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  3. BMS-378806

BMS-378806  (Synonyms: BMS-806)

製品番号: HY-14134 純度: 98.94%
COA 取扱説明書 Technical Support

BMS-378806 is a potent HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions. BMS-378806 selectively inhibits the binding of HIV-1 gp120 to the CD4 receptor with EC50 of 0.85-26.5 nM in virus.

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BMS-378806

BMS-378806 構造式

CAS 番号 : 357263-13-9

容量 価格(税別) 在庫状況 数量
>無料サンプル (0.1 - 0.2 mg)   今すぐ申し込む  
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
USD 75 在庫あり
Solution
10 mM * 1 mL in DMSO USD 75 在庫あり
Solid
5 mg $69 在庫あり
10 mg $110 在庫あり
25 mg $230 在庫あり
50 mg $370 在庫あり
100 mg $540 在庫あり
200 mg   お問い合わせ  
500 mg   お問い合わせ  

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カスタマーレビュー

Based on 7 publication(s) in Google Scholar

Top Publications Citing Use of Products

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製品説明

BMS-378806 is a potent HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions. BMS-378806 selectively inhibits the binding of HIV-1 gp120 to the CD4 receptor with EC50 of 0.85-26.5 nM in virus.

IC50 & Target

HIV-1

 

HIV-2

 

