Home Microbiology CCR antagonist Maraviroc (UK-427857)

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Maraviroc (UK-427857) CCR5 antagonist

제품 번호S2003

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM in cell-free assays, respectively. Maraviroc is used in the treatment of HIV infection.
Maraviroc (UK-427857) CCR antagonist Chemical Structure

화학 구조

분자량: 513.67

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품질 관리 (Quality Control)

배치: 순도: 99.99%
99.99

함께 자주 사용되는 제품 Maraviroc (UK-427857)

Leronlimab (anti-CCR5)

It and Leronlimab (PRO-140) together inhibit HIV-1JR-FL envelope-mediated membrane fusion in the RET cell-cell fusion assay.

Vicriviroc Malate

It and Vicriviroc reduce prostate cancer cell metastasis to the bones, brain, and viscera in immune-competent mice.

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
HeLa-P4 Function assay Antagonist activity at human recombinant CCR5 expressed in human HeLa-P4 cells assessed as inhibition of human HeLa-P4 cells binding to HIV1 gp160 expressing CHO cells by cell-cell fusion assay, IC50 = 0.0002 μM. 19171484
HeLa-P4 Function assay 20 hrs Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay, IC50 = 0.0002 μM. 21128663
TZM-bl Function assay 3 days Inhibition of CCR5 in human TZM-bl cells infected with HIV1 Bal R5 assessed as antiviral activity by measuring reduction in viral infection pre-incubated with cells followed by viral infection measured after 3 days by luciferase reporter gene assay, IC50 = 0.0002 μM. 28082070
TZM-bl Function assay 48 hrs Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 MGC26-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.00037 μM. 24563723
TZM-bl Function assay 48 hrs Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 YU2-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.00043 μM. 24563723
PM1 Antiviral assay Antiviral activity against HIV1 Bal infected in human PM1 cells assessed as inhibition of viral replication, IC90 = 0.0007 μM. 19171484
PM1 Antiviral assay 5 days Antiviral activity against CCR5-dependent HIV1 Ba-L infected in human PM1 cells assessed as reduction in virus infection measured after 5 days by luciferase reporter gene assay, IC50 = 0.001 μM. 30234300
SupT1 Antiviral assay 48 hrs Antiviral activity against HIV-1 infected in human SupT1 cells assessed as inhibition of viral infectivity after 48 hrs by luciferase reporter gene assay, IC50 = 0.0011 μM. 24316669
TZM-bl Function assay 48 hrs Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 92RW-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.0013 μM. 24563723
CHO Function assay 2 hrs Displacement of [128I]RANTES from human CCR5 receptor coexpressed with Galphai6 in CHO cells after 2 hrs by scintillation counting, IC50 = 0.0014 μM. 20137937
TZM-bl Function assay 48 hrs Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 JR-FL-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.0016 μM. 24563723
HOS Antiviral assay 5 days Antiviral activity against CCR5-dependent HIV1 Ba-L infected in human HOS cells assessed as reduction in virus infection measured after 5 days by luciferase reporter gene assay, IC50 = 0.0019 μM. 30234300
HOS Antiviral assay Antiviral activity against HIV1 Ba-L infected in HOS cells assessed as inhibition of viral infection, IC50 = 0.002 μM. 19664920
MOLT4 Function assay 15 mins Antagonist activity at CCR5 in Gqi5 transfected human MOLT4 cells assessed as inhibition of RANTES-stimulated Ca2+ influx preincubated for 15 mins followed by DAMGO challenge, IC50 = 0.0022 μM. 23682308
JC53-BL Antiviral assay 3 days Antiviral activity against CCR5-tropic recombinant HIV1 NLBal virus infected in JC53-BL cells assessed as inhibition of viral replication after 3 days by luciferase reporter gene assay, IC50 = 0.0028 μM. 20137937
JC53-BL Antiviral assay 3 days Antiviral activity against HIV1 NL4-3 infected in human JC53-BL cells assessed as luciferase activity after 3 days post infection, IC50 = 0.003 μM. 20417098
HOS Antiviral assay 5 days Antiviral activity against CCR5-dependent HIV1 SF162 infected in human HOS cells assessed as reduction in virus infection measured after 5 days by luciferase reporter gene assay, IC50 = 0.0047 μM. 30234300
NIH/3T3 Function assay 1 hr Displacement of [125I]-RANTES from CCR5 in mouse NIH/3T3 cells after 1 hr, IC50 = 0.0052 μM. 29425816
SupT1 Antiviral assay 48 hrs Antiviral activity against HIV1 infected in human SupT1 cells exposed to supernatant from HIV1 infected human 293T cells incubated for 48 hrs by firefly luciferase assay based single-cycle HIV1 replication assay, IC50 = 0.0055 μM. 25638498
TZM-bl Antiviral assay 48 hrs Antiviral activity against CCR5-dependent HIV1 SF162 infected in human TZM-bl cells assessed as reduction in virus infection measured after 48 hrs post infection by luciferase reporter gene assay, IC50 = 0.0067 μM. 30234300
HEK293 Function assay 10 mins Antagonist activity at CCR5 (unknown origin) expressed in HEK293 cells co-expressing Galpha16 assessed as inhibition of RANTES-induced calcium flux preincubated for 10 mins followed by RANTES addition by fluo-4AM-based fluorescence assay, IC50 = 0.008 μM. 30234300
CHO Function assay 10 mins Antagonist activity against CCR5 (unknown origin) expressed in CHO cells co-expressing Galpha16 incubated for 10 mins assessed as inhibition of RANTES-induced calcium mobilization, IC50 = 0.0131 μM. 25638498
CHO Function assay 10 mins Inhibition of CCR5 (unknown origin) expressed in CHO cells assessed as inhibition of RANTES-induced intracellular Ca2+ mobilization after 10 mins by Fluo-4 AM staining-based fluorescence assay, IC50 = 0.02543 μM. 24316669
HEK293 Function assay 1.5 mins Inhibition of human MATE1-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay, IC50 = 17.3 μM. 23241029
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells 29435139
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 513.67 화학식

