CZC24832


Catalog No. size PriceQuantity
M6594-2 2mg solid $102
M6594-10 10mg solid $401

Description

Cas:1159824-67-5

Product Information

CZC24832 is the first selective inhibitor of phosphoinositide 3-kinase γ (PI3Kγ) with efficacy in in vitro and in vivo models of inflammation. Extensive target- and cell-based profiling of CZC24832 revealed regulation of interleukin-17-producing T helper cell (T(H)17) differentiation by PI3Kγ, thus reinforcing selective inhibition of PI3Kγ as a potential treatment for inflammatory and autoimmune diseases.

 

Chemical Formula: C15H17FN6O2S

 

Exact Mass: 364.11177

 

Molecular Weight: 364.4

 

Elemental Analysis: C, 49.44; H, 4.70; F, 5.21; N, 23.06; O, 8.78; S, 8.80

 

Synonym: 

 

CZC24832;

CZC-24832;

CZC 24832

 

Chemical Name:

5-(2-amino-8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(tert-butyl)pyridine-3-sulfonamide

 

InChi Key:

RXRZPHQBTHQXSV-UHFFFAOYSA-N

 

InChi Code:

InChI=1S/C15H17FN6O2S/c1-15(2,3)21-25(23,24)11-4-9(6-18-7-11)10-5-12(16)13-19-14(17)20-22(13)8-10/h4-8,21H,1-3H3,(H2,17,20)

 

Smiles Code:

O=S(C1=CC(C2=CN3C(C(F)=C2)=NC(N)=N3)=CN=C1)(NC(C)(C)C)=O

 

 

Technical Data:

 

Appearance: 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

 

In Vitro

CZC24832 is active in PI3Kγ-dependent cellular C5a-induced AKT Ser473 phosphorylation (IC50=1.2 μM) and N-formyl-methionine-leucinephenylalanine (fMLP)-induced neutrophil migration assays (IC50=1.0 μM).

 

In Vivo

CZC24832 shows suitable pharmacokinetic properties including low clearance (0.84 L per h per kg body weight) and high oral bioavailability (37%), thus allowing further characterization of the inhibitor in rodent models of inflammation. In an IL-8-dependent air pouch model, CZC24832 shows a dose-dependent reduction of granulocyte recruitment (80% inhibition at 10 mg per kg body weight) consistent with the degree of inhibition observed in PI3Kγ-null mice. Mice treated orally with 10 mg CZC24832 per kg body weight twice per day show a substantial decrease of bone and cartilage destruction (53% reduction by histopathological analysis) as well as of overall clinical parameters (38% reduction).

 

 

References

 

  1. Bell K, Sunose M, Ellard K, Cansfield A, Taylor J, Miller W, Ramsden N, Bergamini G, Neubauer G. SAR studies around a series of triazolopyridines as potent and selective PI3Kγ inhibitors. Bioorg Med Chem Lett. 2012 Aug 15;22(16):5257-63. doi: 10.1016/j.bmcl.2012.06.049. Epub 2012 Jun 23. PubMed PMID: 22819766.

 

  1. Bergamini G, Bell K, Shimamura S, Werner T, Cansfield A, MA¼ller K, Perrin J, Rau C, Ellard K, Hopf C, Doce C, Leggate D, Mangano R, Mathieson T, O'Mahony A, Plavec I, Rharbaoui F, Reinhard F, Savitski MM, Ramsden N, Hirsch E, Drewes G, Rausch O, Bantscheff M, Neubauer G. A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation. Nat Chem Biol. 2012 Apr 29;8(6):576-82. doi: 10.1038/nchembio.957. Erratum in: Nat Chem Biol. 2012 Aug;8(8):737. PubMed PMID: 22544264.

Products are for research use only. Not for human use.

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