PI-3065

Protein target name:

PIK3CD

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 500 nM

Probe Availability

MedChemExpress

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

Lipid kinase

Subclass:

Class I

HUGO ID:

HGNC:8977

Entrez gene ID:

5293

UNIPROT ID:

O00329

Target alias:

APDS; PI3K; IMD14; p110D; P110DELTA

Probe Details

Chemical Probes Portal ID:

CPP2170

PubChem CID:

24937012

SMILES string:

FC(C=CC1=C2C=CN1)=C2C3=NC4=C(SC(CN5CCN(CC6CC6)CC5)=C4)C(N7CCOCC7)=N3

InChi Key:

YDNOHCOYQVZOMC-UHFFFAOYSA-N

Orthogonal probe:

Pictilisib, Idelalisib

Physico-chemical properties

NMR:

1H-NMR δH (400 MHz, CD3OD) 0.10-0.14 (m, 2H), 0.49-0.54 (m, 2H), 0.81-0.91 (m, 1H), 2.28 (d, J = 6.8, 2H), 3.81 (m, 8H), 3.89 (2, 2H), 4.00-4.04 (m, 8H), 6.30 (dd, J = 8.8, 11.0, 1H), 6.58 (dd, J = 0.9, 3.4, 1H), 7.29 (m, 2H), 7.41 (ddd, J = 0.9, 3.8, 8.8, 1H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

Ki, IC50

1.5 nM, 15 nM

Potency assay:

Enzymatic Activity

Structure-activity relationship:

Off target activity

Probe Selectivity in Vitro:

Selective against PI3K family members: p110alpha, beta and gamma (1.1, 2.3, 27.5 uM). No significant activity against 72 protein kinases was observed at ≤ 10 μM in a KinaseProfiler assay (Millipore).

In cell validation

On target activity in cells

Potency in cells:

IC50

36, 38 nM

Potency assay (cells):

anti-IgM Stimulation followed by FACS for CD69, Cell Proliferation Assay

In vivo validation

Organism:

Mouse

Dose:

75 mg/Kg

Route of delivery:

Oral

Cmax:

6.88 uM

Tmax:

Primary Reference

Reference (doi):

10.1038/nature13444

Reference (PMID):

24919154

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

2 review(s)

Rating for use in Model Organisms

2 review(s)

SAB Members

SAB Comments

PI-3065 is an older and well-studied PI3Kdelta inhibitor. The compound lacks a negative control and overall, off-target evaluation is somewhat modest. While the selectivity within the family has been established, the broader selectivity profile has not been fully elucidated. As a tool in conjunction with several more recently published PI3Kdelta inhibitors of similar and more different structures, this compound can be used as one of several tools to interrogate PI3kdelta inhibition. In vivo, the levels of target engagement in relevant tissues and cell types have not been studied in detail and 75 mpk appears to modulate the target, there is insufficient dose-response and time-course data available to determine whether 75 mpk is indeed the best dose for this compound in mice.

Jun 18 2021 - 10:13am

PI-3065

Probe Availability

Probe Information

Target Details

APDS; PI3K; IMD14; p110D; P110DELTA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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PI-3065

Probe Availability

Probe Information

Target Details

APDS; PI3K; IMD14; p110D; P110DELTA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?