Name: Ispinesib (SB-715992)
Brand: Selleck Chemicals
SKU: S1452
Rating: 5 (28 reviews)

Spring naar

Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.97%

99.97

Gerelateerde doelwitten	Akt Wnt/beta-catenin PKC HSP ROCK Microtubule Associated Integrin Bcr-Abl Actin FAK
Overig Kinesin Inhibitoren	GSK-923295 SB743921 HCl Monastrol ARQ 621 GW406108X H-Cys(Trt)-OH K 858 BTB-1 SB-743921 VLS-1488(KIF18A-IN-6 )

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by Alamar blue assay, GI50=0.025μM	22248262
hTERT-HME1	Antiproliferative assay		72 hrs	Antiproliferative activity against human hTERT-HME1 cells after 72 hrs by Alamar blue assay, GI50=0.032μM	22248262
K562	Antiproliferative assay		72 hrs	Antiproliferative activity against human K562 cells after 72 hrs by Alamar blue assay, GI50=0.071μM	22248262
BxPC3	Antiproliferative assay		72 hrs	Antiproliferative activity against human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08μM	22248262
NCI-H1299	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H1299 cells after 72 hrs by Alamar blue assay, GI50=0.082μM	22248262
LNCAP	Growth inhibition assay		72 hrs	Growth inhibition of human LNCAP cells after 72 hrs by Alamar blue assay, GI50=0.022μM	23394180
HCT116	Growth inhibition assay		72 hrs	Growth inhibition of human HCT116 cells after 72 hrs by Alamar blue assay, GI50=0.025μM	23394180
PC3	Growth inhibition assay		72 hrs	Growth inhibition of human PC3 cells after 72 hrs by Alamar blue assay, GI50=0.05μM	23394180
BxPC3	Growth inhibition assay		72 hrs	Growth inhibition of human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08μM	23394180
NCI-H1299	Growth inhibition assay		72 hrs	Growth inhibition of human NCI-H1299 cells after 72 hrs by Alamar blue assay, GI50=0.082μM	23394180
LXFS 538	Antitumor assay	6 mg/kg		Antitumor activity against human LXFS 538 cells xenografted in NMRI nu/nu mouse assessed as tumor regression at 6 mg/kg, ip measured on day 13	23394180
HeLa	Antiproliferative assay		48 hrs	Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay, IC50=1μM	24184776
MCF7	Antiproliferative assay		48 hrs	Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=1.3μM	24184776
HCT116	Growth inhibition assay		72 hrs	Growth inhibition of human HCT116 cells after 72 hrs by MTS assay, IC50=0.0011μM	26396688
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	517.06	Formule	C₃₀H₃₃ClN₄O₂	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	336113-53-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	CK0238273			Smiles	CC1=CC=C(C=C1)C(=O)N(CCCN)C(C2=NC3=C(C=CC(=C3)Cl)C(=O)N2CC4=CC=CC=C4)C(C)C

