LITRONESIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H37N5O4S2
Molecular Weight	511.701
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNCCS(=O)(=O)NC[C@]1(SC(NC(=O)C(C)(C)C)=NN1C(=O)C(C)(C)C)C2=CC=CC=C2

InChI

InChIKey=YVAFBXLHPINSIK-QHCPKHFHSA-N

InChI=1S/C23H37N5O4S2/c1-8-24-14-15-34(31,32)25-16-23(17-12-10-9-11-13-17)28(19(30)22(5,6)7)27-20(33-23)26-18(29)21(2,3)4/h9-13,24-25H,8,14-16H2,1-7H3,(H,26,27,29)/t23-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H37N5O4S2
Molecular Weight	511.701
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/litronesib | https://adisinsight.springer.com/drugs/800023760 | https://www.ncbi.nlm.nih.gov/pubmed/24752449 | https://www.ncbi.nlm.nih.gov/pubmed/26304237

Litronesib is a specific, ATP-uncompetitive, allosteric, and potent small-molecule inhibitor of Eg5 with potential antineoplastic activity. Litronesib selectively inhibits the activity of Eg5, which may result in mitotic disruption, apoptosis and consequently cell death in tumor cells that are actively dividing. Histone-H3 phosphorylation of tumor and proliferating skin cells is a promising pharmacodynamic biomarker for in vivo anticancer activity of litronesib. Litronesib had been in phase I clinical trial for the treatment of solid tumors. The most frequent-related adverse events were hematologic such as neutropenia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Kinesin-like protein KIF11 5 Target ID: P52732 Gene ID: 3832.0 Gene Symbol: KIF11 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24752449	Inhibitor 8297

PubMed

Title	Date	PubMed
Investigation of the mechanism of racemization of litronesib in aqueous solution: unexpected base-catalyzed inversion of a fully substituted carbon chiral center.	2014 Sep	24633856
A Novel Eg5 Inhibitor (LY2523355) Causes Mitotic Arrest and Apoptosis in Cancer Cells and Shows Potent Antitumor Activity in Xenograft Tumor Models.	2015 Nov	26304237
Two Phase 1 dose-escalation studies exploring multiple regimens of litronesib (LY2523355), an Eg5 inhibitor, in patients with advanced cancer.	2017 Feb	28097385
Crystal structure of the Eg5 - K858 complex and implications for structure-based design of thiadiazole-containing inhibitors.	2018 Aug 5	30031975

Patents

Sample Use Guides

In Vivo Use Guide

Days 1, 2, and 3 every 3 weeks at dose level - 5 mg/m²/day

Route of Administration: Intravenous

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:04:56 GMT 2023` Edited by `admin` on `Fri Dec 15 16:04:56 GMT 2023`
Record UNII	6611F8KYCV
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LITRONESIB

Official Name

English

LY-2523355

Code

English

LY 2523355

Code

English

PROPANAMIDE, N-(4-(2,2-DIMETHYL-1-OXOPROPYL)-5-((((2-(ETHYLAMINO)ETHYL)SULFONYL)AMINO)METHYL)-4,5-DIHYDRO-5-PHENYL-1,3,4-THIADIAZOL-2-YL)-2,2-DIMETHYL-, (5R)-

Common Name

English

KF89617

Code

English

Litronesib [WHO-DD]

Common Name

English

KF-89617

Code

English

(-)-N-(4-(2,2-DIMETHYLPROPANOYL)-5-((((2-(ETHYLAMINO)ETHYL)SULFONYL)AMINO)METHYL)-5- PHENYL-4,5-DIHYDRO-1,3,4-THIADIAZOL-2-YL)-2,2-DIMETHYLPROPANAMIDE

Systematic Name

English

LY2523355

Code

English

PROPANAMIDE, N-(4-(2,2-DIMETHYL-1-OXOPROPYL)-5-((((2-(ETHYLAMINO)ETHYL)SULFONYL) AMINO)METHYL)-4,5-DIHYDRO-5-PHENYL-1,3,4-THIADIAZOL-2-YL)-2,2-DIMETHYL-, (-)-

Common Name

English

N-(4-(2,2-DIMETHYLPROPIONYL)-(5R)-5-((2-ETHYLAMINO-ETHANESULFONYLAMINO)METHYL)-5-PHENYL-4,5-DIHYDRO-(1,3,4)THIADIAZOL-2-YL)-2,2-DIMETHYLPROPIONAMIDE

Systematic Name

English

LITRONESIB [USAN]

Common Name

English

KF 89617

Code

English

(R)-N-(4-(2,2-DIMETHYL-PROPIONYL)-5-((2-ETHYLAMINO-ETHANESULFONYLAMINO)-METHYL)-5- PHENYL-4,5-DIHYDRO-(1,3,4)THIADIAZOL-2-YL)-2,2-DIMETHYL-PROPIONAMIDE

Systematic Name

English

litronesib [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67440