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Eribulin Mesylate

Product Name
Eribulin Mesylate
CAS No.
441045-17-6
Chemical Name
Eribulin Mesylate
Synonyms
Halaven;Eribulin Mesilate;E7389 mesylate;B1939 mesylate;Ibrine mesylate;Ezebrine mesylate;Eribulin Mesylate;Irebulin mesylate;ER-086526 mesylate;Eribulin Mesylate (E7389)
CBNumber
CB32563308
Molecular Formula
C41H63NO14S
Formula Weight
826.01
MOL File
441045-17-6.mol
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Eribulin Mesylate Property

storage temp. 
Store at -20°C, protect from light, stored under nitrogen
solubility 
Soluble in DMSO
form 
Powder
color 
White to off-white
InChI
InChI=1/C40H59NO11.CH4O3S/c1-19-11-24-5-7-28-20(2)12-26(45-28)9-10-40-17-33-36(51-40)37-38(50-33)39(52-40)35-29(49-37)8-6-25(47-35)13-22(42)14-27-31(16-30(46-24)21(19)3)48-32(34(27)44-4)15-23(43)18-41;1-5(2,3)4/h19,23-39,43H,2-3,5-18,41H2,1,4H3;1H3,(H,2,3,4)/t19-,23+,24+,25-,26+,27+,28+,29+,30-,31+,32-,33-,34-,35+,36+,37+,38-,39+,40+;/s3
InChIKey
QAMYWGZHLCQOOJ-PEKQNERQNA-N
SMILES
S(O)(=O)(=O)C.C=C1[C@]2([H])CC[C@@]3([H])C[C@@H](C)C(=C)[C@@]([H])(C[C@]4([H])O[C@H](C[C@H](O)CN)[C@H](OC)[C@@]4([H])CC(=O)C[C@@]4([H])CC[C@]5([H])O[C@]6([H])[C@@]7([H])O[C@@]8([H])[C@]6([H])O[C@](C8)(O[C@@]7([H])[C@@]5([H])O4)CC[C@]([H])(O2)C1)O3 |&1:7,11,14,18,21,24,26,30,33,39,43,46,48,51,53,56,59,61,66,r|
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

ChemScene
Product number
CS-2803
Product name
Eribulin(mesylate)
Purity
99.52%
Packaging
500ug
Price
$1020
Updated
2021/12/16
ChemScene
Product number
CS-2803
Product name
Eribulin(mesylate)
Purity
99.52%
Packaging
1mg
Price
$1200
Updated
2021/12/16
ApexBio Technology
Product number
B3386
Product name
Eribulinmesylate
Packaging
500ug
Price
$1559
Updated
2021/12/16
ApexBio Technology
Product number
B3386
Product name
Eribulinmesylate
Packaging
1mg
Price
$1969
Updated
2021/12/16
American Custom Chemicals Corporation
Product number
API0024271
Product name
ERIBULIN MESYLATE
Purity
95.00%
Packaging
1MG
Price
$5355
Updated
2021/12/16
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Eribulin Mesylate Chemical Properties,Usage,Production

Uses

Eribulin Mesylate is a synthetic analog of the marine natural product halichondrin B.

Definition

ChEBI: Eribulin mesylate is a methanesulfonate salt obtained by reaction of eribulin with one equivalent of methanesulfonic acid. A fully synthetic macrocyclic ketone analogue of marine sponge natural products. Inhibits growth phase of microtubules via tubulin-based antimitotic mechanism, which leads to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. It has a role as an antineoplastic agent and a microtubule-destabilising agent. It contains an eribulin(1+).

Clinical Use

Eribulin is a highly potent cytotoxic agent approved in the U.S. for the treatment of metastatic breast cancer for patients who have received at least two previous chemotherapeutic regimens. Eribulin was discovered and developed by Eisai and it is currently undergoing clinical evaluation for the treatment of sarcoma (PhIII) and non-small cell lung cancer which shows progression after platinumbased chemotherapy and for the treatment of prostate cancer (PhII). Early stage clinical trials are also underway to evaluate eribulin’s efficacy against a number of additional cancers. Eribulin is a structural analog of the marine natural product halichondrin B. Its mechanism of action involves the disruption of mitotic spindle formation and inhibition of tubulin polymerization which results in the induction of cell cycle blockade in the G2/M phase and apoptosis.

