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。
RET-IN-16
RET-IN-16 是一种有效且具有选择性的 RET 抑制剂，对 RET(WT)，RET(M918T)，RET(V804L)，RET(V804M)，RET-CCDC6 和 RET-KIF5B 的 IC50 分别为 3.98 nM，8.42 nM，15.05 nM，7.86 nM，5.43 nM 和 8.86 nM。RET-IN-16 具有抗癌作用。
RET-IN-16 Chemical Structure
CAS No. : 2259657-48-0
| 规格 |
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是否有货 |
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| 100 mg |
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询价 |
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| 250 mg |
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询价 |
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| 500 mg |
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询价 |
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* Please select Quantity before adding items.
| 生物活性 |
RET-IN-16 is a potent and selective RET inhibitor with IC50s of 3.98 nM, 8.42 nM, 15.05 nM, 7.86 nM, 5.43 nM and 8.86 nM for RET(WT), RET(M918T), RET(V804L), RET(V804M), RET-CCDC6 and RET-KIF5B, respectively. RET-IN-16 has anticancer effects[1].
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IC50 & Target |
IC50: 3.98 nM (RET(WT)), 8.42 nM (RET(M918T)), 15.05 nM (RET(V804L)), 7.86 nM (RET(V804M)), 5.43 nM (RET-CCDC6), 8.86 nM (RET-KIF5B)[1]
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体外研究
(In Vitro) |
RET-IN-16 (compound 9x) (0.005-10 μM; 48 hours) exhibits potent activity against CCDC6-RET-Ba/F3 and KIF5B-RET-Ba/F3 with GI50 of 9 nM and 17 nM, respectively[1].
RET-IN-16 (1 μM; 48 hours) selectively suppresses the proliferation of CCDC6-RET fusion cells[1].
RET-IN-16 (50 and 100 μM; 4 hours) remarkably blocks the autophosphorylation of RET in KIF5B-RET and KIF5B-RETV804M Ba/F3 cells, and the phosphorylation of the adapter protein SHC is also inhibited with a dose-dependent manner[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay
| Cell Line: |
LC-2/ad, A549, H3122, MDA-MB-231 and A375, SKGT4, HepG2, KYSE450 and BGC823 cells[1] |
| Concentration: |
1 μM |
| Incubation Time: |
48 hours |
| Result: |
Potently suppressed the proliferation of LC-2/ad NSCLC cells harboring the CCDC6-RET fusion, but dramatically decreased potency against other RET-negative cancer cells. |
Western Blot Analysis
| Cell Line: |
KIF5B-RET and KIF5B-RETV804M Ba/F3 cells[1] |
| Concentration: |
50 and 100 μM |
| Incubation Time: |
4 hours |
| Result: |
Remarkably blocked the autophosphorylation of RET, and the phosphorylation of the adapter protein SHC was also inhibited in a dose-dependent manner. |
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体内研究
(In Vivo) |
RET-IN-16 (1 mg/kg; IV; single) exhibits a good drug exposure (AUC0-t = 6959 ± 762 ng·h/mL) and a moderate half-life (T1/2 = 4.28 ± 0.43 h)[1].
RET-IN-16 (10 mg/kg; PO; single) exhibits a low maximum plasma concentration (Cmax = 194 ± 47 ng·h/mL) and drug exposure (AUC0-t = 2112 ± 117 ng·h/mL)[1].
RET-IN-16 (30 and 50 mg/kg; IV; daily; for 8 days) suppresses tumor growth in a dose-dependent manner, and significantly suppresses p-RET and p-SHC in both KIF5B-RET and KIF5B-RETV804M in tumor tissues, as well as significantly induces apoptosis in vivo[1].
Pharmacokinetic Parameters of RET-IN-16 in male Sprague-Dawley rats[1].
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IV (1 mg/kg) |
PO (10 mg/kg) |
| T1/2 (h) |
4.28 ± 0.43 |
7.59 ± 1.02 |
| Tmax (h) |
0.083 ± 0 |
0.75 ± 0.43 |
| Cmax (ng/mL) |
6097 ± 623 |
194 ± 47 |
| AUC0-t (ng/mL·h) |
6959 ± 762 |
2112 ± 117 |
| AUC0-∞ (ng/mL·h) |
7014 ± 753 |
2343 ± 157 |
| F (%) |
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3.0 |
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male Sprague-Dawley rats[1] |
| Dosage: |
1 mg/kg for IV, 10 mg/kg for PO |
| Administration: |
IV and PO; single (Pharmacokinetic Analysis) |
| Result: |
Exhibited a good drug exposure (AUC0-t = 6959 ± 762 ng·h/mL) and a moderate half-life (T1/2 = 4.28 ± 0.43 h) at 1 mg/kg IV; observed a low maximum plasma concentration (Cmax = 194 ± 47 ng·h/mL) and drug exposure (AUC0-t = 2112 ± 117 ng·h/mL) at 10 mg/kg PO. |
| Animal Model: |
Half male and female BALB/c-nu mice (6-8 weeks; injected with KIF5B-RET Ba/F3 and KIF5B-RETV804M Ba/F3)[1] |
| Dosage: |
30 and 50 mg/kg |
| Administration: |
IV; daily; for 8 days |
| Result: |
Suppressed tumor growth in a dose-dependent manner, and significantly suppressed p-RET and p-SHC in both KIF5B-RET and KIF5B-RETV804M in tumor tissues, as well as significantly induced apoptosis in vivo. |
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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]. Li X, Su J, Yang Y, et al. Discovery of 4-methyl-N-(4-((4-methylpiperazin- 1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((6-(pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-oxy)benzamide as a potent inhibitor of RET and its gatekeeper mutant. Eur J Med Chem. 2020;207:112755.
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