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Vismodegib (GDC-0449) inibitore di Hedgehog

Name: Vismodegib (GDC-0449)
Brand: Selleck Chemicals
SKU: S1082
Rating: 5 (217 reviews)

N. Cat.S1082

Vismodegib (GDC-0449) è un potente, nuovo e specifico inibitore di hedgehog con IC50 di 3 nM e inibisce anche la P-gp con IC50 di 3,0 μM in un saggio senza cellule.

Vismodegib (GDC-0449) Hedgehog/Smoothened inibitore Chemical Structure

Struttura chimica

Peso molecolare: 421.3

Vai a

Controllo Qualità

Lotto: Purezza: 99.99%

99.99

Target correlati	JAK TGF-beta/Smad Wnt/beta-catenin ERK GSK-3 ROCK PKA Secretase STAT Casein Kinase
Altro Hedgehog/Smoothened Inibitori	SAG (Smoothened Agonist) Hydrochloride Purmorphamine Cyclopamine (11-Deoxojervine) GANT61 SAG (Smoothened Agonist) SANT-1 HPI-4 (Ciliobrevin A) BMS-833923 Taladegib (LY2940680) Ciliobrevin D

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dellattività	PMID
IGROV-1	Growth Inhibition Assay			IC50=0.07248 μM	SANGER
HCE-T	Growth Inhibition Assay			IC50=1.32247 μM	SANGER
D-542MG	Growth Inhibition Assay			IC50=1.86737 μM	SANGER
23132-87	Growth Inhibition Assay			IC50=4.40147 μM	SANGER
HDLM-2	Growth Inhibition Assay			IC50=8.04766 μM	SANGER
ACN	Growth Inhibition Assay			IC50=8.50109 μM	SANGER
HuO-3N1	Growth Inhibition Assay			IC50=9.60108 μM	SANGER
BHT-101	Growth Inhibition Assay			IC50=11.38 μM	SANGER
KYSE-150	Growth Inhibition Assay			IC50=11.5841 μM	SANGER
MC-IXC	Growth Inhibition Assay			IC50=12.2292 μM	SANGER
D-423MG	Growth Inhibition Assay			IC50=12.7657 μM	SANGER
NY	Growth Inhibition Assay			IC50=14.8903 μM	SANGER
HOS	Growth Inhibition Assay			IC50=15.6719 μM	SANGER
NB7	Growth Inhibition Assay			IC50=15.891 μM	SANGER
DMS-273	Growth Inhibition Assay			IC50=16.6713 μM	SANGER
MDA-MB-361	Growth Inhibition Assay			IC50=17.2711 μM	SANGER
DU-145	Growth Inhibition Assay			IC50=18.32 μM	SANGER
NCI-H82	Growth Inhibition Assay			IC50=19.8386 μM	SANGER
NCI-SNU-1	Growth Inhibition Assay			IC50=20.0196 μM	SANGER
GCT	Growth Inhibition Assay			IC50=20.8824 μM	SANGER
C2BBe1	Growth Inhibition Assay			IC50=21.1058 μM	SANGER
LB2241-RCC	Growth Inhibition Assay			IC50=21.8441 μM	SANGER
COLO-829	Growth Inhibition Assay			IC50=22.1871 μM	SANGER
EW-11	Growth Inhibition Assay			IC50=22.8022 μM	SANGER
NCI-H526	Growth Inhibition Assay			IC50=23.4717 μM	SANGER
SF295	Growth Inhibition Assay			IC50=24.0252 μM	SANGER
D-566MG	Growth Inhibition Assay			IC50=25.2943 μM	SANGER
8505C	Growth Inhibition Assay			IC50=25.6331 μM	SANGER
HT-29	Growth Inhibition Assay			IC50=26.0431 μM	SANGER
NBsusSR	Growth Inhibition Assay			IC50=26.8006 μM	SANGER
BV-173	Growth Inhibition Assay			IC50=28.3182 μM	SANGER
CTB-1	Growth Inhibition Assay			IC50=30.1031 μM	SANGER
JAR	Growth Inhibition Assay			IC50=32.5371 μM	SANGER
CAMA-1	Growth Inhibition Assay			IC50=33.4615 μM	SANGER
CAL-51	Growth Inhibition Assay			IC50=34.7176 μM	SANGER
A172	Growth Inhibition Assay			IC50=37.4921 μM	SANGER
QIMR-WIL	Growth Inhibition Assay			IC50=38.0708 μM	SANGER
AsPC-1	Growth Inhibition Assay			IC50=38.4651 μM	SANGER
MKN7	Growth Inhibition Assay			IC50=39.0079 μM	SANGER
ONS-76	Growth Inhibition Assay			IC50=43.3057 μM	SANGER
RS4-11	Growth Inhibition Assay			IC50=44.0752 μM	SANGER
