BMS-378806Gp120/CD4 inhibitor CAS# 357263-13-9 |
- MRT67307
Catalog No.:BCC1779
CAS No.:1190378-57-4
- IKK-2 inhibitor VIII
Catalog No.:BCC1642
CAS No.:406209-26-5
- TPCA-1
Catalog No.:BCC2473
CAS No.:507475-17-4
- Bay 65-1942 HCl salt
Catalog No.:BCC1409
CAS No.:600734-06-3
- IKK-3 Inhibitor
Catalog No.:BCC1643
CAS No.:862812-98-4
- IMD 0354
Catalog No.:BCC4556
CAS No.:978-62-1
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 357263-13-9 | SDF | Download SDF |
PubChem ID | 5495818 | Appearance | Powder |
Formula | C22H22N4O4 | M.Wt | 406.43 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | BMS-806 | ||
Solubility | Soluble to 81 mg/mL (199.29 mM) in DMSO | ||
Chemical Name | 1-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione | ||
SMILES | CC1CN(CCN1C(=O)C(=O)C2=CNC3=NC=CC(=C23)OC)C(=O)C4=CC=CC=C4 | ||
Standard InChIKey | OKGPFTLYBPQBIX-CQSZACIVSA-N | ||
Standard InChI | InChI=1S/C22H22N4O4/c1-14-13-25(21(28)15-6-4-3-5-7-15)10-11-26(14)22(29)19(27)16-12-24-20-18(16)17(30-2)8-9-23-20/h3-9,12,14H,10-11,13H2,1-2H3,(H,23,24)/t14-/m1/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | BMS-378806 is a selective inhibitor of HIV-1 CD4-gp120 interactions with an EC50 value of 0.85-26.5 nM. | |||||
Targets | CD4-gp120 interactions | |||||
IC50 | 0.85 nM-26.5 nM(EC50) |
BMS-378806 Dilution Calculator
BMS-378806 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.4604 mL | 12.3022 mL | 24.6045 mL | 49.209 mL | 61.5112 mL |
5 mM | 0.4921 mL | 2.4604 mL | 4.9209 mL | 9.8418 mL | 12.3022 mL |
10 mM | 0.246 mL | 1.2302 mL | 2.4604 mL | 4.9209 mL | 6.1511 mL |
50 mM | 0.0492 mL | 0.246 mL | 0.4921 mL | 0.9842 mL | 1.2302 mL |
100 mM | 0.0246 mL | 0.123 mL | 0.246 mL | 0.4921 mL | 0.6151 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
BMS-378806 is a novel attachment inhibitor of HIV with EC50 values of 2.68±1.64nM, 26.5±3.5nM, 2.94±2.01nM,15.5±6.8nM, 3.46±0.81nM, 1.47±0.63nM and 0.85±0.13nM for LAI(T), SF-2(T),NL4-3(T), Bal(M), SF-162(M), JRFL(M) and TLAV(dual), respectively [1].
In a series of in vitro biochemical assay, BMS-378806 has been found to be not an effective inhibitor of HIV integrase, protease, or reverse transcriptase, but compete with soluble CD4 binding to a monomeric form of gp120 protein in an ELISA assay with an IC50 value of ~100nM. In addition, BMS-378806 has shown no overt cytotoxicity toward the host cell with a CC50 value of >225μM [1].
References:
[1] Wang T1, Zhang Z, Wallace OB, Deshpande M, Fang H, Yang Z, Zadjura LM, Tweedie DL, Huang S, Zhao F, Ranadive S, Robinson BS, Gong YF, Ricarrdi K, Spicer TP, Deminie C, Rose R, Wang HG, Blair WS, Shi PY, Lin PF, Colonno RJ, Meanwell NA. Discovery of 4-benzoyl-1-[(4-methoxy-1H- pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2- (R)-methylpiperazine (BMS-378806): a novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions. J Med Chem. 2003 Sep 25;46(20):4236-9.
