GLPBio

CMPD101

Catalog No.: GC43286Purity:>98.00%
COASDSData Sheet
CMPD101 هو مثبط جزيء صغير قوي وانتقائي للغاية ونفاذ الغشاء لـ GRK2 / 3 مع IC50 من 18 نانومتر و 5.4 نانومتر ، على التوالي

المنتجات مخصصة للاستخدام البحثي فقط، وليست للاستخدام البشري. نحن لا نبيع للمرضى.

CMPD101
Cas No.: 865608-11-3
10mM (in 1mL DMSO)In Stock
$126.00
1
1mgIn Stock
$47.00
1
5mgIn Stock
$123.00
1
10mgIn Stock
$197.00
1
25mgIn Stock
$355.00
1
Tel: (909) 407-4943 / (909) 689-7124Email: sales@glpbio.com

المراجع (Citations)

لا تتوفر حاليًا مراجع لهذا المنتج. فيما يلي مجموعة مختارة من المنشورات التي تستشهد بمنتجات GlpBio.
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    632, 686–694 (2024)
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    618, 1017–1023 (2023)
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    610, 366–372 (2022)
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    Cell
    187(9):2288-2304 (2024)
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    183(7):1867-1883 (2020)
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الوصف (Description)

CMPD101 is a potent, highly selective and membrane-permeable small-molecule inhibitor of G protein-coupled receptor kinase 2 (GRK2) and GRK3 (IC50s=18 and 5.4nM, respectively)[1]. GRKs phosphorylate GPCRs, regulate their desensitization, internalization, and signaling, are crucial for cellular and physiological regulation[2]. CMPD101 can be used for the research of GPCR desensitization and internalization, opioid tolerance, heart failure, signal transduction mechanisms, and drug development[3][4].

In vitro, treatment of HEK293 cells with CMPD101 (30µM; 30min) completely blocked histamine H1 receptor–mediated ERK1/2 phosphorylation (IC50=6µM)[5]. CMPD101 (3-30µM; 30min) inhibits the desensitization of µ-opioid receptors (MOPr) induced by agonists such as Met-Enk and DAMGO in locus coeruleus (LC) neurons of rats and mice, with an IC50 of approximately 6µM. In HEK293 cells, CMPD101 (30µM; 30min) almost completely inhibits [D-Ala2, N-MePhe4, Gly-ol5]-enkephalin(DAMGO)-induced m-opioid receptor (MOPr) phosphorylation at Ser375, arrestin translocation, and MOPr internalization[6].

In vivo, pretreatment with CMPD101(0.3mg/kg, i.p.) 15min before the drinking session enhanced the effect of nalfurafine on reducing alcohol intake in mice by inhibiting GRK2/3 activity[7].

References:
[1] Okawa T, Aramaki Y, Yamamoto M, et al. Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure. J Med Chem. 2017;60(16):6942-6990.
[2] Mayor F Jr, Murga C. G Protein-Coupled Receptor Kinases Take Central Stage. Cells. 2022;12(1):23.
[3] Mann A, Keen AC, Mark H, et al. New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling. Sci Rep. 2021;11(1):8288.
[4] Thal DM, Yeow RY, Schoenau C, Huber J, Tesmer JJ. Molecular mechanism of selectivity among G protein-coupled receptor kinase 2 inhibitors. Mol Pharmacol. 2011;80(2):294-303.
[5] Michinaga S, Nagata A, Ogami R, Ogawa Y, Hishinuma S. Differential regulation of histamine H1 receptor-mediated ERK phosphorylation by Gq proteins and arrestins. Biochem Pharmacol. 2023;213:115595.
[6] Lowe JD, Sanderson HS, Cooke AE, et al. Role of G Protein-Coupled Receptor Kinases 2 and 3 in μ-Opioid Receptor Desensitization and Internalization. Mol Pharmacol. 2015;88(2):347-356.
[7] Zhou Y, Liang Y. Involvement of GRK2 in modulating nalfurafine-induced reduction of excessive alcohol drinking in mice. Neurosci Lett. 2021;760:136092.

