OSI-7904

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H24N4O6
Molecular Weight	500.5027
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NC2=C(C(=O)N1)C3=CC(CNC4=CC=C5C(=O)N(CC5=C4)[C@@H](CCC(O)=O)C(O)=O)=CC=C3C=C2

InChI

InChIKey=BRVFNEZMTRVUGW-QFIPXVFZSA-N

InChI=1S/C27H24N4O6/c1-14-29-21-7-4-16-3-2-15(10-20(16)24(21)25(34)30-14)12-28-18-5-6-19-17(11-18)13-31(26(19)35)22(27(36)37)8-9-23(32)33/h2-7,10-11,22,28H,8-9,12-13H2,1H3,(H,32,33)(H,36,37)(H,29,30,34)/t22-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C27H24N4O6
Molecular Weight	500.5027
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14982966 | https://www.ncbi.nlm.nih.gov/pubmed/17364234

OSI-7904L is a liposomal formulation of the highly specific, noncompetitive thymidylate synthase inhibitor OSI-7904 (also known as GW1843, BW1843U89, and GS7904). The liposome formulation was developed to enhance the therapeutic index and dose schedule convenience of this potent antifolate compound. This drug was studied in phase II clinical trial in patients to treat head and neck cancer, gastroesophageal adenocarcinoma and advanced biliary cancer, but these studies were discontinued. As an example in case of OSI-7904L, was revealed that its activity was below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilization.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidylate synthase 32 Target ID: P04818 Gene ID: 7298.0 Gene Symbol: TYMS Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14982966	Inhibitor 8297		0.5 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Advanced biliary cancer 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17364234	Primary	Phase II 1132	Unknown Approved Use Unknown
Gastroesophageal junction adenocarcinoma 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16880795	Primary	Phase II 1132	Unknown Approved Use Unknown
Head and neck cancer 50 Sources: https://clinicaltrials.gov/ct2/show/NCT00116909	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
797 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14982966	50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		OSI-7904 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
16900 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14982966	50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		OSI-7904 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
AChemBlock	L22026	http://www.achemblock.com/catalogsearch/result/?q=L22026
AstaTech	P10154	http://astatechinc.com/CPSResult.php?CRNO=P10154
BLD Pharm	BD284708	http://www.bldpharm.com/search/Search.html?keyword=BD284708
Compound Cloud	60863
KeyOrganics	AS-50416	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-50416
MuseChem	I008508	https://www.musechem.com/product/I008508.html
Norris Pharm	NSZB-A219351
eMolecules	205734214	https://orderbb.emolecules.com/search/#?query=205734214
eMolecules	271382851	https://orderbb.emolecules.com/search/#?query=271382851
eMolecules	50281301	https://orderbb.emolecules.com/search/#?query=50281301
eMolecules	56748269	https://orderbb.emolecules.com/search/#?query=56748269
eNovation Chemicals	D497749	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D497749&searchbtn.x=0&searchbtn.y=0

PubMed

Title	Date	PubMed
Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells.	1994	7987985
Pharmacokinetics, safety, and efficacy of a liposome encapsulated thymidylate synthase inhibitor, OSI-7904L [(S)-2-[5-[(1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl]amino-1-oxo-2-isoindolynl]-glutaric acid] in mice.	2004 Jun	14982966
A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer.	2008 Apr	17520255
Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors.	2008 Dec 1	19047127

Sample Use Guides

In Vivo Use Guide

Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI-7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5-FU/LV every 14 days.

Route of Administration: Intravenous

In Vitro Use Guide

The thymidylate synthase-inhibitory effects induced by a 24-h exposure to the folate-based TS inhibitors CB3717, C2-desamino analogs of CB3717 including D1694, and BW1843U89 (OSI-7904L) were quantitated using the MGH-U1 human bladder carcinoma. D1694 and BW1843U89 were the most active TS inhibitors with IC50 values of 2.4 and 0.5 nM, respectively.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:58:36 UTC 2023` Edited by `admin` on `Fri Dec 15 15:58:36 UTC 2023`
Record UNII	ON177ZCE7M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

OSI-7904

Code

English

GW-1843

Code

English

OSI 7904L [WHO-DD]

Code

English

GS7904

Code

English

OSI-7904L

Code

English

BW1843

Code

English

GS-7904

Common Name

English

BW-1843

Code

English

PENTANEDIOIC ACID, 2-(5-(((1,2-DIHYDRO-3-METHYL-1-OXOBENZO(F)QUINAZOLIN-9-YL)METHYL)AMINO)-1,3-DIHYDRO-1-OXO-2H-ISOINDOL-2-YL)-, (2S)-

Systematic Name

English

OSI 7904 [WHO-DD]

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C2021