NOS-1	Growth Inhibition Assay			IC50=44.6031 μM	SANGER
A101D	Growth Inhibition Assay			IC50=44.8023 μM	SANGER
HCC1806	Growth Inhibition Assay			IC50=46.1148 μM	SANGER
CAL-27	Growth Inhibition Assay			IC50=47.7246 μM	SANGER
BT-549	Growth Inhibition Assay			IC50=48.5315 μM	SANGER
LCLC-97TM1	Growth Inhibition Assay			IC50=49.2413 μM	SANGER
A4-Fuk	Growth Inhibition Assay			IC50=49.849 μM	SANGER
OVCAR-4	Growth Inhibition Assay			IC50=50.0601 μM	SANGER
HD-MY-Z	Growth Inhibition Assay			IC50=50.7764 μM	SANGER
NCI-H292	Growth Inhibition Assay			IC50=50.8758 μM	SANGER
Sk-ChA-1	Growth Inhibition Assay	0.25–50 μM	72 h	IC50=74.54±2.58μM	25742482
Mz-ChA-1	Growth Inhibition Assay	0.25–50 μM	72 h	IC50=54.97±3.45μM	25742482
Smo-WT	Growth Inhibition Assay			IC50 of 14 nM	24291104
Smo-D473H	Growth Inhibition Assay			IC50 of 7.1 μM	24291104
K562	Function Assay	10 μM	72 h	reduces the expression of Gli1	23319824
T315I BCR-ABL BaF3	Function Assay	10 μM	72 h	reduces the expression of Gli1	23319824
TF-1 BCR-ABL	Function Assay	10 μM	72 h	reduces the expression of Gli1	23319824
Shh-Light 2	Function assay		2 days	Antagonist activity at Smo in mouse Shh-Light 2 cells assessed as inhibition of Shh-induced Gli1-reporter activity after 2 days by dual-luciferase reporter gene method, IC50 = 0.0015 μM.	23063522
NIH/3T3	Function assay			Inhibition of hedgehog signaling (unknown origin) expressed in mouse NIH/3T3 cells by Gli-dual-luciferase reporter assay, IC50 = 0.0023 μM.	27180012
NIH/3T3 Light2	Function assay			Inhibition of hedgehog signaling pathway in mouse NIH/3T3 Light2 cells by Gli-luciferase reporter gene assay, IC50 = 0.0023 μM.	28688278
Light2	Function assay		48 hrs	Inhibition of hedgehog signaling pathway in mouse Light2 cells after 48 hrs by Gli-luciferase reporter gene assay, IC50 = 0.00246 μM.	29739714
HEPM	Function assay			Inhibition of SHH in human HEPM cells by Gli-luciferase reporter gene assay, INH = 0.0028 μM.	19716296
Shh Light2	Function assay			Inhibition of SHH in mouse Shh Light2 cells by GLI-responsive firefly luciferase reporter gene assay, IC50 = 0.003 μM.	19309080
HEPM	Function assay			Inhibition of Hedgehog signaling in human HEPM cells assessed as reduction in receptor-mediated Gli1 mRNA expression by reporter gene assay, INH = 0.003 μM.	20875741
C3H10T1/2	Function assay		20 hrs	Inhibition of Smo in mouse C3H10T1/2 cells using human recombinant SHH assessed as effect on SMO/SHH transient transcriptional activation after 20 hrs by Gli-luciferase reporter assay, IC50 = 0.005 μM.	24900436
NIH/3T3	Function assay		24 hrs	Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells measured after 24 hrs by Gli-dual luciferase reporter gene assay, IC50 = 0.005 μM.	27810591
NIH3T3	Function assay		48 hrs	Inhibition of smo-mediated hedgehog signaling pathway in mouse NIH3T3 cells expressing GRE-Luc reporter gene assessed as inhibition of SAG-induced GRE-Luc reporter activity after 48 hrs by luminescence assay, IC50 = 0.006 μM.	29499483
Shh-light2	Function assay			Inhibition of Smo-mediated Hh signaling in human Shh-light2 cells by luciferase reporter gene assay, IC50 = 0.007 μM.	22268551
