Pemigatinib
(Synonyms: 培米加替尼,INCB054828) 目录号 : GC32915
An FGFR inhibitor
Cas No.:1513857-77-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pemigatinib is an inhibitor of FGFR (IC50s = 0.4, 0.5, and 1 nM for FGFR1, FGFR2, and FGFR3, respectively).1 It is selective for FGFR1, FGFR2, and FGFR3 over FGFR4 and the kinase insert domain receptor (KDR; IC50s = 30 and 70 nM, respectively), as well as over a panel of 56 tyrosine and serine/threonine kinases at 10 ?M. Pemigatinib reduces phosphorylation of FGFR, ERK1/2, and STAT5 in KG-1a acute myeloid leukemia cells in a concentration-dependent manner. It inhibits growth in a panel of cancer cell lines expressing constitutively active FGFR, including lung, bladder, and gastric cancer cells, with GI50 values ranging from 3 to 362 nM. Pemigatinib (0.3 mg/kg per day) reduces tumor growth in KATO III, KG-1, and RT-112 mouse xenograft models.
1.Liu, P.C.C., Koblish, H., Wu, L., et al.INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor modelsPLoS One15(4)e0231877(2020)
| Cas No. | 1513857-77-6 | SDF | |
| 别名 | 培米加替尼,INCB054828 | ||
| Canonical SMILES | CCN(C(N(C(C(F)=C(OC)C=C1OC)=C1F)C2)=O)C(C2=CN3)=C4C3=NC(CN5CCOCC5)=C4 | ||
| 分子式 | C24H27F2N5O4 | 分子量 | 487.5 |
| 溶解度 | DMSO : 41.67 mg/mL (85.48 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0513 mL | 10.2564 mL | 20.5128 mL |
| 5 mM | 0.4103 mL | 2.0513 mL | 4.1026 mL |
| 10 mM | 0.2051 mL | 1.0256 mL | 2.0513 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pemigatinib: First Approval
Drugs 2020 Jun;80(9):923-929.PMID:32472305DOI:10.1007/s40265-020-01330-y.
Pemigatinib (PEMAZYRE™), a small molecule inhibitor of fibroblast growth factor receptor (FGFR) 1, FGFR2 and FGFR3, received accelerated approval in April 2020 in the USA for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or other rearrangement, as detected by a US FDA-approved test. Developed by Incyte Corporation, it is the first targeted treatment for cholangiocarcinoma in the USA. The recommended dosage of Pemigatinib is 13.5 mg once daily, administered orally with or without food, on days 1-14 of a 21-day cycle until disease progression or unacceptable toxicity. Pemigatinib received orphan designation for the treatment of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2 in August 2019 in the USA. A regulatory assessment for Pemigatinib as a treatment for adults with locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or rearrangement that is relapsed or refractory after ≥ 1 line of systemic therapy is underway in the EU. Pemigatinib is also undergoing clinical development in various countries worldwide for use in several other FGFR-driven malignancies (e.g. solid tumour, urothelial carcinoma). This article summarizes the milestones in the development of Pemigatinib leading to this first approval for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or other rearrangement, as detected by a US FDA-approved test.
Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study
Lancet Oncol 2020 May;21(5):671-684.PMID:32203698DOI:10.1016/S1470-2045(20)30109-1.
Background: Fibroblast growth factor receptor (FGFR) 2 gene alterations are involved in the pathogenesis of cholangiocarcinoma. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. This study evaluated the safety and antitumour activity of Pemigatinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements. Methods: In this multicentre, open-label, single-arm, multicohort, phase 2 study (FIGHT-202), patients aged 18 years or older with disease progression following at least one previous treatment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 recruited from 146 academic or community-based sites in the USA, Europe, the Middle East, and Asia were assigned to one of three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF/FGFR alterations, or patients with no FGF/FGFR alterations. All enrolled patients received a starting dose of 13·5 mg oral Pemigatinib once daily (21-day cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary endpoint was the proportion of patients who achieved an objective response among those with FGFR2 fusions or rearrangements, assessed centrally in all patients who received at least one dose of Pemigatinib. This study is registered with ClinicalTrials.gov, NCT02924376, and enrolment is completed. Findings: Between Jan 17, 2017, and March 22, 2019, 146 patients were enrolled: 107 with FGFR2 fusions or rearrangements, 20 with other FGF/FGFR alterations, 18 with no FGF/FGFR alterations, and one with an undetermined FGF/FGFR alteration. The median follow-up was 17·8 months (IQR 11·6-21·3). 38 (35·5% [95% CI 26·5-45·4]) patients with FGFR2 fusions or rearrangements achieved an objective response (three complete responses and 35 partial responses). Overall, hyperphosphataemia was the most common all-grade adverse event irrespective of cause (88 [60%] of 146 patients). 93 (64%) patients had a grade 3 or worse adverse event (irrespective of cause); the most frequent were hypophosphataemia (18 [12%]), arthralgia (nine [6%]), stomatitis (eight [5%]), hyponatraemia (eight [5%]), abdominal pain (seven [5%]), and fatigue (seven [5%]). 65 (45%) patients had serious adverse events; the most frequent were abdominal pain (seven [5%]), pyrexia (seven [5%]), cholangitis (five [3%]), and pleural effusion (five [3%]). Overall, 71 (49%) patients died during the study, most frequently because of disease progression (61 [42%]); no deaths were deemed to be treatment related. Interpretation: These data support the therapeutic potential of Pemigatinib in previously treated patients with cholangiocarcinoma who have FGFR2 fusions or rearrangements. Funding: Incyte Corporation.
