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MCC950 (CP-456773) (Synonyms: CP 456,773)

Catalog No.GC31644

MCC950(CP-456773)(CP-456773, CRID3)은 BMDM 및 HMDM에서 각각 7.5 및 8.1nM의 IC50을 갖는 강력하고 선택적인 NLRP3 억제제입니다.

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MCC950 (CP-456773) Chemical Structure

Cas No.: 210826-40-7

Size 가격 재고 수량
10mM (in 1mL DMSO)
US$56.00
재고 있음
5mg
US$50.00
재고 있음
10mg
US$63.00
재고 있음
50mg
US$260.00
재고 있음
100mg
US$483.00
재고 있음

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 9 publications

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

BMDM are seeded at 5×105/mL or 1×106/mL, HMDM at 5×105/mL and PBMC at 2×106/mL or 5×106/mL in 96 well plates. The following day the overnight medium is replaced and cells are stimulated with 10 ng/mL LPS from Escherichia coli serotype EH100 (ra) TLRgrad for 3 h. Medium is removed and replaced with serum free medium (SFM) containing DMSO (1:1,000), MCC950 (0.001-10 µM), glyburide (200 µM), Parthenolide (10 µM) or Bayer cysteinyl leukotriene receptor antagonist 1-(5-carboxy-2{3-[4-(3-cyclohexylpropoxy)phenyl]propoxy}benzoyl)piperidine-4-carboxylic acid (40 µM) for 30 min. Cells are then stimulated with inflammasome activators: 5 mM adenosine 5’-triphosphate disodium salt hydrate (ATP) (1 h), 1 µg/mL Poly(deoxyadenylic-thymidylic) acid sodium salt (Poly dA:dT) transfected with Lipofectamine 200 (3-4 h), 200 µg/mL MSU (overnight) and 10 µM nigericin (1 h) or S. typhimurium UK-1 strain. Cells are also stimulated with 25 µg/mL Polyadenylic-polyuridylic acid (4 h). For non-canonical inflammasome activation cells are primed with 100 ng/mL Pam3CSK4 for 4 h, medium is removed and replaced with SFM containing DMSO or MCC950 and 2 µg/mL LPS is transfected using 0.25% FuGENE for 16 h. Supernatants are removed and analysed using ELISA kits. LDH release is measured using the CytoTox96 non-radioactive cytotoxicity assay[1].

Animal experiment:

Mice[1] C57BL/6 mice are immunized subcutaneously with 150 µg of MOG peptide 35-55 emulsified in CFA containing 4 mg/mL (0.4.mg/mouse) of heat-killed MTB. Mice are injected i.p. with 500 ng pertussis toxin (PT: kaketsuken) on days 0 and 2. MCC950 is administered i.p. to mice (10 mg/kg) at induction of the disease, day 0, 1 and 2 and every 2 days thereafter. Control mice are administered vehicle (PBS) at the same time points. Mice are observed for clinical signs of disease daily (unblinded). Disease severity is scored as follows: no clinical signs, 0; limp tail, 1; ataxic gait, 2; hind limb weakness, 3; hind limb paralysis, 4; and tetra paralysis, 5.

References:

[1]. Coll RC, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015 Mar;21(3):248-55.
[2]. Gan W, et al. The SGK1 inhibitor EMD638683, prevents Angiotensin II-induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation. Biochim Biophys Acta. 2017 Oct 3;1864(1):1-10.
[3]. Zhang XY, et al. Propofol Does Not Reduce Pyroptosis of Enterocytes and Intestinal Epithelial Injury After Lipopolysaccharide Challenge. Dig Dis Sci. 2018 Jan;63(1):81-91.
[4]. Qi Y, et al. NLRP3-dependent synaptic plasticity deficit in an Alzheimer's disease amyloidosis model in vivo. Neurobiol Dis. 2018 Feb 23;114:24-30.

Background

MCC950는 BMDMs와 HMDMs에서 각각 7.5nM과 8.1nM의 IC50를 가진 강력하고 선택적인 NLRP3 억제제입니다.

