phosphatidylinositol 3-kinase catalytic subunit type 3 | Phosphatidylinositol 3-kinase family | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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phosphatidylinositol 3-kinase catalytic subunit type 3

Target id: 2152

Nomenclature: phosphatidylinositol 3-kinase catalytic subunit type 3

Abbreviated Name: VPS34

Family: Phosphatidylinositol 3-kinase family, Phosphatidylinositol kinases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 887 18q12.3 PIK3C3 phosphatidylinositol 3-kinase catalytic subunit type 3
Mouse - 887 18 B1 Pik3c3 phosphatidylinositol 3-kinase catalytic subunit type 3
Rat - 887 18 p12 Pik3c3 phosphatidylinositol 3-kinase, catalytic subunit type 3
Previous and Unofficial Names
catalytic phosphatidylinositol 3-kinase 3 | phosphatidylinositol 3-kinase | phosphatidylinositol 3-kinase, catalytic subunit type 3 | Phosphatidylinositol 3-kinase p100 subunit | phosphoinositide-3-kinase, class 3 | PI3-kinase type 3 | PI3K type 3 | PI-3K Vps34p | ptdIns-3-kinase type 3
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Human PIK3C3 crystal structure
Resolution:  2.8Å
Species:  Human
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human PIK3C3 in complex with 3-[4-(4-Morpholinyl)thieno[3,2-d]pyrimidin-2-yl]-phenol
PDB Id:  3LS8
Resolution:  2.25Å
Species:  Human
Image of receptor 3D structure from RCSB PDB
Description:  The crystal structure of Human VPS34 in complex with PIK-III
PDB Id:  4PH4
Ligand:  PIK-III
Resolution:  2.8Å
Species:  Human
References:  5
Enzyme Reaction
EC Number:

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SAR405 Hs Inhibition 8.8 pKd 8
pKd 8.8 (Kd 1.52x10-9 M) [8]
PQR620 Hs Inhibition 5.6 pKd 7
pKd 5.6 (Kd 2.75x10-6 M) [7]
compound 12b [PMID: 31465220] Hs Inhibition 5.5 pKd 2
pKd 5.5 (Kd 3.2x10-6 M) [2]
compound 82 [PMID: 21332118] Hs Inhibition 7.5 pKi 4
pKi 7.5 (Ki 3.1x10-8 M) [4]
VPS34-IN-1 Hs Inhibition 8.4 pIC50 9
pIC50 8.4 (IC50 4x10-9 M) [9]
torin 2 Hs Inhibition 8.1 pIC50 6
pIC50 8.1 (IC50 8.58x10-9 M) [6]
PIK-III Hs Inhibition 7.7 pIC50 5
pIC50 7.7 (IC50 1.8x10-8 M) [5]
SAR260301 Hs Inhibition 6.7 pIC50 3
pIC50 6.7 (IC50 1.83x10-7 M) [3]
General Comments
VPS34 is the only Class III PI 3-kinase (a lipid kinase) identified. Human VPS34 is ubiquitously expressed and is the enzymatic component of a multiprotein complex. VPS34 substrate specificity is limited to phosphatidylinositol. Mammalian VPS34 may be involved in nutrient sensing and autophagy, which permits modulation of cellular activty in response to nutritional changes [1].


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1. Backer JM. (2008) The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem. J., 410 (1): 1-17. [PMID:18215151]

2. Borsari C, Rageot D, Dall'Asen A, Bohnacker T, Melone A, Sele AM, Jackson E, Langlois JB, Beaufils F, Hebeisen P et al.. (2019) A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor. J. Med. Chem., 62 (18): 8609-8630. [PMID:31465220]

3. Certal V, Carry JC, Halley F, Virone-Oddos A, Thompson F, Filoche-Rommé B, El-Ahmad Y, Karlsson A, Charrier V, Delorme C et al.. (2014) Discovery and optimization of pyrimidone indoline amide PI3Kβ inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers. J. Med. Chem., 57 (3): 903-20. [PMID:24387221]

4. D'Angelo ND, Kim TS, Andrews K, Booker SK, Caenepeel S, Chen K, D'Amico D, Freeman D, Jiang J, Liu L et al.. (2011) Discovery and optimization of a series of benzothiazole phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors. J. Med. Chem., 54 (6): 1789-811. [PMID:21332118]

5. Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S, Triantafellow E, Menon S, Wang Z, Honda A, Pardee G et al.. (2014) Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol., 16 (11): 1069-79. [PMID:25327288]

6. Liu Q, Wang J, Kang SA, Thoreen CC, Hur W, Ahmed T, Sabatini DM, Gray NS. (2011) Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. J. Med. Chem., 54 (5): 1473-80. [PMID:21322566]

7. Rageot D, Bohnacker T, Melone A, Langlois JB, Borsari C, Hillmann P, Sele AM, Beaufils F, Zvelebil M, Hebeisen P et al.. (2018) Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders. J. Med. Chem., 61 (22): 10084-10105. [PMID:30359003]

8. Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F, Bachelot MF, Lamberton A, Mathieu M, Bertrand T et al.. (2014) A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat. Chem. Biol., 10 (12): 1013-9. [PMID:25326666]

9. Taracido IC, Harrington EM, Honda A, Keaney E. (2014) Bi-heteroaryl compounds as Vps34 inhibitors. Patent number: US8685993. Assignee: Novartis Ag. Priority date: 21/12/2010. Publication date: 01/04/2014.

How to cite this page

Phosphatidylinositol 3-kinase family: phosphatidylinositol 3-kinase catalytic subunit type 3. Last modified on 13/09/2019. Accessed on 14/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY,