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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].
Shanghai Jinpan Biotech Co Ltd 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 |
Shanghai Jinpan Biotech Co Ltd 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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