Cellular Effect
Cell Line Type Value Description References
HeLa EC50
1 1
Compound: 7, BMS-378806
Antiviral activity against HIV1 JR-FL in human HeLa cells expressing CD4, CCR5 assessed as inhibition of integration of viral DNA into cell genome after 3 days by luciferase reporter gene assay
Antiviral activity against HIV1 JR-FL in human HeLa cells expressing CD4, CCR5 assessed as inhibition of integration of viral DNA into cell genome after 3 days by luciferase reporter gene assay
[PMID: 23200254]
HeLa CC50
> 300 3
Compound: 7, BMS-378806
Cytotoxicity against human HeLa cells expressing CD4, CCR5 after 3 days
Cytotoxicity against human HeLa cells expressing CD4, CCR5 after 3 days
[PMID: 23200254]
U-87MG ATCC IC50
8 1
Compound: 26, BMS-378806
Antiviral activity against HIV1 pseudovirus in U87 cells expressing CD4 and CCR5 after 72 hrs by M33 pseudotyped assay
Antiviral activity against HIV1 pseudovirus in U87 cells expressing CD4 and CCR5 after 72 hrs by M33 pseudotyped assay
[PMID: 18052117]
HeLa EC50
1 1
Compound: 7, BMS-378806
Antiviral activity against HIV1 JR-FL in human HeLa cells expressing CD4, CCR5 assessed as inhibition of integration of viral DNA into cell genome after 3 days by luciferase reporter gene assay
Antiviral activity against HIV1 JR-FL in human HeLa cells expressing CD4, CCR5 assessed as inhibition of integration of viral DNA into cell genome after 3 days by luciferase reporter gene assay
[PMID: 23200254]
HeLa CC50
> 300 3
Compound: 7, BMS-378806
Cytotoxicity against human HeLa cells expressing CD4, CCR5 after 3 days
Cytotoxicity against human HeLa cells expressing CD4, CCR5 after 3 days
[PMID: 23200254]
MT2 CC50
> 300 3
Compound: 3, BMS-377806
Cytotoxicity against human MT2 cells after 3 days by XTT assay
Cytotoxicity against human MT2 cells after 3 days by XTT assay
[PMID: 19769332]
HeLa CC50
>300 3
Compound: 7, BMS-378806
Cytotoxicity against human HeLa cells expressing CD4, CCR5 after 3 days
Cytotoxicity against human HeLa cells expressing CD4, CCR5 after 3 days
[PMID: 23200254]
HeLa EC50
1 1
Compound: 7, BMS-378806
Antiviral activity against HIV1 JR-FL in human HeLa cells expressing CD4, CCR5 assessed as inhibition of integration of viral DNA into cell genome after 3 days by luciferase reporter gene assay
Antiviral activity against HIV1 JR-FL in human HeLa cells expressing CD4, CCR5 assessed as inhibition of integration of viral DNA into cell genome after 3 days by luciferase reporter gene assay
[PMID: 23200254]
MT2 CC50
>300 3
Compound: 3
Cytotoxicity activity of compound in MT-2 cells against LAI (T) tropic virus that utilizes the CXCR-4 co-receptor virus was determined
Cytotoxicity activity of compound in MT-2 cells against LAI (T) tropic virus that utilizes the CXCR-4 co-receptor virus was determined
[PMID: 13678401]
U-87MG ATCC CC50
> 40000 1
Compound: 1, BMS-378806,BMS-806
Cytotoxicity against human U87 cells coexpressing CD4, CxCR4 receptors after 72 hrs
Cytotoxicity against human U87 cells coexpressing CD4, CxCR4 receptors after 72 hrs
[PMID: 19534463]
MT2 CC50
>300 3
Compound: 3, BMS-377806
Cytotoxicity against human MT2 cells after 3 days by XTT assay
Cytotoxicity against human MT2 cells after 3 days by XTT assay
[PMID: 19769332]
U-87MG ATCC IC50
8 1
Compound: 26, BMS-378806
Antiviral activity against HIV1 pseudovirus in U87 cells expressing CD4 and CCR5 after 72 hrs by M33 pseudotyped assay
Antiviral activity against HIV1 pseudovirus in U87 cells expressing CD4 and CCR5 after 72 hrs by M33 pseudotyped assay
[PMID: 18052117]
MT2 CC50
> 300 3
Compound: 3
Cytotoxicity activity of compound in MT-2 cells against LAI (T) tropic virus that utilizes the CXCR-4 co-receptor virus was determined
Cytotoxicity activity of compound in MT-2 cells against LAI (T) tropic virus that utilizes the CXCR-4 co-receptor virus was determined
[PMID: 13678401]
MT2 CC50
> 300 3
Compound: 3
Cytotoxicity activity of compound in MT-2 cells against TLAV (dual) virus that utilizes both CXR4 and CCR5 co-receptor virus was determined
Cytotoxicity activity of compound in MT-2 cells against TLAV (dual) virus that utilizes both CXR4 and CCR5 co-receptor virus was determined
[PMID: 13678401]
MT2 IC50
0.032 3
Compound: 45; BMS-378806
Antiviral activity against HIV1 3B infected in MT2 cells assessed as reduction cell viability
Antiviral activity against HIV1 3B infected in MT2 cells assessed as reduction cell viability
[PMID: 26509831]
MT2 CC50
> 300 3
Compound: 3, BMS-377806
Cytotoxicity against human MT2 cells after 3 days by XTT assay
Cytotoxicity against human MT2 cells after 3 days by XTT assay
[PMID: 19769332]
U-87MG ATCC CC50
>40 3
Compound: 1, BMS-378806,BMS-806
Cytotoxicity against human U87 cells coexpressing CD4, CxCR4 receptors after 72 hrs
Cytotoxicity against human U87 cells coexpressing CD4, CxCR4 receptors after 72 hrs
[PMID: 19534463]
MT2 IC50
0.032 3
Compound: 45; BMS-378806
Antiviral activity against HIV1 3B infected in MT2 cells assessed as reduction cell viability
Antiviral activity against HIV1 3B infected in MT2 cells assessed as reduction cell viability
[PMID: 26509831]
U-87MG ATCC CC50
>40 3
Compound: 26, BMS-378806
Cytotoxicity against human U87 cells expressing CD4 and CXCR4
Cytotoxicity against human U87 cells expressing CD4 and CXCR4
[PMID: 18052117]
U-87MG ATCC CC50
> 40000 1
Compound: 1, BMS-378806,BMS-806
Cytotoxicity against human U87 cells coexpressing CD4, CxCR4 receptors after 72 hrs
Cytotoxicity against human U87 cells coexpressing CD4, CxCR4 receptors after 72 hrs
[PMID: 19534463]
U-87MG ATCC CC50
> 40000 1
Compound: 26, BMS-378806
Cytotoxicity against human U87 cells expressing CD4 and CXCR4
Cytotoxicity against human U87 cells expressing CD4 and CXCR4
[PMID: 18052117]
U-87MG ATCC IC50
8 1
Compound: 26, BMS-378806
Antiviral activity against HIV1 pseudovirus in U87 cells expressing CD4 and CCR5 after 72 hrs by M33 pseudotyped assay
Antiviral activity against HIV1 pseudovirus in U87 cells expressing CD4 and CCR5 after 72 hrs by M33 pseudotyped assay
[PMID: 18052117]
体外実験

