SMIFH2 | CAS# 340316-62-3 | Formin-Mediated Actin Inhibitor

MedKoo Cat#: 565430 | Name: SMIFH2

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Description:

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

SMIFH2 is the first small molecule inhibitor of formin-mediated actin assembly that disrupts formin dependent processes from yeast to mammals.

Chemical Structure

SMIFH2

CAS#340316-62-3

Theoretical Analysis

MedKoo Cat#: 565430

Name: SMIFH2

CAS#: 340316-62-3

Chemical Formula: C15H9BrN2O3S

Exact Mass: 375.9517

Molecular Weight: 377.21

Elemental Analysis: C, 47.76; H, 2.41; Br, 21.18; N, 7.43; O, 12.72; S, 8.50

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 380.00	2 Weeks
50mg	USD 1,050.00	2 Weeks

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Related CAS #

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Synonym

SMIFH-2; SMIFH 2; SMIFH2

IUPAC/Chemical Name

1-(3-Bromophenyl)-5-(2-furanylmethylene)dihydro-2-thioxo-4,6(1H,5H)-pyrimidinedione

InChi Key

MVFJHEQDISFYIS-XYOKQWHBSA-N

InChi Code

InChI=1S/C15H9BrN2O3S/c16-9-3-1-4-10(7-9)18-14(20)12(13(19)17-15(18)22)8-11-5-2-6-21-11/h1-8H,(H,17,19,22)/b12-8+

SMILES Code

O=C(/C(C(N1C2=CC=CC(Br)=C2)=O)=C\C3=CC=CO3)NC1=S

Appearance

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

Shelf Life

>3 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

Instruction

View handling instruction

Biological target:

SMIFH2 inhibits assembly of profilin-actin mediated by mouse formin mDia1(FH1FH2) (IC50 ≈ 15 μM). It also inhibits actin assembly mediated by FH1FH2 constructs of mDia2, C. elegans CYK-1, S. pombe Cdc12 or Fus1, or S. cerevisiae Bni1. SMIFH2 is cytotoxic to NIH3T3 fibroblasts (IC50 = 28 μM).

In vitro activity:

SMIFH2 has off-target effects on different myosin types. SMIFH2 hampered the backward movement of myosin 2 filaments and stress fiber contraction. It inhibited non-muscle myosin 2A and skeletal muscle myosin 2 activities, affecting ATPase function and actin filament translocation in vitro. SMIFH2 also efficiently inhibited various non-muscle myosin types, such as bovine myosin 10 and Drosophila myosins 7a and 5. Reference: J Cell Sci. 2021 Apr 15;134(8):jcs253708. https://pubmed.ncbi.nlm.nih.gov/33589498/

In vivo activity:

SMIFH2 differentially affects the cardiac contraction of amphibian and mammalian by differentially modulating their Ca2+ handling. In isolated frog hearts, SMIFH2 enhanced cardiac contractility and Ca2+ transients, leading to improved performance. In mouse cardiomyocytes, SMIFH2 reduced contractility with decreased Ca2+ transients. SMIFH2 also suppressed Ca2+ release via type 2 ryanodine receptor (RyR2) in mice but not in frogs, indicating species-specific modulation of Ca2+ handling. Reference: Genes Cells. 2021 Aug;26(8):583-595. https://onlinelibrary.wiley.com/doi/10.1111/gtc.12873

