Crenigacestat (LY3039478)

For research use only.

Catalog No.S7169

6 publications

Crenigacestat (LY3039478) Chemical Structure

CAS No. 1421438-81-4

Crenigacestat (LY3039478) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch.

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Selleck's Crenigacestat (LY3039478) has been cited by 6 publications

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  • Effect of LY3039478 on Hes protein in SGC7901/DDP cells. A, Protein expression of Hes-1 by Western blot. B, Expression level of Hes-1 by Western blot experiment. (*p < 0.05 control with LY3039478 0 μmol/L group; **p < 0.01 control with LY3039478 0 μmol/L group).

    Eur Rev Med Pharmacol Sci, 2018, 22(13):4121-4127. Crenigacestat (LY3039478) purchased from Selleck.

Purity & Quality Control

Choose Selective Notch Inhibitors

Biological Activity

Description Crenigacestat (LY3039478) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch.
Targets
Notch-1 [1]
~1 nM
In vitro

LY3039478 is a novel small molecule that is an exquisitely potent inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with an IC50 of ∼1nM in most of the tumor cell lines tested. LY3039478 also potently inhibits mutant Notch receptor activity[2]. Treatment with a gamma secretase inhibitor, LY3039478, significantly inhibited the growth of 2 CCRCC(Clear cell renal cell carcinoma) cell lines in a concentration dependent manner. LY3039478 treatment also led to decreased expression of Myc and Cyclin A1, two genes that were part of the NOTCH driven proliferative signature in murine and human model systems. LY3039478 treatment also led to G0/G1 cell cycle arrest in CCRCC cells[3].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SW480 cells MofQSpVv[3Srb36gZZN{[Xl? M3rzV|I1KGh? MljsTY5pcWKrdHnvckBw\iCpYX3tZU1{\WO{ZYThd4UhdWWmaXH0[YQh[2ynYY\h[4Uhd2ZiTn;0Z4ghOSCrbjDoeY1idiCVV{S4NEBk\WyuczDhd5Nme3OnZDDhd{BvfWOuZXHyJIFk[3WvdXzheIlwdiCxZjDOc5RkcCBzIHnueJJi[2WubIXsZZIh\G:vYXnuJEhPOUmFRDmgZYZ1\XJiMkSgbJJ{KGK7IFXMTXNCNCCLQ{WwQVAvODByMTFOwG0> NVX5TFdTOjR7MEC2O|g>
HEL 92.1.7 cells NYPl[oF3TnWwY4Tpc44h[XO|YYm= MWiyOEBp MnL3TY5pcWKrdHnvckBw\iCpYX3tZU1{\WO{ZYThd4UhdWWmaXH0[YQh[2ynYY\h[4Uhd2ZiTn;0Z4ghOSCrbjDoeY1idiCKRVygPVIvOS55IHPlcIx{KGG|c3Xzd4VlKGG|IH71Z4xm[XJiYXPjeY12dGG2aX;uJI9nKE6xdHPoJFEhcW62cnHj[YxtfWyjcjDkc41icW5iKF6xTWNFMSCjZoTldkAzPCCqcoOgZpkhTUyLU1GsJGlEPTB;MD6wNFAzOyEQvF2= NUPvNpF6OjR7MEC2O|g>