C29H41F2N5O

 보관 (수령일로부터)
CAS 번호 376348-65-1 SDF 다운로드 원액 보관

동의어 UK-427857 Smiles CC1=NN=C(N1C2CC3CCC(C2)N3CCC(C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (194.67 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 100 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
CCR5
(Cell-free assay)
MIP-1α
(Cell-free assay)
3.3 nM
RANTES
(Cell-free assay)
5.2 nM
MIP-1β
(Cell-free assay)
7.2 nM
시험관 내(In vitro)

Maraviroc inhibits MIP-1β-stimulated γ-S-GTP binding to HEK-293 cell membranes, indicating its ability to inhibit chemokine-dependent stimulation of GDP-GTP exchange at the CCR5/G protein complex. This compound also inhibits the downstream event of chemokine-induced intracellular calcium redistribution, with IC50s ranging from 7 to 30 nM obtained against MIP-1β, MIP-1α and RANTES. In the same experiments, it does not trigger release of intracellular calcium at concentrations up to 10 μM, indicating that it is devoid of CCR5 agonist activity. Consistent with this, this chemical fails to induce CCR5 internalization. It is active at low nanomolar concentrations against HIV-1 Ba-L. This compound inhibits all 200 pseudotyped viruses with a geometric mean IC90 of 13.7 nM. At concentrations >1000 times the 50% inhibitory concentration, it did not inhibit other chemokine receptors (CCR1, 2, 3, 4, 7, and 8; CXCR1 and 2) to a clinically relevant degree.
키나아제 분석
Inhibition of chemokine binding to CCR5
Binding of 125I-labeled MIP-1α, MIP-1β, and RANTES to CCR5 is measured using intact HEK-293 cells stably expressing the receptor or membrane preparations thereof. Briefly, cells are resuspended in binding buffer (50 mM HEPES containing 1 mM CaCl2, 5 mM MgCl2, and 0.5% bovine serum albumin [BSA] and adjusted to pH 7.4) to a density of 2 × 106 cells/ml. For membrane preparations, phosphate-buffered saline (PBS)-washed cells are resuspended in lysis buffer (20 mM HEPES, 1 mM CaCl2, 1 tablet COMPLETE per 50 mL, pH 7.4) prior to homogenization in a Polytron hand-held homogenizer, ultracentrifugation (40,000× g for 30 min), and resuspension in binding buffer to a protein concentration of 0.25 mg/mL (12.5 μg of membrane protein is used in each well of a 96-well plate). 125I-radiolabeled MIP-1α, MIP-1β, and RANTES are prepared and diluted in binding buffer to a final concentration of 400 pM in the assay. This compound dilutions are added to each well to a final volume of 100 μL, the assay plates incubate for 1 hour, and the contents filter through preblocked and washed Unifilter plates which are counted following overnight drying.
생체 내(In vivo)

The half-life values of Maraviroc are 0.9 hour in the rat and 2.3 hours in the dog. Following oral administration (2 mg/kg) to the dog, the Cmax (256 ng/ml) occurred 1.5 hours post-dose, and the bioavailability is 40%. For the rat, approximately 30% of the administered dose is absorbed from the intestinal tract. Female RAG-hu mice are challenged vaginally with HIV-1 an hour after intravaginal application of the compound gel. This gel treated mice are fully protected against vaginal HIV-1 challenge in contrast to placebo gel treated mice which all became infected. Vaginal administration of this compound fully protects mice against HIV-1 vaginal challenge. While there is a clear pattern of CD4 T cell decline in placebo-gel treated and viral challenged mice, their levels are stable in mice receiving this chemical gel.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot cleaved caspase-3 / cleaved caspase-9 / cleaved PARP / XIAP / Survivin / c-IAP1 / c-IAP2 / Bax / Bad / Bcl2 / Bcl-xl
S2003-WB1
28469959

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT04966429 Recruiting
Post Stroke Cognitive Impairment
Tel-Aviv Sourasky Medical Center|Hadassah Medical Organization|Soroka University Medical Center
 May 1 2021 Phase 2
NCT04710199 Completed
Virus Diseases
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
 February 23 2021 Phase 2
NCT02881762 Completed
Hepatitis C|Human Immunodeficiency Virus
University of Maryland Baltimore|ViiV Healthcare
 June 1 2017 Phase 4
NCT02778204 Completed
HIV Infections
National Institute of Allergy and Infectious Diseases (NIAID)|Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|ViiV Healthcare|GlaxoSmithKline
 June 5 2017 Phase 1
NCT02741323 Completed
HIV Infections|Kidney Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
 January 1 2017 Phase 2

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
What vehicle do you recommend to dissolve it for in vivo experiments?

답변:
It can be dissolved in 5% DMSO/castor oil at 62 mg/ml as suspension for oral administration. As to a clear solution for injection, following three vehicles at 10mg/ml will help: 1. 2% DMSO/castor oil; 2. 2%DMSO/sunflower oil; 3. 2%DMSO/30%PEG 300/ddH2O.