RGFP966 | CAS#1357389-11-7 | HDAC3 inhibitor

MedKoo Cat#: 510215 | Name: RGFP966

Description:

WARNING: This product is for research use only, not for human or veterinary use.

RGFP966 is a selective HDAC3 inhibitor . S ystemic treatment with RGFP966 facilitates extinction in mice in a manner resistant to reinstatement. A single treatment of RGFP966 enhances extinction of a previously established cocaine-conditioned place preference, while simultaneously enhancing long-term object-location memory within subjects. During extinction consolidation, HDAC3 inhibition promotes a distinct pattern of histone acetylation linked to gene expression within the infralimbic cortex, hippocampus, and nucleus accumbens. Thus, the facilitated extinction of drug-seeking cannot be explained by adverse effects on performance.

Chemical Structure

RGFP966

CAS#1357389-11-7

Theoretical Analysis

MedKoo Cat#: 510215

Name: RGFP966

CAS#: 1357389-11-7

Chemical Formula: C21H19FN4O

Exact Mass: 362.1543

Molecular Weight: 362.40

Elemental Analysis: C, 69.60; H, 5.28; F, 5.24; N, 15.46; O, 4.41

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 4,250.00	Ready to ship
2g	USD 6,550.00	2 Weeks

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Related CAS #

1396841-57-8

Synonym

RGFP966; RGFP 966; RGFP-966

IUPAC/Chemical Name

(E)-N-(2-amino-4-fluorophenyl)-3-(1-cinnamyl-1H-pyrazol-4-yl)acrylamide

InChi Key

BLVQHYHDYFTPDV-VCABWLAWSA-N

InChi Code

InChI=1S/C21H19FN4O/c22-18-9-10-20(19(23)13-18)25-21(27)11-8-17-14-24-26(15-17)12-4-7-16-5-2-1-3-6-16/h1-11,13-15H,12,23H2,(H,25,27)/b7-4+,11-8+

SMILES Code

O=C(NC1=CC=C(F)C=C1N)/C=C/C2=CN(C/C=C/C3=CC=CC=C3)N=C2.

Appearance

White solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC70328

View CoA: current batch, Lot#B3B09C26

QC Data

View QC data: current batch, Lot#BBC70328

View QC data: current batch, Lot#B3B09C26

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

RGFP966 is an HDAC3 inhibitor with IC50 of 0.08 μM in cell-free assay, exhibits > 200-fold selectivity over other HDAC.

In vitro activity:

RGFP966 was applied in cell-based model systems for inflammatory lung diseases using mouse RAW 264.7 macrophages, human bronchial epithelial (HBE) cells and human airway smooth muscle (hASM) cells that were subjected to LPS/IFNγ-stimulation. First, cytotoxicity of RGFP966 was investigated in these cell types and there was no significant observed decrease in cell viability at the applied concentrations, as compared to control cells (data not shown). In LPS/IFNγ-stimulated RAW 264.7 macrophages treatment with RGFP966 did not change the expression of the genes TNFα, iNOS, and IL-10 but provided a significant downregulation of the expression of the pro-inflammatory genes IL-1β, IL-6 and IL-12b (Fig. 2C). This effect was specific for macrophages as in HBE cells and hASM cells the expression of the investigated genes was not affected except for pro-inflammatory gene IL-6, which was upregulated in HBE cells. Reference: Biochem Pharmacol. 2016 May 15;108:58-74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844503/

In vivo activity:

