PKI-402
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MedKoo CAT#: 406324

CAS#: 1173204-81-3

Description: 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

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PKI-402
CAS# 1173204-81-3

Theoretical Analysis

MedKoo Cat#: 406324
Name: PKI-402
CAS#: 1173204-81-3
Chemical Formula: C29H34N10O3
Exact Mass: 570.28
Molecular Weight: 570.658
Elemental Analysis: C, 61.04; H, 6.01; N, 24.55; O, 8.41

Price and Availability

Size Price Availability Quantity
5mg USD 400 2 Weeks
10mg USD 650 2 Weeks
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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 – 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:
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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 2.8 4.82

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.

Recalculate based on batch purity %
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: 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.
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.

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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. PubMed 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. PubMed PMID: 19968288.