Referencia número: HY-17044

Duvelisib

(Synonyms: IPI-145; INK1197)

17 Cited Publications

Revisión del cliente

Based on 17 publication(s) in Google Scholar

Duvelisib (IPI-145) is a selectivite p100δ inhibitor with IC₅₀ of 2.5 nM, 27.4 nM, 85 nM and 1602 nM for p110δ, P110γ, p110β and p110α, respectively.

Para uso exclusivo en investigación. No vendemos a pacientes.

Pureza: 99.88%
No. CAS: 1201438-56-3
Fòrmula: C₂₂H₁₇ClN₆O
Peso molecular:416.86

Almacenamiento:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months

Duvelisib Chemical Structure

No. CAS: 1201438-56-3

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Actividad biológica
- Descripciòn
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Ensayo clínico
Chemical Information
Publications (17)
Solvente y solubilidad
- In Vitro
- In Vivo
Pureza y Documentación
Referencias
Help & FAQs
Classifications
Bioz

Actividad biológica

Descripciòn

Duvelisib (IPI-145) is a selectivite p100δ inhibitor with IC₅₀ of 2.5 nM, 27.4 nM, 85 nM and 1602 nM for p110δ, P110γ, p110β and p110α, respectively^[1]^[2].

IC₅₀ & Target^[2]

p110δ

2.5 nM (IC₅₀)

p110γ

27.4 nM (IC₅₀)

p110β

85 nM (IC₅₀)

p110α

1602 nM (IC₅₀)

Ver todos los productos específicos de isoformas PI3K :

