Home PI3K/Akt/mTOR mTOR inhibitor Rapamycin (Sirolimus)

연구용

Rapamycin (Sirolimus) mTOR inhibitor

제품 번호S1039

Rapamycin is a specific mTOR inhibitor with IC50 of ~0.1 nM in HEK293 cells. This compound binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. It is an autophagy activator and an immunosuppressant.
Rapamycin (Sirolimus) mTOR inhibitor Chemical Structure

화학 구조

분자량: 914.18

바로가기

품질 관리 (Quality Control)

배치: 순도: 99.63%
99.63

함께 자주 사용되는 제품 Rapamycin (Sirolimus)

Imidazole Ketone Erastin (IKE)

It and Imidazole ketone erastin induce cell death in ALL cell lines, resulting in a longer survival time for xenograft mice with ALL.

MG132

This compound and MG132 combination synergize the apoptotic and autophagic effects of curcumol in nasopharyngeal carcinoma.

Y-27632 Dihydrochloride

Explore the effect of both on epigenetic ageing.

Z-VAD-FMK

Combined use of this compound reduces photoreceptor necrosis and preserve the ONL thickness after retinal detachment.

SB431542

Explore role of TGFβ receptor in its-induced upregulation of CTGF Expression.

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
COS7 cells expressing EGFP-LC3 Autophagy Assay 0.2 μM 24 h DMSO Induces autophagy 18391949
H4 Function Assay 0.2 μM 24 h DMSO Increases the ratio of light chain 3 subunit 2 to light chain 3 subunit 1 in human H4 cells 18024584
COS7 cells expressing EGFP-HDQ74/rheb Autophagy Assay 0.2 μM 24 h DMSO Induces autophagy 18391949
PBMC Function Assay 1 nM 14 d DMSO Reduces CCR5 density 17485501
HEK293T Antiviral Assay 1 nM 4 d DMSO Induces antiviral activity against HIV1 X4 with EC50 of 0.3 nM 17485501
U87MG Kinase Assay 1 μM 6 h DMSO Potently inhibits mTOR-mediated S6 phosphorylation 19848404
cells from the thymus of normal BALB/c mice Growth Inhibition Assay 10 nM 72 h DMSO Inhibits lymphoproliferation (LAF) with IC50 of 3 nM 10021948
PC3 Growth Inhibition Assay 1.5 μM 1 h DMSO Induces antiproliferative activity against human PC3 cells with IC50 of <10 nM 21978683
HT-29 Cytotoxic Assay 10 nM 72 h DMSO Potentiates digitoxin-induced cytotoxicity 24900873
Drosophila melanogaster S2 cells transfected with N-luc and C-luc Function Assay 100 nM 4 h DMSO Induces luciferase protein trans-splicing in Drosophila melanogaster S2 cells transfected with N-luc and C-luc 17128262
SYF Function Assay 100 nM 24 h DMSO Induces FRB-FKBP complex interaction 17563385
HEK293 Function Assay 100 nM 8 h DMSO Inhibits TPA-induced degradation of Pdcd4 with EC50 of 50 nM 21539301
HeLa Function Assay 100 nM 36 h DMSO Induces FRB K2095P, T2098L, W2101F mutant-ubiquitinC interaction 17563385
BT-20 Kinase Assay 20 μM DMSO Does not inhibit mTORC2 dependent pAkT S473 phosphorylation 21353551
PC3 Kinase Assay 100 nM 1 h DMSO Potently inhibits mTOR-mediated S6 phosphorylation with IC50 of <10 nM. 21978683
Human mixed lymphocyte Growth Inhibition Assay 5 nM DMSO IC50=1.6 nM. 16185865
MCF-7 Autophagy Assay 30 nM 4 h DMSO Induces autophagy 20028134
Lewis rat lymph node cells Growth Inhibition Assay 5 μM DMSO IC50=2.6 μM 16185865
HEK293 cells Kinase Assay 50 nM 45 min DMSO Inhibits mTOR kinase activity with IC50 of 0.1 nM 17350953
U937 Antibacterial Assay 50 μM 48 h DMSO Induces antibacterial activity against wild type Legionella pneumophila Philadelphia-1 JR32 in U937 cells 21142106
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 914.18 화학식

