Synonym
Cariporide; HOE642; HOE-642; HOE 642;
IUPAC/Chemical Name
N-(Diaminomethylidene)-3-methylsulfonyl-4-propan-2-ylbenzamide
InChi Key
IWXNYAIICFKCTM-UHFFFAOYSA-N
InChi Code
InChI=1S/C12H17N3O3S/c1-7(2)9-5-4-8(11(16)15-12(13)14)6-10(9)19(3,17)18/h4-7H,1-3H3,(H4,13,14,15,16)
SMILES Code
O=C(/N=C(N)\N)C1=CC=C(C(C)C)C(S(=O)(C)=O)=C1
Purity
>95% (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
2934.99.03.00
Biological target:
Cariporide (HOE-642) is a selective Na+/H+ exchange inhibitor.
In vitro activity:
Cariporide significantly decreased NHE1 expression in breast cancer cells (Fig. (Fig.2e,2e, f), where it inhibited the proliferation of MCF-7 and MCF-7/ADR cells in a dose- and time- dependent manner, as assessed by CCK8 assays with a range of concentrations (Fig. (Fig.2a),2a), of doxorubicin (Fig. (Fig.2b)2b) or paclitaxel (Fig. (Fig.2c)2c) in culture for 24 and 48 h. In addition, after cotreatment with cariporide and doxorubicin, the IC50 value decreased to 17.16 ± 0.06 μg/ml(2.463-fold), which was significantly lower than in cells treated with doxorubicin only. The same results were observed in the paclitaxel-only and cotreatment groups (Fig. (Fig.2c,2c, d). These results suggest that cariporide can sensitize drug-resistant cells to chemotherapeutic drugs after the cotreatment with cariporide and doxorubicin or paclitaxel.
Reference: BMC Cancer. 2019 Mar 8;19(1):211. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30849956/
In vivo activity:
After continuous intraperitoneal injection of cariporide (3 mg/kg) for 7 days, the body weight and behavior of nude mice showed no significant toxic effects. However, cariporide significantly retarded the growth of tumors in vivo (Fig. (Fig.4e).4e). The tumor volumes and weights significantly decreased in the two cariporide-treated groups compared to the other assayed groups (Fig. (Fig.4f,4f, g). In detail, no significant difference in the body weight of each group was detected initially, but decreases in body weight were observed 15 days after administration, and even the control group and single ADR group were significantly lower on day 21 (Fig. (Fig.4f).4f). These data suggest that NHE1 is an upstream effector of the process of cariporide-induced inhibition of breast cancer cell proliferation. Collectively, cariporide inhibited the growth of implanted breast cancer and increased its sensitivity to doxorubicin in nude mice.
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30849956/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
87.0 |
307.04 |
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
283.34
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 |
In vitro protocol:
1. Chen Q, Liu Y, Zhu XL, Feng F, Yang H, Xu W. Increased NHE1 expression is targeted by specific inhibitor cariporide to sensitize resistant breast cancer cells to doxorubicin in vitro and in vivo. BMC Cancer. 2019 Mar 8;19(1):211. doi: 10.1186/s12885-019-5397-7. PMID: 30849956; PMCID: PMC6408845.
2. Teshima Y, Akao M, Jones SP, Marbán E. Cariporide (HOE642), a selective Na+-H+ exchange inhibitor, inhibits the mitochondrial death pathway. Circulation. 2003 Nov 4;108(18):2275-81. doi: 10.1161/01.CIR.0000093277.20968.C7. Epub 2003 Oct 20. PMID: 14568900.
In vivo protocol:
1. Chen Q, Liu Y, Zhu XL, Feng F, Yang H, Xu W. Increased NHE1 expression is targeted by specific inhibitor cariporide to sensitize resistant breast cancer cells to doxorubicin in vitro and in vivo. BMC Cancer. 2019 Mar 8;19(1):211. doi: 10.1186/s12885-019-5397-7. PMID: 30849956; PMCID: PMC6408845.