U-87-MG cells NHrtPVhHfW6ldHnvckBie3OjeR?= MoXFNlQhcA>? NHX5XmJKdmirYnn0bY9vKG:oIHfhcY1iNXOnY4LleIF{\SCvZXTpZZRm\CClbHXheoFo\SCxZjDOc5RkcCBzIHnuJIh2dWGwIGWtPFcuVUdiY3XscJMh[XO|ZYPz[YQh[XNiboXjcIVieiCjY3P1cZVt[XSrb36gc4YhVm:2Y3igNUBqdnS{YXPlcIx2dGG{IHTvcYFqdiBqTkHJR2QqKGGodHXyJFI1KGi{czDifUBGVEmVQTygTWM2OD1yLkCwNFI5KM7:TR?= M4m1dFI1QTByNke4
BxPC3 cells M4izVWZ2dmO2aX;uJIF{e2G7 MnT1NlQhcA>? NVnDZYVQUW6qaXLpeIlwdiCxZjDnZY1u[S2|ZXPy[ZRie2VibXXkbYF1\WRiY3zlZZZi\2Vib3[gUo91[2hiMTDpckBpfW2jbjDCfHBEOyClZXzsd{Bie3Onc4Pl[EBieyCwdXPs[YFzKGGlY4XteYxifGmxbjDv[kBPd3SlaDCxJIlvfHKjY3XscJVt[XJiZH;tZYlvKCiQMVnDSEkh[W[2ZYKgNlQhcHK|IHL5JGVNUVODLDDJR|UxRTBwMECwN|kh|ryP MnPUNlQ6ODB4N{i=
A375 cells M1nWU2Z2dmO2aX;uJIF{e2G7 MX2yOEBp Mkn6TY5pcWKrdHnvckBw\iCpYX3tZU1{\WO{ZYThd4UhdWWmaXH0[YQh[2ynYY\h[4Uhd2ZiTn;0Z4ghOSCrbjDoeY1idiCDM{e1JINmdGy|IHHzd4V{e2WmIHHzJI52[2ynYYKgZYNkfW23bHH0bY9vKG:oIF7veINpKDFiaX70doFk\WyudXzhdkBld22jaX6gLG4yUUOGKTDh[pRmeiB{NDDodpMh[nliRVzJV2EtKEmFNUC9NE4xODB2ODFOwG0> NEiyWpAzPDlyME[3PC=>
MDA-MB-231 NUi0SWltTnWwY4Tpc44h[XO|YYm= NHL4bo0zPCCq M{nCZWlvcGmkaYTpc44hd2ZiZ3HtcYEue2WlcnX0ZZNmKG2nZHnheIVlKGOuZXH2ZYdmKG:oIF7veINpKDFiaX6gbJVu[W5iTVTBMW1DNTJ|MTDj[YxteyCjc4Pld5Nm\CCjczDueYNt\WG{IHHjZ5VufWyjdHnvckBw\iCQb4TjbEAyKGmwdILhZ4VtdHWuYYKg[I9u[WmwIDjONWlETCliYX\0[ZIhOjRiaILzJIJ6KEWOSWPBMEBKSzVyPUCuNFAxPSEQvF2= M2W0fVI1QTByNke4
MOLT-3 cells MV3GeY5kfGmxbjDhd5NigQ>? M4fmUVI1KGh? MYHJcohq[mm2aX;uJI9nKGejbX3hMZNm[3KndHHz[UBu\WSrYYTl[EBkdGWjdnHn[UBw\iCQb4TjbEAyKGmwIHj1cYFvKE2RTGStN{Bk\WyuczDhd5Nme3OnZDDhd{BvfWOuZXHyJIFk[3WvdXzheIlwdiCxZjDOc5RkcCBzIHnueJJi[2WubIXsZZIh\G:vYXnuJEhPOUmFRDmgZYZ1\XJiMkSgbJJ{KGK7IFXMTXNCNCCLQ{WwQVAvODByNkGg{txO M{Gy[|I1QTByNke4
MIAPaCa2 cells MmfISpVv[3Srb36gZZN{[Xl? MofoNlQhcA>? MlfkTY5pcWKrdHnvckBw\iCpYX3tZU1{\WO{ZYThd4UhdWWmaXH0[YQh[2ynYY\h[4Uhd2ZiTn;0Z4ghOSCrbjDoeY1idiCPSVHQZWNiOiClZXzsd{Bie3Onc4Pl[EBieyCwdXPs[YFzKGGlY4XteYxifGmxbjDv[kBPd3SlaDCxJIlvfHKjY3XscJVt[XJiZH;tZYlvKCiQMVnDSEkh[W[2ZYKgNlQhcHK|IHL5JGVNUVODLDDJR|UxRTBwMECwO|Eh|ryP MmHENlQ6ODB4N{i=
