JPS014
JPS014 is a PROTAC degrader targeting HDAC1, HDAC2 and HDAC3, with DC50 values of 0.91 μM, 4.19 μM and 0.64 μM, respectively. JPS014 recruits the VHL E3 ligase to mediate the ubiquitination and proteasomal degradation of HDAC1, HDAC2 and HDAC3. JPS014 acts as a submicromolar inhibitor of the HDAC1-CoREST, HDAC2-CoREST and HDAC3-SMRT complexes in vitro. JPS014 increases the level of H3K56ac, reduces the stability of LSD1 and SIN3A, and induces cell apoptosis (apoptosis). JPS014 can be used for the research of colon cancer.
(Pink: HDAC1 and HDAC2 and HDAC3 ligand (HY-50934); Blue: VHL ligand (HY-125845); Black: linker).
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- CAS No.: 2669785-76-4
- Formule: C46H59N7O7S
- Masse moléculaire:854.07
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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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Chemical Information
- Pureté et documentation
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Activité biologique
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HDAC1 0.91 μM (DC50) |
HDAC2 4.19 μM (DC50) |
HDAC3 0.64 μM (DC50) |
VHL |
JPS014 (0.1-10 μM; 24-48 h) induces submicromolar degradation of HDAC1 (DC50 = 0.91 μM), HDAC2 (DC50 = 4.19 μM), and HDAC3 (DC50 = 0.64 μM) in HCT116 cells, increases H3K56ac levels, reduces corepressor complex components SIN3A and LSD1, and exhibits a hook effect for HDAC3 at concentrations above 1 μM[1].
JPS014 (10 μM; 24-48 h) reduces viability of HCT116 cells with an EC50 of 7.3 μM after 48 h and induces significant apoptosis, as measured by sub-G1 population, at 10 μM after 24 and 48 h[1].
JPS014 (10 μM; 24 h) induces widespread transcriptional changes, with 3724 total DEGs, and enriches pathways linked to cell cycle regulation and apoptosis in HCT116 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT116 human colon carcinoma cells
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Concentration:0.1, 1, 10 μM (24 h); 10 μM (48 h)
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Incubation Time:24 h (0.1, 1, 10 μM); 48 h (10 μM)
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Result:Induced degradation of HDAC1, HDAC2, and HDAC3 at 0.1, 1, and 10 μM for 24 h, with HDAC3 degradation significantly enhanced at 1 μM compared to PROTAC 1 (JPS004).
Increased H3K56ac levels to comparable or greater levels than HDAC inhibitor CI-994 and PROTAC 1.
Reduced SIN3A levels to 50% of control abundance after 24 h at 10 μM.
Significantly reduced LSD1 levels compared to DMSO and CI-994 controls after 48 h at 10 μM.
Exhibited a hook effect for HDAC3 at concentrations greater than 1 μM, where HDAC3 abundance increased rather than decreased, while HDAC1/2 levels continued to decrease.
Achieved degradation DC50 values of 0.91 μM for HDAC1, 4.19 μM for HDAC2, and 0.64 μM for HDAC3, with maximal degradation (Dmax) values of 74% for HDAC1, 56% for HDAC2, and 59% for HDAC3.
Showed submicromolar inhibitory activity against purified HDAC complexes, with IC50 values of 0.22 μM for HDAC1-CoREST, 0.36 μM for HDAC2-CoREST, and 0.14 μM for HDAC3-SMRT.
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Cell Line:HCT116 human colon carcinoma cells
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Concentration:10 μM
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Incubation Time:24 h ; 48 h
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Result:Caused a substantial percentage of cells to enter the sub-G1 phase, indicating significant apoptosis after 24 h at 10 μM.
Induced sub-G1 population levels comparable to PROTAC 1 and CI-994 after 48 h at 10 μM.
Reduced cell viability with an EC50 of 7.3 μM after 48 h.
Chemical Information
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CAS No. 2669785-76-4
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Masse moléculaire 854.07
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Formule C46H59N7O7S
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SMILES
O=C(N[C@@H](C(C)(C)C)C(N1[C@H](C(NCC2=CC=C(C3=C(C)N=CS3)C=C2)=O)C[C@@H](O)C1)=O)CCCCCCCCOCC(NC4=CC=C(C(NC5=CC=CC=C5N)=O)C=C4)=O
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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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JPS014 Related Classifications
HY-145815 Related Classifications
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