MTP-B1
MTP-B1 is a POLRMT MtPTAC degrader that activates mitochondrial ClpP. MTP-B1 recruits ClpP as a protease module to POLRMT, inducing ClpP-dependent proteolysis and reducing POLRMT protein levels. MTP-B1 induces ROS and apoptosis. MTP-B1 inhibits proliferation, clonogenic growth, oxidative phosphorylation pathway gene expression, and mitochondrial transcription. MTP-B1 inhibits tumor growth in xenograft tumor mouse models and reduces tumor Ki67. MTP-B1 can be used for pancreatic cancer research (pink: POLRMT inhibitor: HY-181072; blue: small molecule that activates mitochondrial protease ClpP: HY-189815.
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- Fòrmula: C52H51F4N7O7
- Peso molecular:962.00
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MIA PaCa-2 | DC50 |
187.2 nM
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Half-maximal degradation of POLRMT in human MIA PaCa-2 pancreatic cancer cells after 24 hrs incubation by Western blot.
Half-maximal degradation of POLRMT in human MIA PaCa-2 pancreatic cancer cells after 24 hrs incubation by Western blot.
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42819300 |
| ASPC1 | DC50 |
416.9 nM
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Half-maximal degradation of POLRMT in human AsPC-1 pancreatic cancer cells.
Half-maximal degradation of POLRMT in human AsPC-1 pancreatic cancer cells.
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42819300 |
| MIA PaCa-2 | IC50 |
5.08 nM
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Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells by SRB assay.
Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells by SRB assay.
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42819300 |
| ASPC1 | IC50 |
57.76 nM
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Antiproliferative activity against human AsPC-1 pancreatic cancer cells by SRB assay.
Antiproliferative activity against human AsPC-1 pancreatic cancer cells by SRB assay.
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42819300 |
| MIA PaCa-2 | DC50 |
8.81 nM
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Half-maximal degradation of POLRMT in human MIA PaCa-2 pancreatic cancer cells after 7 days incubation.
Half-maximal degradation of POLRMT in human MIA PaCa-2 pancreatic cancer cells after 7 days incubation.
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42819300 |
| MIA PaCa-2 | IC50 |
6.32 nM
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Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells expressing negative control by SRB assay.
Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells expressing negative control by SRB assay.
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42819300 |
| MIA PaCa-2 | IC50 |
94.15 nM
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Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells overexpressing POLRMT by SRB assay.
Antiproliferative activity against human MIA PaCa-2 pancreatic cancer cells overexpressing POLRMT by SRB assay.
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42819300 |
In Vitro
MTP-B1 (0.5-5 μM and 125-5000 nM; 24 h) potently degrades POLRMT in MIA PaCa-2 cells with a DC50 of 187.2 nM and a Dmax of 98.18%; in AsPC-1 cells, the DC50 is 416.9 nM[1].
MTP-B1 (1 μM; 0-48 h) rapidly degrades POLRMT in MIA PaCa-2 cells, and the degradation persists after compound washout[1].
MTP-B1 (0.1-1 μM) reduces POLRMT immunofluorescence in MIA PaCa-2 cells in a dose-dependent manner[1].
MTP-B1 (7 days) exhibits potent antiproliferative activity against MIA PaCa-2 and AsPC-1 cells with IC50 values of 5.08 and 57.76 nM, respectively, and degrades POLRMT with a DC50 of 8.81 nM[1].
MTP-B1 broadly inhibits OXPHOS gene expression and mitochondrial transcription[1].
MTP-B1 (1-500 nM) inhibits clonogenic growth of MIA PaCa-2 cells and induces ROS and apoptosis without affecting cell cycle progression or mitochondrial membrane potential[1].
MTP-B1 (1 μM)-induced POLRMT degradation requires simultaneous binding to both POLRMT and ClpP, and is independent of CRL-dependent ubiquitination and the autophagy-lysosomal pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MIA PaCa-2 cells
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Concentration:0.5, 1, 5 μM
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Incubation Time:24 h
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Result:Retained potent POLRMT degradation activity in the initial screen;
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Cell Line:MIA PaCa-2 and AsPC-1 cells
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Concentration:125, 250, 500, 1000, 5000 nM
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Incubation Time:24 h
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Result:Dose-response assays gave a DC50 of 187.2 nM and Dmax of 98.18% in MIA PaCa-2 cells.
Showed a DC50 of 416.9 nM in AsPC-1 cells.
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Cell Line:MIA PaCa-2 cells
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Concentration:1 μM (time-course); 1 μM for 24 h followed by washout
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Incubation Time:0, 4, 8, 16, 24 h; washout 24 h; 48 h
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Result:MTP-B1 induced more than 50% POLRMT degradation within 16 h and near-complete degradation by 24 h.
A lower-molecular-weight POLRMT species appeared with degradation.
After washout, no appreciable POLRMT recovery was detected within 24 h, with only partial restoration at 48 h.
Parmacokinetics
| Species | Dose | Route | Cmax | AUC0-∞ | T1/2 |
|---|---|---|---|---|---|
| Mice[1] | 50 mg/kg | i.v. | 61966.67 ng/mL | 26,100.84 ng·h/mL | 3.47 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:mice with MIA PaCa-2 xenograft[1]
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Dosage:25, 50, 100 mg/kg
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Administration:i.v.; every other day; 25 days
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Result:Achieved a tumor growth inhibition (TGI) of 70.1% at 100 mg/kg.
No significant body weight
loss.
Exhibited POLRMT degradation, reduced the
proliferation marker Ki67 and significant increased
TUNEL-positive apoptotic cells in tumors.
- RT-PCR
- Western Blot
- RNA extraction experimental
- Annexin V plus membrane-impermeant dye apoptosis staining
- ROS/oxidative-stress fluorescent staining
- Patient-Derived Orthotopic Xenograft (PDOX)
- Real Time qPCR (Q-PCR)
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Ki-67 Immunostaining Proliferation Assay
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Soft Agar Colony Formation Assay
- Protocol for Kinase activity and phosphorylation assays
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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Peso molecular 962.00
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Fòrmula C52H51F4N7O7
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SMILES
O=C(NCCCN(C1=C(CN(CC2=CC=CC(C#N)=C2)CC1)C(N3CC4=CC=C(C(F)(F)F)C=C4)=O)C3=O)CCN5CCN(C([C@H](OC6=CC(O7)=C(C=C6F)C(C8=CC=CC=C8C)=CC7=O)C)=O)CC5
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MTP-B1 Related Classifications
HY-189711 Related Classifications
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