- Tropanyl trans-cinnamate
Catalog No.:BCN1931
CAS No.:35721-92-7
- Pemetrexed disodium hemipenta hydrate
Catalog No.:BCC1844
CAS No.:357166-30-4
- Moslosooflavone
Catalog No.:BCN5301
CAS No.:3570-62-5
- Albaspidin AA
Catalog No.:BCN5300
CAS No.:3570-40-9
- Galantamine
Catalog No.:BCN2868
CAS No.:357-70-0
- Brucine
Catalog No.:BCN2390
CAS No.:357-57-3
- Naloxone HCl
Catalog No.:BCC4612
CAS No.:357-08-4
- Valerenic acid
Catalog No.:BCC7546
CAS No.:3569-10-6
- Questinol
Catalog No.:BCN7443
CAS No.:35688-09-6
- Dihydrobaicalein
Catalog No.:BCN3887
CAS No.:35683-17-1
- Deoxylapachol
Catalog No.:BCN5299
CAS No.:3568-90-9
- Fmoc-Leu-OH
Catalog No.:BCC3509
CAS No.:35661-60-0
- Hygrophylline
Catalog No.:BCN2116
CAS No.:3573-82-8
- Cynaropicrin
Catalog No.:BCC8161
CAS No.:35730-78-0
- Brivaracetam
Catalog No.:BCC5497
CAS No.:357336-20-0
- Fmoc-ß-Ala-OH
Catalog No.:BCC3038
CAS No.:35737-10-1
- Fmoc-Trp-OH
Catalog No.:BCC3556
CAS No.:35737-15-6
- 3beta-Acetoxy-11alpha,12alpha-epoxyoleanan-28,13beta-olide
Catalog No.:BCN6664
CAS No.:35738-25-1
- Oxyimperatorin
Catalog No.:BCN2736
CAS No.:35740-18-2
- NNC 55-0396
Catalog No.:BCC1803
CAS No.:357400-13-6
- Cabraleone
Catalog No.:BCN5302
CAS No.:35761-54-7
- N-(3-Hydroxypropyl)-1H-indole-2-carboxamide
Catalog No.:BCC8773
CAS No.:357616-16-1
- Chrysin 7-O-beta-D-glucopyranuronoside
Catalog No.:BCN3249
CAS No.:35775-49-6
- Beta-Hederin
Catalog No.:BCN5381
CAS No.:35790-95-5
Preclinical pharmacokinetics of a novel HIV-1 attachment inhibitor BMS-378806 and prediction of its human pharmacokinetics.[Pubmed:16142720]
Biopharm Drug Dispos. 2005 Dec;26(9):387-402.
BMS-378806 is a prototype of novel HIV attachment inhibitors that block the gp120 and CD4 interaction, the first step of HIV-1 entry into cells. The present work investigated the pharmacokinetics of BMS-378806 in rats, dogs and monkeys and assessed its in vitro permeability and metabolism. BMS-378806 exhibited species-dependent oral bioavailability which was 19%-24% in rats and monkeys and 77% in dogs. In rats and monkeys, absorption was prolonged, with an apparent terminal half-life of 2.1 and 6.5 h, respectively. In rats, linear pharmacokinetics was observed between i.v. doses of 1 and 5 mg/kg and between p.o. doses of 5 and 25 mg/kg. The total body clearance was intermediate in rats and low in dogs and monkeys. The steady-state volume of distribution was moderate (0.4-0.6 l/kg), contributing to a short half-life (0.3-1.2 h) after i.v. dosing. Studies in bile-duct cannulated rats together with intraportal infusion studies revealed that the renal and hepatic clearance each accounted for 30% and 70% of the total elimination in rats, with the hepatic clearance largely being oxidative metabolism. In vitro, BMS-378806 was not highly protein bound (44%-73%). The Caco-2 permeability was modest (51 nm/s) and confounded by P-glycoprotein mediated efflux transport. Both of these may contribute to the low brain penetration observed in rats (brain/plasma AUC ratio=0.06). In human liver microsomes BMS-378806 was equally metabolized by cytochrome P450 1A2, 2D6 and 3A4 and did not inhibit major drug-metabolizing enzymes to a significant extent. Based on in vitro and animal data, a mechanistic approach that factors in absorption and first-pass metabolism was employed to predict the human oral bioavailability of BMS-378806 (ca 20%). This, together with the complex Dedrick plot method, was used to simulate human oral profiles and to project an efficacious dose. These study results offer a comprehensive assessment of the developability of BMS-378806 and provide important guidance to improving absorption and half-life of future compounds in the series. The current studies also demonstrate the value and approaches of understanding pharmacokinetic properties in the early stage of drug discovery.
