HA14-1

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

Description:HA14-1 is a potent Bcl-2 inhibitor with potential anticancer activity. HA14-1 induces apoptosis in various human cancer cells. HA14-1 suppressed NF-kappaB activation through inhibition of phosphorylation and degradation of IkappaBalpha. This inhibition was correlated with suppression of NF-kappaB-dependent gene products (c-myc, cyclin D1, cox-2, and IAP-1). Additionally, HA14-1 also markedly sustained TNF-alpha-mediated JNK activation.

Price and Availability

HA14-1, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201460Name: HA14-1CAS#: 65673-63-4Chemical Formula: C17H17BrN2O5Exact Mass: 408.03208Molecular Weight: 409.23Elemental Analysis:C, 49.89; H, 4.19; Br, 19.53; N, 6.85; O, 19.55

Synonym:HA-141, HA 141, HA141

IUPAC/Chemical Name:(R)-ethyl 2-amino-6-bromo-4-((R)-1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate

InChi Key:SXJDCULZDFWMJC-AAEUAGOBSA-N

InChi Code:InChI=1S/C17H17BrN2O5/c1-3-23-16(21)11(8-19)13-10-7-9(18)5-6-12(10)25-15(20)14(13)17(22)24-4-2/h5-7,11,13H,3-4,20H2,1-2H3/t11-,13-/m0/s1

SMILES Code:O=C(C1=C(N)OC2=C(C=C(Br)C=C2)[C@H]1[C@H](C#N)C(OCC)=O)OCC

Technical Data

Additional Information

HA14-1 is a novel cell-permeable low molecular weight Bcl-2 ligand which antagonizes its function and induces apoptosis. In HL-60 cells 50 µM HA14-1 effectively induced apoptosis associated with loss of mitochondrial membrane potential and activation of caspases -9 and -3.  

References

1: Niino S, Nakamura Y, Hirabayashi Y, Nagano-Ito M,Ichikawa S. A small molecule inhibitor of Bcl-2, HA14-1, also inhibitsceramide glucosyltransferase. Biochem Biophys Res Commun. 2013 Feb 26.doi:pii: S0006-291X(13)00312-4. 10.1016/j.bbrc.2013.02.052. [Epub aheadof print] PubMed PMID: 23485465.

2: Akl H, Vandecaetsbeek I, Monaco G, Kauskot A, Luyten T, WelkenhuyzenK, Hoylaerts M, De Smedt H, Parys JB, Bultynck G. HA14-1, but not theBH3 mimetic ABT-737, causes Ca2+ dysregulation in platelets and humancell lines. Haematologica. 2013 Feb 12. [Epub ahead of print] PubMedPMID: 23403318.

3: Nyhan MJ, O"Donovan TR, Elzinga B, Crowley LC, O"Sullivan GC, McKennaSL. The BH3 mimetic HA14-1 enhances 5-fluorouracil-induced autophagy andtype II cell death in oesophageal cancer cells. Br J Cancer. 2012 Feb14;106(4):711-8. doi: 10.1038/bjc.2011.604. Epub 2012 Jan 12. PubMedPMID: 22240779; PubMed Central PMCID: PMC3322956.

4: Weyland M, Manero F, Paillard A, Grée D, Viault G, Jarnet D, Menei P,Juin P, Chourpa I, Benoit JP, Grée R, Garcion E. Mitochondrial targetingby use of lipid nanocapsules loaded with SV30, an analogue of thesmall-molecule Bcl-2 inhibitor HA14-1. J Control Release. 2011 Apr10;151(1):74-82. doi: 10.1016/j.jconrel.2010.11.032. Epub 2010 Dec 5.PubMed PMID: 21138749.

5: Moon DO, Kim MO, Kang SH, Choi YH, Park SY, Kim GY. HA14-1 sensitizesTNF-alpha-induced apoptosis via inhibition of the NF-kappaB signalingpathway: involvement of reactive oxygen species and JNK. Cancer Lett.2010 Jun 1;292(1):111-8. doi: 10.1016/j.canlet.2009.11.014. Epub 2009Dec 22. PubMed PMID: 20022690.

6: Simonin K, Brotin E, Dufort S, Dutoit S, Goux D, N"diaye M, DenoyelleC, Gauduchon P, Poulain L. Mcl-1 is an important determinant of theapoptotic response to the BH3-mimetic molecule HA14-1 in cisplatin-resistantovarian carcinoma cells. Mol Cancer Ther. 2009 Nov;8(11):3162-70. doi:10.1158/1535-7163.MCT-09-0493. Epub 2009 Nov 3. PubMed PMID: 19887550.