The effects of RGFP966 ((E)-N-(2-amino-4-fluorophenyl)-3-(1-cinnamyl-1H-pyrazol-4-yl)acrylamide), a benzamide-type HDAC inhibitor that selectively targets HDAC3, was tested in the N171-82Q transgenic mouse model of HD. It was found that RGFP966 at doses of 10 and 25 mg/kg improves motor deficits on rotarod and in open field exploration, accompanied by neuroprotective effects on striatal volume. In light of previous studies implicating HDAC3 in immune function, gene expression changes were measured for 84 immune-related genes elicited by RGFP966 using quantitative PCR arrays. RGFP966 treatment did not cause widespread changes in cytokine/chemokine gene expression patterns, but did significantly alter the striatal expression of macrophage migration inhibitory factor (Mif), a hormone immune modulator associated with glial cell activation, in N171-82Q transgenic mice, but not WT mice. Accordingly, RGFP966-treated mice showed decreased glial fibrillary acidic protein (GFAP) immunoreactivity, a marker of astrocyte activation, in the striatum of N171-82Q transgenic mice compared to vehicle-treated mice. Reference: PLoS One. 2016 Mar 31;11(3):e0152498. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27031333/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	137.97
	DMF	50.0	137.97

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 362.40 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Leus NG, van der Wouden PE, van den Bosch T, Hooghiemstra WTR, Ourailidou ME, Kistemaker LE, Bischoff R, Gosens R, Haisma HJ, Dekker FJ. HDAC 3-selective inhibitor RGFP966 demonstrates anti-inflammatory properties in RAW 264.7 macrophages and mouse precision-cut lung slices by attenuating NF-κB p65 transcriptional activity. Biochem Pharmacol. 2016 May 15;108:58-74. doi: 10.1016/j.bcp.2016.03.010. Epub 2016 Mar 16. PMID: 26993378; PMCID: PMC4844503. 2. Jia H, Wang Y, Morris CD, Jacques V, Gottesfeld JM, Rusche JR, Thomas EA. The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3) in Huntington's Disease Mice. PLoS One. 2016 Mar 31;11(3):e0152498. doi: 10.1371/journal.pone.0152498. PMID: 27031333; PMCID: PMC4816519. 3. Bieszczad KM, Bechay K, Rusche JR, Jacques V, Kudugunti S, Miao W, Weinberger NM, McGaugh JL, Wood MA. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation. J Neurosci. 2015 Sep 23;35(38):13124-32. doi: 10.1523/JNEUROSCI.0914-15.2015. PMID: 26400942; PMCID: PMC4579377.

In vitro protocol:

In vivo protocol:

1. Jia H, Wang Y, Morris CD, Jacques V, Gottesfeld JM, Rusche JR, Thomas EA. The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3) in Huntington's Disease Mice. PLoS One. 2016 Mar 31;11(3):e0152498. doi: 10.1371/journal.pone.0152498. PMID: 27031333; PMCID: PMC4816519. 2. Bieszczad KM, Bechay K, Rusche JR, Jacques V, Kudugunti S, Miao W, Weinberger NM, McGaugh JL, Wood MA. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation. J Neurosci. 2015 Sep 23;35(38):13124-32. doi: 10.1523/JNEUROSCI.0914-15.2015. PMID: 26400942; PMCID: PMC4579377.