Discovery of small molecular inhibitors targeting HIV-1 gp120-CD4 interaction drived from BMS-378806.[Pubmed:25203778]
Eur J Med Chem. 2014 Oct 30;86:481-90.
The HIV-1 entry into host cells is a complex, multi-factors involved, and multi-step process. Especially, the attachment of HIV-1 envelope glycoprotein gp120 to the host cell receptor CD4 is the first key step during entry process, representing a promising antiviral therapeutic target. Among the HIV-1 attachment inhibitors blocking the interaction between gp120 and CD4 cells, BMS-378806 and NBD-556 are two representative small molecular chemical entities. Particularly, BMS-378806 and its derivatives are newly identified class of orally bioavailable HIV-1 inhibitors that interfere gp120-CD4 interaction. In this review, we focused on describing the structure-activity relationships (SARs), structural modifications, in vitro or even in vivo pharmacodynamics and pharmacokinetics of BMS-378806 and its analogues as HIV-1 gp120 attachment inhibitors. In addition, the brief SARs, structural modifications of NBD-556 and its derivatives targeting the "Phe-43 cavity" as CD4 mimics were also described.
Prediction of the binding mode between BMS-378806 and HIV-1 gp120 by docking and molecular dynamics simulation.[Pubmed:16455315]
Biochim Biophys Acta. 2006 Apr;1764(4):766-72.
BMS-378806 is a newly discovered small molecule that effectively blocks the binding of CD4 with gp120. The binding mode of this kind of inhibitor remains unknown. In this paper, AutoDock 3.0 in conjunction with molecular dynamics simulation, accommodating the receptor's flexibility, was used to explore the binding mode between BMS-378806 and gp120. Two structures, Mode I and Mode II, with the lowest docking energy were selected as different representative binding modes. The analysis of the results from the molecular dynamics simulation indicated that the binding of BMS-348806 in Mode II is more stable. The average structure of Mode II was analyzed and compared with the experimental data. The conclusion was that BMS-378806 inserts the azaindole ring deeply into the PHE43 cavity and makes contact with a number of residues in the cavity, on the cavity and near the cavity. This study benefits the understanding of the mechanism of this kind of inhibitor and may provide useful information for rational drug design.
Quantitative determination of BMS-378806 in human plasma and urine by high-performance liquid chromatography/tandem mass spectrometry.[Pubmed:17623467]
J Sep Sci. 2007 Jun;30(9):1267-75.
BMS-378806 is a human immunodeficiency virus (HIV) entry inhibitor that is being developed for the oral treatment of HIV infection. Human plasma and urine LC/MS/ MS methods have been developed and validated for the quantitation of BMS-378806. For human plasma method, methyl t-butyl ether was used to extract BMS-378806 from plasma in a 96-well format, and the organic layers were dried down and then reconstituted for the injection, while a dilute-and-shoot approach was used for human urine method in a 96-well format. Chromatographic separation was achieved isocratically on a Phenomenex C18 (2) Luna column (2 x 50 mm2, 5 microm). The mobile phase contained 60:40 v/v of 0.1% formic acid in water and ACN. Detection was by positive ion electrospray MS/MS. The standard curves ranged from 1.25 to 1000 ng/mL for the plasma assay and from 10 to 5000 ng/mL for the urine assay. The curves were fitted to a 1/x2 weighted quadratic regression model for both methods. The validation results demonstrated that both methods had satisfactory precision and accuracy across the calibration ranges. The methods were applied to the analysis of human plasma and urine samples from a single ascending dose clinical study to assess the pharmacokinetics of the drug. The pharmacokinetic analysis results indicated the absorption and disposition of the drug was rapid. The systemic exposure of BMS-378806 was generally dose proportional among the doses from 100 to 1200 mg, but not dose proportional to 1600 mg. There were modest increases in the systemic exposure when the drug was given with food or given as a solution formulation. Renal excretion was not a substantial elimination pathway of the drug. BMS378806 was safe and well tolerated over a dose range of 100-1600 mg administered as a single oral dose.