MCC950는 나노몰 농도에서 일반 및 비일반적인 NLRP3 활성화를 차단합니다. MCC950는 특히 NLRP3를 억제하지만 AIM2, NLRC4 또는 NLRP1 활성화에는 영향을 주지 않습니다. MCC950의 NLRP3 인플라마솜 활성에 대한 영향은 마우스 골수 유래 매크로파지와 인간 유래 모노사이트 매크로파지에서 검사됩니다. BMDM에서의 IC50 값은 약 7.5 nM이며, HMDM에서도 유사한 억제 능력 (IC50 = 8.1 nM)을 가집니다. MCC950는 IL-1β 분비를 용량 의존적으로 억제하지만 TNF-α 분비에는 영향을 주지 않습니다.MCC950는 카스패이즈-11 지향적인 NLRP3 활성화 및 비일반적 경로 자극 시 IL-1β 분비를 특이적으로 차단합니다. 살모넬라 파형균에 의해 활성화되어진 NLRC4 자극된 IL-1β 및 TNF-α 분비(MCC950가 10 μm의 농도에서도 억제되지 않음)는 MCC950에 의해 억제되지 않습니다. MCC950는 S. typhimurium에 대한 반응에서 카스패이즈-1 활성화 또는 IL-1β 처리를 억제하지 않습니다. 세포 리세이트 내의 pro-caspase-1 및 pro-IL-1β 발현은 MCC950 처리로 크게 영향을 받지 않습니다[1].

MCC950는 다발성 경화증의 질병 모델인 실험적 자가면역 뇌척수염(EAE)의 심도를 완화시키며, 인터루킨-1p (IL-1β) 생산을 감소시킵니다. MCC950의 예방 치료는 IL-1β 및 IL-6 혈중 농도를 감소시키지만 TNF-α 양은 크게 줄이지 않습니다. MCC950으로 마우스를 치료하면 EAE 발생을 지연시키고 심도를 감소시킵니다. 제 22일에 희생된 마우스의 뇌 단핵 세포에서 세포 내 사이트카인 염색과 FACS 분석 결과, MCC950 처리된 마우스에서 CD3+ T 세포에서 IL-17 및 IFN-γ 생성세포 수가 약간 감소한 것으로 나타났으며 PBS 처리된 마우스와 비교하여 CD4+ 및 γδ+ 하위 군집에서 IFN-γ와 특별하게 IL-17 생성세포 수가 줄어든 것으로 나타났습니다[1].

[1]. Coll RC, et al. 염증성 질환 치료를 위한 NLRP3 인플라마좀의 소분자 억제제. Nat Med. 2015 Mar;21(3):248-55. [2]. Gan W, et al. SGK1 억제제 EMD638683은 NLRP3 인플라마좀 활성화 차단을 통해 Angiotensin II 유도 심근 염증 및 섬유화를 예방한다. Biochim Biophys Acta. 2017 Oct 3;1864(1):1-10. [3]. Zhang XY, et al. 프로포폴은 리판당 내독소 도전 후 Enterocytes의 파이로프토시스와 장 상피세포 손상을 감소시키지 않는다.Dig Dis Sci . 2018 Jan;63(1):81-91.[4]. Qi Y, et al.NLRP3 종속적인 알츠하이머병 아밀로이드증 모델에서 생체 외 신경 연결 가소성 결함.Neurobiol Dis . 2018 Feb23 ;114:24-30.

Chemical Properties

Cas No. 210826-40-7 SDF
Synonyms CP 456,773
Canonical SMILES O=S(C1=CC(C(C)(O)C)=CO1)(NC(NC2=C3CCCC3=CC4=C2CCC4)=O)=O
Formula C20H24N2O5S M.Wt 404.48
Solubility DMSO : ≥ 28 mg/mL (69.22 mM) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.4723 mL 12.3616 mL 24.7231 mL
5 mM 0.4945 mL 2.4723 mL 4.9446 mL
10 mM 0.2472 mL 1.2362 mL 2.4723 mL
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    MCC950 (CP-456773) - GlpBio

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