Art. -Nr.: HY-18595

BI 224436

6 Cited Publications

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Based on 6 publication(s) in Google Scholar

BI 224436 is a novel HIV-1 noncatalytic site integrase inhibitor with EC₅₀ values of less than 15 nM against different HIV-1 laboratory strains.

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

The BI 224436 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.

Reinheit: 98.01%
CAS. Nr.: 1155419-89-8
Formel: C₂₇H₂₆N₂O₄
Molecular Weight:442.51

Speicherung:

-20°C, protect from light

* The compound is unstable in solutions, freshly prepared is recommended.

BI 224436 Chemical Structure

CAS. Nr.: 1155419-89-8

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

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (6)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

BI 224436 is a novel HIV-1 noncatalytic site integrase inhibitor with EC₅₀ values of less than 15 nM against different HIV-1 laboratory strains.

IC₅₀ & Target

EC50: 15 nM (HIV-1)^[1]

Alle HIV Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
MT2	CC₅₀	>40 μM Compound: 1; BI-224436	Cytotoxicity against human MT2 cells assessed as reduction in cell viability after 4 days by XTT assay Cytotoxicity against human MT2 cells assessed as reduction in cell viability after 4 days by XTT assay	[PMID: 30609350]
MT2	CC₅₀	3339.15 μM Compound: BI-224436	Cytotoxicity against human MT2 cells measured after 4 days by XTT assay Cytotoxicity against human MT2 cells measured after 4 days by XTT assay	[PMID: 32081010]
MT4	CC₅₀	>50000 nM Compound: BI-224436	Cytotoxicity against human MT4 cells assessed as reduction in cell viability measured after 4 days by MTT assay Cytotoxicity against human MT4 cells assessed as reduction in cell viability measured after 4 days by MTT assay	[PMID: 32773094]
MT4	CC₅₀	>50000 nM Compound: BI 224436	Cytotoxicity against human MT4 cells by MTT assay Cytotoxicity against human MT4 cells by MTT assay	[PMID: 33316407]
MT4	CC₅₀	>50000 nM Compound: BI-224436	Cytotoxicity against human MT4 cells assessed as reduction in cell viability by MTT assay Cytotoxicity against human MT4 cells assessed as reduction in cell viability by MTT assay	[PMID: 35272008]

In Vitro

BI 224436 has cellular cytotoxicity of more than 90 μM. BI 224436 has a low, 2.1-fold decrease in antiviral potency in the presence of 50% human serum. BI 224436 retains full antiviral activity against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. BI 224436 displays an additive effect in combination with most approved antiretrovirals, including INSTIs. BI 224436 has drug-like in vitro absorption, distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell permeability, solubility, and low cytochrome P450 inhibition^[1].

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

In Vivo

BI 224436 exhibits excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic flow [CL], 0.7%; bioavailability [F], 54%), monkey (CL, 23%; F, 82%), and dog (CL, 8%; F, 81%)^[1].

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

Clinical Trial

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

Chemical Information

CAS. Nr. 1155419-89-8
Appearance Solid
Molecular Weight 442.51
Formel C₂₇H₂₆N₂O₄
Color White to yellow
SMILES

CC1=C([C@@H](C(O)=O)OC(C)(C)C)[C@@]([C@@]2=CC=C3C4=C2N=CC=C4CCO3)=C5C(C=CC=C5)=N1
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

-20°C, protect from light

* The compound is unstable in solutions, freshly prepared is recommended.

Publications (6)

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Journal Impact Factor

Sci Adv

GRL-142 binds to and impairs HIV-1 integrase nuclear localization signal and potently suppresses highly INSTI-resistant HIV-1 variants. [Abstract]

2023 Jul 14;9(28):eadg2955. PMID: 37436982
Elife

HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors. [Abstract]

2019 May 23:8:e46344. PMID: 31120420
Retrovirology

Influence of the amino-terminal sequence on the structure and function of HIV integrase. [Abstract]

2020 Aug 31;17(1):28. PMID: 32867805
J Biol Chem

Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. [Abstract]

2017 Dec 1;292(48):19814-19825. PMID: 28972144
J Virol

A Conformational Escape Reaction of HIV-1 against an Allosteric Integrase Inhibitor. [Abstract]

2020 Sep 15;94(19):e00486-20. PMID: 32611758
Ann Med Res

Evaluation of a flavonoid library for inhibition of interaction of HIV-1 integrase with human LEDGF/p75 towards a structure-activity relationship. [Abstract]

2022 Dec;54(1):1590-1600. PMID: 35658757

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : ≥ 50 mg/mL (112.99 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

* "≥" means soluble, but saturation unknown.

