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Chemical Structure| 1290543-63-3 Chemical Structure| 1290543-63-3

Structure of Nirogacestat
CAS No.: 1290543-63-3

Chemical Structure| 1290543-63-3

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PF-3084014 is a reversible inhibitor of γ-secretase with IC50 of 6.2 nM.

Synonyms: PF-03084014; PF-3084014

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Product Details of Nirogacestat

CAS No. :1290543-63-3
Formula : C27H41F2N5O
M.W : 489.64
SMILES Code : 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
Synonyms :
PF-03084014; PF-3084014
MDL No. :MFCD19980705
InChI Key :VFCRKLWBYMDAED-REWPJTCUSA-N
Pubchem ID :46224413

Safety of Nirogacestat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Nirogacestat

GPCR

Isoform Comparison

Biological Activity

Description
Nirogacestat (PF-3084014) functions as an orally available, reversible, non-competitive, and selective inhibitor of γ-secretase, demonstrating an IC50 of 6.2 nM. Its ability to suppress Notch signaling effectively while reducing the risk of gastrointestinal side effects makes it a valuable candidate for the exploration of cancers dependent on Notch receptor activity[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
Human T-ALL cell lines 1µM 72 h demonstrates synergistic antileukemic effects PMC3392513
Enza-R, Doce-R and E+D-R cells 5, 10, 20, 30, 40, 60, 80 and 100 µM 48 h evaluate the antitumor effect PMC5958706
Du145 cells 0.1μM, 0.5μM, 1μM, 5μM, 10μM 48 hours To evaluate the effect of PF-03084014 on prostate cancer cell proliferation, results showed that PF-03084014 inhibited growth in all cell lines. PMC4609279
PC3 cells 0.1μM, 0.5μM, 1μM, 5μM, 10μM 48 hours To evaluate the effect of PF-03084014 on prostate cancer cell proliferation, results showed that PF-03084014 inhibited growth in all cell lines. PMC4609279
Du145R cells 0.1μM, 0.5μM, 1μM, 5μM, 10μM 48 hours To evaluate the effect of PF-03084014 on prostate cancer cell proliferation, results showed that PF-03084014 inhibited growth in all cell lines. PMC4609279
PC3R cells 0.1μM, 0.5μM, 1μM, 5μM, 10μM 48 hours To evaluate the effect of PF-03084014 on prostate cancer cell proliferation, results showed that PF-03084014 inhibited growth in all cell lines. PMC4609279

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD-SCID mice xenograft model of glucocorticoid-resistant T-cell lymphoblastic lymphoma Oral gavage 150 mg/kg 5 days abrogated tumor growth and induced leukemic regression PMC3392513
Mice Pancreatic cancer xenograft model Oral 150 mg/kg Twice daily, 4 weeks, 7 days on/7 days off PF-03084014 monotherapy failed to significantly inhibit tumor growth, but the combination with gemcitabine significantly suppressed tumor growth and induced tumor regression in 3/4 xenograft models. PMC3665739
NOD/SCID mice NOD/SCID mice Oral 150mg/kg daily for 4 weeks, 7 days on/7 days off To evaluate the effect of PF-03084014 in combination with docetaxel on prostate cancer tumor growth, results showed that the combination had a greater anti-tumor effect than either agent alone. PMC4609279

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT05348356 Ovarian Granulosa-Stromal Tumo... More >>r|Ovarian Granulosa Cell Tumor|Ovarian Cancer Less << PHASE2 ACTIVE_NOT_RECRUITING 2025-12-27 USC/Norris Comprehensive Cance... More >>r Center, Los Angeles, California, 90033, United States|UCLA-JCCC Dept. of OBGYN - Women's Health Clinical Research Unit, Los Angeles, California, 90095, United States|AdventHealth Orlando, Orlando, Florida, 32804, United States|Orlando Health Cancer Institute, Orlando, Florida, 32806, United States|H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, 33612, United States|Women's Cancer Care, Covington, Louisiana, 70433, United States|Greater Baltimore Medical Center, Baltimore, Maryland, 21204, United States|Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States|David C. Pratt Cancer Center, Saint Louis, Missouri, 63141, United States|University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, 87102, United States|Columbia University Medical Center, New York, New York, 10032, United States|Memorial Sloan Kettering Cancer Institute, New York, New York, 10065, United States|Women's Cancer Center at Kettering, Kettering, Ohio, 45429, United States|OU Health Stephenson Cancer Center, Oklahoma City, Oklahoma, 73104, United States|UW/Fred Hutch Cancer Center, Seattle, Washington, 98109, United States|Froedtert and Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, United States|Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada|Maria Sklodowska-Curie Bialystok Oncology Center, Bia?ystok, 15-027, Poland|Jagiellonian Innovation Centre Clinical Research Centre, Kraków, 30-348, Poland|University Teaching Hospital Poznan, Department of Oncological Gynaecology, Poznań, 60-569, Poland|Maria Sklodowska-Curie National Institute of Oncology-National Research Institute, Clinic of Oncological Gynecology, Warsaw, 02-781, Poland Less <<
NCT02462707 Advanced Solid Tumors PHASE1 WITHDRAWN 2025-10-16 -
NCT05879146 Tumor PHASE2 RECRUITING 2028-01-31 M D Anderson Cancer Center, Ho... More >>uston, Texas, 77030, United States Less <<
NCT01981551 Desmoid Tumors|Aggressive Fibr... More >>omatosis Less << PHASE2 COMPLETED 2023-12-01 National Institutes of Health ... More >>Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States Less <<
NCT00878189 Neoplasms by Histologic Type PHASE1 COMPLETED 2016-11-22 Anschutz Cancer Pavilion, Auro... More >>ra, Colorado, 80045, United States|University of Colorado Denver CTRC, Aurora, Colorado, 80045, United States|University of Colorado Hospital, Aurora, Colorado, 80045, United States|Massachusetts General Hospital Clinical Laboratory, Boston, Massachusetts, 02114, United States|Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02115, United States|Dana Ferber Cancer institute, Boston, Massachusetts, 02215, United States|Karmanos Cancer Center / Wayne State University, Detroit, Michigan, 48201, United States|The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030-4009, United States|DIPRTMNT CLIN Scienze RADIOL e Istocitopatologiche, Bologna, 40138, Italy|Istituto di Ematologia Seragnoli, Bologna, 40138, Italy Less <<
NCT02955446 Neoplasm|Desmoid Tumor NO_LONGER_AVAILABLE - University of Colorado, Aurora... More >>, Colorado, 80045, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.04mL

0.41mL

0.20mL

10.21mL

2.04mL

1.02mL

20.42mL

4.08mL

2.04mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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