Cat. No.: HY-12449

Crenigacestat

(Synonyms: LY3039478)

7 Cited Publications

Customer Review

Based on 7 publication(s) in Google Scholar

Crenigacestat (LY3039478) is an orally active Notch and γ-secretase inhibitor, with an IC₅₀ of 1 nM in most of the tumor cell lines tested.

For research use only. We do not sell to patients.

Purity: 99.01%
CAS No.: 1421438-81-4
Formula: C₂₂H₂₃F₃N₄O₄
Molecular Weight:464.44

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Crenigacestat Chemical Structure

CAS No.: 1421438-81-4

Size

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (7)
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

Crenigacestat (LY3039478) is an orally active Notch and γ-secretase inhibitor, with an IC₅₀ of 1 nM in most of the tumor cell lines tested^[1]^[2]^[3]^[4].

Cellular Effect

Cell Line	Type	Value	Description	References
A2780	IC₅₀	1.03 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human A2780 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human A2780 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
A-375	IC₅₀	0.48 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human A375 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human A375 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
BXPC-3	IC₅₀	0.39 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human BxPC3 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human BxPC3 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
CCRF-CEM	IC₅₀	0.76 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human CCRF-CEM cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human CCRF-CEM cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
DLD-1	IC₅₀	0.98 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human DLD1 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human DLD1 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
HCT-116	IC₅₀	0.72 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human HCT 116 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human HCT 116 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
Jurkat	IC₅₀	5.95 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human Jurkat cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human Jurkat cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
K562	IC₅₀	0.74 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human K562 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human K562 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
MDA-MB-231	IC₅₀	0.5 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MDA-MB-231 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MDA-MB-231 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
MIA PaCa-2	IC₅₀	0.71 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MIAPaCa2 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MIAPaCa2 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
MOLT-3	IC₅₀	0.61 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MOLT-3 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MOLT-3 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
MOLT-4	IC₅₀	0.74 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MOLT-4 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human MOLT-4 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
SUP-T1	IC₅₀	1.24 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human SUP-T1 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human SUP-T1 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
SW480	IC₅₀	0.1 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human SW480 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human SW480 cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]
U-87MG ATCC	IC₅₀	0.28 nM Compound: 1	Inhibition of gamma-secretase mediated cleavage of Notch 1 in human U-87-MG cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA Inhibition of gamma-secretase mediated cleavage of Notch 1 in human U-87-MG cells assessed as nuclear accumulation of Notch 1 intracellular domain (N1ICD) after 24 hrs by ELISA	[PMID: 24900678]

In Vitro

Crenigacestat (100 nM) exhibits anti-cancer activity in K07074 cells (a primary mouse liver tumor cell line)^[2].
Crenigacestat (LY3039478) decreases expression of Myc and cyclin A1 (part of the NOTCH-driven proliferative signature) in murine and human model systems. Crenigacestat (LY3039478) treatment also leads to G0/G1 cell cycle arrest in CCRCC cells^[3].

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

Cell Viability Assay^[2].

Cell Line:

K07074 cells.
Concentration:

100 nM.
Incubation Time:

24-96 hours.
Result:

Effectively reduced the growth of K07074 cells.

In Vivo

Crenigacestat (8 mg/kg, oral gavage three times a week) resulted in significantly increases survival and delayed tumor growth in independent cohorts of mice demonstrating in vivo efficacy in CCRCC^[3].

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

Animal Model:

CCRCC xenografts were established in NOD-scid IL2R null mice with subcutaneous implantation using the 769-P cell line^[3].
Dosage:

8 mg/kg.
Administration:

Oral gavage three times a week.
Result:

Resulted in increased overall survival when compared with vehicle control in CCRCC xenografts.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 1421438-81-4
Appearance Solid
Molecular Weight 464.44
Formula C₂₂H₂₃F₃N₄O₄
Color White to off-white
SMILES

O=C(N[C@@H](C)C(N[C@H]1C2=CC=CC=C2C3=CC=CN=C3N(CCO)C1=O)=O)CCC(F)(F)F
Synonyms

LY3039478
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (7)

All IFWBFlow Cytometry

Sort by:

Journal Impact Factor

Cell Mol Immunol

Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling. [Abstract]

2022 Dec;19(12):1373-1391. PMID: 36241874

Crenigacestat purchased from MedChemExpress. Usage Cited in: Cell Mol Immunol. 2022 Dec;19(12):1373-1391. [Abstract]

Crenigacestat (8 mg/kg). Representative confocal images of primary tumor sections stained with anti-α-SMA antibody.
Nat Commun

Quadruple gene-engineered natural killer cells enable multi-antigen targeting for durable antitumor activity against multiple myeloma. [Abstract]

2022 Nov 29;13(1):7341. PMID: 36446823
Cell Commun Signal

The interplay of cancer-associated fibroblasts and apoptotic cancer cells suppresses lung cancer cell growth through WISP-1-integrin ανβ3-STAT1 signaling pathway. [Abstract]

2025 Feb 18;23(1):98. PMID: 39966869
NPJ Precis Oncol

Integrative profiling strategies to guide personalized therapy in mantle cell lymphoma: a pilot study. [Abstract]

2025 Nov 21;9(1):373. PMID: 41272086
Mol Cell Biochem

FOXM1 upregulation, promotes immune escape in gastric cancer through activation of Notch signaling pathway. [Abstract]

2025 Jun 11. PMID: 40498401

Crenigacestat purchased from MedChemExpress. Usage Cited in: Mol Cell Biochem. 2025 Jun 11. [Abstract]

After treating GC cells with the Notch inhibitor Crenigacestat (10 μM) for 2 hours, FOXM1 cells were transfected, and Western blot analysis was performed to detect that Crenigacestat treatment reduced the expression levels of Notch signaling pathway-related proteins.

