1. PI3K/Akt/mTOR
  2. PI3K

IPI549 

Cat. No.: HY-100716 Purity: 99.34%
Handling Instructions

IPI549 is a potent and selective PI3Kγ Inhibitor with an IC50 of 16 nM.

For research use only. We do not sell to patients.

IPI549 Chemical Structure

IPI549 Chemical Structure

CAS No. : 1693758-51-8

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 98 In-stock
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Estimated Time of Arrival: December 31
5 mg USD 84 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 119 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 348 In-stock
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Estimated Time of Arrival: December 31
100 mg USD 588 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
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500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

IPI549 is a potent and selective PI3Kγ Inhibitor with an IC50 of 16 nM.

IC50 & Target[1]

PI3Kγ

16 nM (IC50)

PI3Kα

3.2 μM (IC50)

PI3Kβ

3.5 μM (IC50)

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[1].

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[1].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.8919 mL 9.4597 mL 18.9193 mL
5 mM 0.3784 mL 1.8919 mL 3.7839 mL
10 mM 0.1892 mL 0.9460 mL 1.8919 mL
Please refer to the solubility information to select the appropriate solvent.
Animal Administration
[2]

IPI-549 is dissolved at 5% 1-Methyl-2-pyrrolidinone.

C57BL/6J and Balb/c mice (6 to 8 weeks old) are used in this study. On day 0 of the experiments, tumor cells are injected intradermally (i.d.) in the right flank. IPI-549 is administered by oral gavage once a day at 15 mg/kg. Treatment is initiated on day 7 ending on day 21 post tumor implant. Control groups receive vehicle (5% NMP, 95% PEG). Tumors are measured every second or third day with a caliper, and the volume (length×width×height) is calculated. Animals are euthanized for signs of distress or when the total tumor volume reaches 2500 mm3. Finally, Tumors are isolated, and frozen until needed[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

528.56

Formula

C₃₀H₂₄N₈O₂

CAS No.

1693758-51-8

SMILES

O=C(C1=C2N=CC=CN2N=C1N)N[[email protected]](C3=CC4=C(C(N3C5=CC=CC=C5)=O)C(C#CC6=CN(C)N=C6)=CC=C4)C

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 15 mg/mL

5% NMP+40% PEG300+55% PBS: Insoluble

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.34%

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Product Name:
IPI549
Cat. No.:
HY-100716
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