CK-636

Arp2/3 complex inhibitor CAS# 442632-72-6

CK-636

Catalog No. BCC5107----Order now to get a substantial discount!

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Chemical structure

CK-636

3D structure

Chemical Properties of CK-636

Cas No. 442632-72-6 SDF Download SDF
PubChem ID 588963 Appearance Powder
Formula C16H16N2OS M.Wt 284.38
Type of Compound N/A Storage Desiccate at -20°C
Synonyms CK-0944636
Solubility DMSO : ≥ 49 mg/mL (172.30 mM)
H2O : < 0.1 mg/mL (insoluble)
*"≥" means soluble, but saturation unknown.
Chemical Name N-[2-(2-methyl-1H-indol-3-yl)ethyl]thiophene-2-carboxamide
SMILES CC1=C(C2=CC=CC=C2N1)CCNC(=O)C3=CC=CS3
Standard InChIKey ACAKNPKRLPMONU-UHFFFAOYSA-N
Standard InChI InChI=1S/C16H16N2OS/c1-11-12(13-5-2-3-6-14(13)18-11)8-9-17-16(19)15-7-4-10-20-15/h2-7,10,18H,8-9H2,1H3,(H,17,19)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of CK-636

DescriptionCK-636(CK-0944636) is a small molecule inhibitor of Arp2/3 complex; Inhibitor of actin polymerization; Cell permeable inhibitor of human (IC50=4μM), fission yeast (IC50=24μM) and bovine (IC50=32μM) Arp2/3 complex between Arp2 and Arp3. Inhibits actin polymerization (IC50=22μM). IC50 value: 4/24/32 uM (Human/fission yeast/bovine Arp2/3) [1] Target: Arp2/3 complex; actin polymerization CK-636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-636 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes.

References:
[1]. Nolen BJ, et al. Characterization of two classes of small molecule inhibitors of Arp2/3 complex. Nature. 2009 Aug 20;460(7258):1031-4.

CK-636 Dilution Calculator

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CK-636 Molarity Calculator

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Preparing Stock Solutions of CK-636

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.5164 mL 17.5821 mL 35.1642 mL 70.3284 mL 87.9105 mL
5 mM 0.7033 mL 3.5164 mL 7.0328 mL 14.0657 mL 17.5821 mL
10 mM 0.3516 mL 1.7582 mL 3.5164 mL 7.0328 mL 8.7911 mL
50 mM 0.0703 mL 0.3516 mL 0.7033 mL 1.4066 mL 1.7582 mL
100 mM 0.0352 mL 0.1758 mL 0.3516 mL 0.7033 mL 0.8791 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on CK-636

CK-636 is an Arp2/3 complex inhibitor with IC50 of 4 μM, 24 μM and 32 μM for inhibition of actin polymerization induced by human, fission yeast and bovine Arp2/3 complex, respectively [1].
The Arp2/3 complex is expected to be involved in morphogenesis and cell adhesion and is essential for epidermal function. It regulates tight junctions and terminal differentiation to promote epidermal barrier formation [2].
CK-636 binds between Arp2 and Arp3 where it appears to block movement of Arp2 and Arp3 into their active conformation and inhibits Arp2/3 complex’s ability to nucleate actin filaments. Using a Listeria motility assay to determine whether CK-636 can inhibit actin polymerization mediated by Arp2/3 complex in live cells. In a concentration dependence way, CK-636 reduced the formation of actin filament comet tails by Listeria with IC50 value of 22 μM in infected SKOV3 cells [1].
References:
[1]. Nolen BJ, Tomasevic N, Russell A, et al. Characterization of two classes of small molecule inhibitors of Arp2/3 complex. Nature, 2009, 460(7258): 1031-1034.
[2]. Zhou K, Muroyama A, Underwood J, et al. Actin-related protein2/3 complex regulates tight junctions and terminal differentiation to promote epidermal barrier formation. Proc Natl Acad Sci, 2013, 110(40): E3820-E3829.

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References on CK-636

Actin-related protein 2/3 complex-based actin polymerization is critical for male fertility.[Pubmed:26223325]

Andrology. 2015 Sep;3(5):937-46.

The actin-related protein 2/3 (Arp2/3) complex is critical for regulation of actin polymerization, which is associated with sperm motility and capacitation status. However, the function of the Arp2/3 complex in male fertility has not yet been fully elucidated. Therefore, this study was designed to investigate the role of the Arp2/3 complex in different processes in spermatozoa and its consequences on fertilization and early embryonic development. In this in vitro study, mouse spermatozoa were incubated with different concentrations (10, 100, and 500 mum) of CK-636, an Arp2/3 complex antagonist. Our results demonstrated that inhibition of the Arp2/3 complex by high concentrations (100 and 500 mum) of CK-636 induced hyper-activated motility and acrosomal reaction, whereas intracellular calcium and tyrosine phosphorylation levels in spermatozoa were inhibited. Moreover, exposure of spermatozoa to the highest concentration of CK-636 reduced fertilization and embryo development. Interestingly, fertilization was significantly increased after treatment with 100 mum CK-636, whereas embryonic development was significantly decreased. Therefore, we conclude that the Arp2/3 complex plays a decisive role in regulation of sperm function and male fertility via actin polymerization. We anticipate that the Arp2/3 complex may have clinical application as marker for male fertility and male contraceptive targeting.

Migration of T cells on surfaces containing complex nanotopography.[Pubmed:24069255]

PLoS One. 2013 Sep 12;8(9):e73960.

T cells navigate complex microenvironments to initiate and modulate antigen-specific immune responses. While recent intravital microscopy study revealed that migration of T cells were guided by various tissue microstructures containing unique nanoscale topographical structures, the effects of complex nanotopographical structures on the migration of T cells have not been systematically studied. In this study, we fabricated surfaces containing nanoscale zigzag structures with various side lengths and turning angles using UV-assisted capillary force lithography and motility of T cells on zigzag patterned surfaces was studied. Motility of T cells was mostly affected by the turning angle, not by the side length, of the zigzag structures. In particular, motility behaviors of T cells near interfaces formed by turning points of zigzag patterns were significantly affected by turning angles. For obtuse turning angles, most of the T cells smoothly crossed the interfaces, but as the turning angle decreased, a substantial fraction of the T cells migrated along the interfaces. When the formation of lamellipodia, thin sheet-like structures typically generated at the leading edges of migrating cells by actin polymerization-driven membrane protrusion, was inhibited by an Arp2/3 inhibitor CK-636, a substantial fraction of T cells on those surfaces containing zigzag patterns with an acute turning angle were trapped at the interfaces formed by the turning points of the zigzag patterns. This result suggests that thin, wide lamellipodia at the leading edges of T cells play critical roles in motility of T cells in complex topographical microenvironments.

Description

CK-636 is a cell permeable inhibitor of Arp2/3 complex, that could inhibit actin polymerization, with IC50 values of 4 μM, 24 μM and 32 μM for human, fission yeast and bovine, respectively.

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