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SPHINX31

Catalog No. T5194   CAS 1818389-84-2

SPHINX31 is a potent inhibitor of serine/arginine-rich protein kinase 1 (SRPK1; IC50: 5.9 nM).

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SPHINX31 Chemical Structure
SPHINX31, CAS 1818389-84-2
Pack Size Availability Price/USD Quantity
1 mg In stock $ 34.00
5 mg In stock $ 76.00
10 mg In stock $ 98.00
25 mg In stock $ 189.00
50 mg In stock $ 283.00
100 mg In stock $ 453.00
500 mg In stock $ 1,050.00
1 mL * 10 mM (in DMSO) In stock $ 89.00
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Purity: 100%
Purity: 99.3%
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Biological Description
Chemical Properties
Storage & Solubility Information
Description SPHINX31 is a potent inhibitor of serine/arginine-rich protein kinase 1 (SRPK1; IC50: 5.9 nM).
Targets&IC50 SRPK1:5.9 nM (cell free)
In vitro SPHINX31 inhibits phosphorylation of serine/arginine-rich splicing factor 1 (SRSF1), an SRPK1 substrate, in PC3 cells (EC50: 360 nM) and increases expression of the anti-angiogenic VEGF-A165b splice variant in retinal pigment epithelial (RPE) cells [1]. SPHINX31 inhibited the growth of MLL-mutant AML cell lines with an IC50? >1 order of magnitude lower than for other AML lines. There was no impact of SPHINX31 on the clonogenic potential of normal mouse hematopoietic stem-progenitor cells (HSPCs). 1.5, 3, and 6?μM SPHINX31 did not affect the colony-forming ability of normal human cord blood CD34+ cells [2].
In vivo In vivo, SPHINX31 (2 μg per eye) inhibits blood vessel growth and macrophage infiltration in the eyes of a mouse model of choroidal neovascularization [1]. Injection of 0.8?mg/kg SPHINX31 (i.p.) into DBA2J mice resulted in a concentration of 0.225?±?0.036?μM in plasma after 24?h. In xenotransplanted RAIL mice with MOLM-13, THP-1 cells or first passage patient-derived AMLs, SPHINX31 (0.8 or 2.0 mg/kg) led to a significant reduction in leukemic cell growth and a dose-dependent prolongation of survival of mice given MOLM-13, THP-1, and patient-derived MLL-X AMLs [2].
Cell Research Cells were transduced with gRNA vectors or treated with SPHINX31 and stained at the indicated time points with anti-mouse CD11b PE/Cy5 and anti-human CD11b PE or anti-human CD13 FITC. Data were analyzed by using LSRFortessa and FlowJo. Apoptosis levels were measured in human and/or mouse AML cells transduced with dual gRNA vectors (against SRPK1 and 3' BCL2 enhancer) and/or treated with 1 or 3?μM SPHINX31 at indicated time points, by using Annexin V. Data were analyzed by using LSRFortessa instruments. Cell cycle stages were measured in human and/or mouse AML cells transduced with dual gRNA vectors against SRPK1 and/or treated with 1 or 3?μM SPHINX31 at indicated time points, using Propidium Iodide. Data were analyzed using LSRFortessa instruments [2].
Animal Research For in vivo experiments, 6–10-week-old female Rosa26Cas9/+ mice were treated triweekly for two weeks with either vehicle or 2?mg/kg SPHINX31. Four weeks post-treatment, bone marrow cells from these mice were freshly extracted (as mentioned above) and blocked with anti-mouse CD16/32 and 10% mouse serum. For the identification of LK/LSK, LT-HSC, myeloid and B-cell subpopulations, staining was performed using CD4 PE/Cy5, CD5 PE/Cy5, CD8a PE/Cy5, CD11b PE/Cy5, B220 PE/Cy5, TER-119 PE/Cy5, GR-1 PE/Cy5, SCA-1 Pacific Blue, CD150 PE/Cy7, CD34 FITC and CD117 APC-eFluor780. In each of the multi-colour flow cytometry experiments, we included the fluorescence minus one (FMO) controls. FMO controls provide a measure of spillover in a given channel. This allows for correct gating and selects only the stained cells in the experimental sample. Flow cytometry analysis was performed using a LSRFortessa instrument and resulting data were subsequently analyzed using FlowJo [2].
Molecular Weight 507.51
Formula C27H24F3N5O2
CAS No. 1818389-84-2

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

Ethanol: 10 mg/mL

H2O: Insoluble

DMSO: 20 mg/mL

TargetMolReferences and Literature

1. Batson J, et al. Development of Potent, Selective SRPK1 Inhibitors as Potential Topical Therapeutics for Neovascular Eye Disease. ACS Chem Biol. 2017 Mar 17;12(3):825-832. 2. Tzelepis K, et al. SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4. Nat Commun. 2018 Dec 19;9(1):5378.

Related compound libraries

This product is contained In the following compound libraries:
Metabolism Compound Library Apoptosis Compound Library NO PAINS Compound Library Kinase Inhibitor Library Inhibitor Library Bioactive Compound Library Target-Focused Phenotypic Screening Library Anti-Aging Compound Library Anti-Cancer Compound Library Cell Cycle Compound Library

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Keywords

SPHINX31 1818389-84-2 Cell Cycle/Checkpoint Metabolism Serine/threonin kinase SPHINX-31 Serine-arginine protein kinases retinal permeability eye disease neovascular SPHINX 31 Inhibitor Norway Brown rats SRPK inhibit Vascular endothelial growth factor receptor HuCCA-1 VEGFR diabetics angiogenic inhibitor

 

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