INDIMITECAN HYDROCHLORIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H21N3O6.ClH
Molecular Weight	495.912
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.COC1=C(OC)C=C2C(=O)N(CCCN3C=CN=C3)C4=C(C(=O)C5=C4C=C6OCOC6=C5)C2=C1

InChI

InChIKey=VZCPAXRDLDYWBE-UHFFFAOYSA-N

InChI=1S/C25H21N3O6.ClH/c1-31-18-8-14-17(11-19(18)32-2)25(30)28(6-3-5-27-7-4-26-12-27)23-15-9-20-21(34-13-33-20)10-16(15)24(29)22(14)23;/h4,7-12H,3,5-6,13H2,1-2H3;1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C25H21N3O6
Molecular Weight	459.4507
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=666716 | http://www.purdue.edu/discoverypark/drug-discovery/clinical-translation/entities/LMP776.php
Curator's Comment: Description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/24517248

Indimitecan, also known as LMP776, is a novel topoisomerase I inhibitor. A substance being studied in the treatment of cancer. It blocks certain enzymes that break and rejoin DNA strands. These enzymes are needed for cells to divide and grow. Blocking them may cause cancer cells to die. Indimitecan (LMP776) also helps anticancer drugs kill cancers that are resistant to some other drugs. LMP776 is a type of indenoisoquinoline and a type of topoisomerase inhibitor. In vitro, LMP776 induces TOP 1 cleavage at unique genomic positions and causes cell cycle arrest in both S and G (2)-M phases. Protein linked DNA breaks were observed in cells treated with nanomolar concentrations of LMP776.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase I 59 Target ID: CHEMBL1781 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24130054\| https://www.ncbi.nlm.nih.gov/pubmed/17974983 \| https://www.ncbi.nlm.nih.gov/pubmed/27029323	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT01051635 http://adisinsight.springer.com/drugs/800044899	Primary		Phase I 428	Unknown Approved Use Unknown
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT01051635 http://adisinsight.springer.com/drugs/800044899	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
438 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30061364	20 mg/m² single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		INDIMITECAN plasma	Canis lupus population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
2004 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30061364	20 mg/m² single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		INDIMITECAN plasma	Canis lupus population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30061364	20 mg/m² single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		INDIMITECAN plasma	Canis lupus population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
MuseChem	I007314	https://www.musechem.com/product/I007314.html

PubMed

Title	Date	PubMed
Alcohol-, diol-, and carbohydrate-substituted indenoisoquinolines as topoisomerase I inhibitors: investigating the relationships involving stereochemistry, hydrogen bonding, and biological activity.	2011 Jul 28	21710981

Patents

Sample Use Guides

In Vivo Use Guide

Indimitecan (LMP 776) administered IV daily x 5 d. Dose level (DL) in mg/m2/day for LMP 776: 1, 2, 3, 4.5 mg

Route of Administration: Intravenous

In Vitro Use Guide

Exponentially growing CEM cells were treated for 1 h with 1 umol/L of Indimitecan (NSC 725776) and processed in the ICE bioassay. NSC 725776 was cytotoxic to the wild-type P388 (IC50 25 nmol/L), MCF-7 (IC50 93 nmol/L), and HCT-116 (IC50 125 nmol/L) cells. Human colon carcinoma HT29 cells were treated with varying doses of NSC 725776 for 6 h. At the lowest concentration used (0.01 umol/L), drug-treated cells accumulated in the G2-phase of the cell cycle. With increasing drug concentrations (>/=0.05 umol/L), the cells also showed an S-phase accumulation.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:15:50 GMT 2023` Edited by `admin` on `Fri Dec 15 17:15:50 GMT 2023`
Record UNII	898F769796
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

INDIMITECAN HYDROCHLORIDE

Common Name

English

5H-(1,3)DIOXOLO(4',5':5,6)INDENO(1,2-C)ISOQUINOLINE-5,12(6H)-DIONE, 6-(3-(1H-IMIDAZOL-1-YL)PROPYL)-2,3-DIMETHOXY-, HYDROCHLORIDE (1:1)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2843