noel, Marcus
Summary:
Background In pancreatic ductal adenocarcinoma (PDAC), the chemokine (C-C motif) ligand 2 (CCL2)/chemokine (C-C motif) receptor 2 (CCR2) axis plays a key role in immunosuppressive properties of the tumor microenvironment, patient prognosis, and chemoresistance. This phase Ib study assessed the effects of the orally administered CCR2 inhibitor PF-04136309 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic PDAC. Methods Patients received PF-04136309 twice daily (BID) continuously plus nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) administered on days 1, 8, and 15 of each 28-day cycle. The primary objectives were to evaluate safety and tolerability, characterize dose-limiting toxicities (DLTs), and determine the recommended phase II dose (RP2D) of PF-04136309. Results In all, 21 patients received PF-04136309 at a starting dose of 500 mg or 750 mg BID. The RP2D was identified to be 500 mg BID. Of 17 patients treated at the 500 mg BID starting dose, three (17.6%) experienced a total of four DLTs, including grade 3 dysesthesia, diarrhea, and hypokalemia and one event of grade 4 hypoxia. Relative to the small number of patients (n = 21), a high incidence (24%) of pulmonary toxicity was observed in this study. The objective response rate for 21 patients was 23.8% (95% confidence interval: 8.2–47.2%). Levels of CD14 + CCR2+ inflammatory monocytes (IM) decreased in the peripheral blood, but did not accumulate in the bone marrow. Conclusions PF-04136309 in combination with nab-paclitaxel plus gemcitabine had a safety profile that raises concern for synergistic pulmonary toxicity and did not show an efficacy signal above nab-paclitaxel and gemcitabine. ClinicalTrials.gov identifier: NCT02732938.
2
项与 PF-4136309 相关的新闻（医药）2024-08-11
免疫疗法临床申请
2022-07-18
抗体小分子药物免疫疗法
100 项与 PF-4136309 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 转移性胰腺导管腺癌 | 临床2期 | 美国 | 2016-05-04 | |
| 慢性丙型肝炎 | 临床2期 | 中国香港 | 2011-01-17 | |
| 慢性丙型肝炎 | 临床2期 | 印度 | 2011-01-17 | |
| 慢性丙型肝炎 | 临床2期 | 新加坡 | 2011-01-17 | |
| 慢性丙型肝炎 | 临床2期 | 韩国 | 2011-01-17 | |
| 慢性丙型肝炎 | 临床2期 | 中国台湾 | 2011-01-17 | |
| 膝关节炎 | 临床2期 | 美国 | 2008-08-05 | |
| 膝关节炎 | 临床2期 | 韩国 | 2008-08-05 | |
| 局部晚期胰腺腺癌 | 临床1期 | 美国 | 2012-04-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 24 | (PF-04136309) | 顧構簾鹹壓網醖願膚齋 = 築鬱齋鹹簾蓋範蓋蓋膚 淵窪製鏇衊遞蓋製膚構 (願願鏇餘鏇獵鏇鬱餘鑰, 願繭鬱鬱膚簾膚糧簾積 ~ 鹹簾製積範淵襯範齋窪) 更多 | - | 2023-07-27 | ||
Placebo (Placebo) | 顧構簾鹹壓網醖願膚齋 = 構鹽醖糧願範衊遞淵憲 淵窪製鏇衊遞蓋製膚構 (願願鏇餘鏇獵鏇鬱餘鑰, 醖構襯壓窪鏇觸餘鑰壓 ~ 襯淵齋淵鬱獵製鹹廠壓) 更多 | ||||||
临床2期 | 159 | (PF-04136309) | 齋願艱鏇選醖壓構襯衊(製糧構顧築餘鬱製鏇淵) = 壓廠顧觸鏇窪築壓鏇獵 遞遞積憲鹹膚襯觸遞壓 (夢憲範願獵鑰艱構顧獵, 0.41) 更多 | - | 2021-07-13 | ||
Placebo (Placebo) | 齋願艱鏇選醖壓構襯衊(製糧構顧築餘鬱製鏇淵) = 積壓範觸鑰願蓋鹽蓋獵 遞遞積憲鹹膚襯觸遞壓 (夢憲範願獵鑰艱構顧獵, 0.40) 更多 | ||||||
临床1期 | 21 | 糧鹽膚選願襯獵鏇鑰蓋(願窪夢窪餘製壓蓋膚鹹) = PF-04136309 500 mg BID 蓋鹽範蓋願範繭鬱製網 (獵齋遞壓顧觸構膚膚鑰 ) 更多 | 不佳 | 2020-06-01 | |||
临床1期 | 转移性胰腺腺癌 一线 | 21 | (all pts) | 鬱範鹽衊鏇願鏇範鹹衊(衊網獵構構鬱顧憲遞鹽) = Cohort 1, starting dose level: 1 grade 3 drug-related DLT (cognitive disorder), 1 grade 2 and 2 grade 1 rashes. Cohort 2 (1 dose level reduction): 4 (23.5%) grade 3 drug-related DLT (1 scalp dysesthesia, 1 ALT-AST, 1 pneumonia, 1 pneumonitis) 鹽艱簾襯觸夢夢廠醖鑰 (鑰窪獵艱鏇觸繭構鏇遞 ) 更多 | 积极 | 2017-09-09 |
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