Clinical Use

Eribulin mesylate, a nontaxane, completely synthetic microtubule inhibitor, has recently been approved by the U.S. Food and Drug Administration as third-line treatment of metastatic breast cancer refractory to anthracyclines and taxanes.

Side effects

Eribulin Mesylate (Halaven) may cause serious side effects including:hives; difficulty breathing; swelling of your face, lips, tongue, or throat; chest pain; severe dizziness; fast or pounding heartbeats, numbness, tingling, or burning pain in your hands or feet; pain or burning when you urinate; confusion; uneven heart rate; extreme thirst; increased urination; leg discomfort; muscle weakness; limp feeling; fever; chill; painful mouth sores; pain when swallowing; cough; trouble breathing; pale skin; easy bruising; sore throat; skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Toxicology

Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5 percent). Single doses of 0.75 mg/kg were lethal to rats and two doses of 0.075 mg/kg were lethal to dogs. The no-observed-adverse-effect level (NOAEL) in rats and dogs were 0.015 and 0.0045 mg/kg/day, respectively.

Synthesis

Several synthetic routes for the preparation of eribulin have been disclosed, each of which utilizes the same strategy described by Kishi and co-workers for the total synthesis of halichondrin B. Although the scales of these routes were not disclosed in all cases, this review attempts to highlight what appears to be the production-scale route based on patent literature. Nonetheless, the synthesis of eribulin represents a significant accomplishment in the field of total synthesis and brings a novel chemotherapeutic option to cancer patients.
The strategy to prepare eribulin mesylate (V) employs a convergent synthesis featuring the following: the late stage coupling of sulfone 22 and aldehylde 23 followed by macrocyclization under Nozaki-Hiyami-Kishi coupling conditions, formation of a challenging cyclic ketal, and installation of the primary amine. Sulfone 22 was further simplified to aldehyde 24 and vinyl triflate 25 which were coupled through a Nozaki-Hiyami-Kishi reaction.




With the three key fragments 23, 24 and 25 along with the entire molecule completed, the next step was to assemble them and complete the synthesis of eribulin. Aldehyde 24 was coupled to vinyl triflate 25 using an asymmetric Nozaki- Hiyami-Kishi reaction using CrCl2, NiCl2, Et3N and chiral ligand 67 (the Scheme) to give alcohol 83 (Scheme 11). Formation of the THP ring was accomplished by reaction with KHMDS which allowed for displacement of the mesylate with the secondary alcohol and provided the THP containing product in 72% yield for the three steps. The pivalate ester group was removed with DIBAL-H to give the western fragment 22 in 92% yield.
The completion of the synthesis of eribulin is illustrated in Scheme 12. The lithium anion of sulfone 22 generated upon reaction with nBuLi was coupled to aldehyde 23 to give diol 84 in 84% yield. Both of the alcohol functional groups of 84 were oxidized using a Dess-Martin oxidation in 90% yield and the resulting sulfone was removed via a reductive cleavage upon reaction with SmI2 to give ketoaldehyde 85 in 85% yield. Macrocyclization of 85 was accomplished via an asymmetric Nozaki Hiyami-Kishi reaction using CrCl2, NiCl2, Et3N and chiral ligand 67 to give alcohol 86 in 70% yield.
Modified Swern oxidation of the alcohol provided the corresponding ketone in 91% yield and this was followed by removal of the five silyl ether protecting groups upon reaction with TBAF and subsequent cyclization to provide ketone 87. Compound 87 was treated with PPTS to provide the ?°caged?± cyclic ketal 88 in 79% over two steps. The vicinal diol of 88 was reacted with Ts2O in collidine to affect selective tosylation of the primary alcohol and this crude product was reacted with ammonium hydroxide to install the primary amine to give eribulin which was treated with methanesulfonic acid in aqueous ammonium hydroxide to give eribulin mesylate (V) in 84% yield over the final 3 steps.


Mode of action

Eribulin Mesylate is the mesylate salt of a synthetic analogue of halichondrin B, a substance derived from a marine sponge (Lissodendoryx sp.) with antineoplastic activity. Eribulin binds to the vinca domain of tubulin and inhibits the polymerization of tubulin and the assembly of microtubules, resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest at G2/M phase, and, potentially, tumor regression.

