Name: Lonafarnib (SCH66336)
Brand: Selleck Chemicals
SKU: S2797
Rating: 5 (27 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.48%

99.48

Dianas relacionadas	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Otros FTase Inhibidores	FTI 277 HCl Tipifarnib (IND 58359) LB42708

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Tiempo de incubación	Descripción de la actividad	PMID
Cos-1 monkey kidney cells	Function assay		Inhibition of Protein farnesyltransferase in Cos-1 monkey kidney cells expressing H-Ras-val, IC50=0.0019 μM	12190309
COS-7 monkey cells	Function assay		Inhibiting the farnesylation of H-ras proteins in COS-7 monkey cells transiently expressing H-ras[Val12]-CVLS in the whole cell assay, IC50=0.01 μM	9822558
MCF-7 tumor cell line	Growth inhibition assay		Compound was measured for inhibition of MCF-7 tumor cell line in breast under soft agar assay, IC50=0.05 μM	9822558
HCT116	Growth inhibition assay		Compound was measured for inhibition of HCT116 tumor cell line in colon under soft agar assay, IC50=0.07 μM	9822558
NIH-H tumor cell lines	Growth inhibition assay		Compound ability to inhibit anchorage-independent growth of NIH-H tumor cell lines in soft agar, IC50=0.072 μM	9822558
NIH3T3 cells	Function assay		Inhibition of Ras farnesylation in H-Ras transformed NIH3T3 cells, EC50=0.1 μM	15454228
NIH-K tumor cell lines	Growth inhibition assay		Compound ability to inhibit anchorage-independent growth of NIH-K tumor cell lines in soft agar, IC50=0.5 μM	9822558
Cos-1	Function assay		Inhibition of Protein farnesyltransferase in Cos-1 monkey kidney cells expressing H-Ras-val, IC50 = 0.0019 μM.	12190309
Cos-1	Function assay		Effect on Ras processing in Cos-1 monkey kidney cells expressing either H-Ras-Val 12-CVLS or H-Ras-Val12, IC50 = 0.01 μM.	10411485
COS7	Function assay		Inhibition of FTase in human COS7 cells, IC50 = 0.01 μM.	20925433
H-Ras transformed cells	Function assay		Inhibition of soft agar colony formation in H-Ras transformed cells, IC50 = 0.07 μM.	15501065
NIH3T3	Function assay		Effective concentration against Ha-RAS processing in NIH3T3 ras-transformed cells, EC50 = 0.16 μM.	12657284
NIH3T3	Function assay		TP_TRANSPORTER: inhibition of DNR efflux (DNR: ? uM) in MDR1-expressing NIH3T3 cells, IC50 = 2.7 μM.	11606389
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
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
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Caco-2	Cytotoxicity assay	48 hours	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging, IC50 = 5.68 μM.	ChEMBL
Caco-2	Toxicity assay	48 hours	Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay, CC50 = 10.71 μM.	ChEMBL
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	638.82	Fórmula	C₂₇H₃₁Br₂ClN₄O₂	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	193275-84-2	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	C1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(CCC5=C3N=CC(=C5)Br)C=C(C=C4Br)Cl)C(=O)N

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 127 mg/mL (198.8 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 127 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
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%PEG300 2 5%Tween80 3 50%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	5.000mg/ml (7.83mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of 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.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC₅₀/Ki	H-ras (Cell-free assay) 1.9 nM N-ras (Cell-free assay) 2.8 nM K-ras-4B (Cell-free assay) 5.2 nM
In vitro	Lonafarnib (SCH66336) at concentrations ranging from 0.1 μM to 8 μM suppresses growth and induces apoptosis of human head and neck squamous carcinoma cells (HNSCC) in a dose- and time-dependent manner. At 8 μM, it suppresses protein kinase B/Akt activity as well as the phosphorylation of the Akt substrates glycogen synthase kinase (GSK)-3β, forkhead transcription factor, and BAD in SqCC/Y1 cells. This compound demonstrates variable antiproliferative effects against the cell lines, with IC50 values ranging from 0.6 μM to 32.3 μM. It induces a CCAAT/enhancer-binding protein homologous protein (CHOP)-dependent transactivation of the DR5 promoter, thus causing CHOP-dependent DR5 up-regulation. At concentrations below 10 μM, it activates caspase-8 and its downstream caspases, thereby inducing caspase-8-dependent apoptosis in H1792 cells. At 5 μM, it up-regulates DR5 expression, increases cell-surface DR5 distribution, and enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in H1792 cells.
In vivo	Lonafarnib (SCH66336) inhibits HTBI77 human lung carcinoma xenograft growth in nude mice in a dose-dependent fashion. When dosed at 50 mg/kg p.o. bid by oral gavage, it inhibits tumor growth with up to 69% growth inhibition after 21 days of treatment in NOD/SCID mice bearing s.c. flank XEN01, XEN05 or XEN08 GBM xenografts.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/9810004/ [2] https://pubmed.ncbi.nlm.nih.gov/12941797/ [3] https://pubmed.ncbi.nlm.nih.gov/11389071/ [4] https://pubmed.ncbi.nlm.nih.gov/17493934/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	p-ERK / p-SAPK / p-JNK PARP / cleaved-PARP / pro-caspase3 / cleaved-caspase3 / Bcl-2 Cyclin D / CDK6 / CDK4 / SKP2 LC3A / LC3B		29285232
Growth inhibition assay	Cell number Cell viability		29069775

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT05953545	Not yet recruiting	Chronic Hepatitis Delta	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)\|National Institutes of Health Clinical Center (CC)	May 15 2024	Phase 2
NCT02579044	Enrolling by invitation	Progeria	Boston Children''s Hospital	December 2015	Phase 1\|Phase 2
NCT02430181	Completed	Chronic Hepatitis D Infection	Eiger BioPharmaceuticals	November 2014	Phase 2
NCT01495585	Completed	Hepatitis D	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)\|National Institutes of Health Clinical Center (CC)	December 2011	Phase 2
NCT01232881	Terminated	Breast Cancer	Hoosier Cancer Research Network\|United States Department of Defense\|Indiana University School of Medicine\|Emory University	August 2009	--
NCT00916747	Active not recruiting	Progeria	Boston Children''s Hospital\|Schering-Plough\|Merck Sharp & Dohme LLC\|Eiger BioPharmaceuticals	August 2009	Phase 2

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Lonafarnib (SCH66336) Farnesyltransferase Inhibitor

Estructura química

Peso molecular: 638.82

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Lonafarnib (SCH66336) Farnesyltransferase Inhibitor

Estructura química

Peso molecular: 638.82

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo (Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)