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PKI-402

PKI-402 is a potent dual PI3K/mTOR inhibitor targeting PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and mTOR with IC50 of 2 nM, 7 nM, 16 nM, 14 nM, and 3 nM, respectively.

Catalog No.S2739

: Tel: +1-832-582-8158[email protected]

PKI-402 Chemical Structure
Molecular Weight: 570.65

Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

PKI-402 is available in the following compound libraries:

Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well)

Product Information

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Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1009	BEZ235 (NVP-BEZ235)	<1 mg/mL	1 mg/mL	<1 mg/mL
S1105	LY294002	<1 mg/mL	36 mg/mL	21 mg/mL
S1065	GDC-0941	<1 mg/mL	44 mg/mL	<1 mg/mL
S2226	CAL-101 (GS-1101)	<1 mg/mL	83 mg/mL	35 mg/mL
S2247	BKM120 (NVP-BKM120)	<1 mg/mL	82 mg/mL	2 mg/mL
S2638	NU7441 (KU-57788)	<1 mg/mL	3 mg/mL	<1 mg/mL
S2814	BYL719	<1 mg/mL	88 mg/mL	5 mg/mL
S1038	PI-103	<1 mg/mL	24 mg/mL	<1 mg/mL
S1169	TGX-221	<1 mg/mL	12 mg/mL	<1 mg/mL
S2758	Wortmannin	<1 mg/mL	86 mg/mL	<1 mg/mL
S2636	A66	<1 mg/mL	79 mg/mL	1 mg/mL
S1072	ZSTK474	<1 mg/mL	21 mg/mL	<1 mg/mL
S1118	XL147	<1 mg/mL	3 mg/mL	<1 mg/mL
S2767	3-Methyladenine	<1 mg/mL	4 mg/mL	4 mg/mL
S1268	IC-87114	<1 mg/mL	0.66 mg/mL	<1 mg/mL
S1410	AS-605240	<1 mg/mL	0.4 mg/mL	<1 mg/mL
S2671	AS-252424	<1 mg/mL	61 mg/mL	<1 mg/mL
S1523	XL765 (SAR245409)	<1 mg/mL	15 mg/mL	<1 mg/mL
S2658	GSK2126458	<1 mg/mL	101 mg/mL	<1 mg/mL
S1205	PIK-75	<1 mg/mL	3 mg/mL	<1 mg/mL
S2743	PF-04691502	<1 mg/mL	14 mg/mL	<1 mg/mL
S1462	AZD6482	<1 mg/mL	82 mg/mL	28 mg/mL
S2628	PF-05212384 (PKI-587)	<1 mg/mL	2 mg/mL	<1 mg/mL
S2696	GDC-0980 (RG7422)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1489	PIK-93	<1 mg/mL	78 mg/mL	<1 mg/mL
S1187	PIK-90	<1 mg/mL	0.28 mg/mL	<1 mg/mL
S2802	BAY80-6946	<1 mg/mL	<1 mg/mL	<1 mg/mL
S1352	TG100-115	<1 mg/mL	9 mg/mL	<1 mg/mL
S1219	YM201636	<1 mg/mL	35 mg/mL	<1 mg/mL
S1360	GSK1059615	<1 mg/mL	2 mg/mL	<1 mg/mL
S2227	PIK-294	<1 mg/mL	98 mg/mL	<1 mg/mL
S2681	AS-604850	<1 mg/mL	57 mg/mL	5 mg/mL
S2699	CH5132799	<1 mg/mL	12 mg/mL	<1 mg/mL
S2682	CAY10505	<1 mg/mL	58 mg/mL	<1 mg/mL
S2749	NVP-BGT226	<1 mg/mL	30 mg/mL	<1 mg/mL
S2759	PI3K/HDAC InhibitorⅠ	<1 mg/mL	102 mg/mL	<1 mg/mL
S2207	PIK-293	<1 mg/mL	80 mg/mL	<1 mg/mL
S2739	PKI-402	<1 mg/mL	0.4 mg/mL	<1 mg/mL
S2870	TG 100713	<1 mg/mL	2 mg/mL	<1 mg/mL
S8002	GSK2636771	<1 mg/mL	87 mg/mL	19 mg/mL
S7028	IPI-145 (INK1197)	<1 mg/mL	84 mg/mL	<1 mg/mL

