Homoharringtonine | CAS#26833-87-4 | CML drug

MedKoo Cat#: 317994 | Name: Homoharringtonine

Description:

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

Homoharringtonine, or Omacetaxine mepesuccinate, is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML). It is a natural product first discovered in Cephalotaxus harringtonia, now manufactured by hemi-synthesis. It was approved by the US FDA in October 2012 for the treatment of adult patients with CML with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs).

Chemical Structure

Homoharringtonine

CAS#26833-87-4

Theoretical Analysis

MedKoo Cat#: 317994

Name: Homoharringtonine

CAS#: 26833-87-4

Chemical Formula: C29H39NO9

Exact Mass: 545.2625

Molecular Weight: 545.62

Elemental Analysis: C, 63.84; H, 7.20; N, 2.57; O, 26.39

Price and Availability

Size	Price	Availability
10mg	USD 120.00	Ready to ship
25mg	USD 240.00	Ready to ship
50mg	USD 420.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,850.00	Ready to Ship
1g	USD 4,350.00	Ready to Ship
2g	USD 6,450.00	2 weeks

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Synonym

Homoharringtonine; Omacetaxine mepesuccinate; CGX635; CGX 635; CGX-635; Myelostat; Ceflatonin; homoharringtonine; homoharringtonine, 3H-labeled, (3(R))-isomer;

IUPAC/Chemical Name

1-((1S,3aR,14bS)-2-methoxy-1,5,6,8,9,14b-hexahydro-4H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]cyclopenta[b]pyrrolo[1,2-a]azepin-1-yl) 4-methyl (S)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)succinate

InChi Key

HYFHYPWGAURHIV-RZCBTRPQSA-N

InChi Code

InChI=1S/C29H39NO9/c1-27(2,33)8-5-10-29(34,16-23(31)36-4)26(32)39-25-22(35-3)15-28-9-6-11-30(28)12-7-18-13-20-21(38-17-37-20)14-19(18)24(25)28/h13-15,24-25,33-34H,5-12,16-17H2,1-4H3/t24-,25-,28+,29+/m1/s1

SMILES Code

O=C(O[C@@H]1C(OC)=C[C@]2(CCC3)N3CCC4=CC5=C(OCO5)C=C4[C@@]21[H])[C@@](CCCC(C)(O)C)(O)CC(OC)=O

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, not in water

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A21T03K22

QC Data

View QC data: current batch, Lot#A21T03K22

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Homoharringtonine (Omacetaxine mepesuccinate; HHT) is a cytotoxic alkaloid with antitumor properties which acts by inhibiting translation elongation.

In vitro activity:

TGF-β stimulation could induce EMT and increase the migration of tumor cells. The study next investigated the effect of HHT (Homoharringtonine) on HCC (hepatocellular carcinoma) cells migration after TGF-β stimulation by transwell migration assay and wound healing assay. As shown in Fig. 4a, c, although the higher number of migration cells was observed in the TGF-β induced HepG2 cells, as compared to controls, the addition of HHT reduced the migrated cells. Importantly, concurrent treatment with HHT and NVP-BHG712 (a small molecule EphB4 kinase-specific inhibitor) had a greater restraint effect on the migration of TGF-β induced HepG2 cells. Wound healing assay showed similar results that HHT could delay the closure of wound gaps in TGF-β induced HepG2 cells, whereas the addition of EphB4 siRNA impaired such effect (Fig. 4b, d). These results indicated that TGF-β induced the migration ability in HepG2 cells, which could be abrogated by EphB4 suppression of HHT. Reference: Cell Death Dis. 2020 Aug; 11(8): 632. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429962/

In vivo activity:

The results of collagen density in the HHT (Homoharringtonine)-treated groups coincided with hematoxylin and eosin staining. Furthermore, HPC analysis was performed to reflect the amount of collagen in intraarticular fibrosis scar tissue. As shown in Fig. Fig.2d, following treatment of HHT, the HPCs of intraarticular scar tissue were significantly decreased compared to that of the control group. The observed results indicated that HHT could inhibit fibroblast proliferation and collagen production, reducing intraarticular fibrosis after knee surgery in rabbits. Reference: J Orthop Surg Res. 2021; 16: 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789651/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	91.62