Pemigatinib in cholangiocarcinoma with a FGFR2 rearrangement or fusion
Expert Rev Anticancer Ther 2022 Dec;22(12):1265-1274.PMID:36408971DOI:10.1080/14737140.2022.2150168.
Introduction: Cholangiocarcinoma (CCA) accounts for approximately 3% of gastrointestinal malignancies and is associated with a high mortality rate. Recent progress in the understanding of cholangiocarcinoma tumorigenesis and molecular markers has led to the development of several targeted therapies applicable to this disease. Fibroblast growth factor receptor 2 (FGFR2) gene fusion or translocation, resulting in constitutive activation of the FGFR tyrosine kinase, has been identified as a driver of oncogenesis in 10-15% of intrahepatic CCA. Pemigatinib is an FGFR inhibitor that has demonstrated survival benefit in the second line setting for treatment of CCA with FGFR2 fusion or rearrangement refractory to chemotherapy. Pemigatinib was the first targeted therapy to be approved by the FDA for treatment of cholangiocarcinoma. Areas covered: This article reviews FGFR and its dysregulation in oncogenesis, FGFR inhibitors, especially Pemigatinib, utilized in treatment of CCA, common adverse events associated with FGFR inhibitors, and future directions in the field of targeted drug development for CCA. Expert opinion: FGFR inhibitors, including Pemigatinib, have shown promise in the management of CCA with FGFR2 fusion or rearrangement; however, acquired resistance remains a major barrier in the field of FGFR inhibitors and requires further study.
FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor Pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies
Ann Oncol 2022 May;33(5):522-533.PMID:35176457DOI:10.1016/j.annonc.2022.02.001.
Background: The phase I/II FIGHT-101 study (NCT02393248) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Pemigatinib, a potent and selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor, as monotherapy or in combination therapy, for refractory advanced malignancies, with and without fibroblast growth factor (FGF) and receptor (FGFR) gene alterations. Patients and methods: Eligible, molecularly unselected patients with advanced malignancies were included in part 1 (dose escalation; 3 + 3 design) to determine the maximum tolerated dose. Part 2 (dose expansion) evaluated the recommended phase II dose in tumors with or where FGF/FGFR activity is relevant. Results: Patients (N = 128) received Pemigatinib 1-20 mg once daily intermittently (2 weeks on/1 week off; n = 70) or continuously (n = 58). No dose-limiting toxicities were reported. Doses ≥4 mg were pharmacologically active (maximum tolerated dose not reached; recommended phase II dose 13.5 mg once daily). The most common treatment-emergent adverse event (TEAE) was hyperphosphatemia (75.0%; grade ≥3, 2.3%); the most common grade ≥3 TEAE was fatigue (10.2%). Dose interruption, dose reduction, and TEAE-related treatment discontinuation occurred in 66 (51.6%), 14 (10.9%), and 13 (10.2%) patients, respectively. Overall, 12 partial responses were achieved, most commonly in cholangiocarcinoma (n = 5) as well as in a broad spectrum of tumors including head and neck, pancreatic, gallbladder, uterine, urothelial carcinoma, recurrent pilocytic astrocytoma, and non-small-cell lung cancer (each n = 1); median duration of response was 7.3 months [95% confidence interval (CI) 3.3-14.5 months]. Overall response rate was highest for patients with FGFR fusions/rearrangements [n = 5; 25.0% (95% CI 8.7% to 49.1%)], followed by those with FGFR mutations [n = 3; 23.1% (95% CI 5.0% to 53.8%)]. Conclusions: Pemigatinib was associated with a manageable safety profile and pharmacodynamic and clinical activity, with responses seen across tumors and driven by FGFR fusions/rearrangements and mutations. These results prompted a registrational study in cholangiocarcinoma and phase II/III trials in multiple tumor types demonstrating the benefit of precision therapy, even in early phase trials.
FIGHT-302: first-line Pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements
Future Oncol 2020 Oct;16(30):2385-2399.PMID:32677452DOI:10.2217/fon-2020-0429.
FGFR2 rearrangements resulting in dysregulated signaling are drivers of cholangiocarcinoma (CCA) tumorigenesis, and occur almost exclusively in intrahepatic CCA. Pemigatinib, a selective, potent, oral inhibitor of FGFR1-3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring FGFR2 fusions/rearrangements. We describe the study design of FIGHT-302, an open-label, randomized, active-controlled, multicenter, global, Phase III study comparing the efficacy and safety of first-line Pemigatinib versus gemcitabine plus cisplatin in patients with advanced CCA with FGFR2 rearrangements (NCT03656536). The primary end point is progression-free survival; secondary end points are objective response rate, overall survival, duration of response, disease control rate, safety and quality of life. Clinical Trial Registration: NCT03656536 (ClinicalTrials.gov).