PKI-402 | CAS#1173204-81-3 | PI3K inhibitor

MedKoo Cat#: 406324 | Name: PKI-402

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PKI-402 is a selective, reversible, ATP-competitive, equipotent inhibitor of class I phosphatidylinositol 3-kinases (PI3K), including PI3K-alpha mutants, and mammalian target of rapamycin (mTOR; IC(50) versus PI3K-alpha = 2 nmol/L). PKI-402 inhibited growth of human tumor cell lines derived from breast, brain (glioma), pancreas, and non-small cell lung cancer tissue and suppressed phosphorylation of PI3K and mTOR effector proteins (e.g., Akt at T308) at concentrations that matched those that inhibited cell growth.

Chemical Structure

PKI-402

CAS#1173204-81-3

Theoretical Analysis

MedKoo Cat#: 406324

Name: PKI-402

CAS#: 1173204-81-3

Chemical Formula: C29H34N10O3

Exact Mass: 570.2815

Molecular Weight: 570.66

Elemental Analysis: C, 61.04; H, 6.01; N, 24.55; O, 8.41

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 550.00	2 Weeks
10mg	USD 825.00	2 Weeks

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Related CAS #

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Synonym

PKI402; PKI 402; PK-I402.

IUPAC/Chemical Name

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

InChi Key

ZAXFYGBKZSQBIV-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H34N10O3/c1-3-39-27-24(34-35-39)26(37-16-18-42-19-17-37)32-25(33-27)20-4-8-22(9-5-20)30-29(41)31-23-10-6-21(7-11-23)28(40)38-14-12-36(2)13-15-38/h4-11H,3,12-19H2,1-2H3,(H2,30,31,41)

SMILES Code

O=C(NC1=CC=C(C(N2CCN(C)CC2)=O)C=C1)NC3=CC=C(C4=NC(N5CCOCC5)=C(N=NN6CC)C6=N4)C=C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs

Storage Condition

0 Â– 4 oC for short term (weeks to 1 month) or -20 oC for long terms (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly.

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PKI-402 is a selective, reversible, ATP-competitive inhibitor of PI3K, including PI3K-α mutants, and mTOR (IC50=2, 3, 7,14 and 16 nM for PI3Kα, mTOR, PI3Kβ, PI3Kδ and PI3Kγ).

In vitro activity:

To investigate whether the mitochondrial apoptotic pathway is one of the apoptotic pathways induced by PI3K/AKT/mTOR pathway inhibitors, SKOV3 cells were treated with Rapamycin, BYL-719, or PKI-402 for 24 h. Then, this study detected the expressions of apoptosis-related proteins and found that cleaved caspase-3 and cleaved caspase-9 were increased, while the expression of anti-apoptotic protein Bcl-2 was decreased and that of pro-apoptotic protein Bax was increased, the ratio of Bax/Bcl-2 was increased significantly after treatment with the dual PI3K/mTOR inhibitor PKI-402 (Fig. 4A). It was worth noting that the expressions of anti-apoptotic protein Mcl-1 were decreased gradually over time when SKVO3 and A2780 cells were treated with the dual PI3K/mTOR inhibitor PKI-402 (Fig. 4B, and Fig S3B). After separation of intracellular organelles, this study found that the expression of Mcl-1 in mitochondria was decreased significantly (Fig. 4C). Reference: Biomed Pharmacother. 2020 Sep;129:110397. https://pubmed.ncbi.nlm.nih.gov/32585451/

In vivo activity:

PKI-402 is a selective, reversible, ATP-competitive, equipotent inhibitor of class I phosphatidylinositol 3-kinases (PI3K), including PI3K-alpha mutants, and mammalian target of rapamycin (mTOR; IC(50) versus PI3K-alpha = 2 nmol/L). In vivo, PKI-402 inhibited tumor growth in MDA-MB-361, glioma (U87MG), and lung (A549) mouse xenograft models. In MDA-MB-361, PKI-402 at 100 mg/kg (daily for 5 days, one round) reduced initial tumor volume of 260 mm(3) to 129 mm(3) and prevented tumor regrowth for 70 days. In MDA-MB-361 tumors, PKI-402 (100 mg/kg, single dose) suppressed Akt phosphorylation (at T308) and induced cleaved PARP. Suppression of phosphorylated Akt (p-Akt) was complete at 8 hours and still evident at 24 hours. Reference: Mol Cancer Ther. 2010 Apr;9(4):976-84. https://pubmed.ncbi.nlm.nih.gov/20371716/