HEK293	Function assay		2 hrs	Displacement of BODIPY-labelled cyclopamine from human Smo receptor expressed in HEK293 cells after 2 hrs by fluorescence microscopy, IC50 = 0.007 μM.	22268551
NIH3T3	Function assay			Inhibition of hedgehog receptor signaling pathway in mouse NIH3T3 cells transfected with Gli-reporter gene by luciferase reporter gene assay, IC50 = 0.00717 μM.	24923765
NIH/3T3	Function assay		48 hrs	Inhibition of Hedgehog signaling pathway in mouse NIH/3T3 cells assessed as reduction in Sonic hedgehog-induced Gli luciferase activity after 48 hrs by Dual-luciferase reporter gene assay, IC50 = 0.00717 μM.	30249494
NIH3T3	Function assay		48 hrs	Inhibition of hedgehog signalling in mouse NIH3T3 cells stably transfected with Gli-luciferase construct incubated for 48 hrs by dual luciferase reporter gene assay, IC50 = 0.0072 μM.	26827136
NIH3T3	Function assay		48 hrs	Inhibition of Sonic-induced hedgehog signalling in mouse NIH3T3 cells after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0072 μM.	26820554
NIH3T3	Function assay		48 hrs	Inhibition of SHH signaling pathway in mouse NIH3T3 cells measured after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0072 μM.	24176396
NIH/3T3	Function assay		48 hrs	Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells after 48 hrs by Gli-luciferase reporter gene assay, IC50 = 0.0072 μM.	24486203
NIH/3T3	Function assay			Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells by Gli1-luciferase reporter gene assay, IC50 = 0.0072 μM.	24405704
NIH/3T3	Function assay			Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells carrying stably transfected Gli-reporter construct by luciferase reporter assay, IC50 = 0.0072 μM.	28642101
C3H10T1/2	Function assay		6 hrs	Inhibition of SAG-induced differentiation of mouse mesenchymal pluripotent C3H10T1/2 cells to alkaline phosphatase positive oeseoblasts after 6 hrs, IC50 = 0.011 μM.	22268551
HCC827	Function assay			Displacement of [3H]-cyclopamine from SMO V404M mutant in gefitinib resistant human HCC827 cells by scintillation counting, Ki = 0.0122 μM.	28787156
C3H10T1/2	Function assay			Inhibition of SHH in mouse C3H10T1/2 cells by Gli-luciferase reporter gene assay, IC50 = 0.013 μM.	19716296
S12	Function assay			Inhibition of Hedgehog signaling in mouse S12 cells assessed as reduction in receptor-mediated Gli1 mRNA expression by reporter gene assay, INH = 0.013 μM.	20875741
TM3	Function assay		48 hrs	Inhibition of Hh signaling pathway in mouse TM3 cells assessed as downregulation of Gli1 gene expression after 48 hrs by luciferase reporter gene assay, EC50 = 0.013 μM.	26976215
NIH/3T3	Function assay			Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells expressing wild type Smo assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 0.0144 μM.	27810591
S12	Function assay		48 hrs	Inhibition of human SHH pathway in mouse S12 cells assessed as GLI-mediated transcriptional activity after 48 hrs by luciferase reporter gene assay, IC50 = 0.015 μM.	21438527
NIH/3T3	Function assay			Inhibition of SMO in mouse NIH/3T3 cells assessed as inhibition of SAG-induced hedgehog-mediated luminescence signaling by GRE-luciferase reporter gene assay, IC50 = 0.016 μM.	26119500
