HA14-1
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.
1: Niino S, Nakamura Y, Hirabayashi Y, Nagano-Ito M, Ichikawa S. A small molecule inhibitor of Bcl-2, HA14-1, also inhibits ceramide glucosyltransferase. Biochem Biophys Res Commun. 2013 Feb 26. doi:pii: S0006-291X(13)00312-4. 10.1016/j.bbrc.2013.02.052. [Epub ahead of print] PubMed PMID: 23485465.
2: Akl H, Vandecaetsbeek I, Monaco G, Kauskot A, Luyten T, Welkenhuyzen K, Hoylaerts M, De Smedt H, Parys JB, Bultynck G. HA14-1, but not the BH3 mimetic ABT-737, causes Ca2+ dysregulation in platelets and human cell lines. Haematologica. 2013 Feb 12. [Epub ahead of print] PubMed PMID: 23403318.
3: Nyhan MJ, O'Donovan TR, Elzinga B, Crowley LC, O'Sullivan GC, McKenna SL. The BH3 mimetic HA14-1 enhances 5-fluorouracil-induced autophagy and type II cell death in oesophageal cancer cells. Br J Cancer. 2012 Feb 14;106(4):711-8. doi: 10.1038/bjc.2011.604. Epub 2012 Jan 12. PubMed PMID: 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 targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1. J Control Release. 2011 Apr 10;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 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: 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 2009 Dec 22. PubMed PMID: 20022690.
6: Simonin K, Brotin E, Dufort S, Dutoit S, Goux D, N'diaye M, Denoyelle C, Gauduchon P, Poulain L. Mcl-1 is an important determinant of the apoptotic response to the BH3-mimetic molecule HA14-1 in cisplatin-resistant ovarian 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 inhibitor HA14-1 and genistein together adeptly down regulated survival factors and activated cysteine proteases for apoptosis in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells. Brain Res. 2009 Aug 4;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. Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells. 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 of apoptosis 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 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-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 forms a fluorescent albumin complex that can be mistaken for several oxidized ROS 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 of selective Bcl-2 inhibitor HA14-1 treatments on functional activity of magnocellular vasopressinergic neurons of rat hypothalamus. Neurosci Lett. 2008 May 23;437(1):59-64. doi: 10.1016/j.neulet.2008.03.060. Epub 2008 Mar 26. PubMed PMID: 18434013.
13: Wlodkowic D, Skommer J, Pelkonen J. Brefeldin A triggers apoptosis associated with mitochondrial breach and enhances HA14-1- and anti-Fas-mediated cell killing in follicular lymphoma cells. Leuk Res. 2007 Dec;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 small molecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemia cells. 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 by the Bcl-2 antagonist HA14-1. Cancer Lett. 2007 May 8;249(2):294-9. Epub 2006 Oct 19. PubMed PMID: 17055152; PubMed Central PMCID: PMC1924967.
16: Separovic D, Wang S, Awad Maitah MY, Hanada K, Kessel D. Ceramide response post-photodamage is absent after treatment with HA14-1. Biochem Biophys Res Commun. 2006 Jun 30;345(2):803-8. Epub 2006 May 2. PubMed PMID: 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 compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells 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 of HA14-1-induced apoptosis in follicular lymphoma cells. Leuk Res. 2006 Sep;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 small molecule Bcl-2 antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicular lymphoma B cells. Leuk Res. 2006 Mar;30(3):322-31. Epub 2005 Oct 6. PubMed PMID: 16213584.
20: Reiners JJ Jr, Kessel D. Susceptibility of myelomonocytic leukemia U937 cells to the induction of apoptosis by the non-peptidic Bcl-2 ligand HA14-1 is cell cycle phase-dependent. Cancer Lett. 2005 Apr 28;221(2):153-63. PubMed PMID: 15808401; PubMed Central PMCID: PMC2965436.
