SKF-83566 hydrochloride
SKF-83566 hydrochloride 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 hydrochloride modulates locomotor behavior and spatial memory by blocking D1 receptors and inhibits glioblastoma progression by targeting the DRD1/c-Myc/UHRF1 pathway. SKF-83566 hydrochloride acts as an inhibitor of the dopamine transporter (DAT) and adenylyl cyclase 2 (AC2). SKF-83566 hydrochloride competitively binds to DAT to inhibit dopamine reuptake and non-competitively inhibits AC2 activity, thereby reducing cAMP accumulation. SKF-83566 hydrochloride 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").
For research use only. We do not sell to patients.
- CAS No.: 164265-49-0
- Formula: C17H19BrClNO
- Molecular Weight:368.70
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Help & FAQs
Biological Activity
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Dopamine D1 receptor |
Dopamine D5 receptor |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| U-251 | IC50 |
163.2 μM
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Inhibition of cell viability against human glioblastoma U251 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
Inhibition of cell viability against human glioblastoma U251 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
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38246990 |
| LN-18 | IC50 |
119.4 μM
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Inhibition of cell viability against human glioblastoma LN18 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
Inhibition of cell viability against human glioblastoma LN18 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
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38246990 |
| LN-229 | IC50 |
138 μM
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Inhibition of cell viability against human glioblastoma LN229 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
Inhibition of cell viability against human glioblastoma LN229 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
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38246990 |
| A 172 | IC50 |
204.7 μM
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Inhibition of cell viability against human glioblastoma A172 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
Inhibition of cell viability against human glioblastoma A172 cells assessed by CellTiter-Glo Luminescent Cell Viability Assay with 48 h or 72 h incubation.
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38246990 |
| HEK293 | IC50 |
10 μM
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Inhibition of PMA-stimulated intracellular cAMP accumulation in human HEK-hAC2 cells assessed via Cisbio time-resolved fluorescence resonance energy transfer (TR-FRET) cAMP assay with 30 min pre-incubation + 1 h stimulation.
Inhibition of PMA-stimulated intracellular cAMP accumulation in human HEK-hAC2 cells assessed via Cisbio time-resolved fluorescence resonance energy transfer (TR-FRET) cAMP assay with 30 min pre-incubation + 1 h stimulation.
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24008337 |
| HEK293 | IC50 |
19 μM
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Inhibition of forskolin-stimulated intracellular cAMP accumulation in human HEK-hAC2 cells assessed via Cisbio time-resolved fluorescence resonance energy transfer (TR-FRET) cAMP assay with 30 min pre-incubation + 1 h stimulation.
Inhibition of forskolin-stimulated intracellular cAMP accumulation in human HEK-hAC2 cells assessed via Cisbio time-resolved fluorescence resonance energy transfer (TR-FRET) cAMP assay with 30 min pre-incubation + 1 h stimulation.
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24008337 |
| HEK293 | IC50 |
21 μM
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Inhibition of PGE2-stimulated intracellular cAMP accumulation in human HEK-hAC2 cells assessed via Cisbio time-resolved fluorescence resonance energy transfer (TR-FRET) cAMP assay with 30 min pre-incubation + 1 h stimulation.
Inhibition of PGE2-stimulated intracellular cAMP accumulation in human HEK-hAC2 cells assessed via Cisbio time-resolved fluorescence resonance energy transfer (TR-FRET) cAMP assay with 30 min pre-incubation + 1 h stimulation.
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24008337 |
| C2C12 | IC50 |
15 μM
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Inhibition of forskolin-stimulated intracellular cAMP accumulation in differentiated mouse C2C12 skeletal muscle myotubes assessed via [3H]cAMP competitive binding assay with 30 min pre-incubation + 1 h stimulation.
Inhibition of forskolin-stimulated intracellular cAMP accumulation in differentiated mouse C2C12 skeletal muscle myotubes assessed via [3H]cAMP competitive binding assay with 30 min pre-incubation + 1 h stimulation.
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24008337 |
SKF-83566 (5 μM; 5 min pre-incubation) hydrochloride acts as a competitive inhibitor of DAT in LLc-PK cells expressing rat dopamine transporter (rDAT), with an IC50 value of 5.73 µM[2].
SKF-83566 (10 pM-1 mM; 15 min) hydrochloride 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) hydrochloride 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) hydrochloride non-competitively inhibits AC2 activity in Sf9 insect cell membranes expressing AC2[7].
SKF-83566 (pre-incubated for 30 min, stimulated for 1 h) hydrochloride 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) hydrochloride inhibits Forskolin-stimulated IL-6 mRNA expression in human bronchial smooth muscle cells (hBSMCs)[7].
SKF-83566 (1-100 μM; pre-incubation for 10 min, followed by stimulation with bile acid for 2 h) hydrochloride almost completely inhibits bile acid-induced chemotaxis of adult Clonorchis sinensis in vitro[3].
SKF-83566 (50-100 μM; 14 days) hydrochloride dose-dependently inhibits the self-renewal and tumorsphere-forming ability of P3, BG5 and BG7 glioma stem cells[6].
SKF-83566 (0-400 µM; 48-72 h) hydrochloride 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) hydrochloride 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) hydrochloride 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 (50-100 µM) hydrochloride induces G0/G1 cell cycle arrest and promotes apoptosis in human GSCs (P3, BG5, BG7)[6].
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.
SKF-83566 (0.02-0.2 mg/kg; i.m.; once daily for 3 consecutive days) hydrochloride 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) hydrochloride reverses ghrelin-induced memory enhancement in male rat models, but has no effect on its orexigenic action [5].
SKF-83566 (20 mg/mL; p.o.; administered consecutively for 7 days) hydrochloride blocks the priming effect of nicotine on cocaine-induced long-term potentiation (LTP) in the hippocampal dentate gyrus (DG) in male mouse models[6].
SKF-83566 (20 mg/kg/day; i.p.; once daily, administered continuously until symptom onset followed by euthanasia) hydrochloride inhibits tumor growth and invasion, reduces the expression of key proteins, and prolongs overall survival in athymic nude mice bearing intracranial orthotopic xenograft tumors of GSC[6].
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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CAS No. 164265-49-0
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Molecular Weight 368.70
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Formula C17H19BrClNO
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SMILES
BrC1=C(O)C=C(C(CN(CC2)C)C3=CC=CC=C3)C2=C1.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[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]
[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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SKF-83566 hydrochloride Related Classifications
HY-103430B Related Classifications
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