1: Gu HP, Wu XF, Gong YT, Mu-Yao Wu, Shi MY, Sun YM, Dang BQ, Chen G. RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats. Heliyon. 2023 Jul 12;9(7):e18160. doi: 10.1016/j.heliyon.2023.e18160. PMID: 37539293; PMCID: PMC10395478. 2: Bian HT, Xiao L, Liang L, Xie YP, Wang HL, Wang GH. RGFP966 is protective against lipopolysaccharide-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation. Int Immunopharmacol. 2021 Dec;101(Pt B):108259. doi: 10.1016/j.intimp.2021.108259. Epub 2021 Oct 16. PMID: 34666303. 3: Zheng XH, Wang LL, Zheng MZ, Zhong JJ, Chen YY, Shen YL. RGFP966 inactivation of the YAP pathway attenuates cardiac dysfunction induced by prolonged hypothermic preservation. J Zhejiang Univ Sci B. 2020 Sept.;21(9):703-715. doi: 10.1631/jzus.B2000026. PMID: 32893527; PMCID: PMC7519627. 4: Zhang W, Sun X, Ba G, Tang R, Lin H. RGFP966, a selective HDAC3 inhibitor, ameliorates allergic and inflammatory responses in an OVA-induced allergic rhinitis mouse model. Int Immunopharmacol. 2021 Apr;93:107400. doi: 10.1016/j.intimp.2021.107400. Epub 2021 Jan 30. PMID: 33529911. 5: Yu X, Yang F, Jiang H, Fan L. RGFP966 Suppresses Tumor Growth and Migration Through Inhibition of EGFR Expression in Hepatocellular Carcinoma Cells in vitro. Drug Des Devel Ther. 2020 Jan 10;14:121-128. doi: 10.2147/DDDT.S234871. PMID: 32021097; PMCID: PMC6959505. 6: Lei L, Bai G, Wang X, Liu S, Xia J, Wu S, Huan Y, Shen Z. Histone deacetylase 3-selective inhibitor RGFP966 ameliorates impaired glucose tolerance through β-cell protection. Toxicol Appl Pharmacol. 2020 Nov 1;406:115189. doi: 10.1016/j.taap.2020.115189. Epub 2020 Aug 13. PMID: 32800772. 7: Liang H, Wang Q, Wang D, Zheng H, Kalvakolanu DV, Lu H, Wen N, Chen X, Xu L, Ren J, Guo B, Zhang L. RGFP966, a histone deacetylase 3 inhibitor, promotes glioma stem cell differentiation by blocking TGF-β signaling via SMAD7. Biochem Pharmacol. 2020 Oct;180:114118. doi: 10.1016/j.bcp.2020.114118. Epub 2020 Jun 23. Erratum in: Biochem Pharmacol. 2020 Dec;182:114223. doi: 10.1016/j.bcp.2020.114223. PMID: 32585142. 8: Sun W, Zhang N, Liu B, Yang J, Loers G, Siebert HC, Wen M, Zheng X, Wang Z, Han J, Zhang R. HDAC3 Inhibitor RGFP966 Ameliorated Neuroinflammation in the Cuprizone-Induced Demyelinating Mouse Model and LPS-Stimulated BV2 Cells by Downregulating the P2X7R/STAT3/NF-κB65/NLRP3 Activation. ACS Chem Neurosci. 2022 Sep 7;13(17):2579-2598. doi: 10.1021/acschemneuro.1c00826. Epub 2022 Aug 10. PMID: 35947794. 9: Zhang MJ, Zhao QC, Xia MX, Chen J, Chen YT, Cao X, Liu Y, Yuan ZQ, Wang XY, Xu Y. The HDAC3 inhibitor RGFP966 ameliorated ischemic brain damage by downregulating the AIM2 inflammasome. FASEB J. 2020 Jan;34(1):648-662. doi: 10.1096/fj.201900394RRR. Epub 2019 Nov 26. PMID: 31914678. 10: Xu L, An T, Jia B, Wu Q, Shen J, Jin J, Liu J, Li C. Histone deacetylase 3-specific inhibitor RGFP966 attenuates oxidative stress and inflammation after traumatic brain injury by activating the Nrf2 pathway. Burns Trauma. 2024 May 4;12:tkad062. doi: 10.1093/burnst/tkad062. PMID: 38708192; PMCID: PMC11069425. 11: Li N, Liu B, Xiong R, Li G, Wang B, Geng Q. HDAC3 deficiency protects against acute lung injury by maintaining epithelial barrier integrity through preserving mitochondrial quality control. Redox Biol. 2023 Jul;63:102746. doi: 10.1016/j.redox.2023.102746. Epub 2023 May 20. PMID: 37244125; PMCID: PMC10199751. 