HCT 116 cells MVHGeY5kfGmxbjDhd5NigQ>? MUeyOEBp NHPDdVZKdmirYnn0bY9vKG:oIHfhcY1iNXOnY4LleIF{\SCvZXTpZZRm\CClbHXheoFo\SCxZjDOc5RkcCBzIHnuJIh2dWGwIFjDWEAyOTZiY3XscJMh[XO|ZYPz[YQh[XNiboXjcIVieiCjY3P1cZVt[XSrb36gc4YhVm:2Y3igNUBqdnS{YXPlcIx2dGG{IHTvcYFqdiBqTkHJR2QqKGGodHXyJFI1KGi{czDifUBGVEmVQTygTWM2OD1yLkCwNFczKM7:TR?= MoDENlQ6ODB4N{i=
K562 cells MneySpVv[3Srb36gZZN{[Xl? MVeyOEBp MX;Jcohq[mm2aX;uJI9nKGejbX3hMZNm[3KndHHz[UBu\WSrYYTl[EBkdGWjdnHn[UBw\iCQb4TjbEAyKGmwIHj1cYFvKEt3NkKgZ4VtdHNiYYPz[ZN{\WRiYYOgcpVkdGWjcjDhZ4N2dXWuYYTpc44hd2ZiTn;0Z4ghOSCrboTyZYNmdGy3bHHyJIRwdWGrbjCoUlFKS0RrIHHmeIVzKDJ2IHjyd{BjgSCHTFnTRUwhUUN3ME2wMlAxODd2IN88US=> MWmyOFkxODZ5OB?=
CCRF-CEM cells NHfhSlhHfW6ldHnvckBie3OjeR?= NUjTUHhwOjRiaB?= MU\Jcohq[mm2aX;uJI9nKGejbX3hMZNm[3KndHHz[UBu\WSrYYTl[EBkdGWjdnHn[UBw\iCQb4TjbEAyKGmwIHj1cYFvKEOFUl[tR2VOKGOnbHzzJIF{e2W|c3XkJIF{KG63Y3zlZZIh[WOldX31cIF1cW:wIH;mJG5wfGOqIEGgbY51emGlZXzseYxieiCmb33hbY4hME5zSVPELUBi\nSncjCyOEBpenNiYomgSWxKW0FuIFnDOVA:OC5yMEC3OkDPxE1? NIDEVIczPDlyME[3PC=>
DLD1 cells M4LxNGZ2dmO2aX;uJIF{e2G7 NH\VT44zPCCq NIDoeXlKdmirYnn0bY9vKG:oIHfhcY1iNXOnY4LleIF{\SCvZXTpZZRm\CClbHXheoFo\SCxZjDOc5RkcCBzIHnuJIh2dWGwIFTMSFEh[2WubIOgZZN{\XO|ZXSgZZMhdnWlbHXhdkBi[2O3bYXsZZRqd25ib3[gUo91[2hiMTDpcpRz[WOnbHz1cIFzKGSxbXHpckApVjGLQ1SpJIFnfGW{IEK0JIhzeyCkeTDFUGlUSSxiSVO1NF0xNjByMEm4JO69VQ>? NUnVeW9SOjR7MEC2O|g>
A2780 cells NV3FflI2TnWwY4Tpc44h[XO|YYm= MoT0NlQhcA>? NF3KZ4tKdmirYnn0bY9vKG:oIHfhcY1iNXOnY4LleIF{\SCvZXTpZZRm\CClbHXheoFo\SCxZjDOc5RkcCBzIHnuJIh2dWGwIFGyO|gxKGOnbHzzJIF{e2W|c3XkJIF{KG63Y3zlZZIh[WOldX31cIF1cW:wIH;mJG5wfGOqIEGgbY51emGlZXzseYxieiCmb33hbY4hME5zSVPELUBi\nSncjCyOEBpenNiYomgSWxKW0FuIFnDOVA:OC5yMEGwN{DPxE1? MYqyOFkxODZ5OB?=
SUP-T1 cells M{fRWGZ2dmO2aX;uJIF{e2G7 NV:5XYVjOjRiaB?= MnnkTY5pcWKrdHnvckBw\iCpYX3tZU1{\WO{ZYThd4UhdWWmaXH0[YQh[2ynYY\h[4Uhd2ZiTn;0Z4ghOSCrbjDoeY1idiCVVWCtWFEh[2WubIOgZZN{\XO|ZXSgZZMhdnWlbHXhdkBi[2O3bYXsZZRqd25ib3[gUo91[2hiMTDpcpRz[WOnbHz1cIFzKGSxbXHpckApVjGLQ1SpJIFnfGW{IEK0JIhzeyCkeTDFUGlUSSxiSVO1NF0xNjByMUK0JO69VQ>? M3TqUlI1QTByNke4
Jurkat cells M2HjOGZ2dmO2aX;uJIF{e2G7 MmDMNlQhcA>? M3LaVmlvcGmkaYTpc44hd2ZiZ3HtcYEue2WlcnX0ZZNmKG2nZHnheIVlKGOuZXH2ZYdmKG:oIF7veINpKDFiaX6gbJVu[W5iSoXyb4F1KGOnbHzzJIF{e2W|c3XkJIF{KG63Y3zlZZIh[WOldX31cIF1cW:wIH;mJG5wfGOqIEGgbY51emGlZXzseYxieiCmb33hbY4hME5zSVPELUBi\nSncjCyOEBpenNiYomgSWxKW0FuIFnDOVA:OC5yMEW5OUDPxE1? NIjuboYzPDlyME[3PC=>