Crenigacestat purchased from MedChemExpress. Usage Cited in: Mol Cell Biochem. 2025 Jun 11. [Abstract]

Western blot analysis revealed that treatment with Crenigacestat (10 μM) reduced the expression of PD-L1 protein.

Crenigacestat purchased from MedChemExpress. Usage Cited in: Mol Cell Biochem. 2025 Jun 11. [Abstract]

The results of CFSE staining confirmed that Crenigacestat (10 μM) treatment partially increased the proliferative capacity of CD8 + T cells.

Crenigacestat purchased from MedChemExpress. Usage Cited in: Mol Cell Biochem. 2025 Jun 11. [Abstract]

Flow cytometry confirmed that Crenigacestat (10 μM) treatment partially reduced the apoptosis rate of CD8 + T cells.
J Cell Biochem

Heme oxygenase-1 attenuates the inhibitory effect of bortezomib against the APRIL-NF-κB-CCL3 signaling pathways in multiple myeloma cells: Corelated with bortezomib tolerance in multiple myeloma. [Abstract]

2019 May;120(5):6972-6987. PMID: 30368867

Crenigacestat purchased from MedChemExpress. Usage Cited in: J Cell Biochem. 2019 May;120(5):6972-6987. [Abstract]

The Western blot analysis results show that LY3039478 inhibits not only Notch1 but also APRIL.
ACS Comb Sci

Benzimidazolyl-pyrazolo[3,4- b]pyridinones, Selective Inhibitors of MOLT-4 Leukemia Cell Growth and Sea Urchin Embryo Spiculogenesis: Target Quest. [Abstract]

2019 Dec 9;21(12):805-816. PMID: 31689077

Solvent & Solubility

In Vitro:

DMSO : ≥ 100 mg/mL (215.31 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

* "≥" means soluble, but saturation unknown.

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.1531 mL

10.7657 mL

21.5313 mL

5 mM

0.4306 mL

2.1531 mL

4.3063 mL

10 mM

0.2153 mL

1.0766 mL

2.1531 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 5 mg/mL (10.77 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 5 mg/mL (10.77 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 5 mg/mL (10.77 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (281 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Yuen E, et al. Evaluation of the effects of an oral notch inhibitor, crenigacestat (LY3039478), on QT interval, and bioavailability studies conducted in healthy subjects. Cancer Chemother Pharmacol. 2019 Mar;83(3):483-492. [Content Brief]

[2]. Mäemets-Allas K, et al. The inhibition of Akt-Pdpk1 interaction efficiently suppresses the growth of murine primary liver tumor cells. Biochem Biophys Res Commun. 2016 May 20;474(1):118-125. [Content Brief]

[3]. Bhagat TD, et al. Notch Pathway Is Activated via Genetic and Epigenetic Alterations and Is a Therapeutic Target in Clear Cell Renal Cancer. J Biol Chem. 2017 Jan 20;292(3):837-846. [Content Brief]

[4]. Mark H. Bender, et al. Abstract 1131: Novel inhibitor of Notch signaling for the treatment of cancer. Experimental and Molecular Therapeutics. 2013.

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.1531 mL	10.7657 mL	21.5313 mL	53.8283 mL
	5 mM	0.4306 mL	2.1531 mL	4.3063 mL	10.7657 mL
	10 mM	0.2153 mL	1.0766 mL	2.1531 mL	5.3828 mL
	15 mM	0.1435 mL	0.7177 mL	1.4354 mL	3.5886 mL
	20 mM	0.1077 mL	0.5383 mL	1.0766 mL	2.6914 mL
	25 mM	0.0861 mL	0.4306 mL	0.8613 mL	2.1531 mL
	30 mM	0.0718 mL	0.3589 mL	0.7177 mL	1.7943 mL
	40 mM	0.0538 mL	0.2691 mL	0.5383 mL	1.3457 mL
	50 mM	0.0431 mL	0.2153 mL	0.4306 mL	1.0766 mL
	60 mM	0.0359 mL	0.1794 mL	0.3589 mL	0.8971 mL
	80 mM	0.0269 mL	0.1346 mL	0.2691 mL	0.6729 mL
	100 mM	0.0215 mL	0.1077 mL	0.2153 mL	0.5383 mL

Keywords

Crenigacestat

7 Cited Publications

100 mg Get Quote

Subscribe to the

MedChemExpress

Newsletter

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

Crenigacestat

Anti-Infection Compound Library

Immunology/Inflammation Compound Library

Neuronal Signaling Compound Library

Stem Cell Signaling Compound Library

Wnt/Hedgehog/Notch Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Anti-Aging Compound Library

Drug Repurposing Compound Library

Differentiation Inducing Compound Library

Reprogramming Compound Library

Anti-COVID-19 Compound Library

Orally Active Compound Library

Anti-Breast Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Neurodegenerative Disease-related Compound Library

Angiogenesis-Related Compound Library

Transcription Factor-Targeted Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Cancer Stem Cells Compound Library

Heterocyclic Compound Library

Membrane Protein-targeted Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Anti-Rheumatic Arthritis Compound Library

Publications Citing Use of MedChemExpress (MCE) Crenigacestat

Biological Activity

Chemical Information

Publications (7)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Crenigacestat Related Classifications

Cat. No.: HY-12449