E7107

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C40H66N2O9
Molecular Weight	718.96
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(O[C@@H]1C[C@@](C)(O)\C=C\C=C(/C)[C@@]2([H])OC(=O)C[C@H](O)CC[C@@](C)(O)[C@@H](OC(=O)N3CCN(CC3)C4CCCCCC4)\C=C\[C@@H]2C)[C@H](C)[C@@H](O)CC

InChI

InChIKey=MNOMBFWMICHMKG-MGYWSNOQSA-N

InChI=1S/C40H66N2O9/c1-7-32(44)29(4)37-33(49-37)26-39(5,47)19-12-13-27(2)36-28(3)16-17-34(40(6,48)20-18-31(43)25-35(45)51-36)50-38(46)42-23-21-41(22-24-42)30-14-10-8-9-11-15-30/h12-13,16-17,19,28-34,36-37,43-44,47-48H,7-11,14-15,18,20-26H2,1-6H3/b17-16+,19-12+,27-13+/t28-,29+,31+,32-,33+,34-,36+,37+,39-,40+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C40H66N2O9
Molecular Weight	718.96
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 10
E/Z Centers	2
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800019245 | https://clinicaltrials.gov/ct2/show/NCT00499499 | https://www.ncbi.nlm.nih.gov/pubmed/27135740 | https://www.ncbi.nlm.nih.gov/pubmed/21363962

E7107 is a semisynthetic derivative of the natural product pladienolide B which was originally isolated from Streptomyces platensis. E7107 is the first compound a new class of anti-cancer agents targeting the spliceosome. Specifically E7107 interacts with the Splicing factor 3B subunit 1 (SF3b1) to block the normal splicing of oncogenes. Development of E7107 was suspended after Phase I clinical trials due to an unacceptable profile of adverse events.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Splicing factor 3B subunit 1 1 Target ID: O75533 Gene ID: 23451.0 Gene Symbol: SF3B1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/21363962	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT00459823/	Primary		Phase I 428	Unknown Approved Use Unknown
Leukemia 87 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27135740	Primary		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
28.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23983259	4 mg/m² single, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		E7107 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
260 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23983259	4 mg/m² 1 times / day steady-state, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		E7107 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
34.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23983259	4 mg/m² single, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		E7107 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
37.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23983259	4 mg/m² 1 times / day steady-state, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		E7107 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23983259	4 mg/m² single, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		E7107 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23983259	4 mg/m² 1 times / day steady-state, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		E7107 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5.7 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 5.7 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 5.7 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	DLT: Diarrhea, Myocardial infarction... Disc. AE: Diarrhea, Vomiting... Dose limiting toxicities: Diarrhea (grade 2, 25%) Myocardial infarction (grade 4, 25%) AEs leading to discontinuation/dose reduction: Diarrhea (grade 3-4, 25%) Vomiting (grade 3-4, 25%) Dehydration (grade 3-4, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5
4.3 mg/m2 1 times / day multiple, intravenous MTD Dose: 4.3 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 4.3 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 6 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	Disc. AE: Vision loss... AEs leading to discontinuation/dose reduction: Vision loss (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5

AEs

AE	Significance	Dose	Population
Diarrhea	grade 2, 25% DLT	5.7 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 5.7 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 5.7 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5
Dehydration	grade 3-4, 25% Disc. AE	5.7 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 5.7 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 5.7 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5
Diarrhea	grade 3-4, 25% Disc. AE	5.7 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 5.7 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 5.7 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5
Vomiting	grade 3-4, 25% Disc. AE	5.7 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 5.7 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 5.7 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5
Myocardial infarction	grade 4, 25% DLT	5.7 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 5.7 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 5.7 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5
Vision loss	16.7% Disc. AE	4.3 mg/m2 1 times / day multiple, intravenous MTD Dose: 4.3 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 4.3 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5	unhealthy, 61.3 n = 6 Health Status: unhealthy Condition: Cancer Age Group: 61.3 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/24258465 Page: p.5

Sourcing

Vendor/Aggregator	ID	URL
THE BioTek	bt-266911	https://www.thebiotek.com/product/inhibitors/bt-266911
eNovation Chemicals	D671969	https://www.enovationchem.com/ProductDetails.asp?ProductID=D671969

PubMed

Title	Date	PubMed
The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region.	2011 Mar 1	21363962
Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors.	2013 Nov 15	23983259
Test-firing ammunition for spliceosome inhibition in cancer.	2013 Nov 15	24097858

Patents

Sample Use Guides

In Vivo Use Guide

Human patients with solid tumors were treated at escalating doses beginning at 0.6 mg/m^2. E7107 was received as a 30-minute intravenous infusion on Days 1 and 8 and repeating this cycle every 21 days. Selection of subsequent dose levels was performed according to accelerated design.

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:26:28 GMT 2023` Edited by `admin` on `Fri Dec 15 16:26:28 GMT 2023`
Record UNII	R60DZX1E2N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

E7107

Common Name

English

1-PIPERAZINECARBOXYLIC ACID, 4-CYCLOHEPTYL-, (2S,3S,4E,6S,7R,10R)-7,10-DIHYDROXY-2-((1E,3E,5R)-5-HYDROXY-6-((2R,3R)-3-((1R,2S)-2-HYDROXY-1-METHYLBUTYL)-2-OXIRANYL)-1,5-DIMETHYL-1,3-HEXADIEN-1-YL)-3,7-DIMETHYL-12-OXOOXACYCLODODEC-4-EN-6-YL ESTER

Common Name

English

1-PIPERAZINECARBOXYLIC ACID, 4-CYCLOHEPTYL-, (2S,3S,4E,6S,7R,10R)-7,10-DIHYDROXY-2-((1E,3E,5R)-5-HYDROXY-6-((2R,3R)-3-((1R,2S)-2-HYDROXY-1-METHYLBUTYL)OXIRANYL)-1,5-DIMETHYL-1,3-HEXADIENYL)-3,7-DIMETHYL-12-OXOOXACYCLODODEC-4-EN-6-YL ESTER

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID10978908