1. Cell Cycle/DNA Damage
    JAK/STAT Signaling
    Epigenetics
    Stem Cell/Wnt
    Protein Tyrosine Kinase/RTK
  2. CDK
    JAK
    FLT3

SB1317 (Synonyms: TG02; SB 1317; TG 02; SB-1317; TG-02)

Cat. No.: HY-15166 Purity: >98.0%
Data Sheet SDS Handling Instructions

SB1317 is a potent inhibitor of CDK2, JAK2, and FLT3 for the treatment of cancer, with IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively.

For research use only. We do not sell to patients.
SB1317 Chemical Structure

SB1317 Chemical Structure

CAS No. : 937270-47-8

Size Price Stock Quantity
10 mM * 1 mL in DMSO $160 In-stock
5 mg $145 In-stock
10 mg $238 In-stock
50 mg $520 In-stock
100 mg $850 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Description

SB1317 is a potent inhibitor of CDK2, JAK2, and FLT3 for the treatment of cancer, with IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively.

IC50 & Target

IC50: 13 nM (CDK2), 73 nM (JAK2), 56 nM (FLT3)[1]

In Vitro

SB1317 has a highly novel kinase inhibitory spectrum inhibiting 17 kinases from a panel of 63, 11 of which are CDK/JAK/FLT family members. The others, Lck, Fyn, Fms, TYRO3, ERK5, and p38δ, are implicated in inflammatory and proliferative processes. Human CYP1A2, 3A4, 2C9, and 2C19 isoforms are not inhibited by SB1317 at the highest tested concentration of 25 μM, but SB1317 inhibits CYP2D6 with IC50=0.95 μM, approximately at the plasma Cmax observed at the maximum tolerated dose. SB1317 inhibits cell proliferation concentrations in HCT-116 (IC50=0.079 μM) and HL-60 (IC50=0.059 μM)[1]. SB1317 is a novel small molecule potent CDK/JAK2/FLT3 inhibitor. SB1317 is mainly metabolized by CYP3A4 and CY1A2 in vitro. SB1317 does not inhibit any of the major human CYPs in vitro except CYP2D6 (IC50=1 μM). SB1317 does not significantly induce CYP1A and CYP3A4 in human hepatocytes in vitro[2].

In Vivo

Treatment with SB1317 at 75 mg/kg po q.d. 3×/week significantly inhibits the growth of tumors with a mean TGI of 82%, while the lower dose of 50 mg/kg po 3×/week is marginally effective. Treatment with SB1317 using either regime significantly inhibits the growth of tumors with mean TGIs of 42% and 63% for the oral and ip delivery methods, respectively[1]. In pharmacokinetic studies SB1317 shows moderate to high systemic clearance (relative to liver blood flow), high volume of distribution (>0.6 L/kg), oral bioavailability of 24%, ~4 and 37% in mice, rats and dogs, respectively; and extensive tissue distribution in mice[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT01204164 Tragara Pharmaceuticals, Inc. AML|ALL|Blast Crisis|MDS|Multiple Myeloma August 2010 Phase 1
NCT01699152 Tragara Pharmaceuticals, Inc. Chronic Lymphocytic Leukemia|Small Lymphocytic Lymphoma September 2012 Phase 1
NCT02933944 Targovax ASA Rectal Cancer September 2016 Phase 1
NCT02942264 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Brain Tumor|Astrocytoma|Astroglioma|Glioblastoma|Gliosarcoma October 17, 2016 Phase 1|Phase 2
NCT03224104 European Organisation for Research and Treatment of Cancer - EORTC|Tragara Pharmaceuticals, Inc. Astrocytoma, Grade III|Glioblastoma December 2017 Phase 1
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.6849 mL 13.4243 mL 26.8485 mL
5 mM 0.5370 mL 2.6849 mL 5.3697 mL
10 mM 0.2685 mL 1.3424 mL 2.6849 mL
Kinase Assay
[1]

The recombinant enzymes (CDK2/cyclin A, JAK2, and FLT3) are used. All assays are carried out in 384-well white microtiter plates using the PKLight assay system. This assay platform is a luminometric assay for the detection of ATP in the reaction using a luciferase-coupled reaction. The compounds are tested at eight concentrations prepared from 3- or 4-fold serial dilution starting at 10 μM. For CDK2/cyclin A assay, the reaction mixture consisted of the following components in 25 μL of assay buffer (50 mM Hepes, pH 7.5, 10 mM MgCl2, 5 mM MnCl2, 5 mM BGP, 1 mM DTT, 0.1 mM sodium orthovanadate), 1.4 μg/mL of CDK2/cyclin A complex, 0.5 μM RbING substrate, and 0.5 μM ATP. The mixture is incubated at room temperature for 2 h. Then 13 μL of PKLight ATP detection reagent is added and the mixture is incubated for 10 min. Luminescence signals are detected on a multilabel plate reader. The analytical software Prism 5.0 is used to generate IC50 values from the data[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

SB1317 is prepared in DMSO and stored, and then diluted with appropriate medium before use[1].

All cell lines are obtained from the American Type Culture Collection and cultured. For proliferation assays in 96-well plates, 20 000 cells are seeded in 100 μL of medium and treated the following day with compounds (e.g., SB1317 ) (in triplicate) at concentrations up to 10 μM for 48 h. Cell viability is monitored using the CellTiter-96 Aqueous One solution cell proliferation assay. Dose-response curves are plotted to determine IC50 values for the compounds using the XL-fit software[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

SB1317 hydrochloride is dissolved in 0.5% methyl cellulose/0.1% Tween 80 (MC/Tween) for oral (po) dosing or in 10% dimethylacetamide (DMA) and 10% Cremophor (DMA/CRE) for ip dosing. Dosing solutions are prepared weekly in a feeding volume of 10 mL per kilogram body weight and stored at 4°C[1].

Mice and Rat[1]
Male BALB/c mice (aged ~10-12 weeks and weighing 17-22 g), male Beagle dogs (~6-7 months of age, weighing 10-14 kg), and male Wistar rats (aged 6-8 weeks, weighing 239-249 g) are used in this study. The oral doses for mice, dogs, and rats are 75, 10, and 10 mg/kg, respectively. The doses are administered by gavage as suspensions (0.5% methylcellulose and 0.1% Tween 80) to mice and rats, and as gelatin capsules (12 Torpac) to dogs. Following oral dosing serial blood samples are collected (cardiac puncture in mice, jugular vein in dogs, and superior vena cava in rats) at different time points (0-24 h) in tubes containing K3EDTA as anticoagulant, centrifuged, and plasma is separated and stored at -70°C until analysis. Plasma samples are processed and analyzed by LC-MS/MS. Pharmacokinetic parameters are estimated by noncompartmental methods using WinNonlin. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
M.Wt

372.46

Formula

C₂₃H₂₄N₄O

CAS No.

937270-47-8

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 26.5 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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