CAL-101 (GS-1101)

• CAT Number: A000804
• CAS Number: 870281-82-6
• Molecular Formula: C₂₂H₁₈FN₇O
• Molecular Weight: 415.42
• Purity: ≥95%
• Target: PI3K
• Solubility: >20.8mg/mL in DMSO
• Storage: 3 years -20C powder
• IUPAC Name: 5-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]quinazolin-4-one
• 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)/t15-/m0/s1
• InChIKey: IFSDAJWBUCMOAH-HNNXBMFYSA-N
• SMILES: CC[C@@H](C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5

CAL-101 (GS-1101)（Cat No.:A000804）is a selective inhibitor of phosphoinositide 3-kinase delta (PI3Kδ), a key enzyme in the PI3K signaling pathway, primarily involved in immune cell function. It is widely used in cancer research, particularly for hematologic malignancies like chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). By inhibiting PI3Kδ, CAL-101 disrupts cell survival and proliferation in malignant B cells, leading to apoptosis. Its specificity for the delta isoform makes it a targeted therapeutic with fewer off-target effects, providing a promising approach for treating B-cell cancers.

Reference

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.