MedKoo product information:

CAL-101

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. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus) .

Current developer:  Calistoga Pharmaceuticals, Inc.

Review on CAL-101: CAL-101 is a highly selective PI3K p110δ inhibitor currently undergoing clinical development. CAL-101  has shown preclinical activity against CLL, NHL, HL and PCM cells. There is early evidence of clinical efficacy in CLL and indolent NHL. Studies using CAL-101 alone or in combination are also ongoing in PCM, HL and aggressive NHL. However, additional studies are needed to prove CAL-101 is effective and safe as the goals of therapy for patients with lymphoid neoplasms are not only directed towards improving response and cure rates but also prolonging survival without affecting quality of life. (source: Expert Opin Investig Drugs. 2012 Jan;21(1):15-22.)

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. 2011 Dec 30. [Epub ahead of print] PubMed PMID: 22210877.

2: 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. Epub 2011 Nov 24. PubMed PMID: 22112004.

3: Luk SK, Piekorz RP, Nürnberg B, Tony To SS. The catalytic phosphoinositol 3-kinase isoform p110δ is required for glioma cell migration and invasion. Eur J Cancer. 2012 Jan;48(1):149-57. Epub 2011 Nov 11. PubMed PMID: 22079609.

4: Norman P. Selective PI3Kδ inhibitors, a review of the patent literature. Expert Opin Ther Pat. 2011 Nov;21(11):1773-90. doi: 10.1517/13543776.2011.629606. PubMed PMID: 22017414.

5: Parekh S, Weniger MA, Wiestner A. New molecular targets in mantle cell lymphoma. Semin Cancer Biol. 2011 Nov;21(5):335-46. Epub 2011 Sep 18. PubMed PMID: 21945517; PubMed Central PMCID: PMC3217176.

6: 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. Epub 2011 Jul 29. PubMed PMID: 21803855.

7: Weniger MA, Wiestner A. Molecular targeted approaches in mantle cell lymphoma. Semin Hematol. 2011 Jul;48(3):214-26. PubMed PMID: 21782064; PubMed Central PMCID: PMC3143377.

8: Herman SE, Lapalombella R, Gordon AL, Ramanunni A, Blum KA, Jones J, Zhang X, Lannutti BJ, Puri KD, Muthusamy N, Byrd JC, Johnson AJ. The role of phosphatidylinositol 3-kinase-δ in the immunomodulatory effects of lenalidomide in chronic lymphocytic leukemia. Blood. 2011 Apr 21;117(16):4323-7. Epub 2011 Mar 4. PubMed PMID: 21378270; PubMed Central PMCID: PMC3087482.

9: 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. Epub 2010 Oct 19. PubMed PMID: 20959606.

10: Kahl BS, Cheson BD, Friedberg JW. Clinical Roundtable Monograph: current treatment options for NHL patients refractory to standard therapy: recent data in single-agent and combination therapy. Clin Adv Hematol Oncol. 2010 May;8(5):1-16. PubMed PMID: 20712081.

11: 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. Epub 2010 Jun 3. PubMed PMID: 20522708; PubMed Central PMCID: PMC2951855.

12: Ikeda H, Hideshima T, Fulciniti M, Perrone G, Miura N, Yasui H, Okawa Y, Kiziltepe T, Santo L, Vallet S, Cristea D, Calabrese E, Gorgun G, Raje NS, Richardson P, Munshi NC, Lannutti BJ, Puri KD, Giese NA, Anderson KC. PI3K/p110{delta} is a novel therapeutic target in multiple myeloma. Blood. 2010 Sep 2;116(9):1460-8. Epub 2010 May 26. PubMed PMID: 20505158; PubMed Central PMCID: PMC2938837.

13: Lin TS. New agents in chronic lymphocytic leukemia. Curr Hematol Malig Rep. 2010 Jan;5(1):29-34. Review. PubMed PMID: 20425394.