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	30.0	265.10

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 377.21 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. Nishimura Y, Shi S, Zhang F, Liu R, Takagi Y, Bershadsky AD, Viasnoff V, Sellers JR. The formin inhibitor SMIFH2 inhibits members of the myosin superfamily. J Cell Sci. 2021 Apr 15;134(8):jcs253708. doi: 10.1242/jcs.253708. Epub 2021 Apr 27. PMID: 33589498; PMCID: PMC8121067. 2. Rizvi SA, Neidt EM, Cui J, Feiger Z, Skau CT, Gardel ML, Kozmin SA, Kovar DR. Identification and characterization of a small molecule inhibitor of formin-mediated actin assembly. Chem Biol. 2009 Nov 25;16(11):1158-68. doi: 10.1016/j.chembiol.2009.10.006. PMID: 19942139; PMCID: PMC2784894. 3. Sakata K, Matsuyama S, Kurebayashi N, Hayamizu K, Murayama T, Nakamura K, Kitamura K, Morimoto S, Takeya R. Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes. Genes Cells. 2021 Aug;26(8):583-595. doi: 10.1111/gtc.12873. Epub 2021 Jun 17. Erratum in: Genes Cells. 2022 Jan;27(1):72. PMID: 34060165. 4. LeCorgne H, Tudosie AM, Lavik K, Su R, Becker KN, Moore S, Walia Y, Wisner A, Koehler D, Alberts AS, Williams FE, Eisenmann KM. Differential Toxicity of mDia Formin-Directed Functional Agonists and Antagonists in Developing Zebrafish. Front Pharmacol. 2018 Apr 10;9:340. doi: 10.3389/fphar.2018.00340. PMID: 29692731; PMCID: PMC5902741.

In vitro protocol:

In vivo protocol:

1. Sakata K, Matsuyama S, Kurebayashi N, Hayamizu K, Murayama T, Nakamura K, Kitamura K, Morimoto S, Takeya R. Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes. Genes Cells. 2021 Aug;26(8):583-595. doi: 10.1111/gtc.12873. Epub 2021 Jun 17. Erratum in: Genes Cells. 2022 Jan;27(1):72. PMID: 34060165. 2. LeCorgne H, Tudosie AM, Lavik K, Su R, Becker KN, Moore S, Walia Y, Wisner A, Koehler D, Alberts AS, Williams FE, Eisenmann KM. Differential Toxicity of mDia Formin-Directed Functional Agonists and Antagonists in Developing Zebrafish. Front Pharmacol. 2018 Apr 10;9:340. doi: 10.3389/fphar.2018.00340. PMID: 29692731; PMCID: PMC5902741.