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 545.62 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. Zhu M, Gong Z, Wu Q, Su Q, Yang T, Yu R, Xu R, Zhang Y. Homoharringtonine suppresses tumor proliferation and migration by regulating EphB4-mediated β-catenin loss in hepatocellular carcinoma. Cell Death Dis. 2020 Aug 14;11(8):632. doi: 10.1038/s41419-020-02902-2. PMID: 32801343; PMCID: PMC7429962. 2. Wang LB, Wang DN, Wu LG, Cao J, Tian JH, Liu R, Ma R, Yu JJ, Wang J, Huang Q, Xiong WY, Zhang X. Homoharringtonine inhibited breast cancer cells growth via miR-18a-3p/AKT/mTOR signaling pathway. Int J Biol Sci. 2021 Mar 2;17(4):995-1009. doi: 10.7150/ijbs.44907. PMID: 33867824; PMCID: PMC8040299. 3. Sun Y, Dai J, Jiao R, Jiang Q, Wang J. Homoharringtonine inhibits fibroblasts proliferation, extracellular matrix production and reduces surgery-induced knee arthrofibrosis via PI3K/AKT/mTOR pathway-mediated apoptosis. J Orthop Surg Res. 2021 Jan 6;16(1):9. doi: 10.1186/s13018-020-02150-2. PMID: 33407698; PMCID: PMC7789651. 4. Wang H, Wang R, Huang D, Li S, Gao B, Kang Z, Tang B, Xie J, Yan F, Liang R, Li H, Yan J. Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway. Front Pharmacol. 2021 Feb 24;12:592071. doi: 10.3389/fphar.2021.592071. PMID: 33716735; PMCID: PMC7943857.

In vitro protocol:

In vivo protocol:

1. Sun Y, Dai J, Jiao R, Jiang Q, Wang J. Homoharringtonine inhibits fibroblasts proliferation, extracellular matrix production and reduces surgery-induced knee arthrofibrosis via PI3K/AKT/mTOR pathway-mediated apoptosis. J Orthop Surg Res. 2021 Jan 6;16(1):9. doi: 10.1186/s13018-020-02150-2. PMID: 33407698; PMCID: PMC7789651. 2. Wang H, Wang R, Huang D, Li S, Gao B, Kang Z, Tang B, Xie J, Yan F, Liang R, Li H, Yan J. Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway. Front Pharmacol. 2021 Feb 24;12:592071. doi: 10.3389/fphar.2021.592071. PMID: 33716735; PMCID: PMC7943857.

