SKF-83566 hydrobromide
Based on 3 publication(s) in Google Scholar
SKF-83566 hydrobromide is an orally active, blood-brain barrier-permeable D1/D5 dopamine receptor antagonist with a Ki value of approximately 0.4-0.56 nM. SKF-83566 hydrobromide modulates locomotor behavior and spatial memory by blocking D1 receptors and inhibits glioblastoma progression by targeting the DRD1/c-Myc/UHRF1 pathway. SKF-83566 hydrobromide acts as an inhibitor of the dopamine transporter (DAT) and adenylyl cyclase 2 (AC2). SKF-83566 hydrobromide competitively binds to DAT to inhibit dopamine reuptake and non-competitively inhibits AC2 activity, thereby reducing cAMP accumulation. SKF-83566 hydrobromide is used in research areas such as dopaminergic system mechanisms, learning and memory, targeted intervention for glioblastoma, AC2 pathophysiology, antiparasitic drug screening, and synaptic plasticity (the "gating effect").
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- No. CAS: 108179-91-5
- Fòrmula: C17H19Br2NO
- Peso molecular:413.15
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Publications Citing Use of MedChemExpress (MCE) SKF-83566 hydrobromide
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
Dopamine D1 receptor |
Dopamine D5 receptor |
In Vitro
SKF-83566 (0-400 µM; 48-72 h) hydrobromide inhibits the viability of U251, LN18, LN229, A172, P3, BG5 and BG7 cells, with IC50 values ranging from 119.4 to 381.7 μM, which are significantly lower than the IC50 of 986 μM measured in normal human astrocytes[6].
SKF-83566 (100 µM; 72-96 h) hydrobromide significantly inhibits tumor invasion in human GSCs (P3, BG5, BG7) co-cultured with brain organoids, and exerts the same effect in the 3D tumor sphere invasion model[6].
SKF-83566 (50-100 μM) hydrobromide dose-dependently downregulates the mRNA and protein expression of c-Myc and UHRF1 in P3, BG5 and BG7 glioma stem cells, but exerts no such effect on normal human astrocytes[6].
SKF-83566 (10 pM-1 mM; 15 min) hydrobromide inhibits [3H]CFT binding in intact LLc-PK-rDAT cells and cell membrane preparations, with IC50 values of 0.51 μM and 0.77 μM, respectively[2].
SKF-83566 (10-30 μM; 30 min pre-incubation + 1 h co-stimulation) hydrobromide potently and completely inhibits the suppression of cAMP accumulation induced by PMA (HY-18739), PGE2 (HY-101952) and Forskolin (HY-15371) in HEK-hAC2 cells, with an IC50 value ranging from 10 to 21 μM[7].
SKF-83566 (75-200 µM; pre-incubated for 10 min) hydrobromide non-competitively inhibits AC2 activity in Sf9 insect cell membranes expressing AC2[7].
SKF-83566 (pre-incubated for 30 min, stimulated for 1 h) hydrobromide inhibits Forskolin-stimulated cAMP accumulation in mouse C2C12 skeletal muscle myotubes, with an IC50 of 15 μM[7].
SKF-83566 (30 µM; pre-incubated for 20 min, stimulated for 1 h) hydrobromide inhibits Forskolin-stimulated IL-6 mRNA expression in human bronchial smooth muscle cells (hBSMCs)[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human GSCs P3, BG5, BG7
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Concentration:50, 100 µM
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Incubation Time:14 days
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Result:Dose-dependently inhibited stem cell self-renewal, leading to a significant reduction or near absence of tumorsphere formation rates after drug treatment.
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Cell Line:Human GSCs P3, BG5, BG7
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Concentration:100 µM
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Incubation Time:96 h
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Result:Significantly reduced the area and distance of tumor cells invading outward into the Matrigel.
In Vivo
SKF-83566 (0.02-0.2 mg/kg; i.m.; once daily for 3 consecutive days) hydrobromide does not significantly alter the ability to learn the eccentric spatial maze in young and aged rhesus monkeys[4].
SKF-83566 (10-100 µg/kg; i.p.; single administration 15 min prior to memory testing or ghrelin injection) hydrobromide reverses ghrelin-induced memory enhancement in male rat models, but has no effect on its orexigenic action [5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Sprague-Dawley rats (2-3 months old), habituated singly, were injected with a non-selective agonist Apomorphine (0.5 mg/kg) or a D2-selective agonist RU24213 (15 mg/kg) to induce a syndrome of stereotyped behavior[1]
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Dosage:0.04 mg/kg, 0.2 mg/kg
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Administration:systemic administration; a single pre-treatment dose was given 30 min before agonist challenge
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Result:Dose-dependently antagonized apomorphine-induced stereotyped behavior syndrome, and dose-dependently antagonized stereotyped sniffing and locomotor responses induced by RU24213.
