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PF-03084014

Cat. No. M9041
PF-03084014 Structure
Synonym:

Nirogacestat

Size Price Availability Quantity
5mg USD 140  USD140 In stock
10mg USD 230  USD230 In stock
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Quality Control
Biological Activity

PF-03084014 is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. PF-03084014 reduces proliferation of HUVECs with IC50 of 0.5 μM, and decreases the lumen formation with an IC50 value of 50 nM. PF-03084014 (1 μM) has no antiproliferative effect in MX1 cells.

In vivo, PF-03084014 orally administrated in a single dose of 200 mg/kg, causes maximal NICD inhibition for ∼80% in xenograft HPB-ALL tumors. PF-03084014 (120 mg/kg) induces apoptosis, antiproliferation, reduces tumor cell self-renewal ability, impaires tumor vasculature, and decreases metastasis activity in breast cancer HCC1599 tumor-bearing mice. PF-03084014 treatment displays significant antitumor activity in various types of the breast xenograft models with TGI value of at least 50%.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 489.64
Formula C27H41F2N5O
CAS Number 1290543-63-3
Purity 98.30%
Solubility DMSO: ≥ 60 mg/mL
Storage at -20°C
References

[1] Aguirre SA, et al. Toxicol Pathol. Intermittent oral coadministration of a gamma secretase inhibitor with dexamethasone mitigates intestinal goblet cell hyperplasia in rats.

[2] Zhang CC, et al. Clin Cancer Res. Biomarker and pharmacologic evaluation of the γ-secretase inhibitor PF-03084014 in breast cancer models.

[3] Wei P, et al. Mol Cancer Ther. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PF-03084014, Nirogacestat supplier, Gamma-secretase, inhibitors

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