Idelalisib (CAL-101)
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MedKoo CAT#: 200586

CAS#: 870281-82-6

Description: Idelalisib, also known as CAL-101, is a PI3K-delta inhibitor with potential immunomodulating and antineoplastic activities. CAL-101 inhibits the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), preventing the activation of the PI3K signaling pathway and thus inhibiting tumor cell proliferation, motility, and survival. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in hematopoietic lineages. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells. CAL-101 has [EC(50)] = 8nM.

Chemical Structure

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Idelalisib (CAL-101)
CAS# 870281-82-6
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 200586
Name: Idelalisib (CAL-101)
CAS#: 870281-82-6
Chemical Formula: C22H18FN7O
Exact Mass: 415.16
Molecular Weight: 415.423
Elemental Analysis: C, 63.61; H, 4.37; F, 4.57; N, 23.60; O, 3.85

Price and Availability

Size Price Availability Quantity
200mg USD 110 Ready to ship
500mg USD 190 Ready to ship
1g USD 350 Ready to ship
2g USD 550 Ready to ship
5g USD 1150 Ready to ship
10g USD 2050 Ready to ship
20g USD 3450 2 weeks
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Synonym: CAL101; CAL 101; CAL-101; GS1101; GS 1101; GS-1101, Idelalisib.

IUPAC/Chemical Name: (S)-2-(1-((9H-purin-6-yl)amino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one

InChi Key: IFSDAJWBUCMOAH-HNNXBMFYSA-N

InChi Code: 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)/t15-/m0/s1

SMILES Code: O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4N=CNC4=NC=N3)CC)=NC5=C1C(F)=CC=C5

Appearance: white 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, DMF, EtOH, and 1:1 DMF:PBS

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

More Info:

Biological target: Idelalisib (CAL-101; GS-1101) is a p110δ inhibitor with an IC50 of 2.5 nM.
In vitro activity: In this study, idelalisib reduced NK-cell proliferation. Moreover, PI3K∂ inhibition led to a decrease in the percentage of cytotoxic NK cells, which also translated into reduced target cell killing by NK cells. Two different apoptosis pathways are affected. Idelalisib impaired cell death through secretion of cytolytic molecules, as well as cell death via the Fas–FasL pathway. NK cells are an important part of the innate immune system and play a key role in the defense against infections. Taken together, this study’s data demonstrate a decrease NK-cell proliferation and cytolytic activity by idelalisib and that this might contribute to the increased frequency of infectious events observed in clinical trials. Reference: Front Immunol. 2021; 12: 608625. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005712/
In vivo activity: To investigate more in detail the potential of Idelalisib as antithrombotic, in vivo tail bleeding and a ferric chloride-induced arterial thrombosis assays were performed in a murine model. Mice treated with Idelalisib (20 mg/kg) showed a plasma concentration of 5.1 ± 2.0 µM after 1 h (Supplementary Figure S1). In the tail bleeding assay in mice (Figure 4A), Idelalisib caused a 3.5-fold increase in bleeding time (5.5 ± 3.5 min vs. 1.63 ± 0.88 min of vehicle) (Figure 4B). Accordingly, the hemoglobin content of blood collected during bleeding in Idelalisib-treated mice was significantly higher than in untreated animals (Figure 4C). Importantly, 9 out of 11 (80%) mice treated with Idelalisib showed bleeding times <10 min. By comparison, 66% of mice treated with ASA or clopidogrel, established antiplatelet therapies, bled over 10 min (Supplementary Figure S2). FeCl3-induced arterial thrombosis was undertaken to further assess the antithrombotic potential of Idelalisib (Figure 4D). Interestingly, drug-treated mice (20 mg/kg) displayed significantly longer occlusion times than control mice, indicating significant protection against thrombosis in this experimental model (Figure 4E). Reference: Int J Mol Sci. 2021 Apr; 22(7): 3304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037016/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 55.9 134.56
DMF 30.0 72.22
DMF:PBS (pH 7.2) (1:1) 0.5 1.20
Ethanol 24.5 58.98

