Home PI3K/Akt/mTOR mTOR inhibitor Torkinib (PP242)

연구용

Torkinib (PP242) mTOR inhibitor

제품 번호: S2218

Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; this compound targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. It induces mitophagy and apoptosis.
Torkinib (PP242) mTOR inhibitor Chemical Structure

화학 구조

분자량: 308.34

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품질 관리 (Quality Control)

배치: 순도: 99.50%
99.50

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
HT-p21 Function Assay 50-1250 nM 24 h DMSO inhibits phosphorylation of S6 kinase (target of mTORC1) and its downstream target phospho-S6 
U87vIII  Function Assay 0.04-2.5 μM 24 h inhibits mTORC1 and mTORC2 activities 
U87vIII  Function Assay 2.5/5 μM 12 h inhibits gap closing in a dose-dependent manner
PC12  Function Assay 40 nM induces lysosomal biogenesis and alleviated α-SYN accumulation 
3T3-L1 Function Assay 15 μM 4 h suppresses expression of the Egr1 protein 
Rh30 Function Assay 1 μM 2 h inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt
HT29 Function Assay 1 μM 2 h inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt
Rh30 Function Assay 1 μM 2 h suppresses the basal or IGF-1-stimulated cell adhesion
HT29 Function Assay 1 μM 2 h suppresses the basal or IGF-1-stimulated cell adhesion
U87 Growth Inhibition Assay 25 nM 24 h increases DUSP10 knocked-down induced cell inhibition
AGS Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
MKN45 Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
MKN28 Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
KATO3 Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
SGC7901 Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
N87 Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
HMEC Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
HUVEC Cell Viability Assay 0-1000 nM 24/48 h DMSO decreases cell viability in time and dose dependent manner
MG63 Function Assay 50-1000 nM 0.5 h dose dependently (50–1000 nM) inhibits phosphorylation of Akt
U2OS  Function Assay 50-1000 nM 0.5 h dose dependently (50–1000 nM) inhibits phosphorylation of Akt
Saos-2  Function Assay 50-1000 nM 0.5 h dose dependently (50–1000 nM) inhibits phosphorylation of Akt
Saos-2 Function Assay 100 nM 0.5 h prevents osteosarcoma cell migration
MG63 Apoptosis Assay 100 nM 36 h promotes apoptosis
U2OS  Apoptosis Assay 100 nM 36 h promotes apoptosis
Saos-2  Apoptosis Assay 100 nM 36 h promotes apoptosis
HT1376 Growth Inhibition Assay IC50=1.88 ± 1.1 μM
T24 Growth Inhibition Assay IC50=1.37 ± 0.4 μM
UM-UC-3 Growth Inhibition Assay IC50=0.63 ±0.1 μM
DLD-1 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Caco2 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
HT29 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
H116 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Hct-8 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Colo320 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Sw948 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Colo205 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Colo320 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
HT29 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
Sw948 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
DLD-1 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
SW620 Growth Inhibition Assay IC50=7.8 μM
SW480 Growth Inhibition Assay IC50=4.6 μM
SK-CO-1 Growth Inhibition Assay IC50=4 μM
LS-513 Growth Inhibition Assay IC50=3.9 μM
SW1116 Growth Inhibition Assay IC50=0.84 μM
LS-174T Growth Inhibition Assay IC50=0.84 μM
HCT 116 Growth Inhibition Assay IC50=0.41 μM
HCT 15 Growth Inhibition Assay IC50=0.3 μM
COLO 205 Growth Inhibition Assay IC50=0.24 μM
HT-29 Growth Inhibition Assay IC50=0.23 μM
COLO 201 Growth Inhibition Assay IC50=0.23 μM
Caco-2 Growth Inhibition Assay IC50=0.22 μM
SW48 Growth Inhibition Assay IC50=0.09 μM
DND-1 Growth Inhibition Assay 0.25/0.5/1 μM DMSO inhibits cell growth dose dependently
TMD8 Growth Inhibition Assay 0.25/0.5/1 μM DMSO inhibits cell growth dose dependently
Jurkat Growth Inhibition Assay 0.25/0.5/1 μM DMSO inhibits cell growth dose dependently
KOPT-K1 Growth Inhibition Assay 0.25/0.5/1 μM DMSO inhibits cell growth dose dependently
TMD7 Growth Inhibition Assay 0.25/0.5/1 μM DMSO inhibits cell growth dose dependently
THP-1 Growth Inhibition Assay 0.25/0.5/1 μM DMSO inhibits cell growth dose dependently
786-O Function Assay 0.1/0.5 μM 24 h DMSO increases E-cadherin mRNA levels dose dependently
786-O Function Assay 0-0.5 μM 24 h DMSO results in a dose dependent increase in E-cadherin protein expression 
OCI-AML3 Apoptosis Assay 2.5 μM 72 h induces apoptosis
Jurkat Function Assay 100/200/400 nM 18 h inhibits mTORC1-dependent S6 S235/236 phosphorylation
p210 BCR-Abl Function Assay 100/200/400 nM 18 h inhibits mTORC1-dependent S6 S235/236 phosphorylation
Jurkat Growth Inhibition Assay 400nM 24/48 h synergize with 17-AAG to suppress cell proliferation
p210 BCR-Abl Growth Inhibition Assay 400nM 24/48 h synergize with 17-AAG to suppress cell proliferation
8226 Function Assay 100-1000 nM 30 min DMSO activates ERK 
MM1.S  Function Assay 100-1000 nM 30 min DMSO activates ERK 
8226 Function Assay 0.5 μM 30 min DMSO induces activation of RAF and phosphorylation of MEK
MM1.S  Function Assay 0.5 μM 30 min DMSO induces activation of RAF and phosphorylation of MEK
MCF-7 Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
T47D Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
MDA-MB-231 Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
Bcap-37 Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
MCF-7 Apoptosis Assay 200 nM 36 h DMSO induces apoptosis
MDA-MB-231 Apoptosis Assay 200 nM 36 h DMSO induces apoptosis
Bcap-37 Apoptosis Assay 200 nM 36 h DMSO induces apoptosis
LS174T Function Assay 10/100/1000 nM 6 h DMSO inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
DLD-1  Function Assay 10/100/1000 nM 6 h DMSO inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
SW480 Function Assay 10/100/1000 nM 6 h DMSO inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
SW-48 Growth Inhibition Assay IC50=0.1 μM
HCT-15 Growth Inhibition Assay IC50=0.3 μM
HCT 116 Growth Inhibition Assay IC50=0.6 μM
SW620-R Growth Inhibition Assay IC50=1.3 μM
SK-CO-1 Growth Inhibition Assay IC50=2.1 μM
SW620 Growth Inhibition Assay IC50=11 μM
BaF3 Growth Inhibition Assay GI50=1.449 μM
NIH 3T3 Function Assay 2 μM 18 h inhibits mTORC2 phosphorylation of Akt on Ser473 and mTORC1 phosphorylation of 4E-BP1 on Thr37/46
HCT15 Function Assay 0.5/2 μM 4 h prevents S6K1 phosphorylation of ribosomal protein S6 at Ser240/244 and mTORC2 phosphorylation of Akt at Ser473
SW620  Function Assay 0.5/2 μM 4 h blocks all three mTOR outputs
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 308.34 화학식

