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Details

Stereochemistry ACHIRAL
Molecular Formula C22H20ClN5O
Molecular Weight 405.88
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of L-778123 FREE BASE

SMILES

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

InChI

InChIKey=JNUGFGAVPBYSHF-UHFFFAOYSA-N
InChI=1S/C22H20ClN5O/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

HIDE SMILES / InChI
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 paclitaxel to determine efficacy as a treatment for both recurrent or refractory solid tumors, and lymphomas.

Originator

Curator's Comment: # Merck Research Laboratories

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
98.0 nM [IC50]
2.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8.09 μM
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
18.1 μM
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.8 μM
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.79 μM
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1310.7 μM × h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3179.5 μM × h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
472.5 μM × h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
134.4 μM × h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.6 h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.7 h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.6 h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.2 h
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
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

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

Patents

Sample Use Guides

Unknown
Route of Administration: Intravenous
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 FREE BASE
Common Name English
BENZONITRILE, 4-((5-((4-(3-CHLOROPHENYL)-3-OXO-1-PIPERAZINYL)METHYL)-1H-IMIDAZOL-1-YL)METHYL)-
Systematic Name English
Code System Code Type Description
CAS
183499-57-2
Created by admin on Sat Dec 16 10:56:27 GMT 2023 , Edited by admin on Sat Dec 16 10:56:27 GMT 2023
PRIMARY
FDA UNII
31ZXM8ZKQ3
Created by admin on Sat Dec 16 10:56:27 GMT 2023 , Edited by admin on Sat Dec 16 10:56:27 GMT 2023
PRIMARY
EPA CompTox
DTXSID501031253
Created by admin on Sat Dec 16 10:56:27 GMT 2023 , Edited by admin on Sat Dec 16 10:56:27 GMT 2023
PRIMARY
PUBCHEM
216454
Created by admin on Sat Dec 16 10:56:27 GMT 2023 , Edited by admin on Sat Dec 16 10:56:27 GMT 2023
PRIMARY