C51H79NO13

 보관 (수령일로부터)
CAS 번호 53123-88-9 SDF 다운로드 원액 보관

동의어 Sirolimus, AY-22989, NSC-2260804 Smiles CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)O)C)C)O)OC)C)C)C)OC

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (109.38 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 25 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
mTOR
(HEK293 cells)
~0.1 nM
시험관 내(In vitro)

Rapamycin inhibits endogenous mTOR activity in HEK293 cells with IC50 of ~0.1 nM, more potently than iRap and AP21967 with IC50 of ~5 nM and ~10 nM, respectively. In Saccharomyces cerevisiae, this compound treatment induces a severe G1/S cell cycle arrest and inhibition of translation initiation to levels below 20% of control. It significantly inhibits the cell viability of T98G and U87-MG in a dose-dependent manner with IC50 of 2 nM and 1 μM, respectively, while displaying little activity against U373-MG cells with IC50 of >25 μM despite the similar extent of the inhibition of mTOR signaling. This chemical (100 nM) induces G1 arrest and autophagy but not apoptosis in Rapamycin-sensitive U87-MG and T98G cells by inhibiting the function of mTOR.

키나아제 분석
Immunoblotting for the mTOR kinase assay
HEK293 cells are plated at 2-2.5×105 cells/well of a 12-well plate and serum-starved for 24 hours in DMEM. Cells are treated with increasing concentrations of Rapamycin (0.05-50 nM) for 15 minutes at 37 °C. Serum is added to a final concentration of 20% for 30 minutes at 37 °C. Cells are lysed, and cell lysates are separated by SDS-PAGE. Resolved proteins are transferred to a polyvinylidene difluoride membrane and immunoblotted with a phosphospecific primary antibody against Thr-389 of p70 S6 kinase. Data are analyzed using ImageQuant and KaleidaGr
생체 내(In vivo)

Treatment with Rapamycin in vivo specifically blocks targets known to be downstream of mTOR such as the phosphorylation and activation of p70S6K and the release of inhibition of eIF4E by PHAS-1/4E-BP1, leading to complete blockage of the hypertrophic increases in plantaris muscle weight and fibre size. Short-term treatment with this compound, even at the lowest dose of 0.16 mg/kg, produces profound inhibition of p70S6K activity, which correlates with increased tumor cell death and necrosis of the Eker renal tumors. This chemical inhibits metastatic tumor growth and angiogenesis in CT-26 xenograft models by reducing the production of VEGF and blockage of VEGF-induced endothelial cell signaling. Treatment with this compound at 4 mg/kg/day significantly reduces tumor growth of C6 xenografts, and tumor vascular permeability.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/11715023/
  • [5] https://pubmed.ncbi.nlm.nih.gov/12384518/
  • [6] https://pubmed.ncbi.nlm.nih.gov/11821896/
  • [7] https://pubmed.ncbi.nlm.nih.gov/16904613/
  • [8] https://pubmed.ncbi.nlm.nih.gov/14976243/
  • [9] https://pubmed.ncbi.nlm.nih.gov/20739560/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-mTOR(S2448)/mTOR
S1039-WB1
23991038
Growth inhibition assay Cell proliferation
S1039-Growth1
30393233
Histomorphology Haematoxylin & Eosin
S1039-histology1
28418837
Immunofluorescence NeuN p62/Beclin
S1039-IF1
28418837
ELISA Type III collagen/Fibronectin
S1039-ELISA1
23364979

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06308445 Not yet recruiting
Familial Adenomatous Polyposis
University Hospital Toulouse
 August 1 2024 Phase 2
NCT06310291 Not yet recruiting
Celiac Disease
Barinthus Biotherapeutics
 April 2024 Early Phase 1
NCT06091332 Not yet recruiting
Cavernous Malformations|Brain Stem Hemorrhage
Huashan Hospital
 December 1 2023 Phase 2
NCT05997056 Recruiting
Neuroendocrine Tumors|NET|Pancreatic Neuroendocrine Tumor|Gastrointestinal Neuroendocrine Tumor|Pulmonary Neuroendocrine Tumor
Aadi Bioscience Inc.
 November 7 2023 Phase 2
NCT06022068 Enrolling by invitation
Alzheimer Disease
Karolinska Institutet|Karolinska University Hospital
 September 1 2023 Phase 1|Phase 2
NCT04989686 Recruiting
Immunosuppression
Children''s Hospital of Philadelphia|Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
 June 8 2023 --