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].
参考文献:
- [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 関連製品 (202)
関連製品 (202)
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MEK/PI3K-IN-2
0 Images製品番号: HY-144693CAS 番号: 2281803-33-4
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PI3Kδ-IN-20
0 Images製品番号: HY-158147CAS 番号: 3038178-85-4
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PI3K-IN-35
0 Images製品番号: HY-147900CAS 番号: 2458163-99-8
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HM5023507
0 Images製品番号: HY-177277CAS 番号: 1549766-06-4HM5023507 is an orally active and selective PI3Kδ/γ inhibitor with IC50s of 4 and 5 μM for PI3Kδ and PI3Kγ over PI3Kβ and PI3Kα. HM5023507 attenuates the PI3Kδ/γ signaling in human basophils. HM5023507 also attenuates the activation and function of human B and T cells and cytokine and IgG production during cocultures, and Th17 differentiation of CD4 T cells. HM5023507 inhibited semiestablished collagen-induced arthritic inflammation in the rat models. HM5023507 can be used for inflammatory diseases like rheumatoid arthritis research.
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PI3Kγ inhibitor 7
0 Images製品番号: HY-153703CAS 番号: 2575863-25-9PI3Kγ inhibitor 7 (compound 2) is a potent and orally active PI3Kγ inhibitor with IC50 values of 4768, 878.1, 3.42, 355.2 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively. PI3Kγ inhibitor 7 shows antitumor activity. PI3Kγ inhibitor 7 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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MEK/PI3K-IN-1
0 Images製品番号: HY-144692CAS 番号: 2281803-28-7
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SRX3305
0 Images製品番号: HY-182671CAS 番号: 2409965-28-0SRX3305 is an BTK/PI3K/BRD4 inhibitor with IC50s of 6.5 nM, 15 nM, and 4 nM toward BTK, PI3Kɑ and PI3Kδ, respectively. SRX3305 attenuates chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 yields potent anti-tumor effects but spares healthy bystander cells. SRX3305 inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals. SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13. SRX3305 maintains its anti-tumor effects in Ibrutinib (HY-10997)-resistant CLL cells. SRX3305 can be used for research in CLL, diffuse large B-cell lymphoma (DLBCL) and MCL.
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IHMT-PI3K-455
0 Images製品番号: HY-149493CAS 番号: 3047746-40-4IHMT-PI3K-455 (Compound 15u) is a potent, selective, orally active PI3Kγ/δ dual inhibitor with IC50s of 7.1 nM and 0.57 nM for PI3Kγ and PI3Kδ, respectively. IHMT-PI3K-455 suppresses the AKT phosphorylation. IHMT-PI3K-455 inhibits tumor growth by recruiting and activating more CD8+ killing T cells.IHMT-PI3K-455 is used in cancer research.
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PI3Kδ-IN-12
0 Images製品番号: HY-149235PI3Kδ-IN-12 (compound 13) is a PI3Kδ inhibitor (pIC50 = 5.8), with pKi values of 8.0/6.5/6.4/6.7 for PI3Kδ/γ/β/α, respectively. PI3Kδ-IN-12 can be used in the study of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
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PI3Kδ-IN-25
0 Images製品番号: HY-175369PI3Kδ-IN-25 is an orally active selective PI3Kδ inhibitor (IC50 = 2.1 nM). PI3Kδ-IN-25 has IC50s of 272, 285, and 1171 nM for PI3Kα, PI3Kγ, and PI3Kβ, respectively. PI3Kδ-IN-25 inhibits AKT Ser473 phosphorylation, suppresses Treg cell proliferation, and downregulates PD-L1 expression in B16F10 cells. PI3Kδ-IN-25 exhibits anticancer effects in B16F10 melanoma and Lewis lung cancer mouse models by reducing tumor-infiltrating Treg cells and enhancing immune responses. PI3Kδ-IN-25 is potentially useful in the study of melanoma, lung cancer, and other cancers.
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PROTAC PI3Kδ degrader-1
0 Images製品番号: HY-176239PROTAC PI3Kδ degrader-1 is a Lysine-targeted covalent PI3Kδ PROTAC degrader with a DC50 of 3.98 nM. PROTAC PI3Kδ degrader-1 has a potent antiproliferative activity and selective PI3Kδ inhibition (IC50: 8 nM). PROTAC PI3Kδ degrader-1 also significantly degrades p-AKT, induces cell cycle arrest in G1 phase and prompts cell apoptosis and autophagy. PROTAC PI3Kδ degrader-1 effectively inhibits the tumor growth in SU-DHL-6 xenograft mice model.
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PI3Kδ/HDAC6-IN-1
0 Images製品番号: HY-174396CAS 番号: 3075011-99-0PI3Kδ/HDAC6-IN-1 (Compound 22E) is an orally active and dual inhibitor of PI3Kδ and HDAC6 with IC50 values of 2.4 nM and 6.2 nM, respectively. PI3Kδ/HDAC6-IN-1 exhibits potent antiproliferative effects on non-Hodgkin lymphoma (NHL) cells and possesses in vivo antitumor activity without significant toxicity. PI3Kδ/HDAC6-IN-1 arrests the cell cycle at the G0/G1 phase and induces apoptosis. PI3Kδ/HDAC6-IN-1 blocks the PI3K/AKT/mTOR signaling pathway and increases the acetylation levels of α-tubulin and histone H3.
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PI3Kδ-IN-21
0 Images製品番号: HY-158688CAS 番号: 3048633-11-7PI3Kδ-IN-21 (Compound 31) is a selective inhibitor for phosphoinositide 3-kinases δ (PI3Kδ), with an IC50 of 13.6 nM. PI3Kδ-IN-21 inhibits proliferation and differentation of T cells through PI3K/AKT/mTOR signaling pathway. PI3Kδ-IN-21 exhibits good pharmacokinetic characters in rat model, and attenuates the experimental autoimmune encephalomyelitis in myelin oligodendrocyte glycoprotein (MOG)-induced EAE model.
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PI3Kδ-IN-18
0 Images製品番号: HY-157128CAS 番号: 3019965-38-6Se15 is a selective inhibitor of PI3Kδ with an IC50 value less than 0.1nM. Se15 can be used in research on autoimmune.
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ST-168
0 Images製品番号: HY-120281CAS 番号: 2126038-25-1ST-168 is an orally active MEK/PI3K inhibitor with an IC50 of 182 nM against MEK1 and IC50 values of 69.2, 41.7, 1482 and 2293 nM against PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ respectively. ST-168 completely inhibits the phosphorylation of ERK1/2 and AKT and induces cancer cell death in a 3D tumor sphere model. ST-168 demonstrates significant antitumor effects in the A375 melanoma mouse model. ST-168 improves the ocular toxicity profile of MEK inhibitors, showing lower caspase activation levels, indicating reduced apoptosis induction. ST-168 can be used in melanoma research.
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PI3Kδ-IN-24
0 Images製品番号: HY-175002CAS 番号: 3051829-20-7PI3Kδ-IN-24 is a selective PI3Kδ inhibitor (IC50 = 0.1 nM). PI3Kδ-IN-24 exhibits significant antiproliferative effects against PI3Kδ-overexpressing cancer cell lines. PI3Kδ-IN-24 reduces p-AKT levels and induces cell cycle arrest and apoptosis in tumor cells. PI3Kδ-IN-24 is useful in cancer research, such as diffuse large B-cell lymphoma (DLBCL).
