KY02111 1118807-13-8

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Molecular Weight:

376.86 KY02111 promotes differentiation of hPSCs to cardiomyocytes by inhibiting Wnt signaling, may act downstream of APC and GSK3β.


Biological Activity


KY02111 (10 μM) increases the ratio of beating cardiac colonies as much
as 70%-94% in cell aggregates of two hESC lines (KhES-1 and KhES-3),
four hiPSC lines (253G1, IMR90-1, IMR90-4, and RCHIPC0003), and a mouse
ESC line (R1). KY02111 (10 μM) results in 73%-85% postive IMR90-1 hiPSCs
expressing the cardiac markers, cardiac troponin T (cTnT), αActinin, or
NKX2.5, whereas only a few DMSO-treated cells are positive for the
markers. KY02111 (10 μM) results in 16% postive IMR90-1 hiPSCs
expressing the cardiac pacemaker marker, HCN4, whereas the ratio of
Vimentin-positive cells (fibroblasts) decreases 3.3-fold.


KY02111-induced cardiomyocytes (KY-CMs) expresses the cardiac markers,
αMHC, NKH2.5, and HCN4, and that all of the ion channel genes examined
are expressed at levels similar to those of adult heart tissue. KY02111
(10 μM) downregulates the expression of 72.7% target genes of canonical
WNT signaling in IMR90-1 hiPSCs, suggesting that KY02111 inhibits
canonical WNT signaling in hPSCs. KY02111 (10 μM) clearly reduces
luciferase activities in both IMR90-1 hiPSCs and HEK293 cells in a
dose-dependent manner in the TOPflash assay. KY02111 (10 μM-25 μM)
increases cardiac differentiation about 80-fold in transgenic monkey
ESCs compared to the control and does not show toxicity to cells even at
high concentration. KY02111 (10 μM) significantly reduces luciferase
activity in the TOPflash assay in SW480 cells, whereas XAV939 and IWP-2
does not.


KY02111 (10 μM) dramatically reduces luciferase activity
induced by GSK3β inhibitor BIO in SW480 cells, compared to that of
XAV939 and IWP-2. KY02111 alone produces approximately 80% cTnT-positive
cells, KY02111 in combination with other WNT Inhibitors does not
significantly increase differentiation efficiency, which shows that
KY02111 effectively produces a high proportion of functional
cardiomyocytes from hPSCs.


Protocol(Only for Reference)


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

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

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)

Chemical Information

Molecular Weight (MW)	376.86
Formula	C18H17ClN2O3S
CAS No.	1118807-13-8

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms

Solubility (25°C) *	In vitro	DMSO	75 mg/mL (199.01 mM)
		Water	<1 mg/mL (
		Ethanol	<1 mg/mL (
* <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	Benzenepropanamide, N-(6-chloro-2-benzothiazolyl)-3,4-dimethoxy-

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Product Categories : Cytoskeletal Signaling > Wnt/beta-catenin Inhibitor