1: Klanova M, Andera L, Brazina J, Svadlenka J, Benesova S, Soukup J, Prukova D, Vejmelkova D, Jaksa R, Helman K, Vockova P, Lateckova L, Molinsky J, Maswabi BC, Alam M, Kodet R, Pytlik R, Trneny M, Klener P. Targeting of BCL2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL2- and MCL1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma. Clin Cancer Res. 2016 Mar 1;22(5):1138-49. doi: 10.1158/1078-0432.CCR-15-1191. Epub 2015 Oct 14. PubMed PMID: 26467384. 2: Zhang T, Shen S, Zhu Z, Lu S, Yin X, Zheng J, Jin J. Homoharringtonine binds to and increases myosin-9 in myeloid leukaemia. Br J Pharmacol. 2016 Jan;173(1):212-21. doi: 10.1111/bph.13359. Epub 2015 Dec 1. PubMed PMID: 26448459. 3: Xiao F, Li Y, Xu W, You L, Yang C, Liu H, Qian W. Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB. Oncol Lett. 2016 Jan;11(1):355-359. Epub 2015 Nov 5. PubMed PMID: 26870217; PubMed Central PMCID: PMC4727161. 4: Wu L, Li X, Chang C, Xu F, He Q, Wu D, Zhang Z, Su J, Zhou L, Song L, Chao X, Zhao Y. Efficacy and toxicity of decitabine versus CHG regimen (low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor) in patients with higher risk myelodysplastic syndrome: a retrospective study. Leuk Lymphoma. 2015 Nov 16:1-8. [Epub ahead of print] PubMed PMID: 26397697. 5: Zhou J, Du Q, Sun F, Liu Q, Zhang Z. Enantioseparation of the Six Important Intermediates of Homoharringtonine With Immobilized Cellulose Chiral Stationary Phase. Chirality. 2015 Aug;27(8):538-42. doi: 10.1002/chir.22451. Epub 2015 May 21. PubMed PMID: 25994419. 6: Wolff NC, Pavía-Jiménez A, Tcheuyap VT, Alexander S, Vishwanath M, Christie A, Xie XJ, Williams NS, Kapur P, Posner B, McKay RM, Brugarolas J. High-throughput simultaneous screen and counterscreen identifies homoharringtonine as synthetic lethal with von Hippel-Lindau loss in renal cell carcinoma. Oncotarget. 2015 Jul 10;6(19):16951-62. PubMed PMID: 26219258; PubMed Central PMCID: PMC4627284. 7: Zhou X, Xu N, Li R, Xiao Y, Gao G, Lu Q, Ding L, Li L, Li Y, Du Q, Liu X. A comparative proteomic study of Homoharringtonine-induced apoptosis in leukemia K562 cells. Leuk Lymphoma. 2015 Jul;56(7):2162-9. doi: 10.3109/10428194.2014.976818. Epub 2015 Jan 14. PubMed PMID: 25330443. 8: Cao W, Liu Y, Zhang R, Zhang B, Wang T, Zhu X, Mei L, Chen H, Zhang H, Ming P, Huang L. Homoharringtonine induces apoptosis and inhibits STAT3 via IL-6/JAK1/STAT3 signal pathway in Gefitinib-resistant lung cancer cells. Sci Rep. 2015 Jul 13;5:8477. doi: 10.1038/srep08477. PubMed PMID: 26166037; PubMed Central PMCID: PMC4499885. 9: Han Q, Fu Y, Tao L, Ye J, Wu L, Chen H, Chen L, Jiang X, Sun M. [Study on the effect and mechanism of HL-60 cell apoptosis induced by matrine combined with homoharringtonine]. Zhonghua Xue Ye Xue Za Zhi. 2015 May;36(5):433-5. doi: 10.3760/cma.j.issn.0253-2727.2015.05.018. Chinese. PubMed PMID: 26031535. 10: Philipp S, Sosna J, Plenge J, Kalthoff H, Adam D. Homoharringtonine, a clinically approved anti-leukemia drug, sensitizes tumor cells for TRAIL-induced necroptosis. Cell Commun Signal. 2015 Apr 29;13:25. doi: 10.1186/s12964-015-0103-0. PubMed PMID: 25925126; PubMed Central PMCID: PMC4411737. 11: Wang Y, Lin D, Wei H, Li W, Liu B, Zhou C, Liu K, Mi Y, Wang J. Long-term follow-up of homoharringtonine plus all-trans retinoic acid-based induction and consolidation therapy in newly diagnosed acute promyelocytic leukemia. Int J Hematol. 2015 Mar;101(3):279-85. doi: 10.1007/s12185-014-1730-8. Epub 2015 Jan 7. PubMed PMID: 25563706. 12: Kantarjian H, O'Brien S, Jabbour E, Barnes G, Pathak A, Cortes J. Effectiveness of homoharringtonine (omacetaxine mepesuccinate) for treatment of acute myeloid leukemia: a meta-analysis of Chinese studies. Clin Lymphoma Myeloma Leuk. 2015 Jan;15(1):13-21. doi: 10.1016/j.clml.2014.09.011. Epub 2014 Oct 5. Review. PubMed PMID: 25458084. 13: Chen C, Xu W, Yang J. Low-dose homoharringtonine and cytarabine in combination with granulocyte colony-stimulating factor for elderly patients with de novo acute myeloid leukemia. Leuk Lymphoma. 2015 Jan;56(1):141-6. doi: 10.3109/10428194.2014.910774. Epub 2014 Jun 16. PubMed PMID: 24724783. 14: Xu G, Mao L, Liu H, Yang M, Jin J, Qian W. Sorafenib in combination with low-dose-homoharringtonine as a salvage therapy in primary refractory FLT3-ITD-positive AML: a case report and review of literature. Int J Clin Exp Med. 2015 Nov 15;8(11):19891-4. eCollection 2015. Review. PubMed PMID: 26884901; PubMed Central PMCID: PMC4723746. 15: Zhang J, Chen B, Wu T, Wang Q, Zhuang L, Zhu C, Fan N, Qing W, Ma Y, Xu X. Synergistic Effect and Molecular Mechanism of Homoharringtonine and Bortezomib on SKM-1 Cell Apoptosis. PLoS One. 2015 Nov 6;10(11):e0142422. doi: 10.1371/journal.pone.0142422. eCollection 2015. PubMed PMID: 26544558; PubMed Central PMCID: PMC4636319. 16: Watari A, Hashegawa M, Yagi K, Kondoh M. Homoharringtonine increases intestinal epithelial permeability by modulating specific claudin isoforms in Caco-2 cell monolayers. Eur J Pharm Biopharm. 2015 Jan;89:232-8. doi: 10.1016/j.ejpb.2014.12.012. Epub 2014 Dec 13. PubMed PMID: 25513955. 17: Guo Y, Han S, Cao J, Liu Q, Zhang T. Screening of allergic components mediated by H(1)R in homoharringtonine injection through H(1)R/CMC-HPLC/MS. Biomed Chromatogr. 2014 Dec;28(12):1607-14. doi: 10.1002/bmc.3188. Epub 2014 May 14. PubMed PMID: 24827904. 18: Lu XY, Cao WK, Ye LL, Deng ZK, Zhang XH, Li YF. [Time rhythm of homoharringtonine inducing K562 cell apoptosis and its mechanism]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Jun;22(3):712-6. doi: 10.7534/j.issn.1009-2137.2014.03.026. Chinese. PubMed PMID: 24989282. 19: Huang BT, Zeng QC, Zhao WH, Tan Y. Homoharringtonine contributes to imatinib sensitivity by blocking the EphB4/RhoA pathway in chronic myeloid leukemia cell lines. Med Oncol. 2014 Feb;31(2):836. doi: 10.1007/s12032-013-0836-9. Epub 2014 Jan 11. PubMed PMID: 24415355. 20: Tong Y, Niu N, Jenkins G, Batzler A, Li L, Kalari KR, Wang L. Identification of genetic variants or genes that are associated with Homoharringtonine (HHT) response through a genome-wide association study in human lymphoblastoid cell lines (LCLs). Front Genet. 2015 Jan 13;5:465. doi: 10.3389/fgene.2014.00465. eCollection 2014. PubMed PMID: 25628645; PubMed Central PMCID: PMC4292778.