WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205744
Description: Duvelisib, also known as IPI-145 and INK-1197, is an orally bioavailable, highly selective and potent small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, PI3K delta/gamma inhibitor IPI 145 prevents the activation of the PI3K delta/gamma-mediated signaling pathways which may lead to a reduction in cellular proliferation in PI3K delta/gamma-expressing tumor cells. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and inflammatory and autoimmune diseases.
MedKoo Cat#: 205744
Name: Duvelisib (IPI-145)
Chemical Formula: C22H17ClN6O
Exact Mass: 416.11524
Molecular Weight: 416.86
Elemental Analysis: C, 63.39; H, 4.11; Cl, 8.50; N, 20.16; O, 3.84
Synonym: IPI145; IPI 145; IPI-145. INK1197; INK 1197; INK-1197; Duvelisib.
IUPAC/Chemical Name: (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one
InChi Key: SJVQHLPISAIATJ-ZDUSSCGKSA-N
InChi Code: InChI=1S/C22H17ClN6O/c1-13(28-21-19-20(25-11-24-19)26-12-27-21)17-10-14-6-5-9-16(23)18(14)22(30)29(17)15-7-3-2-4-8-15/h2-13H,1H3,(H2,24,25,26,27,28)/t13-/m0/s1
SMILES Code: O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4N=CNC4=NC=N3)C)=CC5=C1C(Cl)=CC=C5
History: In July 2010, Intellikine announced a collaborative partnership with Infinity Pharmaceuticals, Inc. under which Infinity obtained global development and commercialization rights to IntellikineÂ’s portfolio of inhibitors of the delta and gamma isoforms of phosphoinositide-3-kinase (PI3K). Among these inhibitors is IPI-145, an orally available PI3Kδ/γ inhibitor which entered clinical study in October 2011. The first Phase 1 trial of IPI-145 is a double-blind, randomized, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple escalating doses of IPI-145 in healthy adult subjects. The second Phase 1 trial is an open-label, dose-escalation study designed to evaluate the safety, pharmacokinetics and clinical activity of IPI-145 in patients with advanced hematologic malignancies. Following the determination of the maximum tolerated dose in the dose escalation phase, an expansion phase will follow in patients with selected hematologic malignancies. (source: http://www.intellikine.com/pipeline/ipi145.html).
1: Balakrishnan K, Peluso M, Fu M, Rosin NY, Burger JA, Wierda WG, Keating MJ, Faia K, O'Brien S, Kutok JL, Gandhi V. The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL. Leukemia. 2015 Apr 28. doi: 10.1038/leu.2015.105. [Epub ahead of print] PubMed PMID: 25917267.
2: Göckeritz E, Kerwien S, Baumann M, Wigger M, Vondey V, Neumann L, Landwehr T, Wendtner CM, Klein C, Liu N, Hallek M, Frenzel LP, Krause G. Efficacy of phosphatidylinositol-3 kinase inhibitors with diverse isoform selectivity profiles for inhibiting the survival of chronic lymphocytic leukemia cells. Int J Cancer. 2015 Apr 24. doi: 10.1002/ijc.29579. [Epub ahead of print] PubMed PMID: 25912635.
3: Lonetti A, Cappellini A, Spartà AM, Chiarini F, Buontempo F, Evangelisti C, Evangelisti C, Orsini E, McCubrey JA, Martelli AM. PI3K pan-inhibition impairs more efficiently proliferation and survival of T-cell acute lymphoblastic leukemia cell lines when compared to isoform-selective PI3K inhibitors. Oncotarget. 2015 Apr 30;6(12):10399-414. PubMed PMID: 25871383.
4: Cervantes-Gomez F, Lamothe B, Woyach JA, Wierda WG, Keating MJ, Balakrishnan K, Gandhi V. Pharmacological and Protein Profiling Suggests Venetoclax (ABT-199) as Optimal Partner with Ibrutinib in Chronic Lymphocytic Leukemia. Clin Cancer Res. 2015 Mar 31. [Epub ahead of print] PubMed PMID: 25829398.
5: Steele AJ. PI3K in CLL: are 2 isoforms better than 1? Blood. 2014 Dec 4;124(24):3508-10. doi: 10.1182/blood-2014-10-605089. PubMed PMID: 25477481.
6: Desai AV, El-Bakkar H, Abdul-Hay M. Novel Agents in the Treatment of Chronic Lymphocytic Leukemia: A Review About the Future. Clin Lymphoma Myeloma Leuk. 2015 Jun;15(6):314-322. doi: 10.1016/j.clml.2014.09.007. Epub 2014 Sep 30. Review. PubMed PMID: 25445466.
7: Dong S, Guinn D, Dubovsky JA, Zhong Y, Lehman A, Kutok J, Woyach JA, Byrd JC, Johnson AJ. IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells. Blood. 2014 Dec 4;124(24):3583-6. doi: 10.1182/blood-2014-07-587279. Epub 2014 Sep 25. PubMed PMID: 25258342; PubMed Central PMCID: PMC4256910.
8: Curran E, Smith SM. Phosphoinositide 3-kinase inhibitors in lymphoma. Curr Opin Oncol. 2014 Sep;26(5):469-75. doi: 10.1097/CCO.0000000000000113. Review. PubMed PMID: 25024054; PubMed Central PMCID: PMC4441952.
9: Rosen ST, Link BK, Fowler NH. Unmet needs in the treatment of mantle cell lymphoma. Clin Adv Hematol Oncol. 2013 Nov;11(11 Suppl 18):1-19. Review. PubMed PMID: 24893041.
10: IPI-145 shows promise in CLL patients. Cancer Discov. 2014 Feb;4(2):136. doi: 10.1158/2159-8290.CD-NB2013-177. Epub 2013 Dec 12. PubMed PMID: 24501284.