2: Akl H, Vandecaetsbeek I, Monaco G, Kauskot A, Luyten T, Welkenhuyzen K, Hoylaerts M, De Smedt H, Parys JB, Bultynck G. HA14-1, but not the BH3 mimetic ABT-737, causes Ca2+ dysregulation in platelets and human cell lines. Haematologica. 2013 Feb 12. [Epub ahead of print] PubMed PMID: 23403318.
3: Nyhan MJ, O'Donovan TR, Elzinga B, Crowley LC, O'Sullivan GC, McKenna SL. The BH3 mimetic HA14-1 enhances 5-fluorouracil-induced autophagy and type II cell death in oesophageal cancer cells. Br J Cancer. 2012 Feb 14;106(4):711-8. doi: 10.1038/bjc.2011.604. Epub 2012 Jan 12. PubMed PMID: 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 targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1. J Control Release. 2011 Apr 10;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 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: 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 2009 Dec 22. PubMed PMID: 20022690.
6: Simonin K, Brotin E, Dufort S, Dutoit S, Goux D, N'diaye M, Denoyelle C, Gauduchon P, Poulain L. Mcl-1 is an important determinant of the apoptotic response to the BH3-mimetic molecule HA14-1 in cisplatin-resistant ovarian 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 inhibitor HA14-1 and genistein together adeptly down regulated survival factors and activated cysteine proteases for apoptosis in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells. Brain Res. 2009 Aug 4;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. Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells. 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 of apoptosis 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 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-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 forms a fluorescent albumin complex that can be mistaken for several oxidized ROS 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 of selective Bcl-2 inhibitor HA14-1 treatments on functional activity of magnocellular vasopressinergic neurons of rat hypothalamus. Neurosci Lett. 2008 May 23;437(1):59-64. doi: 10.1016/j.neulet.2008.03.060. Epub 2008 Mar 26. PubMed PMID: 18434013.
13: Wlodkowic D, Skommer J, Pelkonen J. Brefeldin A triggers apoptosis associated with mitochondrial breach and enhances HA14-1- and anti-Fas-mediated cell killing in follicular lymphoma cells. Leuk Res. 2007 Dec;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 small molecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemia cells. 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 by the Bcl-2 antagonist HA14-1. Cancer Lett. 2007 May 8;249(2):294-9. Epub 2006 Oct 19. PubMed PMID: 17055152; PubMed Central PMCID: PMC1924967.
16: Separovic D, Wang S, Awad Maitah MY, Hanada K, Kessel D. Ceramide response post-photodamage is absent after treatment with HA14-1. Biochem Biophys Res Commun. 2006 Jun 30;345(2):803-8. Epub 2006 May 2. PubMed PMID: 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 compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells 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 of HA14-1-induced apoptosis in follicular lymphoma cells. Leuk Res. 2006 Sep;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 small molecule Bcl-2 antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicular lymphoma B cells. Leuk Res. 2006 Mar;30(3):322-31. Epub 2005 Oct 6. PubMed PMID: 16213584.
20: Reiners JJ Jr, Kessel D. Susceptibility of myelomonocytic leukemia U937 cells to the induction of apoptosis by the non-peptidic Bcl-2 ligand HA14-1 is cell cycle phase-dependent. Cancer Lett. 2005 Apr 28;221(2):153-63. PubMed PMID: 15808401; PubMed Central PMCID: PMC2965436.
| Chemical | |
|---|---|
| CAS Num | 65673-63-4 |
| Chemical Formula | C17H17BrN2O5 |
| Molecular Weight | 409.23 |
| IUPAC Chemical Name | (R)-ethyl 2-amino-6-bromo-4-((R)-1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate |
| Exact Mass | 408.03208 |
| Elemental Analysis | C, 49.89; H, 4.19; Br, 19.53; N, 6.85; O, 19.55 |
| Synonym | HA-141, HA 141, HA141 |
| Solubility | Soluble in DMSO |
| 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 |
| Biological | |
| Targets and Effects | COX-2 inhibitor |
| Pathways | Apoptosis |
| Physical | |
| 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). |
| Shelf Life | >5 years if stored properly |
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