870281-82-6 Usage
Description
CAL-101, also known as Idelalisib, is a potent and selective PI3Kδ inhibitor with an IC50 of 2.5nM. It is a member of the quinazoline class and is used for the treatment of various blood cancers, including refractory indolent non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukemia.
Uses
Used in Oncology:
CAL-101 is used as a PI3K/mTOR pathway inhibitor for the treatment of myeloid leukemia. It works by sensitizing the cells to combatting drugs and acts as a potent PI3K-p110-delta inhibitor.
CAL-101 is also used in the treatment of refractory indolent non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukemia. It has been found to attenuate 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.
Additionally, CAL-101 has been studied for its potential synergistic effects with other treatments. While it has been found to minimally influence rituximaband obinutuzumab-mediated Ab-dependent cellular cytotoxicity in human lymphoma cells, its systemic PI3Kδ inactivation has been shown to antagonize anti-CTLA-4 and anti-PD-L1 treatment.
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
Check Digit Verification of cas no
The CAS Registry Mumber 870281-82-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,7,0,2,8 and 1 respectively; the second part has 2 digits, 8 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 870281-82:
(8*8)+(7*7)+(6*0)+(5*2)+(4*8)+(3*1)+(2*8)+(1*2)=176
176 % 10 = 6
So 870281-82-6 is a valid CAS Registry Number.
InChI:InChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)
870281-82-6Relevant articles and documents
A novel strategy for the manufacture of idelalisib: Controlling the formation of an enantiomer
Mekala, Nagaraju,Buddepu, Srinivasa Rao,Dehury, Sanjay K.,Moturu, Krishna Murthy V. R.,Indukuri, Sunil Kumar V.,Vasireddi, Umamaheswara Rao,Parimi, Atchuta R.
, p. 15863 - 15869 (2018)
A novel and scalable synthesis of 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone, idelalisib 1, has been developed. This strategy controls the desfluoro impurity of 13 during reduction of nitro intermediate 4, and also arrests the formation of the enantiomer during cyclisation of diamide 17, without affecting the neighbouring chiral centre. This process is demonstrated on a larger scale in the laboratory and achieved good chemical and chiral purities coupled with good yields.
Novel idelalisib preparation method
-
, (2018/09/11)
The invention belongs to the field of medicine synthesis and provides a novel idelalisib preparation method. The novel idelalisib preparation method includes steps: in an appropriate solvent, subjecting a compound A to nucleophilic substitution reaction with B in existence of an acid-binding agent to obtain an intermediate C; hydrolyzing the compound C into an intermediate D under appropriate alkali action; subjecting the intermediate D and a compound E to condensation to obtain an intermediate F; in an appropriate solvent, subjecting the intermediate F to ring closing reaction under a catalytic system of HMDS (hexamethyl disilazane)/lewis acid to obtain a final product namely idelalisib.
PROCESS FOR THE PREPARATION OF AMORPHOUS IDELALISIB AND ITS PREMIX
-
, (2016/10/24)
Processes for the preparation of amorphous idelalisib are provided. Processes for the preparation of a premix of amorphous idelalisib are also provided.