12: Campo M, Heater S, Peterson GJ, Simmons JD, Skerrett SJ, Mayanja-Kizza H, Stein CM, Boom WH, Hawn TR. HDAC3 inhibitor RGFP966 controls bacterial growth and modulates macrophage signaling during Mycobacterium tuberculosis infection. Tuberculosis (Edinb). 2021 Mar;127:102062. doi: 10.1016/j.tube.2021.102062. Epub 2021 Feb 18. PMID: 33639591; PMCID: PMC8650124. 13: Zhang L, Chen F, Dong J, Wang R, Bi G, Xu D, Zhang Y, Deng Y, Lin W, Yang Z, Cao W. HDAC3 aberration-incurred GPX4 suppression drives renal ferroptosis and AKI-CKD progression. Redox Biol. 2023 Dec;68:102939. doi: 10.1016/j.redox.2023.102939. Epub 2023 Oct 20. PMID: 37890360; PMCID: PMC10638610. 14: Schmitt HM, Schlamp CL, Nickells RW. Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell Nuclear Atrophy and Apoptosis After Optic Nerve Injury. J Ocul Pharmacol Ther. 2018 Apr;34(3):260-273. doi: 10.1089/jop.2017.0059. Epub 2017 Dec 6. PMID: 29211617; PMCID: PMC5963665. 15: Clayton BLL, Kristell JD, Allan KC, Cohn EF, Karl M, Jerome AD, Garrison E, Maeno-Hikichi Y, Sturno AM, Kerr A, Shick HE, Sepeda JA, Freundt EC, Sas AR, Segal BM, Miller RH, Tesar PJ. A phenotypic screening platform for identifying chemical modulators of astrocyte reactivity. Nat Neurosci. 2024 Apr;27(4):656-665. doi: 10.1038/s41593-024-01580-z. Epub 2024 Feb 20. PMID: 38378993; PMCID: PMC11034956. 16: Wang Y, Jiao B, Hu Z, Wang Y. Critical Role of histone deacetylase 3 in the regulation of kidney inflammation and fibrosis. Kidney Int. 2024 Apr;105(4):775-790. doi: 10.1016/j.kint.2024.01.010. Epub 2024 Jan 28. PMID: 38286179. 17: Liang H, Wang Q, Wang D, Zheng H, Kalvakolanu DV, Lu H, Wen N, Chen X, Xu L, Ren J, Guo B, Zhang L. Corrigendum to "RGFP966, a histone deacetylase 3 inhibitor, promotes glioma stem cell differentiation by blocking TGF-β signaling via SMAD7" [Biochem. Pharmacol. 180 (2020) 114118]. Biochem Pharmacol. 2020 Dec;182:114223. doi: 10.1016/j.bcp.2020.114223. Epub 2020 Oct 8. Erratum for: Biochem Pharmacol. 2020 Oct;180:114118. doi: 10.1016/j.bcp.2020.114118. PMID: 33039815. 18: Phan ML, Gergues MM, Mahidadia S, Jimenez-Castillo J, Vicario DS, Bieszczad KM. HDAC3 Inhibitor RGFP966 Modulates Neuronal Memory for Vocal Communication Signals in a Songbird Model. Front Syst Neurosci. 2017 Sep 5;11:65. doi: 10.3389/fnsys.2017.00065. PMID: 28928640; PMCID: PMC5591857. 19: Bieszczad KM, Bechay K, Rusche JR, Jacques V, Kudugunti S, Miao W, Weinberger NM, McGaugh JL, Wood MA. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation. J Neurosci. 2015 Sep 23;35(38):13124-32. doi: 10.1523/JNEUROSCI.0914-15.2015. PMID: 26400942; PMCID: PMC4579377. 20: Leus NG, van der Wouden PE, van den Bosch T, Hooghiemstra WTR, Ourailidou ME, Kistemaker LE, Bischoff R, Gosens R, Haisma HJ, Dekker FJ. HDAC 3-selective inhibitor RGFP966 demonstrates anti-inflammatory properties in RAW 264.7 macrophages and mouse precision-cut lung slices by attenuating NF-κB p65 transcriptional activity. Biochem Pharmacol. 2016 May 15;108:58-74. doi: 10.1016/j.bcp.2016.03.010. Epub 2016 Mar 16. PMID: 26993378; PMCID: PMC4844503.