Cellular Effect

Cell Line	Type	Value	Description	References
4T1	IC₅₀	22.88 μM Compound: Duvelisib	Cytotoxicity against mouse 4T1 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against mouse 4T1 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
A549	IC₅₀	>100 μM Compound: Duvelisib	Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
B16-F10	IC₅₀	>100 μM Compound: Duvelisib	Cytotoxicity against mouse B16-F10 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against mouse B16-F10 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
DOHH-2	IC₅₀	0.2 μM Compound: 1; IPI-145	Antiproliferative activity against human DOHH-2 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay Antiproliferative activity against human DOHH-2 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	[PMID: 35831917]
HepG2	IC₅₀	>100 μM Compound: Duvelisib	Cytotoxicity against human HepG2 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human HepG2 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
Huh-7	IC₅₀	6.57 μM Compound: Duvelisib	Cytotoxicity against human Huh-7 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human Huh-7 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
Jurkat	IC₅₀	1.9 μM Compound: Duvelisib	Antiproliferative activity against human Jurkat cells after 3 days by CellTiter-Glo assay Antiproliferative activity against human Jurkat cells after 3 days by CellTiter-Glo assay	[PMID: 27774127]
Jurkat	IC₅₀	3.17 μM Compound: Duvelisib	Cytotoxicity against human Jurkat cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human Jurkat cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
L929	IC₅₀	>100 μM Compound: Duvelisib	Cytotoxicity against mouse L929 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against mouse L929 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
LOUCY	IC₅₀	0.98 μM Compound: Duvelisib	Antiproliferative activity against human Loucy cells after 3 days by CellTiter-Glo assay Antiproliferative activity against human Loucy cells after 3 days by CellTiter-Glo assay	[PMID: 27774127]
MCF7	IC₅₀	>100 μM Compound: Duvelisib	Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
MDA-MB-231	IC₅₀	9.76 μM Compound: Duvelisib	Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
MOLM-14	IC₅₀	1.2 μM Compound: Duvelisib	Antiproliferative activity against human MOLM14 cells after 3 days by CellTiter-Glo assay Antiproliferative activity against human MOLM14 cells after 3 days by CellTiter-Glo assay	[PMID: 27774127]
MOLT-4	IC₅₀	2.3 μM Compound: Duvelisib	Antiproliferative activity against human MOLT4 cells after 3 days by CellTiter-Glo assay Antiproliferative activity against human MOLT4 cells after 3 days by CellTiter-Glo assay	[PMID: 27774127]
MV4-11	IC₅₀	4.4 μM Compound: Duvelisib	Antiproliferative activity against human MV4-11 cells after 3 days by CellTiter-Glo assay Antiproliferative activity against human MV4-11 cells after 3 days by CellTiter-Glo assay	[PMID: 27774127]
Raji	IC₅₀	0.36 nM Compound: 15	Cytotoxicity against in human Raji cells Cytotoxicity against in human Raji cells	[PMID: 30582813]
Raji	IC₅₀	2.5 nM Compound: 15	Inhibition of PI3Kdelta in human Raji cells Inhibition of PI3Kdelta in human Raji cells	[PMID: 30582813]
Raji	IC₅₀	27 nM Compound: 15	Inhibition of PI3Kgamma in human Raji cells Inhibition of PI3Kgamma in human Raji cells	[PMID: 30582813]
Ramos	IC₅₀	0.001 μM Compound: 4; IPI-145	Inhibition of PI3Kdelta in human Ramos cells assessed as reduction in antihuman IgM-stimulated AKT phosphorylation at Ser473 residue preincubated for 60 mins followed by antihuman IgM stimulation and measured after 15 mins Inhibition of PI3Kdelta in human Ramos cells assessed as reduction in antihuman IgM-stimulated AKT phosphorylation at Ser473 residue preincubated for 60 mins followed by antihuman IgM stimulation and measured after 15 mins	[PMID: 31033293]
RAW264.7	IC₅₀	0.025 μM Compound: 4; IPI-145	Inhibition of PI3Kgamma in rat RAW264.7 cells assessed as reduction in C5a-stimulated AKT phosphorylation at Ser473 residue preincubated for 30 mins followed by C5a-stimulation and measured after 5 mins Inhibition of PI3Kgamma in rat RAW264.7 cells assessed as reduction in C5a-stimulated AKT phosphorylation at Ser473 residue preincubated for 30 mins followed by C5a-stimulation and measured after 5 mins	[PMID: 31033293]
RAW264.7	IC₅₀	13.2 μM Compound: Duvelisib	Cytotoxicity against mouse RAW264.7 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against mouse RAW264.7 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
Sf21	IC₅₀	0.001 μM Compound: 4; IPI-145	Inhibition of N-terminal His6-tagged recombinant full length human p110delta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate measured after 80 mins by transcreener fluorescence po Inhibition of N-terminal His6-tagged recombinant full length human p110delta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate measured after 80 mins by transcreener fluorescence po	[PMID: 31033293]
Sf21	IC₅₀	0.008 μM Compound: 4; IPI-145	Inhibition of N-terminal His6-tagged recombinant full length human p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate measured after 80 mins by transcreener fluorescence pol Inhibition of N-terminal His6-tagged recombinant full length human p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate measured after 80 mins by transcreener fluorescence pol	[PMID: 31033293]
SUD4	IC₅₀	0.27 μM Compound: 1; IPI-145	Antiproliferative activity against human SU-DHL-4 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay Antiproliferative activity against human SU-DHL-4 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	[PMID: 35831917]
SU-DHL-6	IC₅₀	0.39 μM Compound: 1; IPI-145	Antiproliferative activity against human SU-DHL-6 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay Antiproliferative activity against human SU-DHL-6 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	[PMID: 35831917]
SU-DHL-6	IC₅₀	0.4 nM Compound: 1; IPI-145	Antiproliferative activity against human SUDHL2 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay Antiproliferative activity against human SUDHL2 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	[PMID: 35831917]
T47D	IC₅₀	>100 μM Compound: Duvelisib	Cytotoxicity against human T47D cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human T47D cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]
THP-1	IC₅₀	14.89 μM Compound: Duvelisib	Cytotoxicity against human THP-1 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay Cytotoxicity against human THP-1 cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay	[PMID: 37011446]

In Vitro

PI3Kδ and PI3Kγ inhibition with Duvelisib (IPI-145) has anti-proliferative activity in primary AML cells by inhibiting the activity of AKT and MAPK. Pre-treatment of AML cells with Duvelisib inhibits both adhesion and migration of AML blasts to bone marrow stromal cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Ensayo clínico