U2OS	Function assay		2 hrs	Displacement of [3H]cyclopamine from wild type Smo expressed in U2OS cells after 2 hrs by scintillation counting, Ki = 0.0162 μM.	23063522
NIH3T3	Function assay		30 hrs	Inhibition of Smo receptor (unknown origin) expressed in NIH3T3 cells assessed as inhibition of Smo agonist SAG-induced GRE activation after 30 hrs by luciferase reporter gene assay, IC50 = 0.023 μM.	24726807
medulloblastoma cell	Antiproliferative assay		36 hrs	Antiproliferative activity against Ptch+/- and p53-/- mouse medulloblastoma cells after 36 hrs by Brdu incorporation assay, IC50 = 0.0304 μM.	28688278
Shh Light2	Function assay			Antagonist activity at smoothened (unknown origin) expressed in mouse Shh Light2 cells co-expressing Gli-dependent reporter gene assessed as inhibition of Hh signaling by dual luciferase reporter gene assay, IC50 = 0.033 μM.	24491459
Light2	Function assay			Inhibition of hedgehog signaling pathway in mouse Light2 cells in Shh conditioned medium by Gli-luciferase reporter gene assay, IC50 = 0.039 μM.	28873303
Shh Light2	Function assay			Inhibition of Smo-mediated Hh signalling pathway in mouse Shh Light2 cells by Gli-luciferase reporter gene assay, IC50 = 0.0392 μM.	27736063
ASZ001	Function assay		48 hrs	Inhibition of Hedgehog signaling in mouse ASZ001 cells assessed as downregulation of Gli1 mRNA expression after 48 hrs by RT-PCR analysis, IC50 = 0.04 μM.	24900716
NIH/3T3	Function assay		48 hrs	Antagonist activity at Smo receptor in mouse NIH/3T3 cells harboring GRE-Luc assessed as inhibition of SAG-induced Hh signaling pathway preincubated with cells followed by SAG addition measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.046 μM.	29857275
Light2	Function assay		30 hrs	Inhibition of hedgehog signaling pathway in mouse Light2 cells in Shh conditioned medium after 30 hrs by Gli-Renilla luciferase reporter gene assay, IC50 = 0.05 μM.	30099257
C3H10T1/2	Function assay		6 days	Inhibition of hedgehog signaling pathway-mediated differentiation of mouse C3H10T1/2 cells assessed as decrease in SAG-induced ALP activity after 6 days by chemiluminescence-based assay, IC50 = 0.05 μM.	30099257
DaOY	Function assay		48 hrs	Inhibition of Hedgehog signaling in human DaOY cells assessed as downregulation of Gli1 mRNA expression after 48 hrs by RT-PCR analysis, IC50 = 0.086 μM.	24900716
C3H10T1/2	Function assay		1 hr	Inhibition of Hedgehog signaling pathway in mouse C3H10T1/2 cells assessed as reduction in purmorphamine-induced increase in alkaline phosphatase level using CDP-star as substrate pretreated for 1 hr followed by purmorphamine addition measured after 5 day, IC50 = 0.14 μM.	28947939
M210B4	Function assay		24 hrs	Inhibition of Hedgehog signaling in mouse M210B4 cells assessed as downregulation of Ptch mRNA expression after 24 hrs by RT-PCR analysis, IC50 = 0.14 μM.	24900716
M210B4	Function assay		24 hrs	Inhibition of Hedgehog signaling in mouse M210B4 cells assessed as downregulation of Gli1 mRNA expression after 24 hrs by RT-PCR analysis, IC50 = 0.2 μM.	24900716
Shh Light2	Function assay		1 hr	Inhibition of Hedgehog signaling in mouse Shh Light2 cells assessed as reduction in purmorphamine-induced Gli mediated transcriptional activity pretreated for 1 hr followed by purmorphamine addition measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.98 μM.	28947939