C16H16N6O

 보관 (수령일로부터)
CAS 번호 1092351-67-1 SDF 다운로드 원액 보관

동의어 N/A Smiles CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(N3)C=CC(=C4)O)N

용해도 (Solubility)

In vitro
배치:

DMSO : 61 mg/mL (197.83 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : 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)

특징
One of the first selective inhibitors that targets ATP domain of mTOR.
Targets/IC50/Ki
mTOR
(Cell-free assay)
8 nM
p110δ
(Cell-free assay)
0.10 μM
DNA-PK
(Cell-free assay)
0.41 μM
PDGFR
(Cell-free assay)
0.41 μM
시험관 내(In vitro)
PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. This compound displays some inhibitory activity against Ret, PKCα, PKCβ, and JAK2, while exhibits remarkable selectivity against 215 other protein kinases. Unlike rapamycin, this inhibitor inhibits both mTORC1 and mTORC2. In BT549 cells, this chemical treatment (0.04-10 μM) inhibits the phosphorylation of Akt, the mTOR substrate p70S6K, and its downstream target S6 in a dose-dependent manner. It potently inhibits PKCα with IC50 of 49 nM. Low concentrations of this compound inhibit the phosphorylation of Akt S473 and higher concentrations partially inhibit Akt T308-P in addition to S473-P. As this agent is a more effective mTORC1 inhibitor than rapamycin, it inhibits the proliferation of primary MEFs, and the phosphorylation of 4EBP1 at T36/45 and S65, more potently than rapamycin. This compound but not rapamycin potently inhibits cap-dependent translation, by causing a higher level of binding between 4EBP1 and eIF4E than rapamycin. It potently inhibits the proliferation of p190-transformed murine BM, SUP-B15, and K562 cells with GI50 of 12 nM, 90 nM, and 85 nM, respectively. This inhibitor also inhibits the growth of solid tumor cell lines such as SKOV3, PC3, 786-O, and U87 with GI50 of 0.49 μM, 0.19 μM, 2.13 μM, and 1.57 μM, respectively. It is also more effective than rapamycin in achieving cytoreduction and apoptosis in multiple myeloma (MM) cells.
키나아제 분석
In vitro mTOR (FRAP1) kinase assay
재조합 mTOR를 50-0.001 μM 농도 범위에서 2배 희석한 이 화합물과 함께 50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween, 10 μM ATP(2.5 μCi의 γ-32P-ATP) 및 3 μg/mL BSA를 포함하는 분석액에서 인큐베이션합니다. 쥐 재조합 PHAS-1/4EBP1(2 mg/mL)을 기질로 사용합니다. 반응은 니트로셀룰로오스에 점적하여 종결시키고, 1 M NaCl/1% 인산으로 세척합니다(약 6회, 각 5-10분). 시트를 건조하고 전달된 방사능을 phosphorimaging으로 정량화합니다. IC50 값은 Prism 소프트웨어 패키지를 사용하여 데이터를 시그모이드 용량-반응 곡선에 맞추어 계산합니다.
생체 내(In vivo)
Administration of PP242 is able to completely inhibit the phosphorylation of Akt at S473 and T308 in fat and liver of mice. This compound only partially inhibits the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473, despite able to fully inhibit the phosphorylation of 4EBP1 and S6. Oral administration of this chemical potently delays the leukemia onset in the mice model, and induces leukemia regression by inhibiting mTORC2 and mTORC1 activation that correlates with loss in cell size. This treatment potently inhibits the growth of 8226 cells in mice.
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/20686120/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-mTOR / mTOR / p-AKT / AKT / p-S6 / S6 / p-4E-BP1 / 4E-BP-1
S2218-WB1
23991179
Growth inhibition assay Cell viability
S2218-viability1
23991179

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Do you have any suggestions about potential candidates for vehicles that we could use for in vivo studies of it?

답변:
In the recommended solvent (30% PEG400 + 0.5% Tween80 + 5% Propylene glycol), it is a suspension, and this formulation is for oral gavage. For IV injection, this compound can be dissolved in 2% DMSO+30% PEG 300+5% Tween 80+ddH2O at 5mg/ml as a clear solution.