البروتوكول (Protocol)

Cell experiment [1]:

Cell lines

Human embryonic kidney 293 cells

Preparation Method

Human embryonic kidney 293 cells (HEK 293) cells stably overexpressing hemagglutinin (HA)-tagged rat MOPr (HAMOPr) were cultured at 37°C in 5% CO2 in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum, 10U/ml penicillin, 10mg/ml streptomycin, and 250mg/ml G418. Cells were seeded onto 60mm dishes and grown to 90% confluence, then subjected to serum starvation for 24 hours. HEK 293 cells were prelabeled with primary antibody for 1 hour at 4°C before incubation with CMPD101 (3 or 30µM) for 30 minutes at 37°C. Cells were then stimulated with [D-Ala2, N-MePhe4, Gly-ol5]-enkephalin(DAMGO) (10mM) at 37°C to induce internalization. DAMGO-induced internalization of HAMOPr was assessed by enzyme-linked immunosorbent assay (ELISA) and by confocal microscopy imaging.

Reaction Conditions

3 or 30µM; 30min

Applications

CMPD101 almost completely inhibits DAMGO-induced m-opioid receptor (MOPr) internalization.
Animal experiment [2]:

Animal models

C57BL/6J (B6) mice

Preparation Method

Male adult C57BL/6J mice (8 weeks of age) were placed on a 12-hour reverse lightdark cycle (lights off at 7:00 am) and housed individually in ventilated cages with steel lids and filter tops and given ad libitum access to food and water. In this two-bottle free choice paradigm, mice had access to alcohol for 24 hours every other day for 3 weeks. Both the 15% alcohol solution and water tubes were provided starting at 3 hours after lights off. After 4, 8 and 24 hours of alcohol access, both the water and alcohol intakes were recorded. Following the 3-week chronic intermittent access (CIA) procedure, the mice had high alcohol intake and preference. The CIA mice were pretreated with CMPD101 (0 or 0.3mg/kg, i.p.) 15 min before the drinking session, followed by nalfurafine (0, 1, 3 or 10μg/kg; i.p.) 5min before a drinking session (n=7–8), and then alcohol and water intake values were recorded.

Dosage form

0 or 0.3 mg/kg, i.p.; 15min

Applications

Pretreatment with CMPD101 enhanced the effect of nalfurafine on reducing alcohol intake in mice.

References:
[1] Lowe JD, Sanderson HS, Cooke AE, et al. Role of G Protein-Coupled Receptor Kinases 2 and 3 in ?-Opioid Receptor Desensitization and Internalization. Mol Pharmacol. 2015;88(2):347-356.
[2] Zhou Y, Liang Y. Involvement of GRK2 in modulating nalfurafine-induced reduction of excessive alcohol drinking in mice. Neurosci Lett. 2021;760:136092.

وثائق المنتج (Product Documents)

Purity:>98.00%Appearance:A solid
COASDSData Sheet

الخصائص الكيميائية (Chemical Properties)

رقم CAS
865608-11-3
SMILES
O=C(C1=CC=CC(NCC2=NN=C(C3=CC=NC=C3)N2C)=C1)NCC4=CC=CC=C4C(F)(F)F
الصيغة الجزيئية
C24H21F3N6O
الوزن الجزيئي
466.5
الذوبانية
10mg/mL in ethanol, 20mg/mL in DMSO, or in DMF
التخزين
Store at -20°C
إرشادات عامة
اختر مذيبًا مناسبًا وفقًا لبيانات ذوبانية المنتج. بعد التحضير، قسّم المحلول المخزون إلى أجزاء لتجنب دورات التجميد والذوبان المتكررة.
استخدم المحاليل المخزونة خلال 6 أشهر عند حفظها في -80°C، أو خلال شهر واحد عند حفظها في -20°C.
لتحسين الذوبانية، سخّن الأنبوب إلى 37°C وعرّضه للموجات فوق الصوتية لمدة مناسبة.
شروط الشحن
تُشحن عينات التقييم مع عبوات تبريد. وتُشحن الأحجام الأخرى المتاحة في درجة حرارة الغرفة، أو مع عبوات تبريد عند الطلب.

الحاسبات (Calculators)المولارية / التخفيف / الوزن الجزيئي / تحويل الوحدات / تركيبة داخل الجسم الحي / الذوبانية

g/mol

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