References

Eribulin mesylate: a novel halichondrin B analogue for the treatment of metastatic breast cancer DOI: 10.2146/ajhp110237
From micrograms to grams: scale-up synthesis of eribulin mesylate DOI: 10.1039/c3np70051h
Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent DOI: 10.1158/1078-0432.CCR-14-3252

Eribulin Mesylate Preparation Products And Raw materials

Raw materials

Preparation Products

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Eribulin Mesylate Suppliers

Hubei Zhongshan Medical Technology Co., Ltd
Tel
027-61907345 13397111514
Fax
3443707954
Email
w13397111514@163.com
Country
China
ProdList
1010
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58
WuYan Pharmaceutical Technology (Shanghai) Co., Ltd.
Tel
021-61001086 13671938079
Fax
021-61114075
Email
sales@wuyanpharm.com
Country
China
ProdList
104
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Hefei Hirisun Pharmatech Co., Ltd.
Tel
+86-0551-62678551 +86-15056975894
Fax
0551-62678551
Email
sales@hirisunpharm.com
Country
China
ProdList
181
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Wuhan Wiseman Bioengineering Co.,Ltd
Tel
027-59506022 13419526507
Fax
027-59506022
Email
13419526507@163.com
Country
China
ProdList
2945
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58
Abydos Scientific
Tel
025-84767922 18936879710
Email
sales@abydoscientific.com
Country
China
ProdList
1006
Advantage
58
Shanghai Haoyuan Chemexpress Co., Ltd.
Tel
021-58950125
Fax
021-58955996
Email
info@chemexpress.com
Country
China
ProdList
775
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58
Nanjing Becas pharmatech Ltd.
Tel
13912903754
Email
info@becaspharma.com
Country
China
ProdList
2386
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58
Chemvon Biotechnology Co., Ltd
Tel
021-50790412
Fax
+86-21-50790419
Email
info@chemvon.com
Country
China
ProdList
371
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57
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6005
Advantage
61
Energy Chemical
Tel
021-021-58432009 400-005-6266
Fax
021-58436166
Email
sales8178@energy-chemical.com
Country
China
ProdList
44689
Advantage
61
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View Lastest Price from Eribulin Mesylate manufacturers

WUHAN FORTUNA CHEMICAL CO., LTD
Product
Eribulin Mesylate 441045-17-6
Price
US $0.00/g
Min. Order
1g
Purity
99%min
Supply Ability
100g
Release date
2021-11-09
Hebei Yanxi Chemical Co., Ltd.
Product
Eribulin Mesylate 441045-17-6
Price
US $25.00-10.00/kg
Min. Order
1kg
Purity
0.99
Supply Ability
10 tons
Release date
2023-11-23
Changzhou Rokechem Technology Co., Ltd.
Product
Eribulin Mesylate 441045-17-6
Price
US $0.00-0.00/Kg
Min. Order
1Kg
Purity
99%;USP/EP/CP
Supply Ability
1-10000kgs
Release date
2023-06-27

441045-17-6, Eribulin MesylateRelated Search:


  • Eribulin Mesylate
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  • Eribulin Mesilate
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  • Eribulin Mesylate (E7389)
  • Ibrine mesylate
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  • ER 086526,E-7389,Eribulin,metastatic,B1939,Inhibitor,Eribulin mesylate,inhibit,breast,Microtubule/Tubulin,cancer,Apoptosis,E7389,B 1939,B-1939,microtubule,E 7389,ER-086526,ER086526
  • Irebulin mesylate
  • Eribulin Mesylate iMpurity
  • (2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24S,26R,28R,29aS)-2-[(2S)-3-Amino-2-hydroxypropyl]hexacosahydro-3-methoxy-26-methyl-20,27-bis(methylene)-11,15:18,21:24,28-triepoxy-7,9-ethano-12,15-methano-9H,15H-furo[3,2-i]furo[2′,3′:5,6]pyrano[4,3-b][1,4]dioxacyclopentacosin-5(4H)-one methanesulfonate
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  • 441045-17-6
  • C40H59NO11CH4O3S
  • C41H63NO14S
  • API
  • API
  • 441045-17-6