NIH/3T3	Function assay			Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells harboring Smo D477H mutant assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 1.196 μM.	27810591
S12	Function assay		48 hrs	Inhibition of human SHH pathway in mouse S12 cells assessed as GLI-mediated transcriptional activity after 48 hrs by luciferase reporter gene assay in presence of 0.5 mg/mL human alpha-1-acid glycoprotein, IC50 = 1.75 μM.	21438527
Calu6	Function assay		4 hrs	Plasma concentration in human Calu6 cells xenografted in nude mouse at 75 mg/kg, po bid measured after 4 hrs post fifth dose, Cp = 23 μM.	19716296
Calu-6	Function assay			Plasma concentration in Calu-6 cells xenografted nude mouse PK/PD model at 75 mg/kg, po bid for 5 days measured 4 hrs post last dose relative to untreated control, Cp = 23 μM.	20875741
T47D	Cytotoxicity assay		72 hrs	Cytotoxicity against human T47D cells after 72 hrs by MTT assay, IC50 = 41.34 μM.	29107429
LS180	Antiproliferative assay		72 hrs	Antiproliferative activity against human LS180 cells after 72 hrs by sulforhodamine-B assay, IC50 = 45 μM.	30099257
LS174T	Antiproliferative assay		72 hrs	Antiproliferative activity against human LS174T cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 45.81 μM.	26820554
BxPC3	Antiproliferative assay		72 hrs	Antiproliferative activity against human BxPC3 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 47.95 μM.	26820554
medulloblastoma cell	Antitumor assay			Antitumor activity against mouse medulloblastoma cells xenografted in Ptch +/- mouse assessed as decrease in tumor volume at 12.5 mg/kg, po bid.	19716296
S12	Function assay		48 hrs	Inhibition of human SHH pathway in mouse S12 cells assessed as GLI-mediated transcriptional activity after 48 hrs by luciferase reporter gene assay in presence of 1 mg/mL human alpha-1-acid glycoprotein.	21438527
Shh Light2	Function assay	0.1 uM	36 hrs	Inhibition of Smo-mediated Hh signalling pathway in mouse Shh Light2 cells assessed as suppression of Gli1-mRNA expression at 0.1 uM measured after 36 hrs by RT-qPCR analysis.	27736063
SW1353	Antiproliferative assay	10 uM	48 hrs	Antiproliferative activity against human SW1353 cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay.	24491459
DaOY	Antiproliferative assay	10 uM	48 hrs	Antiproliferative activity against human DaOY cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay.	24491459
A549	Antiproliferative assay	10 uM	48 hrs	Antiproliferative activity against human A549 cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay.	24491459
HCT116	Antiproliferative assay	10 uM	48 hrs	Antiproliferative activity against human HCT116 cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay.	24491459
NIH/3T3	Function assay	10 uM		Inhibition of Hedgehog signaling in mouse NIH/3T3 cells assessed as down regulation of mPTCH1 mRNA expression at 10 uM.	24491459
MSC	Function assay	20 to 80 uM		Inhibition of hedgehog signaling in mouse MSC cells assessed as down regulation of alkaline phosphatase at 20 to 80 uM.	24491459
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells.	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells.	29435139
