E7974

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

MedKoo CAT#: 201110

CAS#: 610787-07-0

Description: E7974 is an analog of the sponge-derived anti-microtubule tripeptide hemiasterlin with antimitotic and potential antineoplastic activities. Hemiasterlin analog E7974 binds to the Vinca domain on tubulin, resulting in inhibition of tubulin polymerization and microtubule assembly; depolymerization of exsiting microtubules; inhibition of mitosis; and inhibition of cellular proliferation. This agent may have more affinity for the beta-3 tubulin isotype. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).


Chemical Structure

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E7974
CAS# 610787-07-0

Theoretical Analysis

MedKoo Cat#: 201110
Name: E7974
CAS#: 610787-07-0
Chemical Formula: C24H43N3O4
Exact Mass: 437.32536
Molecular Weight: 437.61
Elemental Analysis: C, 65.87; H, 9.90; N, 9.60; O, 14.62

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Synonym: E-7974; E 7974; E7974.

IUPAC/Chemical Name: (S,E)-4-((S)-2-((R)-1-isopropylpiperidine-2-carboxamido)-N,3,3-trimethylbutanamido)-2,5-dimethylhex-2-enoic acid.

InChi Key: FWYMMXUDTATKLG-PGLMLKKXSA-N

InChi Code: InChI=1S/C24H43N3O4/c1-15(2)19(14-17(5)23(30)31)26(9)22(29)20(24(6,7)8)25-21(28)18-12-10-11-13-27(18)16(3)4/h14-16,18-20H,10-13H2,1-9H3,(H,25,28)(H,30,31)/b17-14+/t18-,19-,20-/m1/s1

SMILES Code: CC(C)[C@H](N(C)C([C@@H](NC([C@@H]1N(C(C)C)CCCC1)=O)C(C)(C)C)=O)/C=C(C)/C(O)=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: >5 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

Preparing Stock Solutions

The following data is based on the product molecular weight 437.61 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.

Recalculate based on batch purity %
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

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1: Rocha-Lima CM, Bayraktar S, Macintyre J, Raez L, Flores AM, Ferrell A, Rubin EH, Poplin EA, Tan AR, Lucarelli A, Zojwalla N. A phase 1 trial of E7974 administered on day 1 of a 21-day cycle in patients with advanced solid tumors. Cancer. 2012 Sep 1;118(17):4262-70. doi: 10.1002/cncr.27428. Epub 2012 Jan 31. PubMed PMID: 22294459.

2: Meir A, Rubinsky B. Distributed network, wireless and cloud computing enabled 3-D ultrasound; a new medical technology paradigm. PLoS One. 2009 Nov 19;4(11):e7974. doi: 10.1371/journal.pone.0007974. PubMed PMID: 19936236; PubMed Central PMCID: PMC2775631.

3: Kuznetsov G, TenDyke K, Towle MJ, Cheng H, Liu J, Marsh JP, Schiller SE, Spyvee MR, Yang H, Seletsky BM, Shaffer CJ, Marceau V, Yao Y, Suh EM, Campagna S, Fang FG, Kowalczyk JJ, Littlefield BA. Tubulin-based antimitotic mechanism of E7974, a novel analogue of the marine sponge natural product hemiasterlin. Mol Cancer Ther. 2009 Oct;8(10):2852-60. doi: 10.1158/1535-7163.MCT-09-0301. PubMed PMID: 19825803.



Additional Information

E7974 inhibits polymerization of purified tubulin in vitro with IC(50) values similar to those of vinblastine. In cultured human cancer cells, E7974 induces G(2)-M arrest and marked disruption of mitotic spindle formation characteristic of tubulin-targeted anticancer drugs. Extensive hypodiploid cell populations are seen in E7974-treated cells, indicating initiation of apoptosis after prolonged G(2)-M blockage. Consistent with this observation, E7974 induces caspase-3 activation and poly ADP ribose polymerase cleavage, typical biochemical markers of apoptosis. Only a short cellular exposure to E7974 is sufficient to induce maximum mitotic arrest, suggesting that E7974's antitumor effects in vivo may persist even after blood levels of the drug decrease after drug administration. Interactions of E7974 with purified tubulin were investigated using two synthetic tritiated photoaffinity analogues incorporating a benzophenone photoaffinity moiety at two different positions of the E7974 scaffold. Both analogues preferentially photolabeled alpha-tubulin, although minor binding to beta-tubulin was also detected. E7974 thus seems to share a unique, predominantly alpha-tubulin-targeted mechanism with other hemiasterlin-based compounds, suggesting that, unlike many tubulin-targeted natural products and related drugs, the hemiasterlins evolved to mainly target alpha-tubulin, not beta-tubulin subunits. (see http://www.ncbi.nlm.nih.gov/pubmed/19825803 .)      
E7974 inhibits polymerization of purified tubulin in vitro with IC(50) values similar to those of vinblastine. In cultured human cancer cells, E7974 induces G(2)-M arrest and marked disruption of mitotic spindle formation characteristic of tubulin-targeted anticancer drugs. Extensive hypodiploid cell populations are seen in E7974-treated cells, indicating initiation of apoptosis after prolonged G(2)-M blockage. Consistent with this observation, E7974 induces caspase-3 activation and poly ADP ribose polymerase cleavage, typical biochemical markers of apoptosis. Only a short cellular exposure to E7974 is sufficient to induce maximum mitotic arrest, suggesting that E7974's antitumor effects in vivo may persist even after blood levels of the drug decrease after drug administration. Interactions of E7974 with purified tubulin were investigated using two synthetic tritiated photoaffinity analogues incorporating a benzophenone photoaffinity moiety at two different positions of the E7974 scaffold. Both analogues preferentially photolabeled alpha-tubulin, although minor binding to beta-tubulin was also detected. E7974 thus seems to share a unique, predominantly alpha-tubulin-targeted mechanism with other hemiasterlin-based compounds, suggesting that, unlike many tubulin-targeted natural products and related drugs, the hemiasterlins evolved to mainly target alpha-tubulin, not beta-tubulin subunits. (see http://www.ncbi.nlm.nih.gov/pubmed/19825803 .)