Ispinesib (SB-715992)

Catalog No.S1452

Ispinesib (SB-715992) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP) with Ki app of 1.7 nM in a cell-free assay, no inhibition to CENP-E, RabK6, MCAK, MKLP1, KHC or Kif1A. Phase 2.

Price Stock Quantity  
USD 420 In stock
USD 320 In stock
USD 970 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Ispinesib (SB-715992) Chemical Structure

Ispinesib (SB-715992) Chemical Structure
Molecular Weight: 517.06

Validation & Quality Control

4 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Ispinesib (SB-715992) is available in the following compound libraries:

Product Information

  • Compare Kinesin Inhibitors
    Compare Kinesin Products
  • Research Area
  • Ispinesib (SB-715992) Mechanism

Product Description

Biological Activity

Description Ispinesib (SB-715992) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP) with Ki app of 1.7 nM in a cell-free assay, no inhibition to CENP-E, RabK6, MCAK, MKLP1, KHC or Kif1A. Phase 2.
Targets KSP (HsEg5) [1]
(Cell-free assay)
IC50 1.7 nM(Ki app)
In vitro Ispinesib 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. [1] Ispinesib 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. [2] In PC-3 prostate cancer cells, Ispinesib (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. [3] 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, Ispinesib (150 nM) induces apoptosis, as revealed by a higher proportion of apoptotic cells, lower antiapoptotic Bcl-XL level, and higher proapoptotic Bax and Bid levels. [4]
In vivo Ispinesib (4.5 mg/kg–15 mg/kg) exhibits inhibitory effects against Colo205, Colo201, HT-29, but not MX-1 cells, in mouse xenograft models. SB-715992 (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. [2] In mice xenograft models of breast cancer cells MCF-7, HCC1954, MDA-MB-468, and KPL4, Ispinesib (8 mg/kg–10 mg/kg) inhibits tumor growth. [4]
Features An allosteric, potent, specific, and reversible inhibitor of the mitotic kinesin spindle protein (KSP) (HsEg5).

Protocol(Only for Reference)

Kinase Assay: [1]

Steady-State Kinetic Analysis of Human KSP ATPase Activity and Inhibition by Ispinesib Kinesin specificity analysis is carried out using a pyruvate kinase-lactate dehydrogenase detection system that couples the production of ADP to oxidation of NADH. Absorbance changes are monitored at 340 nm. Steady-state studies using nanomolar concentrations of KSP are performed using a sensitive fluorescence-based assay utilizing a pyruvate kinase, pyruvate oxidase, and horseradish peroxidase (HRP) coupled detection system that couples the generation of ADP to oxidation of Amplex Red to fluorescent resorufin. Generation of resorufin is monitored by fluorescence (λexcitation = 520 nm and λemission = 580 nm). Steady-state biochemical experiments are performed in PEM25 buffer [25 mM Pipes-K+ (pH 6.8), 2 mM MgCl2, 1 mM EGTA] supplemented with 10 µM paclitaxel for experiments involving microtubules. The IC50 for steady-state inhibition is determined at 500 µM ATP, 5 µM Microtubules, and 1 nM KSP in PEM25 buffer. Ki app (apparent inhibitor dissociation constant) values of Ispinesib are extracted from the dose-response curves, with explicit correction for enzyme concentration by using the Morrison equation. Inhibitor modality (e.g., competitive, noncompetitive, uncompetitive, or mixed) under steady-state conditions is determined by measuring the effect of inhibitor concentration on initial velocity as a function of substrate concentrations. Data are fit using equations in GraFit to velocity equations for the various modes of inhibition.

Cell Assay: [4]

Cell lines Breast cancer cells, including MCF-7, HCC1954, MDA-MB-468, and KPL4
Concentrations 0.085 nM–33 µM
Incubation Time 72 hours
Method Cells are plated in log phase of growth in 96-well plates and treated with Ispinesib for 72 hours. Then, cell growth is measured using CellTiter-Glo, and luminescence is detected using BioTek FLx800. Data are analyzed and the IC50 value, defined as the drug concentration that results in 50% growth inhibition relative to control, is calculated.

