1. Epigenetics Apoptosis
  2. MicroRNA Apoptosis
  3. Targaprimir-96 TFA

Targaprimir-96 TFA is a potent inhibitor of microRNA-96 (miR-96) processing. Targaprimir-96 TFA selectively modulates miR-96 production in cancer cells and triggers apoptosis. Targaprimir-96 TFA binds primary miR-96 (pri-miR-96) with low nanomolar affinity. Targaprimir-96 TFA directly engages pri-miR-96 in breast cancer cells and is ineffective on healthy breast cells.

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Targaprimir-96 TFA Chemical Structure

Targaprimir-96 TFA Chemical Structure

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Description

Targaprimir-96 TFA is a potent inhibitor of microRNA-96 (miR-96) processing. Targaprimir-96 TFA selectively modulates miR-96 production in cancer cells and triggers apoptosis. Targaprimir-96 TFA binds primary miR-96 (pri-miR-96) with low nanomolar affinity. Targaprimir-96 TFA directly engages pri-miR-96 in breast cancer cells and is ineffective on healthy breast cells[1].

In Vitro

Targaprimir-96 TFA shows a dose-response in MDA-MB-231 triple negative breast cancer cells with an IC50 of ~50 nM by assessing the reduction of mature miR-96 levels. Targaprimir-96 (50 nM) TFA boosts the amount of the pri-miRNA and decreases the levels of the pre-miRNA and mature miRNA in a dose-dependent manner[1].
Targaprimir-96 TFA (50 nM; 48 hours) increases FOXO1 levels and triggers apoptosis in breast cancer cell line 4175[1].
Targaprimir-96 TFA binds RNA3 (contains both the Drosha site and the adjacent 1×1 nt GG internal loop) with a Kd of 85 nM. Targaprimir-96 binds RNA1, RNA2, RNA4, and RNA5 with Kd values of 1.2, 0.9, 1.2, and 1.5 μM, respectively. Thus, Targaprimir-96 TFA is highly RNA-selective and recognizes both the 1×1 nt GG and 1×1 nt UU loops to provide high affinity, effectively discriminating against a variety of related targets[1].

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

In Vivo

Targaprimir-96 TFA (10 mg/kg; i.p.; every other day for 21 days) inhibits tumor growth in a mouse model of triple-negative breast cancer (TNBC)[1].
The amount of Targaprimir-96 (2 or 7 mg/kg; i.p.) in plasma peaks is ~4 h in FVB/n mice. Importantly, even 48 hours postinjection, the concentration of Targaprimir-96 TFA remaining in plasma is much greater than the 50 nM cellular concentration that triggered apoptosis: 1.6 μM for the 2 mg/kg dosage and 1.9 μM for the 7 mg/kg dosage[1].

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

Animal Model: Female NOD/Scid mice (Mouse Model of TNBC)[1]
Dosage: 10 mg/kg
Administration: i.p.; every other day for 21 days
Result: Decreased levels of mature miR-96 by ∼50% and increased levels of pri-miR-96, with a concomitant increase of FOXO1. No toxicity was observed.
Molecular Weight

1505.77

Formula

C79H103F3N18O9

SMILES

OC(C(F)(F)F)=O.O=C(N)CN(C(CN(C(CN(C(CCCOC1=CC=CC(C2=NC3=CC=C(C4=NC5=CC=C(N6CCN(C)CC6)C=C5N4)C=C3N2)=C1)=O)CCC)=O)CCC)=O)CC7=CN(CCCNC(CCCOC8=C(C(C)(C)C)C=C(C9=NC%10=CC=C(N%11CCN(C)CC%11)C=C%10N9)C=C8C(C)(C)C)=O)N=N7

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  • Do most proteins show cross-species activity?

    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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Targaprimir-96 TFA
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HY-135276A
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