上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。
PDGFR-IN-1 (compound 7m) 是一种口服有效的 PDGFR (血小板源性生长因子受体) 抑制剂, PDGFRα 和 PDGFRβ 的 IC50 分别为 2.4 和 0.9 nM。PDGFR-IN-1 具有较强的抗肿瘤作用和低毒性，可用于骨肉瘤的研究。
| 生物活性 |
PDGFR-IN-1 (compound 7m) is a potent and orally active PDGFR (platelet-derived growth factor receptor) inhibitor, with IC50 values of 2.4 and 0.9 nM for PDGFRα and PDGFRβ, respectively. PDGFR-IN-1 displays robust antitumor effects and low toxicity, and can be used to study osteosarcoma[1].
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IC50 & Target |
IC50: 2.4 nM (PDGFRα), 0.9 nM (PDGFRβ)[1]
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体外研究
(In Vitro) |
PDGFR-IN-1 (compound 7m) (0-0.4 μM, 48 h) inhibits osteosarcoma cancer cells (U2OS, MG63, MNNG/HOS, and SAOS-2) proliferation and colony formation[1].
PDGFR-IN-1 (0-0.4 μM, 48 h) induces cell-cycle arrest in a dose-dependent manner[1].
PDGFR-IN-1 (0-1.6 μM, 48 h) induces MNNG/HOS and MG63 cell apoptosis in a dose-dependent manner[1].
PDGFR-IN-1 (0-0.4 μM, 15 min) inhibits the expression of α-tubulin in both MNNG/HOS and MG63 cells[1].
PDGFR-IN-1 (0-0.4 μM, 48 h) inhibits PDGFRβ phosphorylation and downstream signaling transduction (p-STAT3, p-AKT, and p-ERK)[1].
PDGFR-IN-1 (0-0.4 μM, 48 h) significantly inhibits osteosarcoma cancer cell migration and invasion by downregulating the expression of FAK, as well as the distribution in the leading edge of cells[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay
| Cell Line: |
Human osteosarcoma cancer cell lines (U2OS, MG63, MNNG/HOS, and SAOS-2)[1] |
| Concentration: |
0.1, 0.2, and 0.4 μM. |
| Incubation Time: |
48 h |
| Result: |
Showed strong antiproliferative activity against MG63, U2OS, MNNG/HOS, and SAOS-2, with IC50 values of 0.44, 0.42, 1.03, and 0.37 μM, respectively. Showed dose-dependent inhibition colony formation. |
Cell Cycle Analysis
| Cell Line: |
MG63 and MNNG/HOS cells[1] |
| Concentration: |
0, 0.1, 0.2, 0.4 μM |
| Incubation Time: |
48 h |
| Result: |
Induced G2/M cell-cycle arrest in MNNG/HOS and G0/G1 cell-cycle arrest in MG63 cells in a dose-dependent manner. |
Apoptosis Analysis
| Cell Line: |
MG63 and MNNG/HOS cells[1] |
| Concentration: |
0, 0.4, 0.8, 1.6 μM |
| Incubation Time: |
48 h |
| Result: |
Induced MNNG/HOS and MG63 cell apoptosis in a dose-dependent manner. |
Immunofluorescence
| Cell Line: |
MG63 and MNNG/HOS[1] |
| Concentration: |
0, 0.1, 0.2, 0.4 μM |
| Incubation Time: |
15 min |
| Result: |
Inhibited the expression of α-tubulin in both MNNG/HOS and MG63 cells, inhibited proliferation and reduced the PDGFRβ fluorescence intensity in a concentration-dependent manner. |
Western Blot Analysis
| Cell Line: |
MG63 and MNNG/HOS[1] |
| Concentration: |
0, 0.1, 0.2, 0.4 μM |
| Incubation Time: |
48 h |
| Result: |
Effective inhibited PDGFRβ phosphorylation and downstream signaling transduction (p-STAT3, p-AKT, and p-ERK) at the cellular level. |
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体内研究
(In Vivo) |
PDGFR-IN-1 (BALB/c mice, MNNG/HOS xenograft mouse, 15, 30 mg/kg, orally, daily for 14 days) significantly suppresses tumor growth, exhibits a stronger antitumor efficacy with low toxicity[1].
PDGFR-IN-1 (C57/BL6 mice, 40, 80 mg/kg, orally, daily for 10 days) is safe for in vivo investigations[1].
PDGFR-IN-1 (Sprague-Dawley rats, 20 mg/kg PO or 4 mg/kg IP, once) shows a favorable profile with a high maximum concentration and exposure, an acceptable half-life , and a good oral bioavailability[1].
Pharmacokinetic Parameters of PDGFR-IN-1 in male Sprague-Dawley rats[1].
|
7m |
|
| route |
IP |
PO |
| dose (mg/kg) |
4 |
20 |
| Cmax (ng/mL) |
78.3 |
75.2 |
| t1/2 (h) |
2.86 |
2.12 |
| AUC0-∞ (ng/mL*h) |
211.3 |
664.7 |
| F (%) |
|
62.9 |
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Sprague-Dawley rats (male, 200-260 g, Six rats, two groups)[1] |
| Dosage: |
20 mg/kg (PO) or 4 mg/kg (IP) |
| Administration: |
PO, IP, once (Pharmacokinetic Analysis) |
| Result: |
Showed a favorable profile with a high maximum concentration and exposure, an acceptable half-life , and a good oral bioavailability. |
| Animal Model: |
BALB/c mice (18-20 g, MNNG/HOS xenograft mouse, eight groups)[1] |
| Dosage: |
15, 30 mg/kg |
| Administration: |
Orally, daily for 14 days |
| Result: |
Significantly suppressed tumor growth, exhibited a stronger antitumor efficacy, did not cause significant body weight or organ weight (heart, lung, liver, spleen, or kidney) changes, strongly suppressed the proliferation of tumor cells and induced apoptosis in tissues of the tumor. |
| Animal Model: |
C57/BL6 mice[1] |
| Dosage: |
40, 80 mg/kg |
| Administration: |
Orally, daily for 10 days |
| Result: |
Did not reveal any obvious morphological aberration in organ tissues. |
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| 分子量 |
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| Formula |
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| CAS 号 |
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
Please store the product under the recommended conditions in the Certificate of Analysis.
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| 参考文献 |
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[1]. Chen X, Liu L, Liu P, et al. Discovery of Potent and Orally Bioavailable Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for the Treatment of Osteosarcoma. J Med Chem. 2022;65(7):5374-5391.
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