Animal Study: [4]

Animal Models Nude (nu/nu) mice models of MCF7, KPL4, and HCC1954 cells; severe combined immunodeficient (SCID) mice model of MDA-MB-468 cells;
Formulation Dissolved in 10% ethanol, 10% cremophor, and 80% D5W (dextrose 5%)
Dosages 10 mg/kg for nude mice or 8 mg/kg for SCID mice
Administration Intraperitoneal injection on a q4d× schedule (3 doses, every 4 day

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Lad L, et al. Biochemistry, 2008, 47(11), 3576-3585.

[2] Johnson RK, et al. Proc Am Assoc Cancer Res, 2002, 43, 269.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT00607841 Completed Breast Neoplasms Cytokinetics December 2007 Phase 1|Phase 2
NCT00363272 Completed Childhood Burkitt Lymphoma|Childhood Central Nervous System Germ Cell Tumor|Childhood Choroid Plexus Tumor|Childhood Craniopharyngioma|Childhood Gr  ...more 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) June 2006 Phase 1
NCT00354250 Completed Recurrent Renal Cell Cancer|Stage III Renal Cell Cancer|Stage IV Renal Cell Cancer National Cancer Institute (NCI) May 2006 Phase 2
NCT00096499 Completed Adenocarcinoma of the Prostate|Recurrent Prostate Cancer|Stage IV Prostate Cancer National Cancer Institute (NCI) April 2005 Phase 2
NCT00095628 Completed Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma|Recurrent Metastatic Squamous Neck Cancer With Occult Primary|Recurrent  ...more 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) January 2005 Phase 2

view more

Chemical Information

Download Ispinesib (SB-715992) SDF
Molecular Weight (MW) 517.06
Formula

C30H33ClN4O2

CAS No. 336113-53-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms CK0238273
Solubility (25°C) * In vitro DMSO 103 mg/mL (199.2 mM)
Ethanol 103 mg/mL (199.2 mM)
Water <1 mg/mL (<1 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name (R)-N-(3-aminopropyl)-N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamide

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related Kinesin Products

  • FRAX597

    FRAX597 is a potent, ATP-competitive inhibitor of group I PAKs with IC50 of 8 nM, 13 nM, and 19 nM for PAK1, PAK2, and PAK3, respectively.

  • VER155008

    VER-155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78, respectively, >100-fold selectivity over HSP90.

  • PU-H71

    PU-H71 is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.

  • SB743921

    SB743921 is a kinesin spindle protein (KSP) inhibitor with Ki of 0.1 nM, almost no affinity to MKLP1, Kin2, Kif1A, Kif15, KHC, Kif4 and CENP-E. Phase 1/2.

  • AZ 3146

    AZ3146 is a selective Mps1 inhibitor with IC50 of ~35 nM, contributes to recruitment of CENP-E (kinesin-related motor protein), less potent to FAK, JNK1, JNK2, and Kit.

  • GSK923295

    GSK923295 is a first-in-class, specific allosteric inhibitor of CENP-E kinesin motor ATPase with Ki of 3.2 nM, and less potent to mutant I182 and T183. Phase 1.

    Features:The first potent and selective inhibitor of CENP-E.

  • MPI-0479605

    MPI-0479605 is an ATP competitive and selective inhibitor of mitotic kinase Mps1 with IC50 of 1.8 nM, >40-fold selectivity over other kinases.

  • ARQ 621

    ARQ 621 is an allosteric, and selective Eg5 mitotic motor protein inhibitor. Phase 1.

  • Paclitaxel

    Paclitaxel is a microtubule polymer stabilizer with IC50 of 0.1 pM in human endothelial cells.

  • Docetaxel

    Docetaxel, an analog of paclitaxel, is an inhibitor of depolymerisation of microtubules by binding to stabilized microtubules.

Recently Viewed Items

Tags: buy Ispinesib (SB-715992) | Ispinesib (SB-715992) supplier | purchase Ispinesib (SB-715992) | Ispinesib (SB-715992) cost | Ispinesib (SB-715992) manufacturer | order Ispinesib (SB-715992) | Ispinesib (SB-715992) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us