Delving into the Latest Updates on Emivirine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-(ethoxymethyl)-5-(1-methylethyl)-6-(phenylmethyl)pyrimidine-2,4(1H,3H)-dione, 6-benzyl-1-(ethoxymethyl)-5-(1-methylethyl)uracil, Emivirine (USAN/INN)

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Target

RT

Mechanism

RT inhibitors(Reverse transcriptase inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV Infections

Inactive Indication

Brain Cancer

Originator Organization

Mitsubishi Tanabe Pharma Corp.

Active Organization

University of Southern Denmark

Inactive Organization

Abbott Laboratories

Mitsubishi Tanabe Pharma Corp.

Gilead Sciences, Inc.

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Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

Molecular FormulaC17H22N2O3

InChIKeyMLILORUFDVLTSP-UHFFFAOYSA-N

CAS Registry149950-60-7

To compare the proportion of patients whose plasma HIV-1 RNA level falls and remains below the limit of quantification by the Roche Amplicor Monitor (400 copies/ml)[AS PER AMENDMENT 8/4/98: 50 copies/ml] between weeks 0 and 24. To determine the short-term safety and tolerability of MKC-442 plus nelfinavir (Viracept) plus dual nucleoside analogs. To determine the time to viral failure and time to tolerability failure through Week 48 of therapy.

Start Date-

Sponsor / Collaborator

Triangle Pharmaceuticals, Inc.

NCT00002413 / CompletedPhase 2

An Open Label Study of MKC-442 in at Least Triple Drug Combination in Patients Previously Treated With Nucleoside Reverse Transcriptase and Protease Inhibitors and Who Are Naive to Non-Nucleoside Reverse Transcriptase Inhibitors

The purpose of this study is to see if it is safe and effective to give MKC-442 plus at least two other anti-HIV drugs to patients who have never been treated with nonnucleoside reverse transcriptase inhibitors but who have been treated with nucleoside reverse transcriptase inhibitors and protease inhibitors. This study also determines how long a drug combination including MKC-442 is effective.

Start Date-

Sponsor / Collaborator

Triangle Pharmaceuticals, Inc.

NCT00002412 / CompletedPhase 2

A Randomized, Double-Blind Study of MKC-442 Combined With Stavudine, Didanosine, and Hydroxyurea in HIV-Infected Patients Who Are Protease Inhibitor Experienced and Non-Nucleoside Reverse Transcriptase Inhibitor Naive

The purpose of this study is to see if it is safe and effective to give MKC-442 plus stavudine (d4T) plus didanosine (ddI) plus hydroxyurea.

Start Date-

Sponsor / Collaborator

Triangle Pharmaceuticals, Inc.

100 Clinical Results associated with Emivirine

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100 Translational Medicine associated with Emivirine

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100 Patents (Medical) associated with Emivirine

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74

Literatures (Medical) associated with Emivirine

01 Feb 2018·Drug development and industrial pharmacyQ4 · MEDICINE

Effects of crystalline state and self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of the novel anti-HIV compound 6-benzyl-1-benzyloxymethyl-5-iodouracil in rats

Q4 · MEDICINE

Article

Author: Lou, Ya-Qing ; Li, Pu ; Zhang, Qiang ; Liu, Jun-Yi ; Wang, Xin ; Lu, Chuang ; Wang, Xiao-Wei ; Dai, Wen-Bing ; Lu, Ying-Yuan ; Zhang, Guo-Liang

The objective of this study was to investigate the effect of crystalline state and a formulation of self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor, in rats. The crystalline states of W-1 were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The SNEDDS was formulated by medium-chain lipids, characterized by droplet particle size. The plasma concentrations of W-1 were measured by high performance liquid chromatography (HPLC). The results indicated that W-1 compound were presented as crystalline forms, A and B, the degree of crystallization in form B was higher than that in form A. The SNEDDS of W-1 displayed a significant increase in the dissolution rate than W-1 powder. Furthermore, after oral administration of W-1 (100 mg/kg), the pharmacokinetic parameters of form A, form B, and W-1 SNEDDS were as follows: AUC_0-t 526.4 ± 123.5, 305.1 ± 58.5 and 2297 ± 451 ng h/mL (p < .05, when W-1 SNEDDS were compared with either form A or form B), respectively. With SNEDDS formulation, the relative bioavailabilities were enhanced by 4.36-fold and 7.53-fold over the form A and form B of W-1, respectively. In conclusion, the present results suggested that the crystalline states of W-1 might lead to the lower oral bioavailability, and SNEDDS formulation is a promising strategy of improving bioavailability, in spite of that crystalline states usually carry small lot-to-lot variability.

01 Sep 2017·Medical physicsQ3 · MEDICINE

Fast kVp‐switching dual energy contrast‐enhanced thorax and cardiac CT: A phantom study on the accuracy of iodine concentration and effective atomic number measurement

Q3 · MEDICINE

Article

Author: Papadakis, Antonios E. ; Damilakis, John

Purpose:

To assess the effect of vessel diameter and exposure parameters on the estimation accuracy of concentration and effective atomic number (Zeff) of iodine (I) in contrast‐enhanced thorax and cardiac dual‐energy CT using a modern fast kVp‐switching CT scanner.