	Solvent	mg/mL	mM
Solubility
	DMSO	2.8	4.82

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 570.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Hu X, Xia M, Wang J, Yu H, Chai J, Zhang Z, Sun Y, Su J, Sun L. Dual PI3K/mTOR inhibitor PKI-402 suppresses the growth of ovarian cancer cells by degradation of Mcl-1 through autophagy. Biomed Pharmacother. 2020 Sep;129:110397. doi: 10.1016/j.biopha.2020.110397. Epub 2020 Jun 22. PMID: 32585451. 2. Yuan G, Lian Z, Liu Q, Lin X, Xie D, Song F, Wang X, Shao S, Zhou B, Li C, Li M, Yao G. Phosphatidyl inositol 3-kinase (PI3K)-mTOR inhibitor PKI-402 inhibits breast cancer induced osteolysis. Cancer Lett. 2019 Feb 28;443:135-144. doi: 10.1016/j.canlet.2018.11.038. Epub 2018 Dec 9. PMID: 30540926. 3. Mallon R, Hollander I, Feldberg L, Lucas J, Soloveva V, Venkatesan A, Dehnhardt C, Delos Santos E, Chen Z, Dos Santos O, Ayral-Kaloustian S, Gibbons J. Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor. Mol Cancer Ther. 2010 Apr;9(4):976-84. doi: 10.1158/1535-7163.MCT-09-0954. Epub 2010 Apr 6. PMID: 20371716. 4. Dehnhardt CM, Venkatesan AM, Delos Santos E, Chen Z, Santos O, Ayral-Kaloustian S, Brooijmans N, Mallon R, Hollander I, Feldberg L, Lucas J, Chaudhary I, Yu K, Gibbons J, Abraham R, Mansour TS. Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: discovery of PKI-402. J Med Chem. 2010 Jan 28;53(2):798-810. doi: 10.1021/jm9014982. PMID: 19968288.

In vitro protocol:

In vivo protocol:

1. Mallon R, Hollander I, Feldberg L, Lucas J, Soloveva V, Venkatesan A, Dehnhardt C, Delos Santos E, Chen Z, Dos Santos O, Ayral-Kaloustian S, Gibbons J. Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor. Mol Cancer Ther. 2010 Apr;9(4):976-84. doi: 10.1158/1535-7163.MCT-09-0954. Epub 2010 Apr 6. PMID: 20371716. 2. Dehnhardt CM, Venkatesan AM, Delos Santos E, Chen Z, Santos O, Ayral-Kaloustian S, Brooijmans N, Mallon R, Hollander I, Feldberg L, Lucas J, Chaudhary I, Yu K, Gibbons J, Abraham R, Mansour TS. Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: discovery of PKI-402. J Med Chem. 2010 Jan 28;53(2):798-810. doi: 10.1021/jm9014982. PMID: 19968288.