2. Albatany M, Li A, Meakin S, Bartha R. In vivo detection of acute intracellular acidification in glioblastoma multiforme following a single dose of cariporide. Int J Clin Oncol. 2018 Oct;23(5):812-819. doi: 10.1007/s10147-018-1289-0. Epub 2018 May 10. PMID: 29749579.
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8: Madonna R, Cevik C, Nasser M. Electrical plasticity and cardioprotection in myocardial ischemia--role of selective sodium channel blockers. Clin Cardiol. 2013 May;36(5):255-61. doi: 10.1002/clc.22113. Epub 2013 Mar 25. Review. PubMed PMID: 23529949.
9: Karmazyn M. NHE-1: still a viable therapeutic target. J Mol Cell Cardiol. 2013 Aug;61:77-82. doi: 10.1016/j.yjmcc.2013.02.006. Epub 2013 Feb 18. Review. PubMed PMID: 23429008.
10: Avkiran M, Cook AR, Cuello F. Targeting Na+/H+ exchanger regulation for cardiac protection: a RSKy approach? Curr Opin Pharmacol. 2008 Apr;8(2):133-40. doi: 10.1016/j.coph.2007.12.007. Epub 2008 Jan 28. Review. PubMed PMID: 18222727.
11: Saint DA. The role of the persistent Na(+) current during cardiac ischemia and hypoxia. J Cardiovasc Electrophysiol. 2006 May;17 Suppl 1:S96-S103. Review. PubMed PMID: 16686689.
12: Baartscheer A. Chronic inhibition of na(+)/h(+)-exchanger in the heart. Curr Vasc Pharmacol. 2006 Jan;4(1):23-9. Review. PubMed PMID: 16472174.
13: Lee C, Dhalla NS, Hryshko LV. Therapeutic potential of novel Na+-Ca2+ exchange inhibitors in attenuating ischemia-reperfusion injury. Can J Cardiol. 2005 May 1;21(6):509-16. Review. PubMed PMID: 15917880.
14: Moens AL, Claeys MJ, Timmermans JP, Vrints CJ. Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. Int J Cardiol. 2005 Apr 20;100(2):179-90. Review. PubMed PMID: 15823623.
15: Pisarenko OI. [Na+/H+ exchange inhibitors: a new class of cardioprotectors]. Ross Fiziol Zh Im I M Sechenova. 2004 Sep;90(9):1103-12. Review. Russian. PubMed PMID: 15559784.
16: Reffelmann T, Kloner RA. Microvascular alterations after temporary coronary artery occlusion: the no-reflow phenomenon. J Cardiovasc Pharmacol Ther. 2004 Sep;9(3):163-72. Review. Erratum in: J Cardiovasc Pharmacol Ther. 2004 Dec;9(4):following 289. Reffemann, Thorsten [corrected to Reffelmann, Thorsten]. PubMed PMID: 15378136.
17: Bolli R, Becker L, Gross G, Mentzer R Jr, Balshaw D, Lathrop DA; NHLBI Working Group on the Translation of Therapies for Protecting the Heart from Ischemia. Myocardial protection at a crossroads: the need for translation into clinical therapy. Circ Res. 2004 Jul 23;95(2):125-34. Review. PubMed PMID: 15271864.
18: Kloner RA, Rezkalla SH. Cardiac protection during acute myocardial infarction: where do we stand in 2004? J Am Coll Cardiol. 2004 Jul 21;44(2):276-86. Review. PubMed PMID: 15261919.
19: Moukarbel GV, Ayoub CM, Abchee AB. Pharmacological therapy for myocardial reperfusion injury. Curr Opin Pharmacol. 2004 Apr;4(2):147-53. Review. PubMed PMID: 15063358.
20: Linz WJ, Busch AE. NHE-1 inhibition: from protection during acute ischaemia/reperfusion to prevention/reversal of myocardial remodelling. Naunyn Schmiedebergs Arch Pharmacol. 2003 Oct;368(4):239-46. Epub 2003 Sep 19. Review. PubMed PMID: 14504689.
