CAL-101

Bezeichnung:CAL-101

CAS-Nr870281-82-6

Englisch Name:CAL-101

CBNumberCB32538915

SummenformelC22H18FN7O

Molgewicht415.42

MOL-Datei870281-82-6.mol

CAL-101 physikalisch-chemischer Eigenschaften

Schmelzpunkt	250-252oC
Siedepunkt	733.4±70.0 °C(Predicted)
Dichte	1.47
storage temp.	-20°C
Löslichkeit	Soluble in DMSO (>25 mg/ml)
Aggregatzustand	White solid.
pka	10.00±0.10(Predicted)
Farbe	White
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
InChIKey	IFSDAJWBUCMOAH-HNNXBMFYSA-N
SMILES	N1C2=C(C(F)=CC=C2)C(=O)N(C2=CC=CC=C2)C=1[C@@H](NC1=C2C(=NC=N1)NC=N2)CC

Sicherheit

S-Sätze:	V
HS Code	29399990
Giftige Stoffe Daten	870281-82-6(Hazardous Substances Data)

Gefahreninformationscode (GHS)

CAL-101 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Idelalisib (CAS 870281-82-6) is a potent (IC50 = 2.5nM) and selective (IC50’s: PI3Ka = 820nM, PI3Kb = 565nM, PI3Kg = 89nM) PI3Kd inhibitor.1,2 Useful clinical agent for the treatment of various blood cancers. Idelalisib attenuates regulatory T cells (Treg) but not conventional T cells (Tconv) resulting in a significant increase in tumor-infiltrating antigen-specific CD8 T cells in a murine lung cancer model.3 Conversely, systemic PI3Kd inactivation antagonized anti-CTLA-4 and anti-PD-L1 treatment.4 Others have found that Idelalisib minimally influenced rituximab- and obinutuzumab-mediated Ab-dependent cellular cytotoxicity in human lymphoma cells.5
Verwenden
CAL-101 is a PI3K/mTOR pathway inhibitor used in the treatment of myeloid leukemia through sensitizing the cells to combatting drugs. Potent PI3K-p110-delta inhibitor.
Definition
ChEBI: A member of the class of quinazolines that is 5-fluoro-3-phenylquinazolin-4-one in which the hydrogen at position 2 is replaced by a (1S)-1-(3H-purin-6-ylamino)propyl group. used for for the treatment of refractory indol nt non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukemia.
in vitro
CAL-101 (Idelalisib) is a highly selective and potent p110δ inhibitor (EC50=8 nM). Greater selectivity (400- to 4000-fold) is seen against related kinases C2β, hVPS34, DNA-PK, and mTOR, whereas no activity is observed against a panel of 402 diverse kinases at 10 μM. CAL-101 reduces PDGF-induced pAkt by only 25% at 10 μM. Idelalisib (CAL-101) inhibits LPA-induced pAkt with an EC50 of 1.9 μM. Idelalisib (CAL-101) blocks Fc?RI p110δ-mediated CD63 expression with an EC50 of 8 nM, whereas formyl-methionyl-leucyl-phenylalanine activation of p110γ is inhibited with an EC50 of 3 μM. Thus, CAL-101 has 240- to 2500-fold selectivity in cell-based assays for p110δ over the other class I PI3K isoforms. CAL-101Idelalisib (CAL-101)-induced apoptosis of chronic lymphocytic leukemia (CLL) cells is significant compared with vehicle treatment alone (P<0.001). Idelalisib (CAL-101) induces selective cytotoxicity in CLL cells independent of IgVH mutational status or interphase cytogenetics.
in vivo
A significant reduction is observed in the CD11b+Ly6G+ neutrophils from brain homogenates of bothp110δD910A/D910A mice and Idelalisib (CAL-101) (40 mg/kg, i.v.) post-treated mice.
target
p110δ
Lager
Store at -20°C
Einzelnachweise
1) Herman?et al. (2010), Phosphatidylinositol 2-kinase-d inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals; Blood?116 2078 2) Lannutti?et al. (2011), CAL-101, a p110d selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability; Blood 117 591 3) Ahmad?et al. (2017), Differential PI3Kd Signaling in CD4+ T-cell Subsets Enables Selective Targeting of T Regulatory Cells to Enhance Cancer Immunotherapy; Cancer Res. 77 1892 4) Lim?et al. (2018), Phosphoinositide 3-kinase d inhibition promotes antitumor responses but antagonizes checkpoint inhibitors; JCI Insight 3 e120626 5) Palazzo?et al.?(2018),?The PI3Kd-Selective Inhibitor Idelalisib Minimally Interferes with Immune Effector Function Mediated by Rituximab or Obinutuzumab and Significantly Augment B Cell Depletion In Vivo; J.Immunol. 200 2304

CAL-101 Upstream-Materialien And Downstream Produkte

CAL-101 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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