| Identification | More | [Name]
CAL-101 | [CAS]
870281-82-6 | [Synonyms]
GS1101
CAL-101
CAL101,CAL-101
CAL-101 (GS-1101)
Idelalisib(CAL-101)
CAL-101 (Idelalisib, GS-1101)
5-Fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]quinazolin-4-one
5-Fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone
(S)-2-(1-((9H-Purin-6-yl)aMino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
4(3H)-Quinazolinone, 5-fluoro-3-phenyl-2-[(1S)-1-(1H-purin-6-ylaMino)propyl]-
5-Fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone CAL-101 (Idelalisib, GS-1101)
CAL-101 5-Fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone | [EINECS(EC#)]
807-438-9 | [Molecular Formula]
C22H18FN7O | [MDL Number]
MFCD19443647 | [MOL File]
870281-82-6.mol | [Molecular Weight]
415.423 |
| Chemical Properties | Back Directory | [Melting point ]
250-252oC | [Boiling point ]
733.4±70.0 °C(Predicted) | [density ]
1.47 | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (>25 mg/ml) | [form ]
White solid. | [pka]
10.00±0.10(Predicted) | [color ]
White | [Stability:]
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 |
| Hazard Information | Back Directory | [Description]
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 | [Uses]
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 | [storage]
Store at -20°C | [References]
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 |
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