Home PI3K/Akt/mTOR FKBP inhibitor FK506 (Tacrolimus)

연구용

FK506 (Tacrolimus) Calcineurin inhibitor

제품 번호S5003

Tacrolimus (FK506) is a 23-membered macrolide lactone, it reduces peptidyl-prolyl isomerase activity in T cells by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. Tacrolimus also inhibits the phosphatase activity of calcineurin. Tacrolimus induces vascular endothelial autophagy.
FK506 (Tacrolimus) FKBP inhibitor Chemical Structure

화학 구조

분자량: 804.02

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품질 관리 (Quality Control)

배치: 순도: 99.97%
99.97

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
human U251 cells Function assay Inhibition of SAP130 in VEGF-stimulated human U251 cells by PLAP reporter gene assay, IC50=13.8 nM 17643112
human WiDr cells Growth inhibition assay Inhibition of SAP130 mediated cell growth in human WiDr cells, IC50=10.9 nM 17643112
human T-cell Proliferation assay In vitro inhibitory activity against human T-cell proliferation, IC50=0.5 nM 7537331
rat RBL2H3 cells Function assay 15 mins Antiinflammatory activity in rat RBL2H3 cells assessed as inhibition of DNP-BSA-induced TNF-alpha production preincubated for 15 mins prior DNP-BSA challenge measured after 30 mins by ELISA, IC50=0.25 nM 22410084
rat RBL2H3 cells Function assay 16 h Inhibition of TNF-alpha production in rat RBL2H3 cells after 16 hrs by ELISA, IC50=0.25 nM 23791076
PBMCs Function assay Inhibitory activity against IFN-gamma production (Anti-CD3 monoclonal antibody stimulated and cultured CD4 positive cells purified from human peripheral blood mononuclear cell), IC50 = 0.00006 μM. 15369399
PBMCs Function assay Inhibitory activity against IL-5 production (Anti-CD3 monoclonal antibody stimulated and cultured CD4 positive cells purified from human peripheral blood mononuclear cell), IC50 = 0.00006 μM. 15369399
T-cells Function assay The compound was tested for its inhibitory activity against T-cell proliferation using murine splenic T-cells, IC50 = 0.0002 μM. 10450987
RBL-2H3 Function assay Inhibition of DNP7-BSA antigen-induced TNFalpha release in rat RBL-2H3 cells, IC50 = 0.00025 μM. 16901696
Jurkat T Immunosuppressive assay 15 to 30 mins Immunosuppressive activity in PMA/ionomycin stimulated human Jurkat T cells assessed as suppression of IL2 production pretreated for 15 to 30 mins followed by PMA/ionomycin addition measured after 18 to 20 hrs by ELISA, IC50 = 0.36 μM. 28412204
HEK293 Function assay TP_TRANSPORTER: inhibition of Phalloidin uptake (Phalloidin: 1 uM) in OATP-C-expressing HEK293 cells, IC50 = 3.7 μM. 14530907
Jurkat T Antiinflammatory assay 20 mins Anti-inflammatory activity in PMA/ionomycin stimulated human Jurkat T cells assessed as reduction in IL-2 secretion preincubated for 20 mins followed by PMA/ionomycin stimulation measured after 12 hrs by ELISA, IC50 = 5.8 μM. 28509552
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 804.02 화학식

C44H69NO12

 보관 (수령일로부터)
CAS 번호 104987-11-3 SDF 다운로드 원액 보관

동의어 FR900506, Fujimycin Smiles CC1CC(C2C(CC(C(O2)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C(CC(=O)C(C=C(C1)C)CC=C)O)C)C(=CC4CCC(C(C4)OC)O)C)O)C)OC)OC

용해도 (Solubility)

In vitro
배치:

DMSO : 120 mg/mL (149.25 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
FKBP12
(T cells)
calcineurin
시험관 내(In vitro)

Tacrolimus (FK506) and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit in T lymphocytes. This compound prevents T-cell proliferation by inhibiting a Ca(2+)-dependent event required for induction of interleukin-2 transcription. It binds to distinct families of intracellular proteins (immunophilins) termed cyclophilins and FK 506-binding proteins (FKBPs). Tacrolimus specifically inhibits cellular calcineurin at drug concentrations that inhibit interleukin 2 production in activated T cells. It and CsA exert nearly identical biological effects in cells by inhibiting the same subset of early calcium-associated events involved in lymphokine expression, apoptosis, and degranulation. This compound binds to a family of intracellular receptors termed the FK-506 binding proteins (FKBPs).

생체 내(In vivo)

Tacrolimus (FK506) results in an increase in the paw and tail withdrawal threshold as revealed by behavioral pain assessment in rats against hyperalgesic and allodynic stimuli. It also leads to a decrease in the serum nitrate and thiobarbituric acid reactive substance (TBARS) levels along with reduction in tissue myeloperoxidase (MPO) and total calcium levels, whereas, rise in tissue reduced glutathione levels in rats. This compound ameliorates the increase in the neuronal edema and axonal degeneration in rats with ischemia reperfusion (I/R).

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/7509138/
  • [5] https://pubmed.ncbi.nlm.nih.gov/20529260/
  • [6] https://pubmed.ncbi.nlm.nih.gov/18574318/
  • [7] https://pubmed.ncbi.nlm.nih.gov/29863266/
  • [8] https://pubmed.ncbi.nlm.nih.gov/22130237/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot GluA1 / pGluA1(S845) / GluA2 / GluA3 / Calcineurin p-JNK / JNK / p-ERK / ERK / Cytochrome c / cleaved caspase-3 p-S6K(S371) / S6K / p-Erα(S167) / Erα
S5003-WB1
26455952
Immunofluorescence FKBP52 / p23 / hsp90 FKBP51 Tom20 / JC-1 / ROS / NF-κB
S5003-IF1
20796173
Growth inhibition assay Cell viability
S5003-viability1
23470533

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT05702931 Not yet recruiting
Hyperglycemia|Renal Transplant Complication Primary Non-Function|Diabetes
Rigshospitalet Denmark|Aarhus University Hospital|Odense University Hospital
 April 1 2024 Phase 4
NCT06268769 Recruiting
Immunosuppression
Edward Geissler|Chiesi Pharmaceuticals GmbH|University of Regensburg
 March 9 2024 Phase 4
NCT06326775 Active not recruiting
Heart Transplant Patients
Nanjing First Hospital Nanjing Medical University|Wuhan Union Hospital China|Changhai Hospital|Shanghai Zhongshan Hospital
 March 12 2024 --
NCT06235892 Not yet recruiting
Organ Grafts
Nantes University Hospital
 February 10 2024 Phase 3

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
We would like to inject it subcutaneously into rats. Can we mix it with 5% dextrose to a concentration of 5mg/ml to prepare the solution?

답변:
You can dissolve it with DMSO to prepare the stock solution, and then dilute by 5% dextrose. However, we don't have the information about the solubility in this condition. Or you can use the vehicle we tested: 30% PEG400/0.5% Tween80/5% propylene glycol (Solubility: 30mg/ml).