PI3Kδ
PI3Kδ is a class I PI3K isoform that generates PIP3, a second messenger used by cell-surface receptors to control immune-cell movement, growth, survival, and differentiation[1]. Mechanistically, PI3Kδ acts in adaptive immunity, and both loss-of-function and gain-of-function defects in this pathway cause primary immunodeficiency, showing that PI3Kδ activity requires precise dynamic regulation[2]. In B-lineage models, p110δ and p110α are essential for pre-B-cell receptor signaling and B-cell development, while p110α, but not p110β, can compensate for p110δ loss during early bone-marrow B-cell development[3]. Compared with related isoforms, PI3Kα and PI3Kβ are relatively ubiquitous, whereas PI3Kδ is mostly confined to myeloid and lymphoid lineages, making high PI3Kδ expression a characteristic of immune cells[1]. In disease and experimental applications, idelalisib is an orally active selective PI3Kδ inhibitor with antitumor activity in previously treated indolent non-Hodgkin lymphoma and relapsed chronic lymphocytic leukemia[4][5]. Therefore, PI3Kδ supports research designs focused on immune signaling, B-cell receptor biology, primary immunodeficiency, inflammatory models, and selective PI3Kδ inhibitor pharmacology[1][2][3][4][5].
References:
- [1]. Vervloessem T, et al. The type 2 inositol 1,4,5-trisphosphate receptor, emerging functions for an intriguing Ca²⁺-release channel. Biochim Biophys Acta. 2015 Sep;1853(9):1992-2005. [Content Brief]
- [2]. Lucas CL, et al. PI3Kδ and primary immunodeficiencies. Nat Rev Immunol. 2016 Nov;16(11):702-714. [Content Brief]
- [3]. Ramadani F, et al. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci Signal. 2010 Aug 10;3(134):ra60. [Content Brief]
- [4]. Gopal AK, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. [Content Brief]
- [5]. Furman RR, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014 Mar 13;370(11):997-1007. [Content Brief]
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PI3Kδ Related Products (205)
Related Products (205)
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CHMFL-PI3KD-317
0 ImagesCHMFL-PI3KD-317 is a highly potent, selective and orally active PI3Kδ inhibitor, with an IC50 of 6 nM, and exhibits over 10-1500 fold selectivity over other class I, II and III PIKK family isoforms, such as PI3Kα (IC50, 62.6 nM), PI3Kβ (IC50, 284 nM), PI3Kγ (IC50, 202.7 nM), PIK3C2A (IC50, >10000 nM), PIK3C2B (IC50, 882.3 nM), VPS34 (IC50, 1801.7 nM), PI4KIIIA (IC50, 574.1 nM) and PI4KIIIB (IC50, 300.2 nM). CHMFL-PI3KD-317 inhibits PI3Kδ-mediated Akt T308 phosphorylation in Raji cells, with an EC50 of 4.3 nM. CHMFL-PI3KD-317 has antiproliferative effects on cancer cells.
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(S)-GSK-F1
0 Images(S)-GSK-F1 (Compound 28) is an inhibitor for type III phosphatidylinositol 4-kinase α (PI4KIIIα). (S)-GSK-F1 inhibits PI4Kα, PI4Kβ, PI4Kγ, PI3Kα, PI3Kβ and PI3Kδ with pIC50 of 8.3, 6.0, 5.6, 5.6, 5.1 and 5.6, respectively. (S)-GSK-F1 exhibits anti-hepatitis C virus (HCV) activity through inhibition of HCV replication. (S)-GSK-F1 exhibits moderate pharmacokinetic characters in rat model.
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GSK2292767
0 ImagesGSK2292767 is a potent and selective inhibitor of PI3Kδ, with a pIC50 of 10.1. GSK2292767 showing greater than 500-fold selective over the other PI3K isoforms. GSK2292767 can be used for the research of respiratory disease.
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MIPS-9922
0 ImagesMIPS-9922 is a potent and selective PI3Kβ inhibitor with an IC50 of 63 nM. MIPS-9922 inhibits PI3Kβ with >30-fold higher potency than PI3Kδ. MIPS-9922 blocks PI3K mediated activation of platelet glycoprotein αIIbβ3 activation and platelet adhesion in vitro. MIPS-9922 shows anti-platelet and anti-thrombotic activities.
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PARP/PI3K-IN-1
0 ImagesPARP/PI3K-IN-1 (compound 15) is a potent PARP/PI3K inhibitor with pIC50 values of 8.22, 8.44, 8.25, 6.54, 8.13, 6.08 for PARP-1, PARP-2, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ, respectively. PARP/PI3K-IN-1 is a highly effective anticancer compound targeted against a wide range of oncologic diseases.
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PKI-179 hydrochloride
0 ImagesPKI-179 hydrochloride is a potent and orally active dual PI3K/mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 hydrochloride also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 hydrochloride shows anti-tumor activity in vivo.
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FD274
0 ImagesFD274 is a highly potent PI3K/mTOR dual inhibitor with IC50s of 0.65 nM, 1.57 nM, 0.65 nM, 0.42 nM, and 2.03 nM against PI3Kα/β/γ/δ and mTOR, respectively. FD274 exhibits significant anti-proliferation of AML cell lines (HL-60 and MOLM-16). FD274 arrests HL-60 cell cycle at G1 phase and increases apoptosis. FD274 demonstrates dose-dependent inhibition of tumor growth in the HL-60 xenograft model. FD274 has the potential for acute myeloid leukemia research.
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Roginolisib hemifumarate
0 ImagesSynonyms: MSC2360844 hemifumarate; IOA-244 hemifumarate
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IHMT-PI3Kδ-372
0 ImagesIHMT-PI3Kδ-372 is a potent and selective PI3Kδ inhibitor with an IC50 of 14 nM. IHMT-PI3Kδ-372 shows high selectivity over other class I PI3Ks (56～83 fold) and other protein kinases. IHMT-PI3Kδ-372 can be uesd for chronic obstructive pulmonary disease (COPD) research.