1: Ma J, Dong D, Qi H, Li J, Yu H, Hu X, Sun L, Shen L. LARP1, an RNA-binding protein, participates in ovarian cancer cell survival by regulating mitochondrial oxidative phosphorylation in response to the influence of the PI3K/mTOR pathway. Biochim Biophys Acta Mol Basis Dis. 2024 Aug 5;1870(8):167453. doi: 10.1016/j.bbadis.2024.167453. Epub ahead of print. PMID: 39111634. 2: Mahaamnad N, Pocasap P, Kukongviriyapan V, Senggunprai L, Prawan A, Kongpetch S. Dual blockage of PI3K-mTOR and FGFR induced autophagic cell death in cholangiocarcinoma cells. Heliyon. 2024 May 10;10(10):e31112. doi: 10.1016/j.heliyon.2024.e31112. PMID: 38799762; PMCID: PMC11126846. 3: Lin N, Sun L, Chai J, Qi H, Zhao Y, Ma J, Xia M, Hu X. Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response. Cancer Cell Int. 2024 Jan 18;24(1):38. doi: 10.1186/s12935-024-03210-x. PMID: 38238825; PMCID: PMC10795350. 4: Pei L, Hou Y, Feng Y, Li F, Su H, Zhang Y, Song Y, Liu K, Cao G. Equine β-defensin 1 regulates cytokine expression and phagocytosis in S. aureus- infected mouse monocyte macrophages via the Paxillin-FAK-PI3K pathway. Int Immunopharmacol. 2023 Oct;123:110793. doi: 10.1016/j.intimp.2023.110793. Epub 2023 Aug 13. PMID: 37582311. 5: Gasimli R, Kayabasi C, Ozmen Yelken B, Asik A, Sogutlu F, Celebi C, Yilmaz Susluer S, Kamer S, Biray Avci C, Haydaroglu A, Gunduz C. The effects of PKI-402 on breast tumor models' radiosensitivity via dual inhibition of PI3K/mTOR. Int J Radiat Biol. 2023;99(12):1961-1970. doi: 10.1080/09553002.2023.2232019. Epub 2023 Jul 12. PMID: 37389464. 6: Liu N, Wang X, Li X, Lv X, Xie H, Guo Z, Wang J, Dou G, Du Y, Song D. Identification of effective natural PIK3CA H1047R inhibitors by computational study. Aging (Albany NY). 2021 Aug 20;13(16):20246-20257. doi: 10.18632/aging.203409. Epub 2021 Aug 20. PMID: 34415239; PMCID: PMC8436935. 7: Chow Z, Johnson J, Chauhan A, Izumi T, Cavnar M, Weiss H, Townsend CM Jr, Anthony L, Wasilchenko C, Melton ML, Schrader J, Evers BM, Rychahou P. PI3K/mTOR Dual Inhibitor PF-04691502 Is a Schedule-Dependent Radiosensitizer for Gastroenteropancreatic Neuroendocrine Tumors. Cells. 2021 May 20;10(5):1261. doi: 10.3390/cells10051261. PMID: 34065268; PMCID: PMC8160730. 8: Hu X, Xia M, Wang J, Yu H, Chai J, Zhang Z, Sun Y, Su J, Sun L. Dual PI3K/mTOR inhibitor PKI-402 suppresses the growth of ovarian cancer cells by degradation of Mcl-1 through autophagy. Biomed Pharmacother. 2020 Sep;129:110397. doi: 10.1016/j.biopha.2020.110397. Epub 2020 Jun 22. PMID: 32585451. 9: Sheng J, Shen L, Sun L, Zhang X, Cui R, Wang L. Inhibition of PI3K/mTOR increased the sensitivity of hepatocellular carcinoma cells to cisplatin via interference with mitochondrial-lysosomal crosstalk. Cell Prolif. 2019 May;52(3):e12609. doi: 10.1111/cpr.12609. Epub 2019 Apr 29. PMID: 31033054; PMCID: PMC6536453. 10: Yuan G, Lian Z, Liu Q, Lin X, Xie D, Song F, Wang X, Shao S, Zhou B, Li C, Li M, Yao G. Phosphatidyl inositol 3-kinase (PI3K)-mTOR inhibitor PKI-402 inhibits breast cancer induced osteolysis. Cancer Lett. 2019 Feb 28;443:135-144. doi: 10.1016/j.canlet.2018.11.038. Epub 2018 Dec 9. PMID: 30540926. 11: Mallon R, Hollander I, Feldberg L, Lucas J, Soloveva V, Venkatesan A, Dehnhardt C, Delos Santos E, Chen Z, Dos Santos O, Ayral-Kaloustian S, Gibbons J. Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor. Mol Cancer Ther. 2010 Apr;9(4):976-84. doi: 10.1158/1535-7163.MCT-09-0954. Epub 2010 Apr 6. PMID: 20371716. 12: Dehnhardt CM, Venkatesan AM, Delos Santos E, Chen Z, Santos O, Ayral- Kaloustian S, Brooijmans N, Mallon R, Hollander I, Feldberg L, Lucas J, Chaudhary I, Yu K, Gibbons J, Abraham R, Mansour TS. Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: discovery of PKI-402. J Med Chem. 2010 Jan 28;53(2):798-810. doi: 10.1021/jm9014982. PMID: 19968288.