VPS34-IN1
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MedKoo CAT#: 406636

CAS#: 1383716-33-3

Description: VPS34-IN1 is a potent and selective Vps34 inhibitor with potential anticancer activity. VPS34-IN1 inhibits Vps34 with 25 nM IC50 in vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K.


Chemical Structure

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VPS34-IN1
CAS# 1383716-33-3

Theoretical Analysis

MedKoo Cat#: 406636
Name: VPS34-IN1
CAS#: 1383716-33-3
Chemical Formula: C21H24ClN7O
Exact Mass: 425.17309
Molecular Weight: 425.91
Elemental Analysis: C, 59.22; H, 5.68; Cl, 8.32; N, 23.02; O, 3.76

Price and Availability

Size Price Availability Quantity
5.0mg USD 90.0 Ready to ship
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1350.0 Ready to ship
500.0mg USD 2850.0 Ready to ship
1.0g USD 3850.0 Ready to ship
2.0g USD 6450.0 Ready to ship
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Synonym: VPS34IN1, VPS34 IN1, VPS34-IN1

IUPAC/Chemical Name: 1-((2-((2-chloropyridin-4-yl)amino)-4'-(cyclopropylmethyl)-[4,5'-bipyrimidin]-2'-yl)amino)-2-methylpropan-2-ol

InChi Key: AWNXKZVIZARMME-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H24ClN7O/c1-21(2,30)12-26-19-25-11-15(17(29-19)9-13-3-4-13)16-6-8-24-20(28-16)27-14-5-7-23-18(22)10-14/h5-8,10-11,13,30H,3-4,9,12H2,1-2H3,(H,25,26,29)(H,23,24,27,28)

SMILES Code: OC(C)(C)CNC(N=C1CC2CC2)=NC=C1C3=CC=NC(NC4=CC=NC(Cl)=C4)=N3

Appearance: White to off-white 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: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

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

Biological target: Vps34-IN-1 is an inhibitor of Vps34 with an IC50 of 4 nM.
In vitro activity: This study tested the antileukemic activity of the VPS34-IN1 compound in nine AML cell lines. VPS34-IN1 impaired viability and induced dose-dependent cell death in all these tested cell lines (Fig. 1A, B). This study then tested the effects of VPS34-IN1 on the survival of primary leukemic cells from 23 patients with AML. This inhibitor induced a significant death of leukemic cells in this series of AML patients (Fig. (Fig.1C1C and Supplemental Table 1). In contrast, VPS34-IN1 did not induce cell death in normal CD34+ hematopoietic progenitor cells from 6 allogenic BM donors (Fig. 1C). Reference: Oncogenesis. 2020 Oct; 9(10): 94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581748/
In vivo activity: This study first tested the implication of Vps34 in platelet responses in vivo and found a normal tail bleeding time in Pf4-Cre-Pik3c3lox/lox mice (Figure 5A). The prothrombotic function of platelets tested after ferric chloride–induced mouse carotid injury was significantly decreased, with nearly 50% of Pf4-Cre-Pik3c3lox/lox mice protected against occlusive arterial thrombus formation (Figure 5B). Ex vivo thrombus formation assay performed under physiological arterial or arteriolar wall shear rates of 500 and 1500 s−1, respectively, using Pf4-Cre-Pik3c3lox/lox mice blood perfused over a collagen surface showed that Vps34-deficient platelets, despite their ability to normally attach to collagen fibers (supplemental Figure 5A), formed significantly smaller thrombi compared with WT platelets (Figure 5C-D). These data demonstrate that inhibition of Vps34 kinase activity in platelets, independently from its implication in MKs and platelet production, decreases platelet thrombus growth at arterial and arteriolar flows. Reference: Blood. 2017 Nov 2; 130(18): 2032–2042. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669208/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 51.33 120.52
Ethanol 85.0 199.57

Preparing Stock Solutions

The following data is based on the product molecular weight 425.91 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. Yuen CK, Wong WM, Mak LF, Wang X, Chu H, Yuen KY, Kok KH. Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase. J Med Virol. 2021 Apr;93(4):2076-2083. doi: 10.1002/jmv.26583. Epub 2020 Oct 30. PMID: 33026649; PMCID: PMC7675438. 2. Meunier G, Birsen R, Cazelles C, Belhadj M, Cantero-Aguilar L, Kosmider O, Fontenay M, Azar N, Mayeux P, Chapuis N, Tamburini J, Bouscary D. Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia. Oncogenesis. 2020 Oct 22;9(10):94. doi: 10.1038/s41389-020-00278-8. PMID: 33093450; PMCID: PMC7581748. 1. Yuen CK, Wong WM, Mak LF, Wang X, Chu H, Yuen KY, Kok KH. Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase. J Med Virol. 2021 Apr;93(4):2076-2083. doi: 10.1002/jmv.26583. Epub 2020 Oct 30. PMID: 33026649; PMCID: PMC7675438. 2. Meunier G, Birsen R, Cazelles C, Belhadj M, Cantero-Aguilar L, Kosmider O, Fontenay M, Azar N, Mayeux P, Chapuis N, Tamburini J, Bouscary D. Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia. Oncogenesis. 2020 Oct 22;9(10):94. doi: 10.1038/s41389-020-00278-8. PMID: 33093450; PMCID: PMC7581748. 3. Valet C, Levade M, Chicanne G, Bilanges B, Cabou C, Viaud J, Gratacap MP, Gaits-Iacovoni F, Vanhaesebroeck B, Payrastre B, Severin S. A dual role for the class III PI3K, Vps34, in platelet production and thrombus growth. Blood. 2017 Nov 2;130(18):2032-2042. doi: 10.1182/blood-2017-04-781641. Epub 2017 Sep 13. PMID: 28903944; PMCID: PMC5669208.
In vitro protocol: 1. Yuen CK, Wong WM, Mak LF, Wang X, Chu H, Yuen KY, Kok KH. Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase. J Med Virol. 2021 Apr;93(4):2076-2083. doi: 10.1002/jmv.26583. Epub 2020 Oct 30. PMID: 33026649; PMCID: PMC7675438. 2. Meunier G, Birsen R, Cazelles C, Belhadj M, Cantero-Aguilar L, Kosmider O, Fontenay M, Azar N, Mayeux P, Chapuis N, Tamburini J, Bouscary D. Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia. Oncogenesis. 2020 Oct 22;9(10):94. doi: 10.1038/s41389-020-00278-8. PMID: 33093450; PMCID: PMC7581748.
In vivo protocol: 1. Valet C, Levade M, Chicanne G, Bilanges B, Cabou C, Viaud J, Gratacap MP, Gaits-Iacovoni F, Vanhaesebroeck B, Payrastre B, Severin S. A dual role for the class III PI3K, Vps34, in platelet production and thrombus growth. Blood. 2017 Nov 2;130(18):2032-2042. doi: 10.1182/blood-2017-04-781641. Epub 2017 Sep 13. PMID: 28903944; PMCID: PMC5669208.

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1: Bilanges B, Vanhaesebroeck B. Cinderella finds her shoe: the first Vps34 inhibitor uncovers a new PI3K-AGC protein kinase connection. Biochem J. 2014 Dec 1;464(2):e7-10. doi: 10.1042/BJ20141218. PubMed PMID: 25395352.

2: Bago R, Malik N, Munson MJ, Prescott AR, Davies P, Sommer E, Shpiro N, Ward R, Cross D, Ganley IG, Alessi DR. Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. Biochem J. 2014 Nov 1;463(3):413-27. doi: 10.1042/BJ20140889. PubMed PMID: 25177796; PubMed Central PMCID: PMC4209782.

 



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