Research Area
Research Area

Combination Therapy

Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Tech Support & FAQs

Biological Activity

Description	PKI-402 is a potent dual PI3K/mTOR inhibitor targeting PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and mTOR with IC50 of 2 nM, 7 nM, 16 nM, 14 nM, and 3 nM, respectively.
Targets	PI3Kα	PI3Kβ	PI3Kγ	PI3Kδ	mTOR
IC50	2 nM	7 nM	16 nM	14 nM	3 nM ^[1]
In vitro	Equivalent to the IC50 for wild-type PI3Kα, PKI-402 inhibits E545K and H1047R PI3Kα mutants with IC50 of 3 nM. In a panel of 236 human protein kinases, PKI-402 only displays inhibitory activity against C-Raf and B-Raf with IC50 of 7 μM, and displays little activity against all other kinases with IC50 of > 10 μM. PKI-402 inhibits the growth of human tumor cell lines with IC50 of 6-349 nM. Consistently, PKI-402 inhibits phosphorylation of PI3K and mTOR effector proteins, particularly phosphorylated Akt (p-Akt) at T308 and S473 with IC50 of <10 nM and <30 nM, respectively. PKI-402 inhibits both p70S6K and 4EBP1 phosphorylation with IC50 of <10 nM. PKI-402 inhibits Akt phosphorylation of PRAS40 at T246 with IC50 of <30 nM, and inhibits Akt phosphorylation of ENOS at S1177 and GSK3α/GSK3β at S9/S21 with IC50 of <10 nM. In MDAMB-361, a breast tumor line with mutant PI3K-α (E545K) and elevated levels of Her2 receptor, PKI-402 treatment induces cleaved poly(ADP-ribose) polymerase (PARP), a marker for apoptosis. Less than 10% of MDAMB-361 cells exposed to PKI-402 at 0.3 μM (or higher) for 24 hours remain viable. ^[1]
In vivo	Single dose of PKI-402 (100 mg/kg) suppresses Akt phosphorylation (at T308) and induces cleaved PARP in MDA-MB-361 tumors. In normal tissue (heart and lung), PKI-402 (100 mg/kg) has minimal effect on p-Akt, with no detectable cleaved PARP. Consistently, PKI-402 at 100 mg/kg (daily for 5 days, one round) reduces initial tumor volume of 260 mm3 to 129 mm3 and prevents tumor regrowth for 70 days in MDA-MB-361. PKI-402 significantly inhibits the growth of A549 tumors in nude mice at 25 mg/kg and 50 mg/kg. PKI-402 at 100 mg/kg (daily for 5 days, one round) causes significant (P < 0.01) reduction in tumor growth of U87MG. ^[1]
Clinical Trials
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

Fluorescence polarization format assay	Enzyme assays are done in fluorescent polarization (FP) format, adapted from the Echelon K-1100 PI3K FP assay kit protocol. Assay reaction buffer is 20 mM Hepes, pH 7.5, 2 mM MgCl₂, 0.05% CHAPS, and 0.01% βME. Assay STOP/detection buffer is 100 mM Hepes, pH 7.5, 4 mM EDTA, 0.05% CHAPS. FP assays are run in Nunc 384-well black polypropylene fluor plates. The FP reaction is run in 20 μL of reaction buffer containing 20 μM PIP2, 25 μM ATP, and >4% DMSO. The reaction is run for 30 minutes at room temp. The reaction is stopped with 20 μL of STOP/detection buffer containing 10 nM probe and 40 nM GST-GRP. Assay plates are incubated for 2 hours, and fluorescence polarization is measured in a Perkin-Elmer Envision plate reader with TAMRA-FP filters.

Fluorescence polarization format assay

Enzyme assays are done in fluorescent polarization (FP) format, adapted from the Echelon K-1100 PI3K FP assay kit protocol. Assay reaction buffer is 20 mM Hepes, pH 7.5, 2 mM MgCl₂, 0.05% CHAPS, and 0.01% βME. Assay STOP/detection buffer is 100 mM Hepes, pH 7.5, 4 mM EDTA, 0.05% CHAPS. FP assays are run in Nunc 384-well black polypropylene fluor plates. The FP reaction is run in 20 μL of reaction buffer containing 20 μM PIP2, 25 μM ATP, and >4% DMSO. The reaction is run for 30 minutes at room temp. The reaction is stopped with 20 μL of STOP/detection buffer containing 10 nM probe and 40 nM GST-GRP. Assay plates are incubated for 2 hours, and fluorescence polarization is measured in a Perkin-Elmer Envision plate reader with TAMRA-FP filters.

Cell Assay: ^[1]

Cell lines	MDA-MB-361, MDA-MB-468, T47D, MCF7, BT474, HT29, HCT116, DLD1, U87MG, H157, NCI-H460, A549, NCI-H1975, NCI-H1650, NCIH2170, KB, 786-0, A498, MIA-PaCa-2, and PC3
Concentrations	Dissolved in DMSO, final concentrations ~3 μM
Incubation Time	72 hours
Method	Cell growth inhibition is determined using the CellTiter 96 Aqueous nonradioactive cell proliferation assay. This homogeneous colorimetric method determined the number of viable cells in proliferation assays. The assay is carried out in 96-well format, with cell number numbers per well being adjusted on the basis of growth characteristics of the various cell lines used. Assay end point data are quantitated after 72 hours of PKI-402 exposure using a Victor2 V (Wallac) model 1420 multilabel HTS counter.

Animal Study: ^[1]

Animal Models	Female nude mice injected subcutaneously with MDA-361, U87MG, or A549 cells
Formulation	Dissolved in 0.5% methylcellulose and 0.4% polysorbate 80 (Tween-80)
Dosages	~100 mg/kg/day
Administration	Administered by i.v. route

References

Chemical Information

Download PKI-402 SDF

Molecular Weight (MW)	570.65
Formula	C₂₉H₃₄N₁₀O₃
CAS No.	1173204-81-3, 1173204-82-4 (XHCl)
Synonyms	N/A

Solubility (25°C) DMSO 0.4 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	1-(4-(3-ethyl-7-morpholino-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)phenyl)-3-(4-(1-methylpiperazine-4-carbonyl)phenyl)urea

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Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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PKI-402