... Click to View More Cell Line Experimental Data

In vivo In mice, its oral bioavalability(%F) is 65%, clearance(CL)=41 mL/min/kg, VDss = 3.8 L/kg. In Rats, its oral bioavalability(%F) is 65%, CL=98 mL/min/kg, VDss=4.9 L/kg. In Dogs, its oral bioavalability (%F) is 67%, CL=3.8 mL/min/kg, VDss=1.4 L/kg[1]. In a xenograft tumor model, LY3039478 inhibited N1ICD cleavage and expression of Notch-regulated genes in the tumor microenvironment. The inhibition of Notch cleavage also resulted in the induction of apoptosis in a Notch-dependent xenograft model[2]. In immunodeficient NSG mice xenografted with 769-P CCRCC cells, LY3039478 treatment resulted in significantly increased survival and delayed tumor growth in independent cohorts of mice demonstrating in vivo efficacy in CCRCC[3].

Protocol

Cell Research:

[4]

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  • Cell lines: K07074 cells
  • Concentrations: 100 nM
  • Incubation Time: 24, 48, 72, 96 h
  • Method:

    K07074 cells were plated to 24-well plates at 105 cell/well. Viability of cells was assessed in quadruplicates at indicated timepoints using the CellTiter-Glo luminescent cell viability assay. To study the effect of the small molecular compounds on K07074 cell growth the compounds or DMSO were added to the growth media 24 h after seeding. The cells were incubated with inhibitors and DMSO as indicated. Cell viability was assessed as described above. Each experiment was carried out in triplicate and at least 3 independent experiments were performed.


    (Only for Reference)
Animal Research:

[3]

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  • Animal Models: Mice
  • Dosages: 8 mg/kg
  • Administration: oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 92 mg/mL (198.08 mM)
Water Insoluble
Ethanol '''71 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 464.44
Formula

C22H23F3N4O4

CAS No. 1421438-81-4
Storage powder
in solvent
Synonyms
Smiles CC(C(=O)NC1C2=CC=CC=C2C3=C(N=CC=C3)N(C1=O)CCO)NC(=O)CCC(F)(F)F

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02906618 Completed Drug: LY3039478|Drug: 3C 15N 2H-LY3039478 IV Healthy Eli Lilly and Company October 4 2016 Phase 1
NCT02917733 Completed Drug: LY3039478 Healthy Eli Lilly and Company September 2016 Phase 1
NCT02836600 Active not recruiting Drug: LY3039478 Advanced Solid Tumor Eli Lilly and Company September 9 2016 Phase 1
NCT02518113 Completed Drug: LY3039478|Drug: Dexamethasone|Drug: Placebo T-cell Acute Lymphoblastic Leukemia|T-cell Lymphoblastic Lymphoma Eli Lilly and Company October 1 2015 Phase 1|Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID