EHT-1864 HCl
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MedKoo CAT#: 526894

CAS#: 754240-09-0 (HCl)

Description: EHT-1864 is a potent Rac family GTPase inhibitor with Kd of 40 nM, 50 nM, 60 nM and 250 nM for Rac1, Rac1b, Rac2 and Rac3, respectively. EHT 1864 attenuates glucose-stimulated insulin secretion in pancreatic β-cells. EHT 1864 specifically inhibits glucose-induced Rac1 activation and membrane association and associated downstream signaling events culminating in inhibition of GSIS.

Chemical Structure

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EHT-1864 HCl
CAS# 754240-09-0 (HCl)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526894
Name: EHT-1864 HCl
CAS#: 754240-09-0 (HCl)
Chemical Formula: C25H29Cl2F3N2O4S
Exact Mass: 0.00
Molecular Weight: 581.472
Elemental Analysis: C, 51.64; H, 5.03; Cl, 12.19; F, 9.80; N, 4.82; O, 11.01; S, 5.51

Price and Availability

Size Price Availability Quantity
10mg USD 300 2 Weeks
25mg USD 550 2 Weeks
50mg USD 875 2 Weeks
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Synonym: EHT-1864; EHT1864; EHT 1864 HCl; EHT-1864 dihydrochloride.

IUPAC/Chemical Name: 2-(morpholinomethyl)-5-((5-((7-(trifluoromethyl)quinolin-4-yl)thio)pentyl)oxy)-4H-pyran-4-one dihydrochloride

InChi Key: LSECOAJFCKFQJG-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H27F3N2O4S.2ClH/c26-25(27,28)18-4-5-20-21(14-18)29-7-6-24(20)35-13-3-1-2-10-33-23-17-34-19(15-22(23)31)16-30-8-11-32-12-9-30;;/h4-7,14-15,17H,1-3,8-13,16H2;2*1H

SMILES Code: O=C1C(OCCCCCSC2=CC=NC3=C2C=CC(C(F)(F)F)=C3)=COC(CN4CCOCC4)=C1.Cl.Cl

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: >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: Related CAS# CAS#754240-09-0 (EHT-1864 dihydrochloride) CAS#754239-64-0 (EHT-1864 free base)

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: EHT 1864 is an inhibitor of Rac family small GTPases.
In vitro activity: Furthermore, this study noticed a complete inhibition of GSIS by EHT 1864 at 10 μM concentration. It should also be noted that, while 5 μM EHT 1864 exerted no significant effects on basal secretion, it did modestly increase the basal secretion at 10 μM concentration (~ 50%). Therefore, in all the subsequent experiments, this study studied the effects of EHT 1864 at 10 μM. Furthermore, EHT 1864 inhibited GSIS in INS-1 832/13 cells elicited at 10–20 mM glucose (Figure 3). Reference: Cell Signal. 2015 Jun; 27(6): 1159–1167. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380787/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 50.0 85.99
Ethanol 30.0 51.59
PBS (pH 7.2) 10.0 17.20
Water 86.1 147.99

Preparing Stock Solutions

The following data is based on the product molecular weight 581.47 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.

Recalculate based on batch purity %
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. Sidarala V, Veluthakal R, Syeda K, Kowluru A. EHT 1864, a small molecule inhibitor of Ras-related C3 botulinum toxin substrate 1 (Rac1), attenuates glucose-stimulated insulin secretion in pancreatic β-cells. Cell Signal. 2015 Jun;27(6):1159-67. doi: 10.1016/j.cellsig.2015.02.020. Epub 2015 Feb 26. PMID: 25725286; PMCID: PMC4380787. 2. Onesto C, Shutes A, Picard V, Schweighoffer F, Der CJ. Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. Methods Enzymol. 2008;439:111-29. doi: 10.1016/S0076-6879(07)00409-0. PMID: 18374160.
In vitro protocol: 1. Sidarala V, Veluthakal R, Syeda K, Kowluru A. EHT 1864, a small molecule inhibitor of Ras-related C3 botulinum toxin substrate 1 (Rac1), attenuates glucose-stimulated insulin secretion in pancreatic β-cells. Cell Signal. 2015 Jun;27(6):1159-67. doi: 10.1016/j.cellsig.2015.02.020. Epub 2015 Feb 26. PMID: 25725286; PMCID: PMC4380787. 2. Onesto C, Shutes A, Picard V, Schweighoffer F, Der CJ. Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. Methods Enzymol. 2008;439:111-29. doi: 10.1016/S0076-6879(07)00409-0. PMID: 18374160.
In vivo protocol: TBD

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1: Walliser C, Hermkes E, Schade A, Wiese S, Deinzer J, Zapatka M, Désiré L, Mertens D, Stilgenbauer S, Gierschik P. The Phospholipase Cγ2 Mutants R665W and L845F Identified in Ibrutinib-resistant Chronic Lymphocytic Leukemia Patients Are Hypersensitive to the Rho GTPase Rac2 Protein. J Biol Chem. 2016 Oct 14;291(42):22136-22148. PubMed PMID: 27542411.

2: Nagase M, Kurihara H, Aiba A, Young MJ, Sakai T. Deletion of Rac1GTPase in the Myeloid Lineage Protects against Inflammation-Mediated Kidney Injury in Mice. PLoS One. 2016 Mar 3;11(3):e0150886. doi: 10.1371/journal.pone.0150886. eCollection 2016. PubMed PMID: 26939003; PubMed Central PMCID: PMC4777421.

3: Xiang RF, Stack D, Huston SM, Li SS, Ogbomo H, Kyei SK, Mody CH. Ras-related C3 Botulinum Toxin Substrate (Rac) and Src Family Kinases (SFK) Are Proximal and Essential for Phosphatidylinositol 3-Kinase (PI3K) Activation in Natural Killer (NK) Cell-mediated Direct Cytotoxicity against Cryptococcus neoformans. J Biol Chem. 2016 Mar 25;291(13):6912-22. doi: 10.1074/jbc.M115.681544. Epub 2016 Feb 11. PubMed PMID: 26867574; PubMed Central PMCID: PMC4807276.

4: Sidarala V, Veluthakal R, Syeda K, Vlaar C, Newsholme P, Kowluru A. Phagocyte-like NADPH oxidase (Nox2) promotes activation of p38MAPK in pancreatic β-cells under glucotoxic conditions: Evidence for a requisite role of Ras-related C3 botulinum toxin substrate 1 (Rac1). Biochem Pharmacol. 2015 Jun 15;95(4):301-10. doi: 10.1016/j.bcp.2015.04.001. Epub 2015 Apr 14. PubMed PMID: 25881746.

5: Sidarala V, Veluthakal R, Syeda K, Kowluru A. EHT 1864, a small molecule inhibitor of Ras-related C3 botulinum toxin substrate 1 (Rac1), attenuates glucose-stimulated insulin secretion in pancreatic β-cells. Cell Signal. 2015 Jun;27(6):1159-67. doi: 10.1016/j.cellsig.2015.02.020. Epub 2015 Feb 26. PubMed PMID: 25725286; PubMed Central PMCID: PMC4380787.

6: Wang Y, Kunit T, Ciotkowska A, Rutz B, Schreiber A, Strittmatter F, Waidelich R, Liu C, Stief CG, Gratzke C, Hennenberg M. Inhibition of prostate smooth muscle contraction and prostate stromal cell growth by the inhibitors of Rac, NSC23766 and EHT1864. Br J Pharmacol. 2015 Jun;172(11):2905-17. doi: 10.1111/bph.13099. Epub 2015 May 5. PubMed PMID: 25631101; PubMed Central PMCID: PMC4439884.

7: Dütting S, Heidenreich J, Cherpokova D, Amin E, Zhang SC, Ahmadian MR, Brakebusch C, Nieswandt B. Critical off-target effects of the widely used Rac1 inhibitors NSC23766 and EHT1864 in mouse platelets. J Thromb Haemost. 2015 May;13(5):827-38. doi: 10.1111/jth.12861. Epub 2015 Feb 23. PubMed PMID: 25628054.

8: Yoshida S, Ishizawa K, Ayuzawa N, Ueda K, Takeuchi M, Kawarazaki W, Fujita T, Nagase M. Local mineralocorticoid receptor activation and the role of Rac1 in obesity-related diabetic kidney disease. Nephron Exp Nephrol. 2014;126(1):16-24. doi: 10.1159/000358758. Epub 2014 Feb 28. PubMed PMID: 24603367.

9: Baier A, Ndoh VN, Lacy P, Eitzen G. Rac1 and Rac2 control distinct events during antigen-stimulated mast cell exocytosis. J Leukoc Biol. 2014 Jan 7. [Epub ahead of print] PubMed PMID: 24399839.

10: Raynaud F, Moutin E, Schmidt S, Dahl J, Bertaso F, Boeckers TM, Homburger V, Fagni L. Rho-GTPase-activating protein interacting with Cdc-42-interacting protein 4 homolog 2 (Rich2): a new Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase-activating protein that controls dendritic spine morphogenesis. J Biol Chem. 2014 Jan 31;289(5):2600-9. doi: 10.1074/jbc.M113.534636. Epub 2013 Dec 18. PubMed PMID: 24352656; PubMed Central PMCID: PMC3908394.

11: Stanley AC, Wong CX, Micaroni M, Venturato J, Khromykh T, Stow JL, Lacy P. The Rho GTPase Rac1 is required for recycling endosome-mediated secretion of TNF in macrophages. Immunol Cell Biol. 2014 Mar;92(3):275-86. doi: 10.1038/icb.2013.90. Epub 2013 Dec 17. PubMed PMID: 24343664.

12: Babelova A, Jansen F, Sander K, Löhn M, Schäfer L, Fork C, Ruetten H, Plettenburg O, Stark H, Daniel C, Amann K, Pavenstädt H, Jung O, Brandes RP. Activation of Rac-1 and RhoA contributes to podocyte injury in chronic kidney disease. PLoS One. 2013 Nov 7;8(11):e80328. doi: 10.1371/journal.pone.0080328. eCollection 2013. PubMed PMID: 24244677; PubMed Central PMCID: PMC3820652.

13: Wartlick F, Bopp A, Henninger C, Fritz G. DNA damage response (DDR) induced by topoisomerase II poisons requires nuclear function of the small GTPase Rac. Biochim Biophys Acta. 2013 Dec;1833(12):3093-103. doi: 10.1016/j.bbamcr.2013.08.016. Epub 2013 Aug 30. PubMed PMID: 23999236.

14: Dipaolo BC, Davidovich N, Kazanietz MG, Margulies SS. Rac1 pathway mediates stretch response in pulmonary alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2013 Jul 15;305(2):L141-53. doi: 10.1152/ajplung.00298.2012. Epub 2013 May 17. PubMed PMID: 23686855; PubMed Central PMCID: PMC3726945.

15: Hinterleitner C, Huelsenbeck J, Henninger C, Wartlick F, Schorr A, Kaina B, Fritz G. Rac1 signaling protects monocytic AML cells expressing the MLL-AF9 oncogene from caspase-mediated apoptotic death. Apoptosis. 2013 Aug;18(8):963-79. doi: 10.1007/s10495-013-0842-6. PubMed PMID: 23624644.

16: Yamamura M, Noguchi K, Nakano Y, Segawa E, Zushi Y, Takaoka K, Kishimoto H, Hashimoto-Tamaoki T, Urade M. Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells. Int J Oncol. 2013 Mar;42(3):873-80. doi: 10.3892/ijo.2013.1761. Epub 2013 Jan 4. PubMed PMID: 23292068.

17: Katz E, Sims AH, Sproul D, Caldwell H, Dixon MJ, Meehan RR, Harrison DJ. Targeting of Rac GTPases blocks the spread of intact human breast cancer. Oncotarget. 2012 Jun;3(6):608-19. PubMed PMID: 22689141; PubMed Central PMCID: PMC3442288.

18: Stefanini L, Boulaftali Y, Ouellette TD, Holinstat M, Désiré L, Leblond B, Andre P, Conley PB, Bergmeier W. Rap1-Rac1 circuits potentiate platelet activation. Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):434-41. doi: 10.1161/ATVBAHA.111.239194. Epub 2011 Nov 10. PubMed PMID: 22075250; PubMed Central PMCID: PMC3262085.

19: Martinez LA, Tejada-Simon MV. Pharmacological inactivation of the small GTPase Rac1 impairs long-term plasticity in the mouse hippocampus. Neuropharmacology. 2011 Jul-Aug;61(1-2):305-12. doi: 10.1016/j.neuropharm.2011.04.017. Epub 2011 May 5. PubMed PMID: 21569781; PubMed Central PMCID: PMC3106418.

20: Rosenblatt AE, Garcia MI, Lyons L, Xie Y, Maiorino C, Désiré L, Slingerland J, Burnstein KL. Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer. Endocr Relat Cancer. 2011 Feb 23;18(2):207-19. doi: 10.1677/ERC-10-0049. Print 2011 Apr. PubMed PMID: 21118977; PubMed Central PMCID: PMC3644524.