Preparing Stock Solutions

The following data is based on the product molecular weight 415.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Rohrbacher L, Brauchle B, Ogrinc Wagner A, von Bergwelt-Baildon M, Bücklein VL, Subklewe M. The PI3K∂-Selective Inhibitor Idelalisib Induces T- and NK-Cell Dysfunction Independently of B-Cell Malignancy-Associated Immunosuppression. Front Immunol. 2021 Mar 15;12:608625. doi: 10.3389/fimmu.2021.608625. PMID: 33790890; PMCID: PMC8005712. 2. Li K, Yi P, Luo H, Li J, Meng L, Tang M, Zeng W, Yang S, Wang W. Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2020 Dec 28;45(12):1389-1397. English, Chinese. doi: 10.11817/j.issn.1672-7347.2020.190728. PMID: 33472993. 3. Barrachina MN, Izquierdo I, Hermida-Nogueira L, Morán LA, Pérez A, Arroyo AB, García-Barberá N, González-Conejero R, Troitiño S, Eble JA, Rivera J, Martínez C, Loza MI, Domínguez E, García Á. The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential. Int J Mol Sci. 2021 Mar 24;22(7):3304. doi: 10.3390/ijms22073304. PMID: 33804911; PMCID: PMC8037016. 4. Yue D, Sun X. Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular carcinoma. Cell Death Dis. 2018 Sep 17;9(10):935. doi: 10.1038/s41419-018-0960-8. PMID: 30224718; PMCID: PMC6141589.
In vitro protocol: 1. Rohrbacher L, Brauchle B, Ogrinc Wagner A, von Bergwelt-Baildon M, Bücklein VL, Subklewe M. The PI3K∂-Selective Inhibitor Idelalisib Induces T- and NK-Cell Dysfunction Independently of B-Cell Malignancy-Associated Immunosuppression. Front Immunol. 2021 Mar 15;12:608625. doi: 10.3389/fimmu.2021.608625. PMID: 33790890; PMCID: PMC8005712. 2. Li K, Yi P, Luo H, Li J, Meng L, Tang M, Zeng W, Yang S, Wang W. Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2020 Dec 28;45(12):1389-1397. English, Chinese. doi: 10.11817/j.issn.1672-7347.2020.190728. PMID: 33472993.
In vivo protocol: 1. Barrachina MN, Izquierdo I, Hermida-Nogueira L, Morán LA, Pérez A, Arroyo AB, García-Barberá N, González-Conejero R, Troitiño S, Eble JA, Rivera J, Martínez C, Loza MI, Domínguez E, García Á. The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential. Int J Mol Sci. 2021 Mar 24;22(7):3304. doi: 10.3390/ijms22073304. PMID: 33804911; PMCID: PMC8037016. 2. Yue D, Sun X. Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular carcinoma. Cell Death Dis. 2018 Sep 17;9(10):935. doi: 10.1038/s41419-018-0960-8. PMID: 30224718; PMCID: PMC6141589.

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1: Meadows SA, Vega F, Kashishian A, Johnson D, Diehl V, Miller LL, Younes A, Lannutti BJ. PI3Kδ inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood. 2012 Feb 23;119(8):1897-900. doi: 10.1182/blood-2011-10-386763. Epub 2011 Dec 30. PubMed PMID: 22210877.

2: Byrd JC, Woyach JA, Johnson AJ. Translating PI3K-Delta Inhibitors to the Clinic in Chronic Lymphocytic Leukemia: The Story of CAL-101 (GS1101). Am Soc Clin Oncol Educ Book. 2012;32:691-694. doi: 10.14694/EdBook_AM.2012.32.691. PubMed PMID: 24451820.

3: Castillo JJ, Furman M, Winer ES. CAL-101: a phosphatidylinositol-3-kinase p110-delta inhibitor for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2012 Jan;21(1):15-22. doi: 10.1517/13543784.2012.640318. Epub 2011 Nov 24. Review. PubMed PMID: 22112004.

4: Hoellenriegel J, Meadows SA, Sivina M, Wierda WG, Kantarjian H, Keating MJ, Giese N, O'Brien S, Yu A, Miller LL, Lannutti BJ, Burger JA. The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011 Sep 29;118(13):3603-12. doi: 10.1182/blood-2011-05-352492. Epub 2011 Jul 29. PubMed PMID: 21803855.

5: Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, Druker BJ, Puri KD, Ulrich RG, Giese NA. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011 Jan 13;117(2):591-4. doi: 10.1182/blood-2010-03-275305. Epub 2010 Oct 19. PubMed PMID: 20959606; PubMed Central PMCID: PMC3694505.

6: Herman SE, Gordon AL, Wagner AJ, Heerema NA, Zhao W, Flynn JM, Jones J, Andritsos L, Puri KD, Lannutti BJ, Giese NA, Zhang X, Wei L, Byrd JC, Johnson AJ. Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010 Sep 23;116(12):2078-88. doi: 10.1182/blood-2010-02-271171. Epub 2010 Jun 3. PubMed PMID: 20522708; PubMed Central PMCID: PMC2951855.