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

No. CAS 1201438-56-3
Appearance Solid
Peso molecular 416.86
Fòrmula C₂₂H₁₇ClN₆O
Color Off-white to gray
SMILES

O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4N=CNC4=NC=N3)C)=CC5=C1C(Cl)=CC=C5
Synonyms

IPI-145; INK1197
Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Publications (17)

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Journal Impact Factor

Nat Metab

The PI3K pathway preserves metabolic health through MARCO-dependent lipid uptake by adipose tissue macrophages. [Abstract]

2020 Dec;2(12):1427-1442. PMID: 33199895
Nat Commun

Selective inhibition of cancer cell self-renewal through a Quisinostat-histone H1.0 axis. [Abstract]

2020 Apr 14;11(1):1792. PMID: 32286289
Sci Transl Med

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]

2018 Jul 18;10(450):eaaq1093. PMID: 30021885
Phytomedicine

CBX5 loss drives Pl3Kδ inhibitor resistance in mantle cell lymphoma and propolis restores sensitivity by inducing CBX5-mediated ferroptosis. [Abstract]

2025 May 27:143:156911. PMID: 40466505
Blood Adv

BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma. [Abstract]

2025 Jul 2:bloodadvances.2024015322. PMID: 40601898

Duvelisib purchased from MedChemExpress. Usage Cited in: Blood Adv. 2025 Jul 2:bloodadvances.2024015322. [Abstract]

A bar plot reported the percent viability assessed by propidium iodide (PI) incorporation in TLBR2 cells cultured alone or in the presence of MS-5 and treated with navitoclax (1-2 µM) for 72 hours.

Duvelisib purchased from MedChemExpress. Usage Cited in: Blood Adv. 2025 Jul 2:bloodadvances.2024015322. [Abstract]

Heat map reported cell viability of the ALK+ 36 ALCL SUPM2 cell line treated for 72 hours with the indicated drugs (x-axis) and concentrations (y-axis).
Cell Syst

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations. [Abstract]

2018 Apr 25;6(4):424-443.e7. PMID: 29655704
Biochem Pharmacol

Duvelisib upregulates p27 expression and leads to intestinal damage via the NEDD4L/CK1ε axis. [Abstract]

2026 Mar 28;250(Pt 1):117939. PMID: 41905427
Oncoimmunology

RHOA G17V induces T follicular helper cell specification and involves angioimmunoblastic T-cell lymphoma via upregulating the expression of PON2 through an NF-κB-dependent mechanism. [Abstract]

2022 Oct 11;11(1):2134536. PMID: 36249275

Duvelisib purchased from MedChemExpress. Usage Cited in: Oncoimmunology. 2022 Oct 11;11(1):2134536. [Abstract]

Immunoblots showed that Duvelisib (24 h) suppressed the expression of Pon2, decreased the phosphorylated IκB kinase (IKK) complex, and activated the NF-κB p65 in Rhoa G17V-expressing CD4+ T cells.
RSC Adv

Integrative machine learning-guided in silico and in vitro approach reveals selective small molecule inhibitors targeting mutant IDH1. [Abstract]

2025 Dec 18;15(59):50944-50962. PMID: 41426059

Duvelisib purchased from MedChemExpress. Usage Cited in: RSC Adv. 2025 Dec 18;15(59):50944-50962. [Abstract]

RMSD plots showed structural dynamics upon binding with the inhibitors during a 250 ns MD simulation ligand, for standard mutant IDH1 inhibitors, olutasidenib (black) and α-mangostin (red), screened inhibitors, atogepant (green), dacomitinib (blue), duvelisib (yellow), idelalisib (brown), and vandetanib (turquoise), and an inactive reference compound, temozolomide (orange).

