PF-3084014 free base · Synonyms: Nirogacestat | PF-03084014

Nirogacestat is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor.

For research use only. Not for human or veterinary use.

Target γ-secretase Apoptosis

Research area Neurological Disease Cancer

Purity >99% Stock Inquire

Data Sheet SDS COA

PF-3084014 structure

CAS No.: 1290543-63-3

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
500 mg	USD 485.00	BP-01861-500mg	In stock	Get quote
1 g	USD 700.00	BP-01861-1g	In stock	Get quote
2 g	USD 1,250.00	BP-01861-2g	In stock	Get quote
5 g	Inquire	BP-01861-5g	In stock	Inquire
10 g	Inquire	BP-01861-10g	Inquire	Inquire

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Related forms

BP-01861A — Nirogacestat dihydrobromide

Description

Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor with an IC50 of 6.2 nM. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers.

Biological activity

In Vitro The IC50 of Nirogacestat (PF-03084014) for γ-secretase enzyme inhibition in cell-free assay for Aβ production using detergent solubilized membranes derived from HeLa cells is determined to be 6.2 nM. When tested for inhibition of Notch receptor cleavage in cellular assays using HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1, the cell IC50 is determined to be 13.3 nM. Nirogacestat (PF-03084014) causes a significant increase in caspase-3 activities in HPB-ALL and TALL-1 cells as well as an induction of cleaved PARP and cleaved caspase-3 after a 7-day treatment. In Vivo Nirogacestat (PF-03084014) shows robust antitumor activity in this model on 14-day twice daily dosing. Tumor growth inhibition is dose dependent, with maximal tumor growth inhibition of ~92% obtained at high dose levels (150 mg/kg). In tumor growth inhibition studies where mice receive repetitive twice daily dosing for more than a week, Nirogacestat (PF-03084014) is well tolerated at dose levels below 100 mg/kg as no significant weight loss, morbidity, or mortality is observed. When the dose is increased to 150 mg/kg, however, mice have diarrhea and show weight loss (10-15%) approximately 10 days after compound administration. The body weight of treated animals usually returns to normal if dosing holidays are given, suggesting that the toxicity of Nirogacestat (PF-03084014) is reversible.

Identifiers

SMILES: CCC[C@H](N[C@H]1CCC2=C(C1)C(F)=CC(F)=C2)C(=O)NC1=CN(C=N1)C(C)(C)CNCC(C)(C)C
InChIKey: VFCRKLWBYMDAED-REWPJTCUSA-N

Specifications

MW (average): 489.6441
Formula: C₂₇H₄₁F₂N₅O
CAS No.: 1290543-63-3
Physical state: Solid
Color: White to yellow
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃ 3 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1]. Wei P, et al. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther. 2010 Jun;9(6):1618-28.

Same target

Search γ-secretase

Same research area

Search Neurological Disease