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NVP-LDE225

(CAS No:956697-53-3)

Erismodegib (NVP-LDE225) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3.

CAS No:956697-53-3

Molecular Weight(MW):485.5

Purity:99.00%

Specification:500MG;1G;5G;10G;50G;100G

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QC Documents

COA	MSDS	HPLC	NMR

ChemicalInfomation

CAS No:	956697-53-3
Molecular formula(MF)	C₂₆H₂₆F₃N₃O₃
Molecular Weight(MW):	485.5
Alias

Solubility

In vitro	DMSO	97 mg/mL (199.79 mM)
	Ethanol	97 mg/mL warmed (199.79 mM)
	Water	<1 mg/mL
In vivo	2% DMSO+corn oil	10mg/mL

Biological Activity

Description

Erismodegib (NVP-LDE225) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3.

Targets

Smo (mouse) ^[1] (Cell-free assay)	Smo (human) ^[1] (Cell-free assay)
1.3 nM	2.5 nM

In vitro

LDE225 inhibits TM3 luciferized cell line with 0.6 nM and 8 nM, at the presence of 1 nM and 25 nM Hh agonist Ag1.5, respectively. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Formulation	Activity Description	PMID
A2780ip2	Cytoxicity assay	~10 Î¼M		IC50=12 Î¼M	22553355
A2780cp20	Cytoxicity assay	~10 Î¼M		IC50=7.5 Î¼M	22553355
SKOV3ip1	Cytoxicity assay	~10 Î¼M		IC50=24 Î¼M	22553355
SKOV3TRip2	Cytoxicity assay	~10 Î¼M		IC50=12 Î¼M	22553355
HeyA8	Cytoxicity assay	~10 Î¼M		IC50=18 Î¼M	22553355
HeyA8MDR	Cytoxicity assay	~10 Î¼M		IC50=8 Î¼M	22553355
OS5	Growth inhibitory assay	~5 Î¼M		reduces the proliferation	23243595
OS18	Growth inhibitory assay	~5 Î¼M		reduces the proliferation	23243595
Glioblastoma initiating cells	Cytoxicity assay	~10 Î¼M		Inhibits Cell Viability	23482671
Glioblastoma initiating cells	Function assay	~10 Î¼M		inhibits neurosphere formation	23482671
Glioblastoma initiating cells	Cytoxicity assay	~10 Î¼M		induces apoptosis	23482671
Glioblastoma initiating cells	Function assay	~10 Î¼M		downregulates the SHH signaling pathway	23482671
Glioblastoma initiating cells	Function assay	~10 Î¼M		Inhibits the Expression of Genes Involved in Maintaining Pluripotency	23482671
Glioblastoma initiating cells	Function assay	~10 Î¼M		Inhibits Motility, Invasion, and Migration	23482671
LOX IMVI	Function assay	10 Î¼M	DMSO	inhibits Hedgehog-GLI pathway	23935925
UACC 257	Function assay	10 Î¼M	DMSO	inhibits Hedgehog-GLI pathway	23935925
LOX IMVI	Function assay	10 Î¼M	DMSO	induces G1 cell cycle arrest	23935925
UACC 257	Function assay	10 Î¼M	DMSO	induces G1 cell cycle arrest	23935925
LOX IMVI	Cytoxicity assay	10 Î¼M	DMSO	decreases tumor cell viability	23935925
UACC 257	Cytoxicity assay	10 Î¼M	DMSO	decreases tumor cell viability	23935925
LOX IMVI	Apoptosis assay	10 Î¼M	DMSO	induces apoptosis	23935925
UACC 257	Apoptosis assay	10 Î¼M	DMSO	induces apoptosis	23935925
ACHN	Growth inhibitory assay	~5 Î¼M	DMSO	IC50=2-3âÎ¼M	25093491
769-P	Growth inhibitory assay	~5 Î¼M	DMSO	IC50=2-3âÎ¼M	25093491
786-O	Growth inhibitory assay	~5 Î¼M	DMSO	IC50=2-3âÎ¼M	25093491
786-O SuR	Growth inhibitory assay	~5 Î¼M	DMSO	IC50=2-3âÎ¼M	25093491
SP53	Function assay	30 Î¼M	DMSO	inhibits cell adhesion and migration	26885608
SP53	Function assay	30 Î¼M	DMSO	inhibits the VLA4-mediated FAK signaling pathway	26885608
HS5	Function assay	30 Î¼M	DMSO	inhibits cell adhesion and migration	26885608
HS27a	Function assay	30 Î¼M	DMSO	inhibits cell adhesion and migration	26885608
SP53	Cytoxicity assay	30 Î¼M	DMSO	induces autophagy	26885608
Jeko	Cytoxicity assay	30 Î¼M	DMSO	induces autophagy	26885608

... Click to View More Cell Line Experimental Data

In vivo

LDE225 is highly bound to mouse, rat, and human plasma proteins (>99%) and moderately bound to dog and monkey plasma proteins (77 and 85%, respectively). LDE225 has high permeability (90.8% in man) in the PAMPA assay. LDE225 shows good oral bioavailability ranging from 69 to 102% in preclinical species when dosed in solution. LDE225 is a weak base with a measured pK_a of 4.20 and exhibits relatively poor aqueous solubility. LDE225 demonstrates dose-related antitumor activity. At a dose of 5 mg/kg/day qd, LDE225 significantly inhibits tumor growth, corresponding to a T/C value of 33%. When dosed at 10 and 20 mg/kg/day qd, LDE225 gives rise to 51 and 83% regression, respectively. Gli1 mRNA inhibition correlates with tumor and plasma exposure of LDE225. LDE225 successfully penetrates the blood−brain barrier in tumor-bearing animals and results in tumor growth inhibition after 4 days of treatment. ^[1] LDE225 significantly reduces the tumor volume by 95.7% in Rip1-Tag2 mice. LDE225 prolongs survival in Rip1Tag2 mice. LDE225 decreases expression of stromal markers in the LDE225-treated mice. ^[2]