NIH3T3-Luc	Function assay	1 uM	48 hrs	Inhibition of smo-mediated hedgehog signaling pathway in mouse NIH3T3-Luc cells assessed as downregulation of Gli mRNA expression at 1 uM after 48 hrs by real-time PCR analysis.	29499483
C3H10T1/2	Function assay		24 hrs	Inhibition of hedgehog signaling pathway-mediated GLI1 mRNA expression in mouse C3H10T1/2 cells after 24 hrs by RT-PCR analysis in presence of (1R,3aR,4S,7aR)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl 3-hydroxybenzoate.	24730984
C3H10T1/2	Function assay		24 hrs	Inhibition of hedgehog signaling pathway-mediated GLI1 mRNA expression in mouse C3H10T1/2 cells after 24 hrs by RT-PCR analysis in presence of VD3.	24730984
NIH/3T3	Function assay	100 nM	36 hrs	Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as downregulation of Shh-induced Gli1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis.	28873303
C3H10T1/2	Function assay	100 nM	36 hrs	Inhibition of hedgehog signaling pathway in mouse C3H10T1/2 cells assessed as downregulation of Shh-induced Gli1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis.	28873303
NIH/3T3	Function assay	100 nM	36 hrs	Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as downregulation of Shh-induced ptch1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis.	28873303
C3H10T1/2	Function assay	100 nM	36 hrs	Inhibition of hedgehog signaling pathway in mouse C3H10T1/2 cells assessed as downregulation of Shh-induced ptch1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis.	28873303
medulloblastoma cell	Antiproliferative assay	up to 30 uM	72 hrs	Antiproliferative activity against mouse Ptch+/- p53-/- medulloblastoma cells assessed as reduction in cell proliferation up to 30 uM after 72 hrs by MTS assay.	28873303
medulloblastoma cell	Apoptosis assay			Induction of apoptosis in mouse Ptch+/- p53-/- medulloblastoma cells implanted in athymic nude mouse at 12.5 mg/kg, ip bid for 15 consecutive days by TUNEL assay.	28873303
NIH/3T3	Function assay			Inhibition of hedgehog signaling pathway expressed in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Gli-2 accumulation at tip of primary cilia by DAPI staining based confocal microscopic analysis.	27810591
NIH/3T3	Function assay			Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Smo-EGFP ciliary translocation by DAPI staining based confocal microscopic analysis.	27810591
medulloblastoma cell	Anti-tumor assay			Anti-tumor activity against mouse Ptch+/- p53-/- medulloblastoma cells implanted in athymic nude mouse assessed as tumor growth inhibition at 20 mg/kg, po administered twice daily via gavage measured every other day during compound dosing.	29739714
C3H10T1/2	Function assay	4.1 to 1000 nM		Allosteric inhibition of Smo in mouse C3H10T1/2 cells assessed as inhibition of purmorphamine-induced Gli1 transcriptional activity at 4.1 to 1000 nM by qPCr analysis.	23074541
C3H10T1/2	Function assay	4.1 to 1000 nM		Competitive inhibition of Smo in mouse C3H10T1/2 cells assessed as inhibition of SAG-induced Gli1 transcriptional activity at 4.1 to 1000 nM by qPCR analysis.	23074541
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Informazioni chimiche, conservazione e stabilità