Duvelisib purchased from MedChemExpress. Usage Cited in: RSC Adv. 2025 Dec 18;15(59):50944-50962. [Abstract]

Hbond analysis was performed during the 250 ns MD simulation for the standard mutant IDH1 inhibitor duvelisib. Each horizontal line on the y-axis represented the number of hydrogen bonds formed simultaneously, with its duration shown along the time on the (x) axis. A higher and denser clustering of lines suggested stronger and more stable interactions throughout the simulation period.
Arab J Chem

2023 Jul 4, 105117.
Eur J Immunol

Anti-SARS-CoV-2 Spike IgA2 Induces Inflammation by Human Macrophages. [Abstract]

2025 Oct;55(10):e70068. PMID: 41054024
Am J Cancer Res

A long-lasting PI3Kδ inhibitor zandelisib forms a water-shielded hydrogen bond with p110δ and demonstrates sustained inhibitory effects. [Abstract]

2025 May 15;15(5):2097-2110. PMID: 40520883
Anal Methods

Estimation of the metabolic stability of omipalisib in human liver microsomes employing an ultra-fast UPLC-MS/MS approach: in silico screening for structural alarms and metabolic lability. [Abstract]

2026 Feb 5;18(5):1101-1115. PMID: 41586454
University of California

2025.
bioRxiv

Long range mutual activation establishes Rho and Rac polarity during cell migration. [Abstract]

2025 May 13:2024.10.01.616161. PMID: 40236007
Res Sq

2024 Jun 13.
bioRxiv

Neutrophils actively swell to potentiate rapid migration. [Abstract]

2024 Mar 28:2023.05.15.540704. PMID: 37292824

Solvente y solubilidad

In Vitro:

DMSO : 100 mg/mL (239.89 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.3989 mL

11.9944 mL

23.9889 mL

5 mM

0.4798 mL

2.3989 mL

4.7978 mL

10 mM

0.2399 mL

1.1994 mL

2.3989 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Calculadora de molaridad

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculadora de dilución

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 5 mg/mL (11.99 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (6.00 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Pureza y Documentación

Select Batch:

Pureza: 99.98%

Assay: 99.98%

ee.: 99.98%

Ficha de datos (278 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Instrucciones de manejo (2659 KB)

Referencias

[1]. Pillinger G, et al. Targeting PI3Kδ and PI3Kγ signalling disrupts human AML survival and bone marrow stromal cell mediated protection. Oncotarget. 2016 Jun 28;7(26):39784-39795. [Content Brief]

[2]. G?ckeritz E, et al. Efficacy of phosphatidylinositol-3 kinase inhibitors with diverse isoform selectivity profiles for inhibiting the survival of chronic lymphocytic leukemia cells. Int J Cancer. 2015 Nov 1;137(9):2234-42. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.3989 mL	11.9944 mL	23.9889 mL	59.9722 mL
	5 mM	0.4798 mL	2.3989 mL	4.7978 mL	11.9944 mL
	10 mM	0.2399 mL	1.1994 mL	2.3989 mL	5.9972 mL
	15 mM	0.1599 mL	0.7996 mL	1.5993 mL	3.9981 mL
	20 mM	0.1199 mL	0.5997 mL	1.1994 mL	2.9986 mL
	25 mM	0.0960 mL	0.4798 mL	0.9596 mL	2.3989 mL
	30 mM	0.0800 mL	0.3998 mL	0.7996 mL	1.9991 mL
	40 mM	0.0600 mL	0.2999 mL	0.5997 mL	1.4993 mL
	50 mM	0.0480 mL	0.2399 mL	0.4798 mL	1.1994 mL
	60 mM	0.0400 mL	0.1999 mL	0.3998 mL	0.9995 mL
	80 mM	0.0300 mL	0.1499 mL	0.2999 mL	0.7497 mL
	100 mM	0.0240 mL	0.1199 mL	0.2399 mL	0.5997 mL

Keywords

Duvelisib

17 Cited Publications

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Duvelisib

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Publications Citing Use of MedChemExpress (MCE) Duvelisib

Ver todos los productos específicos de isoformas PI3K

Actividad biológica

Chemical Information

Publications (17)

Solvente y solubilidad

Pureza y Documentación

Referencias

Help & FAQs

Complete Stock Solution Preparation Table

Duvelisib Related Classifications

HY-17044 Related Classifications