NCATS Inxight Drugs — L-778123 (2024)

L-778123

2A2059P49U

Investigational

Source:

NCT00004057: Phase 1 Interventional Completed Lymphoma

(1998)

Source URL:

https://clinicaltrials.gov/ct2/show/NCT00004057

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H20ClN5O.ClH
Molecular Weight	442.341
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.ClC1=CC=CC(=C1)N2CCN(CC3=CN=CN3CC4=CC=C(C=C4)C#N)CC2=O

InChI

InChIKey=YNBSQYGTJLIPJS-UHFFFAOYSA-N

InChI=1S/C22H20ClN5O.ClH/c23-19-2-1-3-20(10-19)28-9-8-26(15-22(28)29)14-21-12-25-16-27(21)13-18-6-4-17(11-24)5-7-18;/h1-7,10,12,16H,8-9,13-15H2;1H

HIDE SMILES / InChI

Description
Sources:&nbsphttps://www.ncbi.nlm.nih.gov/pubmed/24312815 | https://www.ncbi.nlm.nih.gov/pubmed/12479371

L-778123 is a dual inhibitor of Farnesyl Protein Transferase (FPTase) and Geranylgeranyl Protein Transferase type-I (GGPTase-I), which can completely inhibit Ki-Ras prenylation. L-778123 has been used in phase I clinical trials to determine its effectiveness in treating patients with recurrent or refractory solid tumors. L-778123 was also studied in combination with pacl*taxel to determine efficacy as a treatment for both recurrent or refractory solid tumors, and lymphomas.

Originator

Merck

216

Sources:&nbsphttps://www.ncbi.nlm.nih.gov/pubmed/12479371

Curator's Comment:&nbsp# Merck Research Laboratories

Approval Year

Unknown

139594

Targets

Primary Target	Pharmacology	Condition	Potency
Geranylgeranyl transferase type I 7 Target ID:&nbspCHEMBL2095164 Sources:&nbsphttps://www.ncbi.nlm.nih.gov/pubmed/12479371	Inhibitor 8297		98.0 nM [IC50]
Protein farnesyltransferase 13 Target ID:&nbspCHEMBL2094108 Sources:&nbsphttps://www.ncbi.nlm.nih.gov/pubmed/12479371	Inhibitor 8297		2.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lymphoma 58 Sources:&nbsphttps://clinicaltrials.gov/ct2/show/study/NCT00004057	Primary		Phase I 428	Unknown Approved Use Unknown
Head and neck cancer 50 Sources:&nbsphttps://clinicaltrials.gov/ct2/show/NCT00003430	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
8.09 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	560 mg/m² 1 times / day steady-state, intravenous dose: 560 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.1 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	1120 mg/m² 1 times / day steady-state, intravenous dose: 1120 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.8 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	140 mg/m² 1 times / day steady-state, intravenous dose: 140 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.79 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	35 mg/m² 1 times / day steady-state, intravenous dose: 35 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1310.7 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	560 mg/m² 1 times / day steady-state, intravenous dose: 560 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3179.5 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	1120 mg/m² 1 times / day steady-state, intravenous dose: 1120 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
472.5 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	140 mg/m² 1 times / day steady-state, intravenous dose: 140 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
134.4 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	35 mg/m² 1 times / day steady-state, intravenous dose: 35 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	560 mg/m² 1 times / day steady-state, intravenous dose: 560 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	1120 mg/m² 1 times / day steady-state, intravenous dose: 1120 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	140 mg/m² 1 times / day steady-state, intravenous dose: 140 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11751480	35 mg/m² 1 times / day steady-state, intravenous dose: 35 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:	L-778123 blood	hom*o sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003RNN	https://www.1pchem.com/search?query=1P003RNN
AstaTech	43292	http://astatechinc.com/CPSResult.php?CRNO=43292
AstaTech	F17426	http://astatechinc.com/CPSResult.php?CRNO=F17426
BLD Pharm	BD217452	http://www.bldpharm.com/search/Search.html?keyword=BD217452
Chem Scene	CS-5280	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5280
ChemShuttle	169530	https://www.chemshuttle.com/catalogsearch/result/?q=169530
Debye Scientific	DA-08984	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-08984
Excenen	EX-A748	http://www.excenen.com/searchresultlist.php?id=EX-A748
Hairui	HR145138	http://www.hairuichem.com/en/product/search.do?q=HR145138
KeyOrganics	AS-47972	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-47972
KeyOrganics	DS-20244	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=DS-20244
MedChem Express	HY-16273A	https://www.medchemexpress.com/search.html?q=HY-16273A&ft=&fa=&fp=
MolPort	MolPort-046-069-380	https://www.molport.com/shop/molecule-link/MolPort-046-069-380
Molnova	M17457	https://www.molnova.com/en/serch-list.html?keywords=M17457
MuseChem	I002867	https://www.musechem.com/product/I002867.html
ShangHai Biochempartner	BCP17750	http://www.biochempartner.com/search_BCP17750
TargetMol	T3182	https://www.targetmol.com/search?keyword=T3182
eMolecules	276263515	https://orderbb.emolecules.com/search/#?query=276263515
eMolecules	301037375	https://orderbb.emolecules.com/search/#?query=301037375
eMolecules	49258702	https://orderbb.emolecules.com/search/#?query=49258702
mcule	MCULE-1309571751	https://mcule.com/MCULE-1309571751/
mcule	MCULE-2534139163	https://mcule.com/MCULE-2534139163/

Title	Date	PubMed
Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I.	2002 Jul	12479371
Comparison of Cytotoxic Activity of L778123 as a Farnesyltranferase Inhibitor and Doxorubicin against A549 and HT-29 Cell Lines.	2013	24312815

Sample Use Guides

In Vivo Use Guide

Sources:&nbsphttps://clinicaltrials.gov/ct2/show/NCT00004057

Unknown

Route of Administration: Intravenous

In Vitro Use Guide

Sources:&nbsphttps://www.ncbi.nlm.nih.gov/pubmed/12479371

L-778,123 is an inhibitor of both Farnesyl:protein transferase (FPTase) and geranylgeranyl:protein transferase type-I (GGPTase-I). Using immunoblotting methods that distinguish between prenylated and unprenylated forms of a protein based on differences in their electrophoretic mobility, it was confirmed the activity of L-778,123 as a dual prenyltransferase inhibitor (DPI) in PSN-1 human pancreatic tumor cells. L-778,123 inhibited the prenylation of the FPTase substrate, HDJ2 (EC50 = 92 nm), the GGPTase-I substrate, Rap1A (EC50=6.760 nM), and because it was a DPI, also blocks the prenylation of Ki-Ras (EC50 = 6.300 nM).

Name

Type

Language

L-778123

Sources:

Common Name

English

L-778,123

Sources:

Code

English

BENZONITRILE, 4-((5-((4-(3-CHLOROPHENYL)-3-OXO-1-PIPERAZINYL)METHYL)-1H-IMIDAZOL-1-YL)METHYL)-, MONOHYDROCHLORIDE

Sources:

Systematic Name

English

BENZONITRILE, 4-((5-((4-(3-CHLOROPHENYL)-3-OXO-1-PIPERAZINYL)METHYL)-1H-IMIDAZOL-1-YL)METHYL)-, HYDROCHLORIDE (1:1)

Sources:

Systematic Name

English

Classification Tree Code System Code

Source:

NCI_THESAURUS

C2020