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 103 mg/mL (199.2 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 103 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
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	2%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	4.000mg/ml (7.74mM)	Taking the 1 mL working solution as an example, add 20 μL of 200 mg/ml clear DMSO stock solution to 980 μL of corn oil and mix evenly. 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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken	An allosteric, potent, specific, and reversible inhibitor of the mitotic kinesin spindle protein (KSP) (HsEg5).
Targets/IC₅₀/Ki	KSP (HsEg5) (Cell-free assay) 1.7 nM(Ki app)
In vitro	Ispinesib (SB-715992) is a potent, allosteric, reversible, and specific inhibitor of KSP, which changes the binding property of KSP to microtubules and disturbs its movement by inhibiting ADP release without altering the release of the KSP-ADP complex from the microtubule. This compound shows potent cytotoxic activity in a panel of tumor cell lines, including Colo205, Colo201, HT-29, M5076, Madison-109, and MX-1, with IC50 of 1.2 nM to 9.5 nM. In PC-3 prostate cancer cells, it (15 nM and 30 nM) blocks cell proliferation and induces apoptosis by regulating the expression levels of genes that controls apoptosis, cell proliferation, cell cycle, and cell signaling, such as EGFR, p27, p15, and IL-11. In a panel of 53 breast cell lines, Ispinesib (7.4 nM–600 nM) demonstrates broad inhibitory activity. In BT-474 and MDA-MB-468 cells, it (150 nM) induces apoptosis, as revealed by a higher proportion of apoptotic cells, lower antiapoptotic Bcl-X_L level, and higher proapoptotic Bax and Bid levels.
Kinase Assay	Steady-State Kinetische Analyse van Menselijke KSP ATPase Activiteit en Remming door Ispinesib
Kinase Assay	Kinesin-specificiteitsanalyse wordt uitgevoerd met behulp van een pyruvaatkinase-lactaatdehydrogenase detectiesysteem dat de productie van ADP koppelt aan de oxidatie van NADH. Absorbantieveranderingen worden gemonitord bij 340 nm. Steady-state studies met nanomolaire concentraties van KSP worden uitgevoerd met behulp van een gevoelige fluorescentie-gebaseerde assay die gebruik maakt van een pyruvaatkinase, pyruvaatoxidase en mierikswortelperoxidase (HRP) gekoppeld detectiesysteem dat de generatie van ADP koppelt aan de oxidatie van Amplex Red tot fluorescerend resorufin. De generatie van resorufin wordt gemonitord door fluorescentie (λ_excitatie = 520 nm en λ_emissie = 580 nm). Steady-state biochemische experimenten worden uitgevoerd in PEM25-buffer [25 mM Pipes-K⁺ (pH 6,8), 2 mM MgCl₂, 1 mM EGTA] voor experimenten met microtubuli. De IC50 voor steady-state remming wordt bepaald bij 500 µM ATP, 5 µM Microtubuli en 1 nM KSP in PEM25-buffer. K_{i app} (schijnbare remmerdissociatieconstante) waarden van Ispinesib (SB-715992) worden geëxtraheerd uit de dosis-respons curve, met expliciete correctie voor enzymconcentratie door gebruik te maken van de Morrison-vergelijking. De remmer-modaliteit (bijv. competitief, niet-competitief, uncompetitief of gemengd) onder steady-state omstandigheden wordt bepaald door het effect van de concentratie op de initiële snelheid te meten als functie van substraatconcentraties. Gegevens worden gefit met behulp van vergelijkingen in GraFit aan snelheidsvergelijkingen voor de verschillende remmingsmodi.
In vivo	Ispinesib (SB-715992) (4.5 mg/kg–15 mg/kg) exhibits inhibitory effects against Colo205, Colo201, HT-29, but not MX-1 cells, in mouse xenograft models. This compound (6 mg/kg–10 mg/kg) also inhibits murine solid tumors, including Madison 109 lung carcinoma, M5076 sarcoma, as well as L1210 and P388 leukemias. In mice xenograft models of breast cancer cells MCF-7, HCC1954, MDA-MB-468, and KPL4, it (8 mg/kg–10 mg/kg) inhibits tumor growth.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/18290633/ [2] http://www.cytokinetics.com/pdf/AACR_2002_Poster_1335.pdf [3] https://pubmed.ncbi.nlm.nih.gov/16433906/ [4] https://pubmed.ncbi.nlm.nih.gov/20068098/

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2017-03-06)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT00095628	COMPLETED	Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity	National Cancer Institute (NCI)	2005-01	PHASE2
NCT00101244	TERMINATED	Adult Grade III Lymphomatoid Granulomatosis; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia	National Cancer Institute (NCI)	2004-11	PHASE1
NCT00103311	COMPLETED	Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer	National Cancer Institute (NCI)	2005-01	PHASE2
NCT00607841	TERMINATED	Breast Neoplasms	Cytokinetics	2007-12	PHASE1
NCT00363272	COMPLETED	Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific	National Cancer Institute (NCI)	2006-06	PHASE1
NCT00098826	COMPLETED	Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia	National Cancer Institute (NCI)	2004-12	PHASE1

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):

Ispinesib (SB-715992) Kinesin Remmer

Molecuulgewicht: 517.06

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

Ispinesib (SB-715992) Kinesin Remmer

Molecuulgewicht: 517.06

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)