Lonafarnib (SCH66336)

製品コード：S2797 純度：99.48%

Lonafarnib (SCH66336) is an orally bioavailable FPTase inhibitor for H-ras, K-ras-4B and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM in cell-free assays, respectively. Phase 3.

CAS No. 193275-84-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40500	国内在庫あり
5mg	JPY 25500	国内在庫あり
10mg	JPY 40500	国内在庫あり
25mg	JPY 74500	国内在庫あり
100mg	JPY 145500	国内在庫なし(納期7~10日)
1g	JPY 745500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（22）

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製品安全説明書

現在のバッチを見る：純度： 99.48%

99.48

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シグナル伝達経路

Transferaseシグナル伝達経路

Transferase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
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
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
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
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
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
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
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
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生物活性

製品説明

Lonafarnib (SCH66336) is an orally bioavailable FPTase inhibitor for H-ras, K-ras-4B and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM in cell-free assays, respectively. Phase 3.

Targets

H-ras ^[1] (Cell-free assay)	N-ras ^[1] (Cell-free assay)	K-ras-4B ^[1] (Cell-free assay)
1.9 nM	2.8 nM	5.2 nM

In Vitro
In vitro	SCH66336 at concentration ranging from 0.1 μM to 8 μM suppress growth and induce apoptosis of human head and neck squamous carcinoma cells (HNSCC) in a dose and time dependent manner. SCH66336 (8 μM) 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. ^[2] SCH66336 demonstrate variable antiproliferative effects against the cell lines, with IC50 ranging from 0.6 μM to 32.3 μM. ^[3] Lonafarnib induces a CCAAT/enhancer-binding protein homologous protein (CHOP)-dependent transactivation of the DR5 promoter, thus induces CHOP-dependent DR5 up-regulation. Lonafarnib (< 10 μM) activates caspase-8 and its downstream caspases, thus induces caspase-8-dependent apoptosis in H1792 cells. Lonafarnib (5 μM) up-regulate DR5 expression, increase cell-surface DR5 distribution, and enhance tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in H1792 cells.^[4]
細胞実験	細胞株	UMSCC10B, UMSCC14B, UMSCC17B, UMSCC22B, and UMSCC35, UMSCC38 cell lines
	濃度	0.1 μM - 8 μM
	反応時間	24 hours
	実験の流れ	The cells are seeded in 96-well cell-culture cluster plates at a density that allowed control cultures to grow exponentially for 5 days. After 24 hours, the cells are treated with different concentrations of SCH66336. SCH66336 is dissolved in DMSO. Control cultures received the same amount of DMSO as the treated cultures do. Cell numbers are estimated after 5 days of treatment by SRB assay. The percentage of growth inhibition is calculated by using the equation: percentage growth inhibition = (1 − At/Ac) × 100, where At and Ac represent the absorbance in treated and control cultures, respectively. The drug concentration causing a 50% cell growth inhibition (IC50), is determined by interpolation from dose-response curves.
実験結果図	Methods	Biomarkers	結果図	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

In Vivo
In Vivo	SCH66336 inhibits HTBI77 human lung carcinoma xenograft growth in nude mice in a dose-dependent fashion. ^[1] SCH66336 dosed at 50 mg/kg p.o. bid by oral gavage 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. ^[3]
動物実験	動物モデル	NOD/SCID mice between 6–12 weeks of age
	投与量	50 mg/kg
	投与経路	p.o. bid by oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考
[1] Liu M, et al. Cancer Res, 1998, 58(21), 4947-4956. [2] Chun KH, et al. Cancer Res, 2003, 63(16), 4796-4800. [3] Feldkamp MM, et al. Cancer Res, 2001, 61(11), 4425-4431. [4] Sun SY, et al. J Biol Chem, 2007, 282(26), 18800-18809. + 展開

参考

[4] Sun SY, et al. J Biol Chem, 2007, 282(26), 18800-18809.

+ 展開

化学情報

分子量	638.82	化学式	C₂₇H₃₁Br₂ClN₄O₂
CAS No.	193275-84-2	SDF	Download Lonafarnib (SCH66336) SDFをダウンロードする
Smiles	C1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(CCC5=C3N=CC(=C5)Br)C=C(C=C4Br)Cl)C(=O)N
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 127 mg/mL ( (198.8 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 127 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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