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Animal Model:4 young Rhesus monkeys (8.25 ± 1.26 years old) and 4 aged Rhesus monkeys (22.75 ± 7.63 years old) subjected to baseline navigation training in a large-scale maze (consisting of four individual small maze units)[4]
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Dosage:0.02 mg/kg, 0.2 mg/kg
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Administration:i.m.; once daily; 3 consecutive days
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Result:Did not significantly alter the total cup errors, cue errors, or spatial working memory errors during the target-searching task compared to baseline in both young and aged monkeys. The compound had no significant impact on the latency to complete the maze task in either animal group.
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Animal Model:Sprague-Dawley (male, 275-300 g at surgery)[5]
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Dosage:10 µg/kg, 100 µg/kg
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Administration:i.p.; single injection; 15 min pre-test (single-agent); 15 min pre-ghrelin administration (combination)
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Result:Ddid not alter the rats' performance in the object location memory task.
Pre-treatment with the SKF-83566 hydrochloride completely reversed the ghrelin-induced enhancement of object location memory performance.
Did not alter food intake and failed to block the orexigenic (appetite-stimulating) effect elicited by ghrelin.
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Animal Model:Foxn1nu mut/mut (4-week-old male, thymus-free, orthotopic xenograft via intracranial injection of 5×105 luciferase-expressing P3 or BG5 human glioma stem cells)[6]
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Dosage:20 mg/kg/day
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Administration:i.p.; once daily; starting on day 10 (for P3) or day 30 (for BG5) post-implantation until mice exhibited obvious neurological signs and weight loss and were euthanized
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Result:Significantly decreased tumor size and bioluminescence intensity as monitored by in vivo imaging, and significantly prolonged the overall survival of tumor-bearing mice. H&E staining and immunohistochemical analysis revealed that the compound markedly decreased tumor volume and local invasion, and significantly reduced the expression levels of the proliferation marker Ki-67, as well as c-Myc and UHRF1 proteins.
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Animal Model:C57BL6/J mice (male, 6-9 weeks old) were given nicotine (10 mg/mL) continuously in drinking water for 7 days, followed by an intraperitoneal injection of cocaine (30 mg/kg) 10 minutes before sacrifice, to induce the priming enhancement effect (Gateway effect) of LTP in the hippocampal dentate gyrus (DG) [cite: 15].[6]
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Dosage:20 mg/mL
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Administration:p.o.; continuously administered for 7 days
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Result:Significantly blocked the enhancement of LTP in the DG region induced by nicotine pre-treatment and cocaine injection .
Did not alter the baseline LTP induction in mice.
Chemical Information
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No. CAS 108179-91-5
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Peso molecular 413.15
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Fòrmula C17H19Br2NO
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SMILES
OC1=C(Br)C=C2CCN(C)CC(C3=CC=CC=C3)C2=C1.[H]Br
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (3)
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Journal Impact Factor
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Most Recent
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Adv Sci (Weinh)
Nigra-Subthalamic Dopaminergic Circuitry Modulates and Represents Distinct Pain Modality in Physiological and Pain States in Mice. [Abstract]2026 Jul;13(37):e19913. PMID: 41944312 -
ACS Chem Neurosci
Estimation of Dopamine D1 Receptor Agonist Binding Kinetics Using Time-Resolved Functional Assays: Relation to Agonist-Induced Receptor Internalization by Investigational Antiparkinsonian Therapeutics. [Abstract]2025 Jul 2;16(13):2502-2512. PMID: 40537032 -
Pureza y Documentación
Referencias
[2]. Stouffer MA, et al. SKF-83566, a D1-dopamine receptor antagonist, inhibits the dopamine transporter. Journal of neurochemistry. 2011 Sep;118(5):714-20. [Content Brief]
[4]. Huang H, et al. The effects of aging and dopaminergic inhibition on large scale maze learning in rhesus monkeys. Brain research bulletin. 2021 Oct;175:63-68. [Content Brief]
[7]. Conley JM, et al. Development of a high-throughput screening paradigm for the discovery of small-molecule modulators of adenylyl cyclase: identification of an adenylyl cyclase 2 inhibitor. The Journal of pharmacology and experimental therapeutics. 2013 Nov;347(2):276-87. [Content Brief]
[8]. Huang YY, et al. D1/D5 receptors and histone deacetylation mediate the Gateway Effect of LTP in hippocampal dentate gyrus. Learn Mem. 2014 Feb 18;21(3):153-60. [Content Brief]
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