Peso molecolare	421.3	Formula	C₁₉H₁₄Cl₂N₂O₃S	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	879085-55-9	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	GDC-0449			Smiles	CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl

Solubilità

In vitro
Lotto:

DMSO : 84 mg/mL (199.38 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	6.250mg/ml (14.84mM)	Taking the 1 mL working solution as an example, add 50 μL of 125 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	12.500mg/ml (29.67mM)	Taking the 1 mL working solution as an example, add 50 μL of 250 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5% DMSO 1 40% PEG 300 2 5% Tween 80 3 50% ddH2O Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	2.000mg/ml (4.75mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL Tween-80 to the above system, mix evenly to clarify it; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

Targets/IC₅₀/Ki	Hedgehog (Cell-free assay) 3 nM
In vitro	Vismodegib (GDC-0449) ha come bersaglio la via di segnalazione Hedgehog, bloccando le attività dei recettori di superficie cellulare PTCH e/o SMO del ligando Hedgehog e sopprimendo la segnalazione Hedgehog. Questo composto previene numerosi trasportatori ABC (ATP-binding cassette) e blocca anche ABCG2, Pgp e MRP1, importanti trasportatori ABC associati alla MDR. È un potente inibitore dei trasportatori ABC, ABCG2/BCRP e ABCB1/Pgp, ed è un lieve inibitore di ABCC1/MRP1. Nelle cellule HEK293 che sovraesprimono ABCG2, aumenta la ritenzione del substrato fluorescente BODIPY di ABCG2 e resensibilizza queste cellule. Nelle cellule renali canine Madin-Darby II ingegnerizzate per sovraesprimere Pgp o MRP1, aumenta la ritenzione di calceina-AM e le resensibilizza. Resensibilizza anche le cellule di carcinoma polmonare non a piccole cellule umane NCI-H460/par e NCI-H460/MX20, che sovraesprimono ABCG2 in risposta a SN-38. I valori di IC50 per la prevenzione di ABCG2 e Pgp sono rispettivamente di circa 1,4 μM e 3,0 μM. Inoltre, altera l'omeostasi intracellulare del Ca²⁺ e inibisce la crescita cellulare nelle cellule di cancro al polmone resistenti.
In vivo	Vismodegib (GDC-0449) è stato utilizzato per trattare il medulloblastoma in modelli animali. Previene la crescita di xenotrapianti pancreatici primari senza inibire in modo non specifico la proliferazione delle cellule pancreatiche. La somministrazione orale di questo composto provoca regressioni tumorali nel modello di allotrapianto di medulloblastoma Ptch(+/-) a dosi ≥25 mg/kg e inibizione della crescita tumorale a dosi fino a 92 mg/kg somministrate due volte al giorno in due modelli di cancro colorettale ligando-dipendenti, D5123 e 1040830. L'analisi dell'attività della via Hh e la modellizzazione PK/PD rivelano che inibisce Gli1 con un IC50 simile sia nei modelli di medulloblastoma che di D5123 (rispettivamente 0,165 μM e 0,267 μM). La modulazione della via è collegata all'efficacia utilizzando un modello PK/PD integrato che rivela una relazione ripida in cui > 50% dell'attività di GDC-0449 è associata a > 80% di repressione della via Hh.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/19443052/ [2] https://pubmed.ncbi.nlm.nih.gov/19107236/ [3] https://pubmed.ncbi.nlm.nih.gov/22213292/ [4] https://pubmed.ncbi.nlm.nih.gov/21610148/

Applicazioni

Metodi	Biomarcatori	PMID
Western blot	Fas / DR4 / DR5 / Cleaved PARP / Bcl-2 / Cleaved caspase-3 / PDGFRα p-GSK3β / GSK3β / p-Akt / Akt / Gli1 Gli1 / SOX2 / OCT4 p53 / Cyclin D1 / p21 Bcl-2 / Bax	22087285
Immunofluorescence	Gli1 / Gli2	22087285
Growth inhibition assay	Cell viability	29042665

Informazioni sullo studio clinico

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
NCT06344052	Recruiting	Basal Cell Carcinoma	Stamford Pharmaceuticals Inc.	April 9 2024	Phase 2
NCT03610022	Completed	Metastatic Basal Cell Carcinoma\|Locally Advanced Basal Cell Carcinoma	University Hospital Bordeaux	September 3 2018	Phase 4
NCT03035188	Completed	Basal Cell Carcinoma	SRH Wald-Klinikum Gera GmbH	January 2017	Phase 2
NCT02781389	Completed	Basal Cell Carcinoma	University Hospital Essen\|OnkoDataMed GmbH	April 29 2016	--
NCT02593760	Completed	Myelofibrosis	Hoffmann-La Roche	January 25 2016	Phase 1
NCT02648048	Completed	Idiopathic Pulmonary Fibrosis	Hoffmann-La Roche	January 15 2016	Phase 1

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