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PZ0298

Sigma-Aldrich

PF-03084014 hydrobromide

≥98% (HPLC)

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Synonym(s):
(2S)-2-[[(2S)-6,8-Difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]amino]-N-[1-[2-[(2,2-dimethylpropyl)amino]-1,1-dimethylethyl]-1H-imidazol-4-yl]-pentanamide hydrobromide, Nirogacestat, PF 03084014 hydrobromide, PF 3084014 hydrobromide, PF-3084014 hydrobromide
Empirical Formula (Hill Notation):
C27H41F2N5O · HBr
CAS Number:
1290543-63-3
Molecular Weight:
570.56
UNSPSC Code:
12352200
PubChem Substance ID:
329823821
NACRES:
NA.77

Quality Level

100

Assay

≥98% (HPLC)

form

powder

storage condition

desiccated

color

white to beige

solubility

H2O: 1 mg/mL, clear

storage temp.

room temp

SMILES string

FC1=C2C(CC[C@H](N[C@@H](CCC)C(NC3=CN(C(C)(C)CNCC(C)(C)C)C=N3)=O)C2)=CC(F)=C1.C

InChI

1S/C27H41F2N5O.CH4/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4;/h11-12,14,17,20,23,30,32H,7-10,13,15-16H2,1-6H3,(H,33,35);1H4/t20-,23-;/m0./s1

InChI key

GLEYBLZDOTUZJH-WCRWPNQISA-N

Biochem/physiol Actions

PF-03084014 inhibits the Notch signalling pathway. It contributes totumor suppression in breast, pancreatic carcinoma, hepatocellular carcinoma and progressive desmoid tumors. PF-03084014 in combination with dexamethasone elicits antileukemic effects in T-cell acute lymphoblastic leukemias (T-ALL).
PF-03084014 is a highly potent γ-secretase inhibitor that reduces Aβ production in vitro. PF-03084014 does not show a paradoxical increase in plasma Aβ at low concentrations in both preclinical species and humans.

Pictograms

Exclamation mark
GHS07

Signal Word

Warning

Hazard Statements

H315,H319,H335

Hazard Classifications

Eye Irrit. 2 - Skin Irrit. 2 - STOT SE 3

Target Organs

Respiratory system

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Regulatory Information

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Preclinical analysis of the gamma-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia
Samon JB, et al.
Molecular Cancer Therapeutics, 11(7), 1565-1565 (2012)
Notch pathway inhibition using PF-03084014, a gamma-secretase inhibitor (GSI), enhances the antitumor effect of docetaxel in prostate cancer
Cui D, et al.
Clinical Cancer Research, 21(20), 4619-4629 (2015)
Clinical activity of the gamma-secretase inhibitor PF-03084014 in adults with desmoid tumors (aggressive fibromatosis)
Kummar S, et al.
Journal of Clinical Oncology, 35(14), 1561-1561 (2017)
Notch inhibitor PF-03084014 inhibits hepatocellular carcinoma growth and metastasis via suppression of cancer stemness due to reduced activation of Notch1-Stat3
Wu CX, et al.
Molecular Cancer Therapeutics, 16(8), 1531-1543 (2017)

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