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Parsaclisib, formerly known as INCB050465, is a novel and potent PI3Kδ inhibitor with anticancer activity. It synergizes with PIM protein kinase inhibition to cause tumor regression in a model of DLBCL. INCB050465 inhibits PI3Kδ with an IC50 of 1 nM at 1 mM ATP, and shows appr 20,000-fold selectivity for PI3Kα, PI3Kβ, PI3Kγ and 57 other kinases. INCB050465 displays potent activity with IC50 ranging from 0.2 to 2 nM. In addition, INCB050465 blocks the proliferation of several DLBCL and MCL cell lines in vitro (EC50 < 10 nM) and can slow tumor growth in the Pfeiffer model of DLBCL in vivo.
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| ln Vitro |
MCL and DLBCL cell lines are inhibited from proliferating by parsaclisib (0.1-3000 nM; 4 d)[2]. In the Ramos Burkitt's lymphoma cell line, parsaclisib (0.1-1000 nM; 2 h) suppresses anti-IgM-induced pAKT (Ser473) with an IC50 of 1 nM[2]. With IC50s ranging from 0.2 to 1.7 nM, parsaclisib reduces the proliferation of primary B cells in humans, dogs, rats, and mice following activation of these receptors[2].
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| ln Vivo |
In BALB/c mice harboring A20 murine lymphoma cells, parsaclisib (10 mg/kg; administered orally twice daily for 7–19 days) suppresses tumor formation [2]. Pfeiffer xenograft tumors grow more slowly when parsaclisib (0.1–10 mg/kg; orally twice daily) is administered. This effect is dose-dependent. It's easy to tolerate parsaclisib [2]. pAKT (Ser473) is inhibited by parsaclisib (0.5–1 mg/kg; single oral dose) in the Pfeiffer subcutaneous mouse xenograft model [2].
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: Jeko-1, Mino, JVM2, Rec-1, Pfeiffer, SU-DHL-5, SU-DHL-6, WSU-NHL, SU-DHL-4, SU-DHL-8, and WILL-2 cells Tested Concentrations: 0.1-3000 nM Incubation Duration: 4 days Experimental Results: Resulted in a maximal inhibition of 70-90%, with IC50s of ≤10 nM in the four MCL cell lines. Pfeiffer, SU-DHL-5, SU-DHL-6, and WSU-NHL were highly sensitive, with IC50s from 2 to 8 nM. |
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| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse (5-9 weeks) were inoculated with A20 cells [2]
Doses: 10 mg/kg Route of Administration: po (oral gavage), twice a day for 7-19 days Experimental Results: Produced significant Tumor Growth Inhibition (TGI). Reduces the percentage of Tregs (CD4+CD25+FOXP3+) in tumors and spleen. Increased ratio of CD4+ and CD8+ T cells to Tregs in spleen and tumors. Reduces the number of CD4+CD44high and CD8+CD44high T cells in the spleen and tumors. |
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| Additional Infomation |
Parsaclisib is under investigation in clinical trial NCT03126019 (An Open-Label Study of Parsaclisib in Relapsed or Refractory Follicular Lymphoma (CITADEL-203)).
Parsaclisib is an inhibitor of the delta isoform of phosphoinositide-3 kinase (PI3K) with potential antineoplastic activity. Parsaclisib inhibits the delta isoform of PI3K and prevents the activation of the PI3K/AKT signaling pathway. This both decreases proliferation and induces cell death in PI3K-delta-overexpressing tumor cells. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in hematopoietic disease and cell lineages. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival. Drug Indication Treatment of mature B-cell malignancies |
| Molecular Formula |
C20H22CLFN6O2
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|---|---|
| Molecular Weight |
432.879086017609
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| Exact Mass |
432.147
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| CAS # |
1426698-88-5
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| Related CAS # |
Parsaclisib hydrochloride;1995889-48-9
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| PubChem CID |
86677874
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
650.9±55.0 °C at 760 mmHg
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| Flash Point |
347.5±31.5 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.704
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| LogP |
1.36
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
632
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCOC1=C(C(=C(C=C1[C@H](C)N2C3=NC=NC(=C3C(=N2)C)N)Cl)F)[C@H]4CC(=O)NC4
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| InChi Key |
ZQPDJCIXJHUERQ-QWRGUYRKSA-N
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| InChi Code |
InChI=1S/C20H22ClFN6O2/c1-4-30-18-12(6-13(21)17(22)16(18)11-5-14(29)24-7-11)10(3)28-20-15(9(2)27-28)19(23)25-8-26-20/h6,8,10-11H,4-5,7H2,1-3H3,(H,24,29)(H2,23,25,26)/t10-,11-/m0/s1
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| Chemical Name |
(4R)-4-{3-[(1S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl}pyrrolidin-2-one
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| Synonyms |
INCB50465 HCl INCB-050465INCB-50465 INCB 050465 INCB 50465 IINCB050465 INCB050465 free base
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~288.76 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.08 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: ≥ 2.08 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3101 mL | 11.5505 mL | 23.1011 mL | |
| 5 mM | 0.4620 mL | 2.3101 mL | 4.6202 mL | |
| 10 mM | 0.2310 mL | 1.1551 mL | 2.3101 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Parsaclisib Plus the Standard Drug Therapy in Patients with Newly Diagnosed, High Risk Diffuse Large B-cell Lymphoma
CTID: NCT04323956
Phase: Phase 1 Status: Active, not recruiting
Date: 2024-09-19
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