In a series of biochemical assays, BMS-378806 is not an effective inhibitor of HIV integrase, protease, or reverse transcriptase, but did compete with soluble CD4 binding to a monomeric form of gp120 in an ELISA assay with IC50=100 nM. The specificity of BMS-378806 toward inhibition of HIV-1 is confirmed by evaluation against HIV-2, SIV, MuLV, RSV, HCMV, BVDV, VSV, and influenza virus, with no significant inhibitory activity observed at concentrations ranging from 10 to 30 μM and no overt cytotoxicity toward the host cells, CC50>225 μM. BMS-378806 is not a potent inhibitor of any of the five major human CYP isoforms, evaluated as recombinant preparations, with IC50 values of >100 μM for CYP1A2 and CYP2C9, 23 μM for CYP2C19, 20 μM for CYP2D6, and 39 to 81 μM for CYP3A4. Moreover, since BMS-378806 is metabolized by CYP450 1A2, 2D6, and 3A4, it is unlikely to lead to severe drug−drug interactions in a clinical setting[1]. BMS-378806 inhibits viral replication by interfering with the binding interactions of gp120 with the cellular CD4 receptor. The IC50s determined for the gp120s from HIV LAI, BAL, NA420LN40, SF162, NL4-3, NA420B33, YU2, AD8, JRCSF, and 92US15.6 are 0.1, 0.1, 0.3, 0.5, 0.6, 0.7, 0.9, 1.0, 1.1, and 1.6 μM, respectively. A similar observation is also made for BMS-378806 (IC50s range from 0.2 to 9.6 μM)[2]. BMS-378806 binds directly to gp120 at a stoichiometry of approximately 1:1, with a binding affinity similar to that of soluble CD4. The potential BMS-378806 target site is localized to a specific region within the CD4 binding pocket of gp120 by using HIV-1 gp120 variants carrying either compound-selected resistant substitutions or gp120-CD4 contact site mutations[3].

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

体内実験

In toxicology studies, BMS-378806 is well tolerated in rats at doses of 100 mg/kg/day for 2 weeks and in dogs at doses of 90 mg/kg for 10 days. The dose-proportional increases in the AUC and Cmax are observed between doses of 5 and 25 mpk, when BMS-378806 is administered either in the solution or suspension formulation. In all three species, plasma levels of drug exceeded the concentrations required to half-maximally inhibit virus replication in vitro. The volume of distribution of BMS-378806 ranges from 0.4 to 0.6 L/kg, indicative of partitioning beyond plasma; however, examination of brain levels in the rat reveals minimal CNS penetration[1].

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

分子量

406.43

分子式

C22H22N4O4

CAS 番号
Appearance

Solid

Color

White to off-white

SMILES

COC1=C2C(NC=C2C(C(N3CCN(C[C@H]3C)C(C4=CC=CC=C4)=O)=O)=O)=NC=C1

輸送条件

Room temperature in continental US; may vary elsewhere.

