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IPI549

Cat. No. M6084
IPI549 Structure
Size Price Availability Quantity
5mg USD 105 In stock
25mg USD 320 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

In vitro: IPI-549 inhibits PI3Kγ with IC50 of 16 nM, with >100-fold selectivity over other lipid and protein kinases (PI3Kα IC50=3.2 μM, PI3Kβ IC50=3.5 μM, PI3Kδ IC50>8.4 μM). IPI549 is evaluated for activity across all Class I PI3K isoforms. The binding affinity of IPI549 for PI3K-γ is determined by measuring the individual rates constants and for PI3K-α, β and δ using equilibrium fluorescent titration. IPI549 is found to be a remarkably tight binder to PI3Kγ with a Kd of 290 pM and >58-fold weaker affinity for other Class I PI3K isoforms (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). In PI3K-α, -β, -γ, and -δ dependent cellular phospho-AKT assays, IPI549 demonstrates excellent PI3K-γ potency (IC50=1.2 nM) and selectivity against other Class I PI3K isoforms (>146-fold). Cellular IC50s for Class I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ(180 nM) are determined in SKOV-3, 786-O, RAW 264.7, and RAJI cells, respectively, by monitoring inhibition of pAKT S473 by ELISA. Furthermore, IPI549 dose dependently inhibits PI3Kγ dependent bone marrow-derived macrophage (BMDM) migration. IPI549 is also found to be selective against a panel of 80 GPCRs, ion channels, and transporters at 10 μM. In vivo: IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration. In vivo (mice, rats, dog, and monkeys), IPI-549 has excellent oral bioavailability, low clearance, and distributed into tissues with a mean volume of distribution of 1.2 L/kg. Overall, IPI-549 has a favorable pharmacokinetic profile to allow potent and selective inhibition of PI3K-γ in vivo. The t1/2 of IPI-549 for mouse, rat, dog and monkey is 3.2, 4.4, 6.7 and 4.3 h, respectively. IPI-549 significantly reduces neutrophil migration in a dose dependent manner in this model when administered orally at all of the tested doses.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 528.56
Formula C30H24N8O2
CAS Number 1693758-51-8
Purity >99%
Solubility 15 mg/mL in DMSO
Storage at -20°C
References

Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells.
De Henau O, et al. Nature. 2016 Nov 17;539(7629):443-447. PMID: 27828943.

Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate.
Evans CA, et al. ACS Med Chem Lett. 2016 Jul 22;7(9):862-7. PMID: 27660692.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: IPI549 supplier, PI3K, inhibitors

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