Methods:

A standard semi‐anthropomorphic cardiac CT phantom devised to simulate the human chest at three different body habitus i.e., medium‐sized, large‐sized, and obese, was scanned using a fast kVp‐switching Revolution‐GSI GE CT scanner. Five cylindrical, 10 mm diameter, vials were filled with solutions prepared by diluting I contrast at five concentrations (2.5, 5, 10, 15, and 20 mg I/ml). To simulate small vessels, pipette tips with a diameter ranging from 5 mm to 0.5 mm were employed. The vials and pipette tips were accommodated within the semi‐anthropomorphic phantom. CT acquisitions were performed in the fast kVp‐switching dual‐energy mode at six different CTDIw values. Acquisitions were also performed at 80, 100, 120, and 140 kVp. Images were acquired at 64 × 0.625 mm beam collimation and reconstructed at 2.5 mm using all available reconstruction filter kernels. Virtual monochromatic spectral (VMS) images, iodine concentration (IMeas), and Zeff maps were reconstructed. Hounsfield unit as a function of energy (HUkeV) in VMS and single‐kVp (HUkVp), IMeas and Zeff were measured at each CTDIw. The effect of vessel diameter on IMeas and Zeff was investigated. Measured HUkeV and Zeff were compared to theoretically estimated values and IMeas were compared to nominal (INom) values.

Results:

In 10 mm diameter vessels, HUkeV values were accurate to 18% for the medium‐sized, 22% for the large‐sized and 39% for the obese phantoms. IMeas was underestimated by up to 10% for the medium‐sized, 26% for the large‐sized and 33% for the obese phantom. IMeas error decreased with increasing CTDIw from ±0.799 mg/ml at 8.61 mGy to ±0.082 mg/ml at 32.01 mGy. The percentage difference between measured and theoretically estimated Zeff ranged from −3.9% to −14.5%. In pipette tip vessels, IMeas was found to depend on the kernel employed. At the standard kernel, IMeas, for INom = 20 mg/ml, was reduced with vessel diameter from 19.25 ± 0.39 mg/ml, at 10 mm, to 2.52 ± 0.31 mg/ml, at 1 mm. Linear regression between IMeas and INom resulted in IMeas/INom factors of 0.925 for 5 mm, 0.815 for 4 mm, 0.651 for 3 mm, 0.377 for 2 mm, and 0.129 for 1 mm vessel diameter. Measured Zeff values were underestimated when vessel diameter was decreased from 5 mm to 1 mm by 27% for the 20 mg I/ml and 21% for the 2.5 mg I/ml.

Conclusions:

HUkeV, IMeas, and Zeff depend on several parameters such as body size, vessel size, exposure parameters, and reconstruction kernel. The limiting spatial resolution of the CT system results in considerable underestimation of HUkVp, IMeas, and Zeff in vessels smaller than 5 mm diameter. The underestimation of I uptake may be experimentally corrected, if the diameter of the investigated vessel is measured and the correction factors produced in this study are employed.

03 Aug 2017·Xenobiotica; the fate of foreign compounds in biological systemsQ4 · MEDICINE

Identification of cytochrome P450s involved in the metabolism of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1) using human recombinant enzymes and rat liver microsomesin vitro

Q4 · MEDICINE

Article

Author: Cheng, Hai-Xu ; Lou, Ya-Qing ; Li, Pu ; Liu, Jun-Yi ; Lu, Chuang ; Li, Jun ; Wang, Xin ; Wang, Xiao-Wei ; Lu, Ying-Yuan ; Zhang, Guo-Liang

1. The aim of this study was to identify the hepatic metabolic enzymes, which involved in the biotransformation of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) in rat and human in vitro. 2. The parent drug of W-1 was incubated with rat liver microsomes (RLMs) or recombinant CYPs (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5, respectively) in the presence or absence of nicotinamide adeninedinucleotide phosphate (NADPH)-regenerating system. The metabolites of W-1 were analyzed with liquid chromatography-ion trap-time of flight-mass spectrometry (LC-IT-TOF-MS). 3. The parent drug of W-1 was metabolized in a NADPH-dependent manner in RLMs. The kinetic parameters of prototype W-1 including K_m, V_max, and CL_int were 2.3 μM, 3.3 nmol/min/mg protein, and 1.4 mL/min/mg protein, respectively. Two metabolites M1 and M2 were observed in shorter retention times (2.988 and 3.188 min) with a higher molecular ion at m/z 463.0160 (both M1 and M2) than that of the W-1 parent drug (6.158 min with m/z 447.0218). The CYP selective inhibition and recombinant enzymes also showed that two hydroxyl metabolites M1 and M2 are mainly mediated by CYP2C19 and CYP3A4. 4. The identification of CYPs involved in W-1 biotransformation is important to understand and minimize, if possible, the potential of drug-drug interactions.

100 Deals associated with Emivirine

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External Link

KEGG	Wiki	ATC	Drug Bank
D01055	Emivirine	-	DB08188

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 3	EU	-	-
HIV Infections	Phase 3	MX	-	-
HIV Infections	Phase 3	ZA	-	-
HIV Infections	Phase 3	-	Mitsubishi Tanabe Pharma Corp.	-
HIV Infections	Phase 3	-	Gilead Sciences, Inc.	-
HIV Infections	Phase 3	-	Abbott Laboratories	-
Brain Cancer	Phase 2	US	-	-
Brain Cancer	Phase 2	-	Gilead Sciences, Inc.	-
Brain Cancer	Phase 2	-	Mitsubishi Tanabe Pharma Corp.	-
Brain Cancer	Phase 2	-	Abbott Laboratories	-