1: LeCorgne H, Tudosie AM, Lavik K, Su R, Becker KN, Moore S, Walia Y, Wisner A, Koehler D, Alberts AS, Williams FE, Eisenmann KM. Differential Toxicity of mDia Formin-Directed Functional Agonists and Antagonists in Developing Zebrafish. Front Pharmacol. 2018 Apr 10;9:340. doi: 10.3389/fphar.2018.00340. eCollection 2018. PubMed PMID: 29692731; PubMed Central PMCID: PMC5902741. 2: Rana MK, Aloisio FM, Choi C, Barber DL. Formin-dependent TGF-β signaling for epithelial to mesenchymal transition. Mol Biol Cell. 2018 Jun 15;29(12):1465-1475. doi: 10.1091/mbc.E17-05-0325. Epub 2018 Apr 18. PubMed PMID: 29668357; PubMed Central PMCID: PMC6014098. 3: Fessenden TB, Beckham Y, Perez-Neut M, Ramirez-San Juan G, Chourasia AH, Macleod KF, Oakes PW, Gardel ML. Dia1-dependent adhesions are required by epithelial tissues to initiate invasion. J Cell Biol. 2018 Apr 2;217(4):1485-1502. doi: 10.1083/jcb.201703145. Epub 2018 Feb 5. PubMed PMID: 29437785; PubMed Central PMCID: PMC5881494. 4: Silveira AAA, Dominical VM, Almeida CB, Chweih H, Ferreira WA Jr, Vicente CP, Costa FTM, Werneck CC, Costa FF, Conran N. TNF induces neutrophil adhesion via formin-dependent cytoskeletal reorganization and activation of β-integrin function. J Leukoc Biol. 2018 Jan;103(1):87-98. doi: 10.1189/jlb.3A0916-388RR. Epub 2017 Dec 28. PubMed PMID: 28798145. 5: Basu S, Kustanovich I, Lamprecht R. Arp2/3 and VASP Are Essential for Fear Memory Formation in Lateral Amygdala. eNeuro. 2016 Nov 29;3(6). pii: ENEURO.0302-16.2016. eCollection 2016 Nov-Dec. PubMed PMID: 27957528; PubMed Central PMCID: PMC5126706. 6: Ziske MA, Pettee KM, Khaing M, Rubinic K, Eisenmann KM. SMIFH2-mediated mDia formin functional inhibition potentiates chemotherapeutic targeting of human ovarian cancer spheroids. Biochem Biophys Res Commun. 2016 Mar 25;472(1):33-9. doi: 10.1016/j.bbrc.2016.02.049. Epub 2016 Feb 17. PubMed PMID: 26898799. 7: Rosero A, Oulehlová D, Stillerová L, Schiebertová P, Grunt M, Žárský V, Cvrčková F. Arabidopsis FH1 Formin Affects Cotyledon Pavement Cell Shape by Modulating Cytoskeleton Dynamics. Plant Cell Physiol. 2016 Mar;57(3):488-504. doi: 10.1093/pcp/pcv209. Epub 2016 Jan 6. PubMed PMID: 26738547. 8: Borinskaya S, Velle KB, Campellone KG, Talman A, Alvarez D, Agaisse H, Wu YI, Loew LM, Mayer BJ. Integration of linear and dendritic actin nucleation in Nck-induced actin comets. Mol Biol Cell. 2016 Jan 15;27(2):247-59. doi: 10.1091/mbc.E14-11-1555. Epub 2015 Nov 25. PubMed PMID: 26609071; PubMed Central PMCID: PMC4713129. 9: Cao L, Henty-Ridilla JL, Blanchoin L, Staiger CJ. Profilin-Dependent Nucleation and Assembly of Actin Filaments Controls Cell Elongation in Arabidopsis. Plant Physiol. 2016 Jan;170(1):220-33. doi: 10.1104/pp.15.01321. Epub 2015 Nov 16. PubMed PMID: 26574597; PubMed Central PMCID: PMC4704583. 10: Arden JD, Lavik KI, Rubinic KA, Chiaia N, Khuder SA, Howard MJ, Nestor-Kalinoski AL, Alberts AS, Eisenmann KM. Small-molecule agonists of mammalian Diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy. Mol Biol Cell. 2015 Nov 1;26(21):3704-18. doi: 10.1091/mbc.E14-11-1502. Epub 2015 Sep 9. PubMed PMID: 26354425; PubMed Central PMCID: PMC4626057. 11: Efremov YM, Dokrunova AA, Efremenko AV, Kirpichnikov MP, Shaitan KV, Sokolova OS. Distinct impact of targeted actin cytoskeleton reorganization on mechanical properties of normal and malignant cells. Biochim Biophys Acta. 2015 Nov;1853(11 Pt B):3117-25. doi: 10.1016/j.bbamcr.2015.05.008. Epub 2015 May 10. PubMed PMID: 25970206. 12: Isogai T, van der Kammen R, Innocenti M. SMIFH2 has effects on Formins and p53 that perturb the cell cytoskeleton. Sci Rep. 2015 Apr 30;5:9802. doi: 10.1038/srep09802. PubMed PMID: 25925024; PubMed Central PMCID: PMC5386218. 13: Kim HC, Jo YJ, Kim NH, Namgoong S. Small molecule inhibitor of formin homology 2 domains (SMIFH2) reveals the roles of the formin family of proteins in spindle assembly and asymmetric division in mouse oocytes. PLoS One. 2015 Apr 2;10(4):e0123438. doi: 10.1371/journal.pone.0123438. eCollection 2015. PubMed PMID: 25837661; PubMed Central PMCID: PMC4383420. 14: Rosero A, Žársky V, Cvrčková F. AtFH1 formin mutation affects actin filament and microtubule dynamics in Arabidopsis thaliana. J Exp Bot. 2013 Jan;64(2):585-97. doi: 10.1093/jxb/ers351. Epub 2012 Dec 1. Erratum in: J Exp Bot. 2015 Oct 22;:. PubMed PMID: 23202131; PubMed Central PMCID: PMC3542049. 15: Rizvi SA, Neidt EM, Cui J, Feiger Z, Skau CT, Gardel ML, Kozmin SA, Kovar DR. Identification and characterization of a small molecule inhibitor of formin-mediated actin assembly. Chem Biol. 2009 Nov 25;16(11):1158-68. doi: 10.1016/j.chembiol.2009.10.006. PubMed PMID: 19942139; PubMed Central PMCID: PMC2784894.