保管条件
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
溶剤 & 溶解度
体外: 

DMSO : 50 mg/mL (123.02 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.4604 mL 12.3022 mL 24.6045 mL
5 mM 0.4921 mL 2.4604 mL 4.9209 mL
10 mM 0.2460 mL 1.2302 mL 2.4604 mL
View the Complete Stock Solution Preparation Table

* 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
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Volume
×
Molecular Weight *

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

一般には略語で表示されます:C1V1 = C2V2

濃度 (開始)

C1

×
体積 (開始)

V1

=
濃度 (終了)

C2

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体積 (終了)

V2

体内:

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

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 (6.15 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.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

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

    Solubility: ≥ 2.5 mg/mL (6.15 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.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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mg/kg

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g

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(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
純度とドキュメンテーション

純度: 98.94%

参考文献
キナーゼ実験
[3]

To measure gp120-CD4 binding, the wild-type or variant gp120 proteins are first captured onto a plate by D7324 antibody. CD4 binding is initiated by adding sCD4 to a gp120-coated plate. To determine the ability of BMS-378806 to compete with sCD4 for gp120 binding, the compound is added simultaneously with sCD4 and reactions are carried out in buffer C (50 mM Tris-HCl [pH 7.5], 100 mM NaCl, 1% bovine serum albumin) for 2 h at room temperature. After washing with buffer B (20 mM Tris-HCl, 500 mM NaCl, 0.05% Tween 20 [pH 7.5]), the bound CD4 is detected with OKT4 antibody (0.36 μg/mL) and goat anti-mouse peroxidase conjugate. Bound antibody is detected with 3,3′,5,5′-tetramethylbenzidine chromogenic substrate for peroxidase[3].

MedChemExpress (MCE) はこれらの方法の精度を確認していません。 こちらは参照専用です。

動物実験
[1]

Rats, Dogs and Monkeys[1]
The pharmacokinetic properties of BMS-378806 in the rat, dog, and cynomolgus monkey are summarized. The oral bioavailability of BMS-378806 in rats, administered as a solution in PEG 400/EtOH (90:10 v/v), is 19% at a dose of 5 mg/kg while an aqueous crystalline suspension of free base in 0.75% (w/w) Methocel A4M Premium administered orally at the same dose afforded a relative bioavailability of 61%.

MedChemExpress (MCE) はこれらの方法の精度を確認していません。 こちらは参照専用です。

参考文献

Complete Stock Solution Preparation Table

* 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.4604 mL 12.3022 mL 24.6045 mL 61.5112 mL
5 mM 0.4921 mL 2.4604 mL 4.9209 mL 12.3022 mL
10 mM 0.2460 mL 1.2302 mL 2.4604 mL 6.1511 mL
15 mM 0.1640 mL 0.8201 mL 1.6403 mL 4.1007 mL
20 mM 0.1230 mL 0.6151 mL 1.2302 mL 3.0756 mL
25 mM 0.0984 mL 0.4921 mL 0.9842 mL 2.4604 mL
30 mM 0.0820 mL 0.4101 mL 0.8201 mL 2.0504 mL
40 mM 0.0615 mL 0.3076 mL 0.6151 mL 1.5378 mL
50 mM 0.0492 mL 0.2460 mL 0.4921 mL 1.2302 mL
60 mM 0.0410 mL 0.2050 mL 0.4101 mL 1.0252 mL
80 mM 0.0308 mL 0.1538 mL 0.3076 mL 0.7689 mL
100 mM 0.0246 mL 0.1230 mL 0.2460 mL 0.6151 mL
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BMS-378806 Related Classifications

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

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

質量   濃度   体積   分子量 *
= × ×

The dilution calculator equation

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

一般には略語で表示されます:C1V1 = C2V2

濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
× = ×
C1   V1   C2   V2
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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製品名:
BMS-378806
製品番号:
HY-14134
数量:
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