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

2.2598 mL

11.2992 mL

22.5984 mL

5 mM

0.4520 mL

2.2598 mL

4.5197 mL

10 mM

0.2260 mL

1.1299 mL

2.2598 mL

Please refer to the solubility information to select the appropriate solvent. The compound is unstable in solutions, freshly prepared is recommended.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

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: ≥ 2.5 mg/mL (5.65 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 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 (5.65 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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (5.65 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

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:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

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

Protokoll

Kinase Assay^[1]

BI 224436 is dissolved in acetonitrile-methanol (50:50, vol/vol) to achieve a concentration of 1.5 mM. Phosphate buffer (pH 7.4), cofactor, and test substance or isoform-selective inhibitors are added to 96-well plates and are prewarmed to 37°C for 10 min. Cofactor concentrations are 1.3 mM NADP, 3.3 mM glucose-6-phosphate, and 0.4 U/mL glucose-6-phosphate dehydrogenase. Reactions are initiated by the addition of prewarmed (37°C) enzyme and substrate. Reaction mixtures are incubated at 37°C and terminated by the addition of 0.038 ml of 40:40:20 (vol/vol) methanol–acetonitrile–0.5 M Tris buffer. Formation of the fluorescent metabolites is measured using a microplate spectrofluorometer at specific excitation and emission wavelengths. The IC₅₀ is determined using the 96-well 32 procedure supplied with the SAS software^[1].

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

Animal Administration^[1]

Rats: For oral PK studies, BI 224436 is administered in a suspension of 0.5% (wt/vol) methyl cellulose (MC), 0.3% (vol/vol) Tween 80, and 1% (vol/vol) N-methyl-2-pyrrolidine (MP) in water. For i.v. dosing, BI 224436 is dissolved in 70% PEG 400–30% water (vol/vol). The appropriate amount of BI 224436 is dissolved in PEG 400 with sonication. The rats receive a single i.v. dose of 0.2 mg/kg of body weight (1 mL/kg) via the jugular vein as a bolus or received a single oral dose of 0.4 mg/kg (10 mL/kg) administered by gavage. Blood samples are obtained at 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 32 h after dosing for analysis^[1].

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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (286 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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)
Handling Instructions (2659 KB)

Verweise

[1]. Fenwick C, et al. Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. Antimicrob Agents Chemother. 2014 Jun;58(6):3233-44. [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

Please refer to the solubility information to select the appropriate solvent. The compound is unstable in solutions, freshly prepared is recommended.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.2598 mL	11.2992 mL	22.5984 mL	56.4959 mL
	5 mM	0.4520 mL	2.2598 mL	4.5197 mL	11.2992 mL
	10 mM	0.2260 mL	1.1299 mL	2.2598 mL	5.6496 mL
	15 mM	0.1507 mL	0.7533 mL	1.5066 mL	3.7664 mL
	20 mM	0.1130 mL	0.5650 mL	1.1299 mL	2.8248 mL
	25 mM	0.0904 mL	0.4520 mL	0.9039 mL	2.2598 mL
	30 mM	0.0753 mL	0.3766 mL	0.7533 mL	1.8832 mL
	40 mM	0.0565 mL	0.2825 mL	0.5650 mL	1.4124 mL
	50 mM	0.0452 mL	0.2260 mL	0.4520 mL	1.1299 mL
	60 mM	0.0377 mL	0.1883 mL	0.3766 mL	0.9416 mL
	80 mM	0.0282 mL	0.1412 mL	0.2825 mL	0.7062 mL
	100 mM	0.0226 mL	0.1130 mL	0.2260 mL	0.5650 mL

Keywords

BI 224436

6 Cited Publications

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BI 224436

MCE Bioactive Compound Library

Clinical Compound Library Plus

Publications Citing Use of MedChemExpress (MCE) BI 224436

Alle HIV Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (6)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

BI 224436

MCE Bioactive Compound Library

Clinical Compound Library Plus

Publications Citing Use of MedChemExpress (MCE) BI 224436

Alle HIV Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (6)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

BI 224436 Related Classifications

HY-18595 Related Classifications