SRPIN340

Names

[ Name ]:
SRPIN340

[Synonym ]:
3,4-Dipropoxy-3-cyclobuten-1,2-dion
SR protein phosphorylation inhibitor 1
4-Pyridinecarboxamide (N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]
4-Pyridinecarboxamide, N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]-
squaric acid dibutyl ester
N-[2-(1-Piperidinyl)-5-(trifluoromethyl)phenyl]isonicotinamide
1,2-di-n-propoxy-cyclobutenedione
di-n-propyl squarate
(SRPIN)340 N-[2-(1-Piperidinyl)-5-(trifluoromethyl)phenyl]-4-pyridinecarboxamide
N4-[2-piperidino-5-(trifluoromethyl)phenyl]isonicotinamide
3-Cyclobutene-1,2-dione,3,4-dipropoxy
SRPIN-340
SRPIN340

Biological Activity

[Description]:

SRPIN340 is an ATP-competitive serine-arginine-rich protein kinase (SRPK) inhibitor, with a Ki of 0.89 μM for SRPK1.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> SRPK

Research Areas >> Cancer

[Target]

Ki: 0.89 μM (SRPK1)[1]

[In Vitro]

SRPIN340 is a serine-arginine-rich protein kinase (SRPK) inhibitor, with a Ki of 0.89 μM for SRPK1. SRPIN340 also inhibits SRPK2, but shows no significant inhibition on other SRPK, such as Clk1 and Clk4. SRPIN340 promotes degradation of SRp75, which is necessary for HIV expression. SRPIN340 suppresses the propagation of Sindbis virus (IC50, 60 μM) as well as severe acute respiratory syndrome virus[1]. SRPIN340 shows inhibitory effect on leukemia cell lines, such as AML HL60, ALL-T Molt4 and Jurkat, with IC50s of 44.7 μM, 92.2 μM and 82.3 μM, respectively[2].

[Cell Assay]

Leukemic cells (5 × 104 cells/well) and isolated PBMCs (8 × 104 cells/well) are seeded in 96-well plates. Each well contained 100 μL of complete RPMI medium and 100 μL of SRPIN340 solution at different concentrations. The compound is diluted in RPMI medium with 10% fetal bovine serum and 0.4% DMSO (v/v). After 48 h of culture, MTT (5 mg/mL) is added to the wells (3 h, 37°C). The plates are centrifuged at room temperature for 30 min 500 ×g, followed by the removal of the MTT solution and the addition of 100 μL/well of DMSO to solubilize the formazan. Absorbance is measured at 540 nm in a microplate reader. Each experimental procedure is performed in triplicate[2].

[References]

[1]. Fukuhara T, et al. Utilization of host SR protein kinases and RNA-splicing machinery during viral replication. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11329-33.

[2]. Siqueira RP, et al. Potential Antileukemia Effect and Structural Analyses of SRPK Inhibition by N-(2-(Piperidin-1-yl)-5-(Trifluoromethyl)Phenyl)Isonicotinamide (SRPIN340). PLoS One. 2015 Aug 5;10(8):e0134882.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
395.9±42.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₈H₁₈F₃N₃O

[ Molecular Weight ]:
349.350

[ Flash Point ]:
193.3±27.9 °C

[ Exact Mass ]:
349.140198

[ PSA ]:
45.23000

[ LogP ]:
4.15

[ Appearance of Characters ]:
light yellow solid

[ Vapour Pressure ]:
0.0±0.9 mmHg at 25°C

[ Index of Refraction ]:
1.578

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma.

Br. J. Cancer 111(3) , 477-85, (2014)

Current therapies for metastatic melanoma are targeted either at cancer mutations driving growth (e.g., vemurafenib) or immune-based therapies (e.g., ipilimumab). Tumour progression also requires angi...

Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization.

Mol. Vis. 19 , 536-43, (2013)

To investigate the applicability of serine/arginine-rich protein kinase (SRPK)-specific inhibitor, SRPIN340, for attenuation of choroidal neovascularization (CNV) formation using a mouse model.Laser p...

Dysregulation of splicing proteins in head and neck squamous cell carcinoma.

Cancer Biol. Ther. 17 , 219-29, (2016)

Signaling plays an important role in regulating all cellular pathways. Altered signaling is one of the hallmarks of cancers. Phosphoproteomics enables interrogation of kinase mediated signaling pathwa...