R-IMPP hydrochloride
R-IMPP hydrochloride (PF-00932239 hydrochloride) is a PCSK9 translation inhibitor and a selective 80S ribosome binder. R-IMPP hydrochloride inhibits the KRAS/MEK/ERK signaling cascade. R-IMPP hydrochloride reduces LPS-induced nuclear translocation of NFkB P65. R-IMPP hydrochloride increases LDL-R levels in cells, promotes LDL-C uptake, and does not alter the secretion of transferrin or albumin. R-IMPP hydrochloride inhibits the growth of colorectal cancer (CRC) cells, organoids and xenografts carrying APC/KRAS mutations, as well as the number and burden of spontaneous mouse tumors. R-IMPP hydrochloride can be used in research related to colorectal cancer with APC/KRAS mutations, hepatic ischemia-reperfusion injury and hypercholesterolemia.
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- CAS No.: 2173005-10-0
- Formule: C24H28ClN3O2
- Masse moléculaire:425.95
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Activité biologique
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| NCM460 | IC50 |
57.5 μM
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Inhibition of cell viability against human NCM460 normal colonic epithelial cells incubated for 72 hrs by cell viability assay.
Inhibition of cell viability against human NCM460 normal colonic epithelial cells incubated for 72 hrs by cell viability assay.
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35803966 |
| DLD-1 | IC50 |
22.5 μM
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Inhibition of cell viability against human DLD1 APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
Inhibition of cell viability against human DLD1 APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
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35803966 |
| HCT-116 | IC50 |
17.6 μM
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Inhibition of cell viability against human HCT116 APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
Inhibition of cell viability against human HCT116 APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
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35803966 |
| LoVo | IC50 |
26.4 μM
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Inhibition of cell viability against human LOVO APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
Inhibition of cell viability against human LOVO APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
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35803966 |
| SW 1116 | IC50 |
26.9 μM
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Inhibition of cell viability against human SW1116 APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
Inhibition of cell viability against human SW1116 APC/KRAS-mutant CRC cells incubated for 72 hrs by cell viability assay.
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35803966 |
| Huh-7 | IC50 |
2.2 μM
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Inhibition of basal PCSK9 secretion in human hepatoma Huh7 cells via AlphaLISA assay following 16-20 h incubation.
Inhibition of basal PCSK9 secretion in human hepatoma Huh7 cells via AlphaLISA assay following 16-20 h incubation.
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27746128 |
| Huh-7 | IC50 |
2.4 μM
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Inhibition of statin-induced PCSK9 secretion in human hepatoma Huh7 cells via AlphaLISA assay following 16-20 h incubation.
Inhibition of statin-induced PCSK9 secretion in human hepatoma Huh7 cells via AlphaLISA assay following 16-20 h incubation.
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27746128 |
In Vitro
R-IMPP (30-60 μM) hydrochloride inhibits the KRAS/MEK/ERK pathway by reducing the protein levels of p-ERK and cyclin D3 in three APC/KRAS-mutant colorectal cancer cell lines, HCT116, LOVO and SW1116[1].
R-IMPP (40 μM) hydrochloride inhibits the expression of active KRAS protein in SW1116 APC/KRAS mutant colorectal cancer cells[1].
R-IMPP (72 h) hydrochloride inhibits cell viability, with stronger inhibitory potency against APC/KRAS mutant colorectal cancer cell lines (72-hour IC50: 17.6-41.8 μM). In comparison, the 72-hour IC50 is 84.8 μM for wild-type 1CT cells and 57.5 μM for normal NCM460 colon cells[1].
R-IMPP (30-60 μM; 24 h) hydrochloride potently inhibits the expression of PCSK9 protein in AML12 hepatocytes[2].
R-IMPP (60 μM; 24 h) hydrochloride impairs the mitochondrial membrane potential of AML12 hepatocytes, while no such effect is observed at the concentration of 30 μM[2].
R-IMPP hydrochloride attenuates hypoxia/reoxygenation-induced apoptosis of AML12 hepatocytes[2].
R-IMPP hydrochloride potently inhibits PCSK9 secretion in CHO-K1 cells expressing recombinant ProLabel-tagged PCSK9, with an IC50 of 4.8 μM. Meanwhile, it exhibits only extremely low cytotoxicity and no non-universal secretion inhibitory effect[3].
R-IMPP (3-30 μM; overnight pre-treatment) hydrochloride promotes the uptake of AF-LDL by Huh7 cells, with a 47.5% increase in uptake at the concentration of 30 μM[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCM460 (normal colonic epithelial cells), 1CT (wildtype colonic cells), 1CT-AK, DLD1, HCT116, LOVO, SW1116 (APC/KRAS-mutant CRC cell lines)
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Concentration:Various concentrations
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Incubation Time:72 h
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Result:Exhibited 72-hour IC50 values of 57.5 μM for NCM460, 84.8 μM for 1CT, 41.8 μM for 1CT-AK, 22.5 μM for DLD1, 17.6 μM for HCT116, 26.4 μM for LOVO, and 26.9 μM for SW1116.
Rendered APC/KRAS-mutant CRC cells more sensitive than wildtype or normal colonic cells.
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Cell Line:human hepatoma Huh7 cells
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Concentration:10 μM, 30 μM
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Incubation Time:overnight
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Result:Caused a dose-dependent increase in LDL-R levels at 10 μM and 30 μM.
Caused a dose-dependent decrease in both pro-PCSK9 and mature PCSK9 levels in cell lysates at 10 μM and 30 μM.
In Vivo
R-IMPP (50 mg/kg; i.p.; 3 times/week) hydrochloride suppresses tumor development in the spontaneous APC/KRAS-mutant CRC mouse model[1].
R-IMPP (50 mg/kg; i.p.) hydrochloride synergizes with Simvastatin (HY-17502) to induce regression of SW1116 APC/KRAS-mutant CRC xenografts in nude mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD/SCID[1]
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Dosage:100 mg/kg
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Administration:i.p.
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Result:Suppressed growth of SW1116 xenografts, with decreased tumor volume and weight.
Caused no significant decrease in body weight.
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Animal Model:Apc^{Min/+}Kras^{G12D/+}Villin-Cre[1]
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Dosage:50 mg/kg
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Administration:i.p.; 3 times/week
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Result:Significantly suppressed tumor number and tumor load.
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Animal Model:Nude[1]
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Dosage:50 mg/kg
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Administration:i.p.
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Result:Triggered tumor regression compared to control or single agent treatments, and reduced tumor weight.
Down-regulated PCSK9 protein and GGPP levels in xenograft tumors.
Chemical Information
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CAS No. 2173005-10-0
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Masse moléculaire 425.95
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Formule C24H28ClN3O2
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SMILES
COC(C=C1)=CC=C1CCC(N([C@@H]2CCCNC2)C3=NC=CC4=C3C=CC=C4)=O.Cl
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Synonyms
PF-00932239 hydrochloride
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[2]. Zhang Y, et al. Blockade of Hepatocyte PCSK9 Ameliorates Hepatic Ischemia-Reperfusion Injury by Promoting Pink1-Parkin-Mediated Mitophagy. Cellular and molecular gastroenterology and hepatology. 2024;17(1):149-169. [Content Brief]
[3]. Petersen DN, et al. A Small-Molecule Anti-secretagogue of PCSK9 Targets the 80S Ribosome to Inhibit PCSK9 Protein Translation. Cell Chem Biol. 2016 Nov 17;23(11):1362-1371. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
R-IMPP hydrochloride Related Classifications
HY-101354A Related Classifications
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