1. Apoptosis
  2. Apoptosis Caspase TNF Receptor
  3. OH14

OH14 is a cellular FLICE-like inhibitory protein (cFLIP) inhibitor and TNF-related apoptosis-inducing ligand (TRAIL) sensitizer. OH14 selectively binds to the DED1 pocket of cFLIP, disrupting its recruitment to the TRAIL-death inducing signalling complex without affecting procaspase-8 recruitment to FADD, allowing procaspase-8 activation. OH14 promotes TRAIL-mediated apoptosis and impairs cell viability in breast cancer systems when combined with TRAIL. OH14 can be used for the research of breast cancer.

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OH14

OH14 Chemical Structure

CAS No. : 1018153-87-1

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Description

OH14 is a cellular FLICE-like inhibitory protein (cFLIP) inhibitor and TNF-related apoptosis-inducing ligand (TRAIL) sensitizer. OH14 selectively binds to the DED1 pocket of cFLIP, disrupting its recruitment to the TRAIL-death inducing signalling complex without affecting procaspase-8 recruitment to FADD, allowing procaspase-8 activation. OH14 promotes TRAIL-mediated apoptosis and impairs cell viability in breast cancer systems when combined with TRAIL. OH14 can be used for the research of breast cancer[1].

In Vitro

OH14 (75-100 μM; 1 h) sensitizes MCF-7 breast cancer cells and HeLa cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in a dose-dependent manner, as measured by increased cleaved caspase 3/7 activity and Annexin V staining, respectively[1].
OH14 (100 μM; 1 h) requires the R38 residue in cFLIP to sensitize HeLa cells to TRAIL-induced apoptosis, while overexpression of wild-type, H7A, or K18I/R45A mutant cFLIP does not impair this sensitizing activity[1].
OH14 (100 μM; 1 h) significantly sensitizes MCF-7, BT474, and MDA-MB-231 breast cancer cell lines to TRAIL-induced cell death, with variable effects across other breast cancer subtypes[1].
OH14 (100 μM; 1 h) disrupts TRAIL-mediated recruitment of cFLIP to FADD in HeLa cells, as measured by loss of FRET signal between cFLIP-YFP and FADD-CFP[1].
OH14 (100 μM; 1 h) specifically disrupts TRAIL-mediated recruitment of cFLIP to the FADD complex in MCF-7 cells, while allowing procaspase-8 cleavage and activation[1].
OH14 (10 μM; 10 days) sensitizes MCF-7 breast cancer cells to TRAIL-induced reduction in colony formation, without affecting colony growth when administered alone[1].
OH14 (10 μM; 24 h) is non-toxic to HEK293 non-tumorigenic human embryonic kidney cells, either alone or in combination with TRAIL[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Apoptosis Analysis[1]

Cell Line: MCF-7 breast cancer cells, HeLa cells
Concentration: 75 μM, 100 μM
Incubation Time: 1 h pre-incubation, followed by 24 h TRAIL treatment
Result: Observed a dose-dependent sensitization effect.
Significantly increased cleaved caspase 3/7 activity in MCF-7 cells.
Significantly increased Annexin V staining in HeLa cells.

Cell Viability Assay[1]

Cell Line: Panel of breast cancer cell lines: MCF-7, BT474, MDA-MB-231, HCC1954, SUM149
Concentration: 100 μM
Incubation Time: 1 h pre-incubation, followed by 18 h TRAIL treatment
Result: Significantly sensitized MCF-7, BT474, and MDA-MB-231 breast cancer cell lines to TRAIL.
Observed similar but statistically insignificant trends in HCC1954 and SUM149 cells.

Western Blot Analysis[1]

Cell Line: MCF-7 breast cancer cells
Concentration: 100 μM
Incubation Time: 1 h pre-incubation, followed by 2 h TRAIL treatment
Result: Disrupted the TRAIL-induced interaction between FADD and both short and long forms of cFLIP.
Did not inhibit the interaction between FADD and procaspase-8.
Increased the ratio of cleaved cFLIP (43 kDa) to noncleaved cFLIP (55 kDa).
Induced cleavage of procaspase-8 to its active 43 kDa form when combined with TRAIL.
Molecular Weight

360.21

Formula

C14H11Cl2NO4S

CAS No.
SMILES

CC1=C(C=C(C(S(=O)(NC2=CC=CC=C2C(O)=O)=O)=C1)Cl)Cl

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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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OH14
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HY-182307
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