7: Mohan N, Karmakar S, Choudhury SR, Banik NL, Ray SK. Bcl-2 inhibitorHA14-1 and genistein together adeptly down regulated survival factorsand activated cysteine proteases for apoptosis in human malignantneuroblastoma SK-N-BE2 and SH-SY5Y cells. Brain Res. 2009 Aug4;1283:155-66. doi: 10.1016/j.brainres.2009.05.097. Epub 2009 Jun 6.PubMed PMID: 19505441; PubMed Central PMCID: PMC3103943.

8: Arisan ED, Kutuk O, Tezil T, Bodur C, Telci D, Basaga H. Smallinhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect ofcisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancercells. Breast Cancer Res Treat. 2010 Jan;119(2):271-81. doi:10.1007/s10549-009-0343-z. Epub 2009 Feb 24. PubMed PMID: 19238538.

9: Heikaus S, van den Berg L, Kempf T, Mahotka C, Gabbert HE, Ramp U.HA14-1 is able to reconstitute the impaired mitochondrial pathway ofapoptosis in renal cell carcinoma cell lines. Cell Oncol.2008;30(5):419-33. PubMed PMID: 18791273.

10: Hamada N, Kataoka K, Sora S, Hara T, Omura-Minamisawa M, Funayama T,Sakashita T, Nakano T, Kobayashi Y. The small-molecule Bcl-2 inhibitorHA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, toheavy-ion radiation. Radiother Oncol. 2008 Nov;89(2):227-30. doi:10.1016/j.radonc.2008.08.006. Epub 2008 Sep 4. PubMed PMID: 18774194.

11: Kessel D, Price M, Reiners JJ Jr. The Bcl-2 antagonist HA14-1 formsa fluorescent albumin complex that can be mistaken for several oxidizedROS probes. Photochem Photobiol. 2008 Sep-Oct;84(5):1272-6. doi:10.1111/j.1751-1097.2008.00371.x. Epub 2008 May 29. PubMed PMID:18513234; PubMed Central PMCID: PMC2743960.

12: Chernigovskaya EV, Nikitina LS, Dorofeeva NA, Glazova MV. Effects ofselective Bcl-2 inhibitor HA14-1 treatments on functional activity ofmagnocellular vasopressinergic neurons of rat hypothalamus. NeurosciLett. 2008 May 23;437(1):59-64. doi: 10.1016/j.neulet.2008.03.060. Epub2008 Mar 26. PubMed PMID: 18434013.

13: Wlodkowic D, Skommer J, Pelkonen J. Brefeldin A triggers apoptosisassociated with mitochondrial breach and enhances HA14-1- and anti-Fas-mediatedcell killing in follicular lymphoma cells. Leuk Res. 2007Dec;31(12):1687-700. Epub 2007 Apr 10. PubMed PMID: 17428536.

14: Oliver L, Mahé B, Gréé R, Vallette FM, Juin P. HA14-1, a smallmolecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemiacells. Leuk Res. 2007 Jun;31(6):859-63. Epub 2007 Jan 16. PubMed PMID:17224180.

15: Kessel D, Reiners JJ Jr. Initiation of apoptosis and autophagy bythe Bcl-2 antagonist HA14-1. Cancer Lett. 2007 May 8;249(2):294-9. Epub2006 Oct 19. PubMed PMID: 17055152; PubMed Central PMCID: PMC1924967.

16: Separovic D, Wang S, Awad Maitah MY, Hanada K, Kessel D. Ceramideresponse post-photodamage is absent after treatment with HA14-1. BiochemBiophys Res Commun. 2006 Jun 30;345(2):803-8. Epub 2006 May 2. PubMedPMID: 16701558; PubMed Central PMCID: PMC2972543.

17: Manero F, Gautier F, Gallenne T, Cauquil N, Grée D, Cartron PF,Geneste O, Grée R, Vallette FM, Juin P. The small organic compoundHA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant gliomacells to induction of cell death. Cancer Res. 2006 Mar 1;66(5):2757-64.PubMed PMID: 16510597.

18: Wlodkowic D, Skommer J, Pelkonen J. Multiparametric analysis ofHA14-1-induced apoptosis in follicular lymphoma cells. Leuk Res. 2006Sep;30(9):1187-92. Epub 2006 Jan 18. PubMed PMID: 16414117.

19: Skommer J, Wlodkowic D, Mättö M, Eray M, Pelkonen J. HA14-1, a smallmolecule Bcl-2 antagonist, induces apoptosis and modulates action ofselected anticancer drugs in follicular lymphoma B cells. Leuk Res. 2006Mar;30(3):322-31. Epub 2005 Oct 6. PubMed PMID: 16213584.

20: Reiners JJ Jr, Kessel D. Susceptibility of myelomonocytic leukemiaU937 cells to the induction of apoptosis by the non-peptidic Bcl-2ligand HA14-1 is cell cycle phase-dependent. Cancer Lett. 2005 Apr28;221(2):153-63. PubMed PMID: 15808401; PubMed Central PMCID:PMC2965436.